bluuebunny/crossref_metadata_2025 huggingface dataset:
Twist1/Dnmt3a and miR186 establish a regulatory circuit that controls inflammation-associated prostate cancer progression
Authors: Zhao X , Deng R , Wang Y , Zhang H , Dou J , Li L , Du Y , Chen R , Cheng J , Yu J
Published: April 2017

Increasing evidences suggest that inflammatory microenvironment has a crucial role in prostate cancer (PCa) progression; however, the underlying mechanisms are unclear. Here, we used the inflammation-associated prostate cellular transformation model to screen out a crucial microRNA, miR186, which was significantly downregulated in the transformed cells and effectively rescued the transformed phenotype. On stimulation of inflammatory cytokines, the activated nuclear factor kappa B (NF-κB)/p65 was able to induce miR186 expression through binding to its promoter in non-transformed cells, whereas this pathway was lost in transformed cells. Interestingly, Twist1, which is a reported downstream target of miR186, was responsible for the loss of NF-κB/p65-miR186 pathway. Twist1 downregulated miR186 expression in a novel negative feedback loop binding to the E-box and simultaneously recruiting Dnmt3a, which facilitated the site-specific CpG methylation of the miR186 promoter, thereby blocked the transcriptional activity of NF-κB/p65 and the responsiveness of miR186 to inflammatory signals. The high level of Twist1 triggered this feedback loop that underlies the epigenetic switch, which was essential for maintaining transformed and advanced PCa state. Finally, our clinical data confirmed that the CpG methylation and miR186 expression levels were closely related with inflammation-associated human PCa progression.
MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation
Authors: Jin X , Pan Y , Wang L , Zhang L , Ravichandran R , Potts P R , Jiang J , Wu H , Huang H
Published: April 2017

Hepatocellular carcinoma (HCC) is one of the leading cause of cancer death in the world. Fructose-1,6-biphosphatase (FBP1), a rate-limiting enzyme in gluconeogenesis, has been identified recently as a tumor suppressor in HCC and other cancer types. In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRIM28. We further showed that expression of TRIM28 increased glucose consumption and lactate production by promoting FBP1 degradation in HCC cells and that FBP1 is a key mediator of TRIM28-induced HCC growth in culture and in mice. Moreover, we demonstrated that FBP1 and TRIM28 protein levels inversely correlated in HCC patient specimens. Finally, we showed that the proteasome inhibitor bortezomib mitigated the Warburg effect by inhibiting FBP1 degradation in HCC. Collectively, our findings not only identify oncogenic MAGE-TRIM28 complex-mediated proteasome degradation of FBP1 as a key mechanism underlying downregulation of FBP1 proteins in HCC, but also reveal that MAGE-TRIM28-regulated reprogramming of cancer cell metabolism and HCC tumorigenesis is mediated, at least in part, through FBP1 degradation.
The Breathing, Thinking, Functioning clinical model: a proposal to facilitate evidence-based breathlessness management in chronic respiratory disease
Authors: Spathis Anna , Booth Sara , Moffat Catherine , Hurst Rhys , Ryan Richella , Chin Chloe , Burkin Julie
Published: April 2017

Refractory breathlessness is a highly prevalent and distressing symptom in advanced chronic respiratory disease. Its intensity is not reliably predicted by the severity of lung pathology, with unhelpful emotions and behaviours inadvertently exacerbating and perpetuating the problem. Improved symptom management is possible if clinicians choose appropriate non-pharmacological approaches, but these require engagement and commitment from both patients and clinicians. The Breathing Thinking Functioning clinical model is a proposal, developed from current evidence, that has the potential to facilitate effective symptom control, by providing a rationale and focus for treatment.
Energy-efficient quantum computing
Authors: Ikonen Joni , Salmilehto Juha , Möttönen Mikko
Published: April 2017

In the near future, one of the major challenges in the realization of large-scale quantum computers operating at low temperatures is the management of harmful heat loads owing to thermal conduction of cabling and dissipation at cryogenic components. This naturally raises the question that what are the fundamental limitations of energy consumption in scalable quantum computing. In this work, we derive the greatest lower bound for the gate error induced by a single application of a bosonic drive mode of given energy. Previously, such an error type has been considered to be inversely proportional to the total driving power, but we show that this limitation can be circumvented by introducing a qubit driving scheme which reuses and corrects drive pulses. Specifically, our method serves to reduce the average energy consumption per gate operation without increasing the average gate error. Thus our work shows that precise, scalable control of quantum systems can, in principle, be implemented without the introduction of excessive heat or decoherence.
Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal
Authors: González Raquel , Moffatt Garrett , Hagner Andrew , Sinha Sarthak , Shin Wisoo , Rahmani Waleed , Chojnacki Andrew , Biernaskie Jeff
Published: April 2017

Hair follicle regeneration is dependent on reciprocal signaling between epithelial cells and underlying mesenchymal cells within the dermal papilla. Hair follicle dermal stem cells reside within the hair follicle mesenchyme, self-renew in vivo, and function to repopulate the dermal papilla and regenerate the connective tissue sheath with each hair cycle. The identity and temporal pattern of signals that regulate hair follicle dermal stem cell function are not known. Here, we show that platelet-derived growth factor signaling is crucial for hair follicle dermal stem cell function and platelet-derived growth factor deficiency results in a progressive depletion of the hair follicle dermal stem cell pool and their progeny. Using αSMACreER
T2
:Rosa
YFP
:Pdgfrα
flox
mice, we ablated Pdgfrα specifically within the adult hair follicle dermal stem cell lineage. This led to significant loss of hair follicle dermal stem cell progeny in connective tissue sheath and dermal papilla of individual follicles, and a progressive reduction in total number of anagen hair follicles containing YFP+ve cells. As well, over successive hair cycles, fewer hair follicle dermal stem cells were retained within each telogen hair follicle suggesting an impact on hair follicle dermal stem cell self-renewal. To further assess this, we grew prospectively isolated hair follicle dermal stem cells (Sox2GFP+ve αSMAdsRed+ve) in the presence or absence of platelet-derived growth factor ligands. Platelet-derived growth factor-BB enhanced proliferation, increased the frequency of Sox2+ve hair follicle dermal stem cell progeny and improved inductive capacity of hair follicle dermal stem cells in an ex vivo hair follicle formation assay. Similar effects on proliferation were observed in adult human SKPs. Our findings impart novel insights into the signals that comprise the adult hair follicle dermal stem cell niche and suggest that platelet-derived growth factor signaling promotes self renewal, is essential to maintain the hair follicle dermal stem cell pool and ultimately their regenerative capacity within the hair follicle.
Differential regulation of PKD isoforms in oxidative stress conditions through phosphorylation of a conserved Tyr in the P+1 loop
Authors: Cobbaut Mathias , Derua Rita , Döppler Heike , Lou Hua Jane , Vandoninck Sandy , Storz Peter , Turk Benjamin E. , Seufferlein Thomas , Waelkens Etienne , Janssens Veerle , Van Lint Johan
Published: April 2017

Protein kinases are essential molecules in life and their crucial function requires tight regulation. Many kinases are regulated via phosphorylation within their activation loop. This loop is embedded in the activation segment, which additionally contains the Mg2+ binding loop and a P + 1 loop that is important in substrate binding. In this report, we identify Abl-mediated phosphorylation of a highly conserved Tyr residue in the P + 1 loop of protein kinase D2 (PKD2) during oxidative stress. Remarkably, we observed that the three human PKD isoforms display very different degrees of P + 1 loop Tyr phosphorylation and we identify one of the molecular determinants for this divergence. This is paralleled by a different activation mechanism of PKD1 and PKD2 during oxidative stress. Tyr phosphorylation in the P + 1 loop of PKD2 increases turnover for Syntide-2, while substrate specificity and the role of PKD2 in NF-κB signaling remain unaffected. Importantly, Tyr to Phe substitution renders the kinase inactive, jeopardizing its use as a non-phosphorylatable mutant. Since large-scale proteomics studies identified P + 1 loop Tyr phosphorylation in more than 70 Ser/Thr kinases in multiple conditions, our results do not only demonstrate differential regulation/function of PKD isoforms under oxidative stress, but also have implications for kinase regulation in general.
Male New Zealand robins (Petroica longipes) cater to their mate’s desire when sharing food in the wild
Authors: Shaw Rachael C. , MacKinlay Regan D. , Clayton Nicola S. , Burns Kevin C.
Published: April 2017

In many species that have bi-parental care, food-sharing males provide vital nutritional resources to their mates during reproduction. However, it is currently unknown whether females can signal specific desires to their mates, or if males can cater to female desire in the wild. Here we investigate whether and how wild male North Island robins (Petroica longipes) respond to changes in their mates’ desires and nutritional need when sharing food. We demonstrate that wild female robins’ desire for particular foods changes over short time periods; when given the choice between two types of insect larvae, females prefer the type they have not recently eaten. In our experiments, wild male robins preferentially shared the larvae type that their mate was most likely to desire and also increased the quantity of food shared if she had begun incubating. Males catered to their mates’ desire when female behaviour was the only cue available to guide their choices. This is the first evidence that females may behaviourally communicate their specific food desires to their mates, enabling males to cater to fine-scale changes in their mates’ nutritional requirements in the wild. Such a simple behaviour-reading mechanism has the potential to be widespread among other food-sharing species.
Balancing Speed and Coverage by Sequential Seeding in Complex Networks
Authors: Jankowski Jarosław , Bródka Piotr , Kazienko Przemysław , Szymanski Boleslaw K. , Michalski Radosław , Kajdanowicz Tomasz
Published: April 2017

Information spreading in complex networks is often modeled as diffusing information with certain probability from nodes that possess it to their neighbors that do not. Information cascades are triggered when the activation of a set of initial nodes – seeds – results in diffusion to large number of nodes. Here, several novel approaches for seed initiation that replace the commonly used activation of all seeds at once with a sequence of initiation stages are introduced. Sequential strategies at later stages avoid seeding highly ranked nodes that are already activated by diffusion active between stages. The gain arises when a saved seed is allocated to a node difficult to reach via diffusion. Sequential seeding and a single stage approach are compared using various seed ranking methods and diffusion parameters on real complex networks. The experimental results indicate that, regardless of the seed ranking method used, sequential seeding strategies deliver better coverage than single stage seeding in about 90% of cases. Longer seeding sequences tend to activate more nodes but they also extend the duration of diffusion. Various variants of sequential seeding resolve the trade-off between the coverage and speed of diffusion differently.
The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness of glioma initiating cells
Authors: Hiramatsu Hiroaki , Kobayashi Kazuyoshi , Kobayashi Kyousuke , Haraguchi Takeshi , Ino Yasushi , Todo Tomoki , Iba Hideo
Published: April 2017

Glioma initiating cells (GICs) are thought to contribute to therapeutic resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in adults. Although the stem-like properties of GICs, such as self-renewal and tumorigenicity, are epigenetically regulated, the role of a major chromatin remodeling complex in human, the SWI/SNF complex, remains unknown in these cells. We here demonstrate that the SWI/SNF core complex, that is associated with a unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays essential roles in stemness maintenance in GICs. The serum-induced differentiation of GICs downregulated the endogenous expression of DPF1 and DPF3a, and the shRNA-mediated knockdown of each gene reduced both sphere-forming ability and tumor-forming activity in a mouse xenograft model. Rescue experiments revealed that DPF1 has dominant effects over DPF3a. Notably, whereas we have previously reported that d4-family members can function as adaptor proteins between the SWI/SNF complex and NF-κB dimers, this does not significantly contribute to maintaining the stemness properties of GICs. Instead, these proteins were found to link a corepressor complex containing the nuclear receptor, TLX, and LSD1/RCOR2 with the SWI/SNF core complex. Collectively, our results indicate that DPF1 and DPF3a are potential therapeutic targets for glioblastoma.
Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments
Authors: Garza-Cervantes Javier A. , Chávez-Reyes Arturo , Castillo Elena C. , García-Rivas Gerardo , Antonio Ortega-Rivera Oscar , Salinas Eva , Ortiz-Martínez Margarita , Gómez-Flores Sara Leticia , Peña-Martínez Jorge A. , Pepi-Molina Alan , Treviño-González Mario T. , Zarate Xristo , Elena Cantú-Cárdenas María , Enrique Escarcega-Gonzalez Carlos , Morones-Ramírez J. Rubén
Published: April 2017

Due to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main drawback of transition metals is their toxicity in eukaryotic cells. Here, we show that the barriers to use them as therapeutic agents could be mitigated by combining them with silver. We demonstrate that synergism of combinatorial treatments (Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8-fold their antimicrobial effect, when compared to their individual effects, against E. coli and B. subtilis. We find that most combinatorial treatments exhibit synergistic antimicrobial effects at low/non-toxic concentrations to human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub-inhibitory concentrations, demonstrating this to be a possible mechanism of the synergistic behavior. Together, these results suggest that these combinatorial treatments will play an important role in the future development of antimicrobial agents and treatments against infections. In specific, the cytotoxicity experiments show that the combinations have great potential in the treatment of topical infections.
Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
Authors: Han Seungrie , Yang Soo Hyun , Kim Jin Yong , Mo Seojung , Yang Esther , Song Ki Myung , Ham Byung-Joo , Mechawar Naguib , Turecki Gustavo , Lee Hyun Woo , Kim Hyun
Published: April 2017

Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair. Moreover, knockdown of CHAT in the rat habenula was sufficient to evoke anhedonia-like behavior. The anhedonia-like behavior induced by CHAT knockdown was not reversed by chronic administration of the selective serotonin reuptake inhibitor fluoxetine. To determine whether habenular cholinergic signaling is associated with regulation of dopamine neurons in the ventral tegmental area (VTA) and serotonin neurons in the dorsal raphe nucleus (DRN), we used CHAT::cre transgenic mice expressing the Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Pharmacogenetic activation of habenular cholinergic neurons induces the excitation of dopamine neurons in the VTA and reduces the immunoreactivity of 5-hydroxytryptamine (5-HT) in the DRN. Habenular cholinergic gene down-regulation was recapitulated in the postmortem habenula of suicide victims diagnosed with major depressive disorder (MDD).
Probing the local nature of excitons and plasmons in few-layer MoS2
Authors: Nerl Hannah Catherine , Winther Kirsten Trøstrup , Hage Fredrik S. , Thygesen Kristian Sommer , Houben Lothar , Backes Claudia , Coleman Jonathan N. , Ramasse Quentin M. , Nicolosi Valeria
Published: April 2017

Excitons and plasmons are the two most fundamental types of collective electronic excitations occurring in solids. Traditionally, they have been studied separately using bulk techniques that probe their average energetic structure over large spatial regions. However, as the dimensions of materials and devices continue to shrink, it becomes crucial to understand how these excitations depend on local variations in the crystal- and chemical structure on the atomic scale. Here, we use monochromated low-loss scanning-transmission-electron-microscopy electron-energy-loss spectroscopy, providing the best simultaneous energy and spatial resolution achieved to-date to unravel the full set of electronic excitations in few-layer MoS2 nanosheets over a wide energy range. Using first-principles, many-body calculations we confirm the excitonic nature of the peaks at ~ 2 and ~ 3 eV in the experimental electron-energy-loss spectrum and the plasmonic nature of higher energy-loss peaks. We also rationalise the non-trivial dependence of the electron-energy-loss spectrum on beam and sample geometry such as the number of atomic layers and distance to steps and edges. Moreover, we show that the excitonic features are dominated by the long wavelength (q = 0) components of the probing field, while the plasmonic features are sensitive to a much broader range of q-vectors, indicating a qualitative difference in the spatial character of the two types of collective excitations. Our work provides a template protocol for mapping the local nature of electronic excitations that open new possibilities for studying photo-absorption and energy transfer processes on a nanometer scale.
Protective molecular passivation of black phosphorus
Authors: Artel Vlada , Guo Qiushi , Cohen Hagai , Gasper Raymond , Ramasubramaniam Ashwin , Xia Fengnian , Naveh Doron
Published: April 2017

Black phosphorus is a fascinating layered material, with extraordinary anisotropic mechanical, optical and electronic properties. However, the sensitivity of black phosphorus to oxygen and moisture poses significant challenges for technological applications of this unique material. Here, we report a viable solution that overcomes degradation of few-layer black phosphorus by passivating the surface with self-assembled monolayers of octadecyltrichlorosilane that provide long-term stability in ambient conditions. Importantly, we show that this treatment does not cause any undesired carrier doping of the bulk channel material, thanks to the emergent hierarchical interface structure. Our approach is compatible with conventional electronic materials processing technologies thus providing an immediate route toward practical applications in black phosphorus devices.
Detection and mapping of DNA methylation with 2D material nanopores
Authors: Qiu Hu , Sarathy Aditya , Schulten Klaus , Leburton Jean-Pierre
Published: April 2017

DNA methylation is an epigenetic modification involving the addition of a methyl group to DNA, which is heavily involved in gene expression and regulation, thereby critical to the progression of diseases such as cancer. In this work we show that detection and localization of DNA methylation can be achieved with nanopore sensors made of two-dimensional materials such as graphene and molybdenum di-sulfide. We label each DNA methylation site with a methyl-CpG binding domain protein (MBD1), and combine molecular dynamics simulations with electronic transport calculations to investigate the translocation of the methylated DNA–MBD1 complex through two-dimensional material nanopores under external voltage biases. The passage of the MBD1-labeled methylation site through the pore is identified by dips in the current blockade induced by the DNA strand, as well as by peaks in the transverse electronic sheet current across the two-dimensional layer. The position of the methylation sites can be clearly recognized by the relative positions of the dips in the recorded ionic current blockade with an estimated error ranging from 0 to 16%. Finally, we define the spatial resolution of the two-dimensional material nanopore device as the minimal distance between two methylation sites identified within a single measurement, which is 15 base pairs by ionic current recognition, but as low as 10 base pairs by transverse electronic conductance detection, indicating better resolution with this latter technique. The present approach opens a new route for precise and efficient profiling of DNA methylation.
Correction: Corrigendum: Narrowing the spread in CMIP5 model projections of air-sea CO2 fluxes
Authors: Wang Lei , Huang Jianbin , Luo Yong , Zhao Zongci
Published: April 2017

Scientific Reports 6: Article number: 37548; published online: 28 November 2016; updated: 10 April 2017. The Acknowledgements section in this Article is incomplete. “We acknowledge the World Climate Research Programme’s Working Group on Coupled Modeling, which is responsible for CMIP. We thank the climate groups (listed in Table 1) for providing the model output.
Metastasis-associated protein 1 is an upstream regulator of DNMT3a and stimulator of insulin-growth factor binding protein-3 in breast cancer
Authors: Deivendran S. , Marzook Hezlin , Santhoshkumar T. R. , Kumar Rakesh , Pillai M. Radhakrishna
Published: April 2017

Despite a recognized role of DNA methyltransferase 3a (DNMT3a) in human cancer, the nature of its upstream regulator(s) and relationship with the master chromatin remodeling factor MTA1, continues to be poorly understood. Here, we found an inverse relationship between the levels of MTA1 and DNMT3a in human cancer and that high levels of MTA1 in combination of low DNMT3a status correlates well with poor survival of breast cancer patients. We discovered that MTA1 represses DNMT3a expression via HDAC1/YY1 transcription factor complex. Because IGFBP3 is an established target of DNMT3a, we investigated the effect of MTA1 upon IGFBP3 expression, and found a coactivator role of MTA1/c-Jun/Pol II coactivator complex upon the IGFBP3 transcription. In addition, MTA1 overexpression correlates well with low levels of DNMT3a which, in turn also correlates with a high IGFBP3 status in breast cancer patients and predicts a poor clinical outcome for breast cancer patients. These findings suggest that MTA1 could regulate the expression of IGFBP3 in both DNMT3a-dependent and -independent manner. Together findings presented here recognize an inherent role of MTA1 as a modifier of DNMT3a and IGFBP3 expression, and consequently, the role of MTA1-DNMT3a-IGFBP3 axis in breast cancer progression.
Correction: Corrigendum: CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses
Authors: Dyer Douglas P. , Pallas Kenneth , Medina-Ruiz Laura , Schuette Fabian , Wilson Gillian J. , Graham Gerard J.
Published: April 2017

Scientific Reports 7: Article number: 42681; published online: 16 February 2017; updated: 10 April 2017. The original version of this Article contained a typographical error in the spelling of the author Laura Medina-Ruiz, which was incorrectly given as Laura Medina Ruiz. This has now been correctedin the PDF and HTML versions of the Article.
Antiviral activity of chlorogenic acid against influenza A (H1N1/H3N2) virus and its inhibition of neuraminidase
Authors: Ding Yue , Cao Zeyu , Cao Liang , Ding Gang , Wang Zhenzhong , Xiao Wei
Published: April 2017

Lonicera japonica Thunb, rich in chlorogenic acid (CHA), is used for viral upper respiratory tract infection treatment caused by influenza virus, parainfluenza virus, and respiratory syncytial virus, ect in China. It was reported that CHA reduced serum hepatitis B virus level and death rate of influenza virus-infected mice. However, the underlying mechanisms of CHA against the influenza A virus have not been fully elucidated. Here, the antiviral effects and potential mechanisms of CHA against influenza A virus were investigated. CHA revealed inhibitory against A/PuertoRico/8/1934(H1N1) (EC50 = 44.87 μM), A/Beijing/32/92(H3N2) (EC50 = 62.33 μM), and oseltamivir-resistant strains. Time-course analysis showed CHA inhibited influenza virus during the late stage of infectious cycle. Indirect immunofluorescence assay indicated CHA down-regulated the NP protein expression. The inhibition of neuraminidase activity confirmed CHA blocked release of newly formed virus particles from infected cells. Intravenous injection of 100 mg/kg/d CHA possessed effective antiviral activity in mice, conferring 60% and 50% protection from death against H1N1 and H3N2, reducing virus titres and alleviating inflammation in the lungs effectively. These results demonstrate that CHA acts as a neuraminidase blocker to inhibit influenza A virus both in cellular and animal models. Thus, CHA has potential utility in the treatment of the influenza virus infection.
Enhanced methane emissions from tropical wetlands during the 2011 La Niña
Authors: Pandey Sudhanshu , Houweling Sander , Krol Maarten , Aben Ilse , Monteil Guillaume , Nechita-Banda Narcisa , Dlugokencky Edward J. , Detmers Rob , Hasekamp Otto , Xu Xiyan , Riley William J. , Poulter Benjamin , Zhang Zhen , McDonald Kyle C. , White James W. C. , Bousquet Philippe , Röckmann Thomas
Published: April 2017

Year-to-year variations in the atmospheric methane (CH4) growth rate show significant correlation with climatic drivers. The second half of 2010 and the first half of 2011 experienced the strongest La Niña since the early 1980s, when global surface networks started monitoring atmospheric CH4 mole fractions. We use these surface measurements, retrievals of column-averaged CH4 mole fractions from GOSAT, new wetland inundation estimates, and atmospheric δ13C-CH4 measurements to estimate the impact of this strong La Niña on the global atmospheric CH4 budget. By performing atmospheric inversions, we find evidence of an increase in tropical CH4 emissions of ∼6–9 TgCH4 yr−1 during this event. Stable isotope data suggest that biogenic sources are the cause of this emission increase. We find a simultaneous expansion of wetland area, driven by the excess precipitation over the Tropical continents during the La Niña. Two process-based wetland models predict increases in wetland area consistent with observationally-constrained values, but substantially smaller per-area CH4 emissions, highlighting the need for improvements in such models. Overall, tropical wetland emissions during the strong La Niña were at least by 5% larger than the long-term mean.
VE-Cadherin Disassembly and Cell Contractility in the Endothelium are Necessary for Barrier Disruption Induced by Tumor Cells
Authors: Aragon-Sanabria Virginia , Pohler Steven E. , Eswar Vikram J. , Bierowski Matthew , Gomez Esther W. , Dong Cheng
Published: April 2017

During metastasis, breakdown of the endothelial barrier is critical for tumor cell extravasation through blood vessel walls and is mediated by a combination of tumor secreted soluble factors and receptor-ligand interactions. However, a complete mechanism governing tumor cell transendothelial migration remains unclear. Here, we investigate the roles of tumor-associated signals in regulating endothelial cell contractility and adherens junction disassembly leading to endothelial barrier breakdown. We show that Src mediates VE-cadherin disassembly in response to metastatic melanoma cells. Through the use of pharmacological inhibitors of cytoskeletal contractility we find that endothelial cell contractility is responsive to interactions with metastatic cancer cells and that reducing endothelial cell contractility abrogates migration of melanoma cells across endothelial monolayers. Furthermore, we find that a combination of tumor secreted soluble factors and receptor-ligand interactions mediate activation of Src within endothelial cells that is necessary for phosphorylation of VE-cadherin and for breakdown of the endothelial barrier. Together, these results provide insight into how tumor cell signals act in concert to modulate cytoskeletal contractility and adherens junctions disassembly during extravasation and may aid in identification of therapeutic targets to block metastasis.
Oldest Varroa tolerant honey bee population provides insight into the origins of the global decline of honey bees
Authors: Brettell L. E. , Martin S. J.
Published: April 2017

The ecto-parasitic mite Varroa destructor has transformed the previously inconsequential Deformed Wing Virus (DWV) into the most important honey bee viral pathogen responsible for the death of millions of colonies worldwide. Naturally, DWV persists as a low level covert infection transmitted between nest-mates. It has long been speculated that Varroa via immunosuppression of the bees, activate a covert infection into an overt one. Here we show that despite Varroa feeding on a population of 20–40 colonies for over 30 years on the remote island of Fernando de Noronha, Brazil no such activation has occurred and DWV loads have remained at borderline levels of detection. This supports the alternative theory that for a new vector borne viral transmission cycle to start, an outbreak of an overt infection must first occur within the host. Therefore, we predict that this honey bee population is a ticking time-bomb, protected by its isolated position and small population size. This unique association between mite and bee persists due to the evolution of low Varroa reproduction rates. So the population is not adapted to tolerate Varroa and DWV, rather the viral quasispecies has simply not yet evolved the necessary mutations to produce a virulent variant.
Evidence for trivial Berry phase and absence of chiral anomaly in semimetal NbP
Authors: Sudesh  , Kumar Pawan , Neha Prakriti , Das Tanmoy , Patnaik Satyabrata
Published: April 2017

The discovery of Weyl semimetals (WSM) has brought forth the condensed matter realization of Weyl fermions, which were previously theorized as low energy excitations in high energy particle physics. Recently, transition metal mono-pnictides are under intense investigation for understanding properties of inversion-symmetry broken Weyl semimetals. Non-trivial Berry phase and chirality are important markers for characterizing topological aspects of Weyl semimetals. Most recently, theoretical calculations predict strong influence of the position of Weyl nodes with respect to Fermi surface and weak disorder that can drive WSMs into chirally symmetric Dirac semimetals. Using magneto-transport measurements in single crystals of WSM NbP, we observe an exceptionally large magnetoresistance at low temperature, which is non-saturating and linear at high fields. The origin of linear transverse magnetoresistance is assigned to charge carrier mobility fluctuations. Negative longitudinal magnetoresistance is not seen, suggesting lack of well-defined chiral anomaly in NbP. Unambiguous Shubnikov-de Haas oscillations are observed at low temperatures that are correlated to a trivial Berry phase corresponding to Fermi surface extrema at 30.5 Tesla. Our results are important towards identifying topological characteristics of Weyl semimetals and their experimental manifestations in the presence of weak disorder.
Water availability drives gas exchange and growth of trees in northeastern US, not elevated CO2 and reduced acid deposition
Authors: Levesque Mathieu , Andreu-Hayles Laia , Pederson Neil
Published: April 2017

Dynamic global vegetation models (DGVM) exhibit high uncertainty about how climate change, elevated atmospheric CO2 (atm. CO2) concentration, and atmospheric pollutants will impact carbon sequestration in forested ecosystems. Although the individual roles of these environmental factors on tree growth are understood, analyses examining their simultaneous effects are lacking. We used tree-ring isotopic data and structural equation modeling to examine the concurrent and interacting effects of water availability, atm. CO2 concentration, and SO4 and nitrogen deposition on two broadleaf tree species in a temperate mesic forest in the northeastern US. Water availability was the strongest driver of gas exchange and tree growth. Wetter conditions since the 1980s have enhanced stomatal conductance, photosynthetic assimilation rates and, to a lesser extent, tree radial growth. Increased water availability seemingly overrides responses to reduced acid deposition, CO2 fertilization, and nitrogen deposition. Our results indicate that water availability as a driver of ecosystem productivity in mesic temperate forests is not adequately represented in DGVMs, while CO2 fertilization is likely overrepresented. This study emphasizes the importance to simultaneously consider interacting climatic and biogeochemical drivers when assessing forest responses to global environmental changes.
Robust rotation of rotor in a thermally driven nanomotor
Authors: Cai Kun , Yu Jingzhou , Shi Jiao , Qin Qing-Hua
Published: April 2017

In the fabrication of a thermally driven rotary nanomotor with the dimension of a few nanometers, fabrication and control precision may have great influence on rotor’s stability of rotational frequency (SRF). To investigate effects of uncertainty of some major factors including temperature, tube length, axial distance between tubes, diameter of tubes and the inward radial deviation (IRD) of atoms in stators on the frequency’s stability, theoretical analysis integrating with numerical experiments are carried out. From the results obtained via molecular dynamics simulation, some key points are illustrated for future fabrication of the thermal driven rotary nanomotor.
Transcriptomic analysis of the biosynthesis, recycling, and distribution of ascorbic acid during leaf development in tea plant (Camellia sinensis (L.) O. Kuntze)
Authors: Li Hui , Huang Wei , Wang Guang-Long , Wang Wen-Li , Cui Xin , Zhuang Jing
Published: April 2017

Ascorbic acid (AsA), known as vitamin C, is an essential nutrient for humans and mainly absorbed from food. Tea plant (Camellia sinensis (L.) O. Kuntze) leaves can be a dietary source of AsA for humans. However, experimental evidence on the biosynthesis, recycling pathway and distribution of AsA during leaf development in tea plants is unclear. To gain insight into the mechanism and distribution of AsA in the tea plant leaf, we identified 18 related genes involved in AsA biosynthesis and recycling pathway based on the transcriptome database of tea plants. Tea plant leaves were used as samples at different developmental stages. AsA contens in tea plant leaves at three developmental stages were measured by reversed-phase high-performance liquid chromatography (RP-HPLC). The correlations between expression levels of these genes and AsA contents during the development of tea plant leaves were discussed. Results indicated that the l-galactose pathway might be the primary pathway of AsA biosynthesis in tea plant leaves. CsMDHAR and CsGGP might play a regulatory role in AsA accumulation in the leaves of three cultivars of tea plants. These findings may provide a further glimpse to improve the AsA accumulation in tea plants and the commercial quality of tea.
Interaction between the exchanged Mn2+ and Yb3+ ions confined in zeolite-Y and their luminescence behaviours
Authors: Ye Shi , Sun Jiayi , Yi Xiong , Wang Yonggang , Zhang Qinyuan
Published: April 2017

Luminescent zeolites exchanged with two distinct and interacted emissive ions are vital but less-studied for the potential applications in white light emitting diodes, solar cells, optical codes, biomedicine and so on. Typical transition metal ion Mn2+ and lanthanide ion Yb3+ are adopted as a case study via their characteristic transitions and the interaction between them. The option is considered with that the former with d-d transition has a large gap between the first excited state 4T1 and the ground state 6A1 (normally >17,000 cm−1) while the latter with f-f transition has no metastable excited state above 10,000 cm−1, which requires the vicinity of these two ions for energy transfer. The results of various characterizations, including BET measurement, photoluminescence spectroscopy, solid-state NMR, and X-ray absorption spectroscopy, etc., show that Yb3+ would preferably enter into the zeolite-Y pores and introduction of Mn2+ would cause aggregation of each other. Herein, cation-cation repulsion may play a significant role for the high valence of Mn2+ and Yb3+ when exchanging the original cations with +1 valence. Energy transfer phenomena between Mn2+ and Yb3+ occur only at elevated contents in the confined pores of zeolite. The research would benefit the design of zeolite composite opto-functional materials.
Dependence of Plant Uptake and Diffusion of Polycyclic Aromatic Hydrocarbons on the Leaf Surface Morphology and Micro-structures of Cuticular Waxes
Authors: Li Qingqing , Li Yungui , Zhu Lizhong , Xing Baoshan , Chen Baoliang
Published: April 2017

The uptake of organic chemicals by plants is considered of great significance as it impacts their environmental transport and fate and threatens crop growth and food safety. Herein, the dependence of the uptake, penetration, and distribution of sixteen polycyclic aromatic hydrocarbons (PAHs) on the morphology and micro-structures of cuticular waxes on leaf surfaces was investigated. Plant surface morphologies and wax micro-structures were examined by scanning emission microscopy, and hydrophobicities of plant surfaces were monitored through contact angle measurements. PAHs in the cuticles and inner tissues were distinguished by sequential extraction, and the cuticle was verified to be the dominant reservoir for the accumulation of lipophilic pollutants. The interspecies differences in PAH concentrations cannot be explained by normalizing them to the plant lipid content. PAHs in the inner tissues became concentrated with the increase of tissue lipid content, while a generally negative correlation between the PAH concentration in cuticles and the epicuticular wax content was found. PAHs on the adaxial and abaxial sides of a leaf were differentiated for the first time, and the divergence between these two sides can be ascribed to the variations in surface morphologies. The role of leaf lipids was redefined and differentiated.
Cisplatin selects short forms of the mitochondrial DNA OriB variant (16184–16193 poly-cytosine tract), which confer resistance to cisplatin
Authors: Amo Taku , Kamimura Naomi , Asano Hiromasa , Asoh Sadamitsu , Ohta Shigeo
Published: April 2017

A number of alternations in mitochondrial DNA (mtDNA) have been reported in different types of cancers, and the role of mtDNA in cancer has been attracting increasing interest. In order to investigate the relationship between mtDNA alternations and chemosensitivity, we constructed cybrid (trans-mitochondrial hybrid) cell lines carrying a HeLa nucleus and the mtDNA of healthy individuals because of the presence of somatic alternations in the mtDNA of many cancer cells. After a treatment with 1.0 μg/mL cisplatin for 10 days, we isolated 100 cisplatin-resistant clones, 70 of which carried the shorter mtDNA OriB variant (16184–16193 poly-cytosine tract), which was located in the control region of mtDNA. Whole mtDNA sequencing of 10 clones revealed no additional alternations. Re-construction of the HeLa nucleus and mtDNA from cisplatin-resistant cells showed that cisplatin resistance was only acquired by mtDNA alternations in the control region, and not by possible alternation(s) in the nuclear genome.
Anti-high mobility group box-1 (HMGB1) antibody inhibits hemorrhage-induced brain injury and improved neurological deficits in rats
Authors: Wang Dengli , Liu Keyue , Wake Hidenori , Teshigawara Kiyoshi , Mori Shuji , Nishibori Masahiro
Published: April 2017

As one of the most lethal stroke subtypes, intracerebral hemorrhage (ICH) is acknowledged as a serious clinical problem lacking effective treatment. Available evidence from preclinical and clinical studies suggests that inflammatory mechanisms are involved in the progression of ICH-induced secondary brain injury. High mobility group box-1 (HMGB1) is a ubiquitous and abundant nonhistone DNA-binding protein, and is also an important proinflammatory molecule once released into the extracellular space from the nuclei. Here, we show that treatment with neutralizing anti-HMGB1 mAb (1 mg/kg, i.v. twice) remarkably ameliorated ICH-injury induced by local injection of collagenase IV in the striatum of rats. Administration of anti-HMGB1 mAb inhibited the release of HMGB1 into the extracellular space in the peri-hematomal region, reduced serum HMGB1 levels and decreased brain edema by protecting blood-brain barrier integrity, in association with decreased activated microglia and the expression of inflammation-related factors at 24 h after ICH. Consequently, anti-HMGB1 mAb reduced the oxidative stress and improved the behavioral performance of rats. These results strongly indicate that HMGB1 plays a critical role in the development of ICH-induced secondary injury through the amplification of plural inflammatory responses. Intravenous injection of neutralizing anti-HMGB1 mAb has potential as a novel therapeutic strategy for ICH.
Four genes essential for recombination define GInts, a new type of mobile genomic island widespread in bacteria
Authors: Bardaji Leire , Echeverría Myriam , Rodríguez-Palenzuela Pablo , Martínez-García Pedro M. , Murillo Jesús
Published: April 2017

Integrases are a family of tyrosine recombinases that are highly abundant in bacterial genomes, actively disseminating adaptive characters such as pathogenicity determinants and antibiotics resistance. Using comparative genomics and functional assays, we identified a novel type of mobile genetic element, the GInt, in many diverse bacterial groups but not in archaea. Integrated as genomic islands, GInts show a tripartite structure consisting of the ginABCD operon, a cargo DNA region from 2.5 to at least 70 kb, and a short AT-rich 3′ end. The gin operon is characteristic of GInts and codes for three putative integrases and a small putative helix-loop-helix protein, all of which are essential for integration and excision of the element. Genes in the cargo DNA are acquired mostly from phylogenetically related bacteria and often code for traits that might increase fitness, such as resistance to antimicrobials or virulence. GInts also tend to capture clusters of genes involved in complex processes, such as the biosynthesis of phaseolotoxin by Pseudomonas syringae. GInts integrate site-specifically, generating two flanking direct imperfect repeats, and excise forming circular molecules. The excision process generates sequence variants at the element attachment site, which can increase frequency of integration and drive target specificity.
Deterministic bead-in-droplet ejection utilizing an integrated plug-in bead dispenser for single bead–based applications
Authors: Kim Hojin , Choi In Ho , Lee Sanghyun , Won Dong-Joon , Oh Yong Suk , Kwon Donghoon , Sung Hyung Jin , Jeon Sangmin , Kim Joonwon
Published: April 2017

This paper presents a deterministic bead-in-droplet ejection (BIDE) technique that regulates the precise distribution of microbeads in an ejected droplet. The deterministic BIDE was realized through the effective integration of a microfluidic single-particle handling technique with a liquid dispensing system. The integrated bead dispenser facilitates the transfer of the desired number of beads into a dispensing volume and the on-demand ejection of bead-encapsulated droplets. Single bead–encapsulated droplets were ejected every 3 s without any failure. Multiple-bead dispensing with deterministic control of the number of beads was demonstrated to emphasize the originality and quality of the proposed dispensing technique. The dispenser was mounted using a plug-socket type connection, and the dispensing process was completely automated using a programmed sequence without any microscopic observation. To demonstrate a potential application of the technique, bead-based streptavidin–biotin binding assay in an evaporating droplet was conducted using ultralow numbers of beads. The results evidenced the number of beads in the droplet crucially influences the reliability of the assay. Therefore, the proposed deterministic bead-in-droplet technology can be utilized to deliver desired beads onto a reaction site, particularly to reliably and efficiently enrich and detect target biomolecules.
Enhanced Terahertz Radiation Generation of Photoconductive Antennas Based on Manganese Ferrite Nanoparticles
Authors: Lai Weien , Mazin Abdulmunem Oday , del Pino Pablo , Pelaz Beatriz , Parak Wolfgang J. , Zhang Qian , Zhang Huaiwu
Published: April 2017

This paper presents a significant effect of manganese ferrite nanoparticles (MnFe2O4 NPs) on the increase of the surface photoconductivity of semiconductors. Herein, the optical characterization of photo-excited carriers of silicon coated with MnFe2O4 NPs was studied by using THz time-domain spectroscopy (THz-TDs). We observed that silicon coated with MnFe2O4 NPs provided a significantly enhanced attenuation of THz radiation in comparison with bare silicon substrates under laser irradiation. The experimental results were assessed in the context of a surface band structure model of semiconductors. In addition, photoconductive antennas coated with MnFe2O4 NPs significantly improved the efficiency of THz radiation generation and signal to noise ratio of the THz signal. This work demonstrates that coating with MnFe2O4 NPs could improve the overall performance of THz systems, and MnFe2O4 NPs could be further used for the implementation of novel optical devices.