bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustaining Integrated Behavioral Health Practice Without Sacrificing the Continuum of Care
Authors: Herbst Rachel Becker , Margolis Kathryn L. , McClellan Brigitte B. , Herndon Jason L. , Millar Amanda M. , Talmi Ayelet
Published: June 2018

This article describes how an innovative model of practice transformation, used by 4 integrated pediatric primary care practices over a 2 year grant period, promoted the practice of integrated primary care (IPC) behavioral health services. Practice transformation was possible through the implementation of an alternative billing strategy to enhance sustainability, effective utilization of clinical productivity to provide meaningful patient services, and the identification of strategies to further the practice of IPC. Specifically, we provide: (a) a description of the diversity of billing strategies typically used by pediatric practices utilizing integrated care and how those strategies are impacted by state health care policies; (b) a description of the grant, including the service delivery model, implementation phase, and data collection procedures; (c) results of implementation and billing/reimbursement data that were collected across the 4 practices; (d) an analysis of how billing strategies are critical in defining implementation strategies within pediatric integrated care; and (e) lessons learned about how billing strategies must be flexible and amenable to change over time to stay current with ever-changing health care policies and reimbursement models.

Implications for Impact Statement

This article describes how an innovative model of practice transformation, used by 4 integrated pediatric primary care practices over a 2 year grant period, promoted the practice of integrated behavioral health services in primary care. We provide lessons learned about financing primary care using innovative billing strategies beyond the use mental health diagnoses and billing codes, which enable psychologists to focus more on preventative and health behavior change services.
An Introduction to Cost-Effectiveness Acceptability Curves
Authors: Yarbro Jessica L. , McKnight Patrick E.
Published: June 2018

Recent changes to health care reimbursement and funding have made cost-effectiveness analyses more relevant for pediatric psychologists. Evaluating and presenting uncertainty around cost-effectiveness estimates is important for proper reporting of results and represents one area where pediatric psychologists may have limited training. This article seeks to address this gap by providing pediatric psychologists with an introduction to cost-effectiveness acceptability curves (CEACs), a method for reporting and presenting uncertainty that is consistent with the Consolidated Health Economic Evaluation Reporting Standards. Using practical examples, we provide information about how CEACs are constructed and interpreted. By supporting a greater understanding about uncertainty in cost-effective estimates, we hope that this article aids pediatric psychologists in their production and consumption of cost-effectiveness research.

Implications for Impact Statement

Cost-effectiveness analyses represent a complex topic that is increasingly relevant for pediatric psychologists. The article provides an overview of cost-effectiveness acceptability curves, which are one method for presenting the results of a cost-effectiveness analysis. Understanding these analyses will help pediatric psychologists better advocate for continued reimbursement of their services.
Mechanically reconfigurable architectured graphene for tunable plasmonic resonances
Authors: Kang Pilgyu , Kim Kyoung-Ho , Park Hong-Gyu , Nam SungWoo
Published: June 2018

Graphene nanostructures with complex geometries have been widely explored for plasmonic applications, as their plasmonic resonances exhibit high spatial confinement and gate tunability. However, edge effects in graphene and the narrow range over which plasmonic resonances can be tuned have limited the use of graphene in optical and optoelectronic applications. Here we present a novel approach to achieve mechanically reconfigurable and strongly resonant plasmonic structures based on crumpled graphene. Our calculations show that mechanical reconfiguration of crumpled graphene structures enables broad spectral tunability for plasmonic resonances from mid- to near-infrared, acting as a new tuning knob combined with conventional electrostatic gating. Furthermore, a continuous sheet of crumpled graphene shows strong confinement of plasmons, with a high near-field intensity enhancement of ~1 × 104. Finally, decay rates for a dipole emitter are significantly enhanced in the proximity of finite-area biaxially crumpled graphene flakes. Our findings indicate that crumpled graphene provides a platform to engineer graphene-based plasmonics through broadband manipulation of strong plasmonic resonances.
Microcavity electrodynamics of hybrid surface plasmon polariton modes in high-quality multilayer trench gratings
Authors: Liu Xiaoyi , Gao Jinbo , Gao Jinsong , Yang Haigui , Wang Xiaoyi , Wang Tongtong , Shen Zhenfeng , Liu Zhen , Liu Hai , Zhang Jian , Li Zizheng , Wang Yanchao , Li Qiang
Published: June 2018

In common plasmonic structures, absorption and radiation losses are often mutually restricted and can seriously influence the device performance. The current study presents a compound structure composed of multilayer grating stripes and multilayer shallow trenches. A small depth was adopted for the trench configuration to exclude the extra bend loss. These two sections supported Fabry–Perot resonance and cavity modes, respectively, with hybrid modes formed through intercoupling. In addition, the total loss for the entire framework was clearly reduced due to the introduction of the trench geometry, indicating that both absorption and radiation losses were successfully taken into consideration in the compound structure. Significantly, such a low loss realized by the hybridization of surface plasmon polariton modes has rarely been seen before. Moreover, the debatable relationship between the total and partial quality factors was described for the first time based on a hybrid mode analysis to establish a new approach to investigate the different resonance modes. In the detailed calculation process, the relative electric field intensity was first adopted to stipulate the effective areas for the various modes, which is more reasonable than using the common definition that is based on a unit structure. The multilayer trench grating exhibited a relatively low loss without weakening energy localization, which is significant in the design of plasmonic devices.
Cocaine engages a non-canonical, dopamine-independent, mechanism that controls neuronal excitability in the nucleus accumbens
Authors: Delint-Ramirez Ilse , Garcia-Oscos Francisco , Segev Amir , Kourrich Saïd
Published: June 2018

Drug-induced enhanced dopamine (DA) signaling in the brain is a canonical mechanism that initiates addiction processes. However, indirect evidence suggests that cocaine also triggers non-canonical, DA-independent, mechanisms that contribute to behavioral responses to cocaine, including psychomotor sensitization and cocaine self-administration. Identifying these mechanisms and determining how they are initiated is fundamental to further our understanding of addiction processes. Using physiologically relevant in vitro tractable models, we found that cocaine-induced hypoactivity of nucleus accumbens shell (NAcSh) medium spiny neurons (MSNs), one hallmark of cocaine addiction, is independent of DA signaling. Combining brain slice studies and site-directed mutagenesis in HEK293T cells, we found that cocaine binding to intracellular sigma-1 receptor (σ1) initiates this mechanism. Subsequently,σ1 binds to Kv1.2 potassium channels, followed by accumulation of Kv1.2 in the plasma membrane, thereby depressing NAcSh MSNs firing. This mechanism is specific to D1 receptor-expressing MSNs. Our study uncovers a mechanism for cocaine that bypasses DA signaling and leads to addiction-relevant neuroadaptations, thereby providing combinatorial strategies for treating stimulant abuse.
Biogeographic patterns of abundant and rare bacterioplankton in three subtropical bays resulting from selective and neutral processes
Authors: Mo Yuanyuan , Zhang Wenjing , Yang Jun , Lin Yuanshao , Yu Zheng , Lin Senjie
Published: June 2018

Unraveling the relative importance of ecological processes regulating microbial community structure is a central goal in microbial ecology. Here, we used high-throughput sequencing to examine the relative contribution of selective and neutral processes in the assembly of abundant and rare subcommunities from three subtropical bays of China. We found that abundant and rare bacterial taxa were distinctly different in diversity, despite the similar biogeographic patterns and strong distance-decay relationships, but the dispersal of rare bacterial taxa was more limited than that of abundant taxa. Furthermore, the environmental (selective processes) and spatial (neutral processes) factors seemed to govern the assembly and biogeography of abundant and rare bacterial subcommunities, although both factors explained only a small fraction of variation within the rare subcommunity. More importantly, variation partitioning (based on adjusted R2 in redundancy analysis) showed that spatial factors exhibited a slightly greater influence on both abundant and rare subcommunities compared to environmental selection; however, the abundant subcommunity had a much stronger response to spatial factors (17.3% of pure variance was explained) than that shown by the rare bacteria (3.5%). These results demonstrate that environmental selection and neutral processes explained the similar biogeographic patterns of abundant and rare subcommunities, but a large proportion of unexplained variation in the rare taxa (91.1%) implies that more complex assembly mechanisms may exist to shape the rare bacterial assemblages in the three subtropical bays.
Correction to: JNK–NQO1 axis drives TAp73-mediated tumor suppression upon oxidative and proteasomal stress
Authors: Kostecka A. , Sznarkowska A. , Meller K. , Acedo P. , Shi Y. , Sakil H. A. Mohammad , Kawiak A. , Lion M. , Królicka A. , Wilhelm M. , Inga A. , Zawacka-Pankau J.
Published: June 2018

Correction to: Cell Death Dis.5, e1484 (2014); https://doi.org/10.1038/cddis.2014.408; published online 23 October 2014.
Loss of Drosha underlies dopaminergic neuron toxicity in models of Parkinson’s disease
Authors: Wang Ronglin , Lu Fangfang , Zhu Gang , Feng Dayun , Nie Tiejian , Tao Kai , Yang Shaosong , Lei Jie , Huang Lu , Mao Zixu , Yang Qian
Published: June 2018

MiRNAs, a group of powerful modulator of gene expression, participate in multiple cellular processes under physiological and pathological conditions. Emerging evidence shows that Drosha, which controls the initial step in canonical miRNA biogenesis, is involved in modulating cell survival and death in models of several diseases. However, the role of Drosha in Parkinson’s disease (PD) has not been well established. Here, we show that the level of Drosha decreases in 6-OHDA-induced cellular and animal models of PD. 6-OHDA induced a p38 MAPK-dependent phosphorylation of Drosha. This triggered Drosha degradation. Enhancing the level of Drosha protected the dopaminergic (DA) neurons from 6-OHDA-induced toxicity in both in vitro and in vivo models of PD and alleviated the motor deficits of PD mice. These findings reveal that Drosha plays a critical role in the survival of DA neurons and suggest that stress-induced destabilization of Drosha may be part of the pathological process in PD.
Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis
Authors: Ding Suling , Abudupataer Mieradilijiang , Zhou Zheliang , Chen Jinmiao , Li Hui , Xu Lili , Zhang Weiwei , Zhang Shuning , Zou Yunzeng , Hong Tao , Wang Timothy C. , Yang Xiangdong , Ge Junbo
Published: June 2018

Histamine is a widely distributed biogenic amine involved in the regulation of an array of biological processes. Serum histamine level is markedly elevated in the early stages of acute myocardial infarction, whereas the role it plays remains unclear. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine production, and cardiac injury is significantly aggravated in HDC knockout mice (HDC−/−), in which histamine is deficient. We also observed that autophagy was highly activated in cardiomyocytes of HDC−/− mice post acute myocardial infarction (AMI), which was abolished by compensation of exogenous histamine. The in vivo and in vitro results showed that acting through histamine 1 receptor, histamine increased miR-206 and miR-216b, which worked in concert to target to Atg13, resulting in the reduction of autophagy activation under hypoxia and AMI condition. Further study revealed that Atg13 interacted with FADD to promote the activation of caspase-8 and cell apoptosis. Taken together, these data unveil a novel intracellular signaling pathway involved in histamine regulating myocardial autophagy and apoptosis under hypoxia and AMI condition, which might help to more comprehensively evaluate the usage of histamine receptor antagonists and to develop new therapeutic targets for myocardial infarction.
Cardiomyocyte-specific disruption of Cathepsin K protects against doxorubicin-induced cardiotoxicity
Authors: Guo Rui , Hua Yinan , Ren Jun , Bornfeldt Karin E. , Nair Sreejayan
Published: June 2018

The lysosomal cysteine protease Cathepsin K is elevated in humans and animal models of heart failure. Our recent studies show that whole-body deletion of Cathepsin K protects mice against cardiac dysfunction. Whether this is attributable to a direct effect on cardiomyocytes or is a consequence of the global metabolic alterations associated with Cathepsin K deletion is unknown. To determine the role of Cathepsin K in cardiomyocytes, we developed a cardiomyocyte-specific Cathepsin K-deficient mouse model and tested the hypothesis that ablation of Cathepsin K in cardiomyocytes would ameliorate the cardiotoxic side-effects of the anticancer drug doxorubicin. We used an α-myosin heavy chain promoter to drive expression of Cre, which resulted in over 80% reduction in protein and mRNA levels of cardiac Cathepsin K at baseline. Four-month-old control (Myh-Cre-; Ctskfl/fl) and Cathepsin K knockout (Myh-Cre+; Ctskfl/fl) mice received intraperitoneal injections of doxorubicin or vehicle, 1 week following which, body and tissue weight, echocardiographic properties, cardiomyocyte contractile function and Ca2+-handling were evaluated. Control mice treated with doxorubicin exhibited a marked increase in cardiac Cathepsin K, which was associated with an impairment in cardiac structure and function, evidenced as an increase in end-systolic and end-diastolic diameters, decreased fractional shortening and wall thickness, disruption in cardiac sarcomere and microfilaments and impaired intracellular Ca2+ homeostasis. In contrast, the aforementioned cardiotoxic effects of doxorubicin were attenuated or reversed in mice lacking cardiac Cathepsin K. Mechanistically, Cathepsin K-deficiency reconciled the disturbance in cardiac energy homeostasis and attenuated NF-κB signaling and apoptosis to ameliorate doxorubicin-induced cardiotoxicity. Cathepsin K may represent a viable drug target to treat cardiac disease.
The natural compound GL22, isolated from Ganoderma mushrooms, suppresses tumor growth by altering lipid metabolism and triggering cell death
Authors: Liu Ge , Wang Kai , Kuang Shan , Cao Ruobing , Bao Li , Liu Rui , Liu Hongwei , Sun Chaomin
Published: June 2018

Cancer cells rewire their metabolism to satisfy the demands of uncontrolled proliferation and survival. The reprogramming of lipid metabolism supports tumor growth, metastasis, and therapy-resistance. Therefore, targeting lipid metabolic reprogramming is a potential cancer treatment strategy. We recently isolated the novel natural triterpene GL22 from Ganoderma leucocontextum, a traditional Chinese medicine. Here, we show that GL22 significantly inhibits the growth of the liver cancer cell line Huh7.5 in vitro and of Huh7.5-derived tumor xenografts in vivo. We further find that GL22 induces mitochondrial dysfunction and cell death in Huh7.5 cells, in part due to fatty acid immobilization and loss of the mitochondrial lipid cardiolipin, which has vital structural and metabolic functions. Importantly, we demonstrate that GL22 treatment decreases the expression of fatty acid-binding proteins (FABPs), which likely underlies the loss of cardiolipin, mitochondrial dysfunction, and cell death. The over-expressions of FABPs prevented the GL22-induced cell death, loss of cardiolipin, decrease of ATP production, and reduction of oxygen consumption rate in Huh7.5 cells. Our results support targeting lipid metabolism via manipulating FABPs as a cancer treatment strategy, and promote Chinese medicine as an important source of novel anticancer drugs.
The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis
Authors: Ren Lin-Lin , Yan Ting-Ting , Shen Chao-Qin , Tang Jia-Yin , Kong Xuan , Wang Ying-Chao , Chen Jinxian , Liu Qiang , He Jie , Zhong Ming , Chen Hao-Yan , Hong Jie , Fang Jing-Yuan
Published: June 2018

The abnormal expression of microRNAs (miRNAs) in colorectal cancer (CRC) progression has been widely investigated. It was reported that the same hairpin RNA structure could generate mature products from each strand, termed 5p and 3p, which binds different target mRNAs. Here, we explored the expression, functions, and mechanisms of miR-514b-3p and miR-514b-5p in CRC cells and tissues. We found that miR-514b-3p was significantly down-regulated in CRC samples, and the ratio of miR-514b-3p/miR-514b-5p increased from advanced CRC, early CRC to matched normal colorectal tissues. Follow-up functional experiments illustrated that miR-514b-3p and miR-514b-5p had distinct effects through interacting with different target genes: MiR-514b-3p reduced CRC cell migration, invasion and drug resistance through increasing epithelial marker and decreasing mesenchymal marker expressions, conversely, miR-514b-5p exerted its pro-metastatic properties in CRC by promoting EMT progression. MiR-514b-3p overexpressing CRC cells developed tumors more slowly in mice compared with control cells, however, miR-514b-5p accelerated tumor metastasis. Overall, our data indicated that though miR-514b-3p and miR-514b-5p were transcribed from the same RNA hairpin, each microRNA has distinct effect on CRC metastasis.
Mesenchymal stromal cells-derived matrix Gla protein contribute to the alleviation of experimental colitis
Authors: Feng Yuan , Liao Yan , Huang Weijun , Lai Xingqiang , Luo Jing , Du Cong , Lin Junyi , Zhang Zhongyuan , Qiu Dongbo , Liu Qiuli , Shen Huiyong , Xiang Andy Peng , Zhang Qi
Published: June 2018

Crohn’s disease (CD) is a chronic inflammatory bowel disease that is difficult to treat. However, previous preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach, whereas the exact underlying molecular mechanisms of MSCs in treating CD remain unclear. Furthermore, the heterogeneity of MSCs, as well as the in vivo microenvironments may influence the therapeutic efficacy. In our previous study, we found that a subpopulation of mouse MSCs with a high expression of matrix Gla protein (MGP), one of the members of vitamin K-dependent protein family, possessed better immunoregulatory properties. Therefore, in this study we investigate whether the abundant MSCs-derived MGP participate in the therapeutic mechanisms for MSCs treating CD. Obvious suppression of cell proliferation and cytokine production in T cells were observed in vitro through MSCs-derived MGP. Moreover, MGP alleviated the clinical and histopathological severity of colonic inflammation in mouse experimental colitis models to a remarkable degree. Our results indicate that MGP might be a novel important mediator of MSCs-mediated immunomodulation in treating CD.
Ablation of somatostatin cells leads to impaired pancreatic islet function and neonatal death in rodents
Authors: Li Na , Yang Zhao , Li Qing , Yu Zhen , Chen Xu , Li Jia-Cheng , Li Bo , Ning Shang-Lei , Cui Min , Sun Jin-Peng , Yu Xiao
Published: June 2018

The somatostatin (SST)-secreting cells were mainly distributed in the pancreatic islets, brain, stomach and intestine in mammals and have many physiological functions. In particular, the SST-secreting δ cell is the third most common cell type in the islets of Langerhans. Recent studies have suggested that dysregulation of paracrine interaction between the pancreatic δ cells and β cells results in impaired glucose homeostasis and contributes to diabetes development. However, direct evidence of the functional importance of SST cells in glucose homeostasis control is still lacking. In the present study, we specifically ablated SST-secreting cells by crossing Sst-cre transgenic mice with R26
DTA
mice (Sst
Cre
R26
DTA
). The Sst
Cre
R26
DTA
mice exhibited neonatal death. The life spans of these mice with severe hypoglycemia were extended by glucose supplementation. Moreover, we observed that SST cells deficiency led to increased insulin content and excessive insulin release, which might contribute to the observed hypoglycemia. Unexpectedly, although SST is critical for the regulation of insulin content, factors other than SST that are produced by pancreatic δ cells via their endogenous corticotropin-releasing hormone receptor 2 (CRHR2) activity play the main roles in maintaining normal insulin release, as well as neonatal glucose homeostasis in the resting state. Taken together, our results identified that the SST cells in neonatal mouse played critical role in control of insulin release and normal islet function. Moreover, we provided direct in vivo evidence of the functional importance of the SST cells, which are essential for neonatal survival and the maintenance of glucose homeostasis.
FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells
Authors: Nguyen Minh Binh , Cohen Idan , Kumar Vinod , Xu Zijian , Bar Carmit , Dauber-Decker Katherine L. , Tsai Pai-Chi , Marangoni Pauline , Klein Ophir D. , Hsu Ya-Chieh , Chen Ting , Mikkola Marja L. , Ezhkova Elena
Published: June 2018

Merkel cells are innervated mechanosensory cells responsible for light-touch sensations. In murine dorsal skin, Merkel cells are located in touch domes and found in the epidermis around primary hairs. While it has been shown that Merkel cells are skin epithelial cells, the progenitor cell population that gives rise to these cells is unknown. Here, we show that during embryogenesis, SOX9-positive (+) cells inside hair follicles, which were previously known to give rise to hair follicle stem cells (HFSCs) and cells of the hair follicle lineage, can also give rise to Merkel Cells. Interestingly, while SOX9 is critical for HFSC specification, it is dispensable for Merkel cell formation. Conversely, FGFR2 is required for Merkel cell formation but is dispensable for HFSCs. Together, our studies uncover SOX9(+) cells as precursors of Merkel cells and show the requirement for FGFR2-mediated epithelial signalling in Merkel cell specification.
Structural and functional analysis of mRNA export regulation by the nuclear pore complex
Authors: Lin Daniel H. , Correia Ana R. , Cai Sarah W. , Huber Ferdinand M. , Jette Claudia A. , Hoelz André
Published: June 2018

The nuclear pore complex (NPC) controls the passage of macromolecules between the nucleus and cytoplasm, but how the NPC directly participates in macromolecular transport remains poorly understood. In the final step of mRNA export, the DEAD-box helicase DDX19 is activated by the nucleoporins Gle1, Nup214, and Nup42 to remove Nxf1•Nxt1 from mRNAs. Here, we report crystal structures of Gle1•Nup42 from three organisms that reveal an evolutionarily conserved binding mode. Biochemical reconstitution of the DDX19 ATPase cycle establishes that human DDX19 activation does not require IP6, unlike its fungal homologs, and that Gle1 stability affects DDX19 activation. Mutations linked to motor neuron diseases cause decreased Gle1 thermostability, implicating nucleoporin misfolding as a disease determinant. Crystal structures of human Gle1•Nup42•DDX19 reveal the structural rearrangements in DDX19 from an auto-inhibited to an RNA-binding competent state. Together, our results provide the foundation for further mechanistic analyses of mRNA export in humans.
Implementation of multilayer perceptron network with highly uniform passive memristive crossbar circuits
Authors: Bayat F. Merrikh , Prezioso M. , Chakrabarti B. , Nili H. , Kataeva I. , Strukov D.
Published: June 2018

The progress in the field of neural computation hinges on the use of hardware more efficient than the conventional microprocessors. Recent works have shown that mixed-signal integrated memristive circuits, especially their passive (0T1R) variety, may increase the neuromorphic network performance dramatically, leaving far behind their digital counterparts. The major obstacle, however, is immature memristor technology so that only limited functionality has been reported. Here we demonstrate operation of one-hidden layer perceptron classifier entirely in the mixed-signal integrated hardware, comprised of two passive 20 × 20 metal-oxide memristive crossbar arrays, board-integrated with discrete conventional components. The demonstrated network, whose hardware complexity is almost 10× higher as compared to previously reported functional classifier circuits based on passive memristive crossbars, achieves classification fidelity within 3% of that obtained in simulations, when using ex-situ training. The successful demonstration was facilitated by improvements in fabrication technology of memristors, specifically by lowering variations in their I–V characteristics.
Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels
Authors: Zheng Wang , Yang Xiaoyong , Hu Ruikun , Cai Ruiqi , Hofmann Laura , Wang Zhifei , Hu Qiaolin , Liu Xiong , Bulkley David , Yu Yong , Tang Jingfeng , Flockerzi Veit , Cao Ying , Cao Erhu , Chen Xing-Zhen
Published: June 2018

PKD2 and PKD1 genes are mutated in human autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to respond to ligand(s) and/or mechanical stimuli. Here, we identify a two-residue hydrophobic gate in PKD2L1, and a single-residue hydrophobic gate in PKD2. We find that a PKD2 gain-of-function gate mutant effectively rescues PKD2 knockdown-induced phenotypes in embryonic zebrafish. The structure of a PKD2 activating mutant F604P by cryo-electron microscopy reveals a π- to α-helix transition within the pore-lining helix S6 that leads to repositioning of the gate residue and channel activation. Overall the results identify hydrophobic gates and a gating mechanism of PKD2 and PKD2L1.
Publisher Correction: Studying light-harvesting models with superconducting circuits
Authors: Potočnik Anton , Bargerbos Arno , Schröder Florian A. Y. N. , Khan Saeed A. , Collodo Michele C. , Gasparinetti Simone , Salathé Yves , Creatore Celestino , Eichler Christopher , Türeci Hakan E. , Chin Alex W. , Wallraff Andreas
Published: June 2018

The original HTML version of this Article contained an error in the second mathematical expression in the fourth sentence of the fourth paragraph of the ‘Excitation transfer with uniform white noise’ section of the Results. This has been corrected in the HTML version of the Article.

The original PDF version of this Article incorrectly stated that ‘Correspondence and requests for materials should be addressed to A. Pčn.’, instead of the correct ‘Correspondence and requests for materials should be addressed to A. Potočnik’. This has been corrected in the PDF version of the Article.
A surface-modified antiperovskite as an electrocatalyst for water oxidation
Authors: Zhu Yanping , Chen Gao , Zhong Yijun , Chen Yubo , Ma Nana , Zhou Wei , Shao Zongping
Published: June 2018

An efficient and cost-effective oxygen evolution reaction (OER) electrocatalyst is key for electrochemical energy generation and storage technologies. Here, the rational design and in situ formation of an antiperovskite-based hybrid with a porous conductive Cu1−xNNi3−y (x and y represent defect) core and amorphous FeNiCu (oxy)hydroxide shell is reported as a promising water oxidation electrocatalyst, showing outstanding performance. Benefiting from the unique advantage of core–shell structure, as well as the synergistic effect of Fe, Ni, and Cu and the highly porous hierarchical structure, the hybrid catalyst exhibits highly efficient and robust OER performance in alkaline environments, outperforming the benchmark IrO2 catalyst in several aspects. Our findings demonstrate the application potential of antiperovskite-based materials in the field of electrocatalysis, which may inspire insights into the development of novel materials for energy generation and storage applications.
Coherent exciton-vibrational dynamics and energy transfer in conjugated organics
Authors: Nelson Tammie R. , Ondarse-Alvarez Dianelys , Oldani Nicolas , Rodriguez-Hernandez Beatriz , Alfonso-Hernandez Laura , Galindo Johan F. , Kleiman Valeria D. , Fernandez-Alberti Sebastian , Roitberg Adrian E. , Tretiak Sergei
Published: June 2018

Coherence, signifying concurrent electron-vibrational dynamics in complex natural and man-made systems, is currently a subject of intense study. Understanding this phenomenon is important when designing carrier transport in optoelectronic materials. Here, excited state dynamics simulations reveal a ubiquitous pattern in the evolution of photoexcitations for a broad range of molecular systems. Symmetries of the wavefunctions define a specific form of the non-adiabatic coupling that drives quantum transitions between excited states, leading to a collective asymmetric vibrational excitation coupled to the electronic system. This promotes periodic oscillatory evolution of the wavefunctions, preserving specific phase and amplitude relations across the ensemble of trajectories. The simple model proposed here explains the appearance of coherent exciton-vibrational dynamics due to non-adiabatic transitions, which is universal across multiple molecular systems. The observed relationships between electronic wavefunctions and the resulting functionalities allows us to understand, and potentially manipulate, excited state dynamics and energy transfer in molecular materials.
UBXN3B positively regulates STING-mediated antiviral immune responses
Authors: Yang Long , Wang Leilei , Ketkar Harshada , Ma Jinzhu , Yang Guang , Cui Shuang , Geng Tingting , Mordue Dana G. , Fujimoto Toyoshi , Cheng Gong , You Fuping , Lin Rongtuan , Fikrig Erol , Wang Penghua
Published: June 2018

The ubiquitin regulatory X domain-containing proteins (UBXNs) are likely involved in diverse biological processes. Their physiological functions, however, remain largely unknown. Here we present physiological evidence that UBXN3B positively regulates stimulator-of-interferon genes (STING) signaling. We employ a tamoxifen-inducible Cre-LoxP approach to generate systemic Ubxn3b knockout in adult mice as the Ubxn3b-null mutation is embryonically lethal. Ubxn3b−/−, like Sting−/− mice, are highly susceptible to lethal herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infection, which is correlated with deficient immune responses when compared to Ubxn3b+/+ littermates. HSV-1 and STING agonist-induced immune responses are also reduced in several mouse and human Ubxn3b−/− primary cells. Mechanistic studies demonstrate that UBXN3B interacts with both STING and its E3 ligase TRIM56, and facilitates STING ubiquitination, dimerization, trafficking, and consequent recruitment and phosphorylation of TBK1. These results provide physiological evidence that links the UBXN family with antiviral immune responses.
Soft transparent graphene contact lens electrodes for conformal full-cornea recording of electroretinogram
Authors: Yin Rongkang , Xu Zheng , Mei Ming , Chen Zhaolong , Wang Kai , Liu Yanlin , Tang Tao , Priydarshi Manish Kr. , Meng Xuejuan , Zhao Siyuan , Deng Bing , Peng Hailin , Liu Zhongfan , Duan Xiaojie
Published: June 2018

Visual electrophysiology measurements are important for ophthalmic diagnostic testing. Electrodes with combined optical transparency and softness are highly desirable, and sometimes indispensable for many ocular electrophysiology measurements. Here we report the fabrication of soft graphene contact lens electrodes (GRACEs) with broad-spectrum optical transparency, and their application in conformal, full-cornea recording of electroretinography (ERG) from cynomolgus monkeys. The GRACEs give higher signal amplitude than conventional ERG electrodes in recordings of various full-field ERG responses. High-quality topographic mapping of multifocal ERG under simultaneous fundus monitoring is realized. A conformal and tight interface between the GRACEs and cornea is revealed. Neither corneal irritation nor abnormal behavior of the animals is observed after ERG measurements with GRACEs. Furthermore, spatially resolved ERG recordings on rabbits with graphene multi-electrode array reveal a stronger signal at the central cornea than the periphery. These results demonstrate the unique capabilities of the graphene-based electrodes for in vivo visual electrophysiology studies.
The role of water in fault lubrication
Authors: Diao Yijue , Espinosa-Marzal Rosa M.
Published: June 2018

The friction between two adjacent tectonic plates under shear loading may dictate seismic activities. To advance the understanding of mechanisms underlying fault strength, we investigate the frictional characteristics of calcite in an aqueous environment. By conducting single-asperity friction experiments using an atomic force microscope, here we show three pathways of energy dissipation with increasing contact stresses: viscous shear of a lubricious solution film at low normal stresses; shear-promoted thermally activated slip, similar to dry friction but influenced by the hydrated ions localized at the interface; and pressure-solution facilitated slip at sufficiently high stresses and slow sliding velocities, which leads to a prominent decrease in friction. It is also shown that the composition of the aqueous solution affects the frictional response. We use this nanoscale evidence to scrutinize the role of brines on fault behavior and argue that pressure solution provides a weakening mechanism of the fault strength at the level of single-asperity contacts.
Co-speciation in bedbug Wolbachia parallel the pattern in nematode hosts
Authors: Balvín Ondřej , Roth Steffen , Talbot Benoit , Reinhardt Klaus
Published: June 2018

Wolbachia bacteria, vertically transmitted intracellular endosymbionts, are associated with two major host taxa in which they show strikingly different symbiotic modes. In some taxa of filarial nematodes, where Wolbachia are strictly obligately beneficial to the host, they show complete within- and among-species prevalence as well as co-phylogeny with their hosts. In arthropods, Wolbachia usually are parasitic; if beneficial effects occurs, they can be facultative or obligate, related to host reproduction. In arthropods, the prevalence of Wolbachia varies within and among taxa, and no co-speciation events are known. However, one arthropod species, the common bedbug Cimex lectularius was recently found to be dependent on the provision of biotin and riboflavin by Wolbachia, representing a unique case of Wolbachia providing nutritional and obligate benefits to an arthropod host, perhaps even in a mutualistic manner. Using the presence of presumably functional biotin gene copies, our study demonstrates that the obligate relationship is maintained at least in 10 out of 15 species of the genera Cimex and Paracimex. The remaining five species harboured Wolbachia as well, demonstrating the first known case of 100% prevalence of Wolbachia among higher arthropod taxa. Moreover, we show the predicted co-cladogenesis between Wolbachia and their bedbug hosts, also as the first described case of Wolbachia co-speciation in arthropods.
Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy
Authors: Yuasa Kazuki , Okubo Kazumasa , Yoda Masaki , Otsu Kinya , Ishii Yasuyuki , Nakamura Masaya , Itoh Yoshiki , Horiuchi Keisuke
Published: June 2018

The loss of skeletal muscle mass is a major cause of falls and fractures in the elderly, leading to compromised independence and a decrease in the quality of life. However, only a few therapeutic interventions leading to marginal clinical benefits in patients with this condition are currently available. Therefore, the demand to further understand the pathology of muscle atrophy and establish a treatment modality for patients with muscle atrophy is significant. p38α mitogen-activated protein kinase (p38α MAPK) is a ubiquitous signaling molecule that is implicated in various cellular functions, including cell proliferation, differentiation, and senescence. In the present study, we generated a mutant line in which p38α MAPK is specifically abrogated in muscle tissues. Compared with the control mice, these mutant mice are significantly resistant to denervation-induced muscle atrophy, suggesting that p38α MAPK positively regulates muscle atrophy. We also identified CAMK2B as a potential downstream target of p38α MAPK and found that the pharmacological inhibition of CAMK2B activity suppresses denervation-induced muscle atrophy. Altogether, our findings identify p38α MAPK as a novel regulator of muscle atrophy and suggest that the suppression of intracellular signaling mediated by p38α MAPK serves as a potential target for the treatment of muscle atrophy.
Publisher Correction: Kif1bp loss in mice leads to defects in the peripheral and central nervous system and perinatal death
Authors: Hirst Caroline S. , Stamp Lincon A. , Bergner Annette J. , Hao Marlene M. , Tran Mai X. , Morgan Jan M. , Dutschmann Matthias , Allen Andrew M. , Paxinos George , Furlong Teri M. , McKeown Sonja J. , Young Heather M.
Published: June 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Development of a Nanobody-based lateral flow assay to detect active Trypanosoma congolense infections
Authors: Pinto Torres Joar E. , Goossens Julie , Ding Jianzu , Li Zeng , Lu Shaohong , Vertommen Didier , Naniima Peter , Chen Rui , Muyldermans Serge , Sterckx Yann G.-J. , Magez Stefan
Published: June 2018

Animal African trypanosomosis (AAT), a disease affecting livestock, is caused by parasites of the Trypanosoma genus (mainly T. vivax and T. congolense). AAT is widespread in Sub-Saharan Africa, where it continues to impose a heavy socio-economic burden as it renders development of sustainable livestock rearing very strenuous. Active case-finding and the identification of infected animals prior to initiation of drug treatment requires the availability of sensitive and specific diagnostic tests. In this paper, we describe the development of two heterologous sandwich assay formats (ELISA and LFA) for T. congolense detection through the use of Nanobodies (Nbs). The immunisation of an alpaca with a secretome mix from two T. congolense strains resulted in the identification of a Nb pair (Nb44/Nb42) that specifically targets the glycolytic enzyme pyruvate kinase. We demonstrate that the Nb44/Nb42 ELISA and LFA can be employed to detect parasitaemia in plasma samples from experimentally infected mice and cattle and, additionally, that they can serve as ‘test-of-cure’ tools. Altogether, the findings in this paper present the development and evaluation of the first Nb-based antigen detection LFA to identify active T. congolense infections.
Treating the Intestine with Oral ApoA-I Mimetic Tg6F Reduces Tumor Burden in Mouse Models of Metastatic Lung Cancer
Authors: Chattopadhyay Arnab , Yang Xinying , Mukherjee Pallavi , Sulaiman Dawoud , Fogelman Hannah R. , Grijalva Victor , Dubinett Steven , Wasler Tonya C. , Paul Manash K. , Salehi-Rad Ramin , Mack Julia J. , Iruela-Arispe M. Luisa , Navab Mohamad , Fogelman Alan M. , Reddy Srinivasa T.
Published: June 2018

Having demonstrated that apolipoprotein A-I (apoA-I) mimetic peptides ameliorate cancer in mouse models, we sought to determine the mechanism for the anti-tumorigenic function of these peptides. CT-26 cells (colon cancer cells that implant and grow into tumors in the lungs) were injected into wild-type BALB/c mice. The day after injection, mice were either continued on chow or switched to chow containing 0.06% of a concentrate of transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F). After four weeks, the number of lung tumors was significantly lower in Tg6F-fed mice. Gene expression array analyses of jejunum and lung identified Notch pathway genes significantly upregulated, whereas osteopontin (Spp1) was significantly downregulated by Tg6F in both jejunum and lung. In jejunum, Tg6F increased protein levels for Notch1, Notch2, Dll1, and Dll4. In lung, Tg6F increased protein levels for Notch1 and Dll4 and decreased Spp1. Tg6F reduced oxidized phospholipid levels (E06 immunoreactivity) and reduced 25-hydroxycholesterol (25-OHC) levels, which are known to inhibit Notch1 and induce Spp1, respectively. Notch pathway promotes anti-tumorigenic patrolling monocytes, while Spp1 facilitates pro-tumorigenic myeloid derived suppressor cells (MDSCs) formation. Tg6F-fed mice had higher numbers of patrolling monocytes in jejunum and in lung (p < 0.02), and lower plasma levels of Spp1 with reduced numbers of MDSCs in jejunum and in lung (p < 0.03). We conclude that Tg6F alters levels of specific oxidized lipids and 25-OHC to modulate Notch pathways and Spp1, which alter small intestine immune cells, leading to similar changes in lung that reduce tumor burden.
(−)-Gochnatiolide B, synthesized from dehydrocostuslactone, exhibits potent anti-bladder cancer activity in vitro and in vivo
Authors: Chen Yuwen , Li Wenhua , Zeng Zhongqiu , Tang Yaxiong
Published: June 2018

With limited success achieved in bladder cancer patient management, novel agents are in urgent need for the purpose of therapy and prevention. As a sesquiterpenoid dimmer isolated from Gochnatia pomculat, (−)-gochnatiolide B has been bio-mimetically synthesized in multiple steps with a poor yield, which heavily limited the further research and clinical application. Herein, (−)-gochnatiolide B was synthesized beginning with dehydrocostuslactone in four steps with a total yield of 26%. MTT assays showed that (−)-gochnatiolide B inhibited the growth of vast majority of human cancer cells especially bladder cancer cells. Mechanistically, (−)-gochnatiolide B induced the increased expression of pro-apoptotic proteins and the decreased expression of anti-apoptosis proteins and further resulted in apoptosis of T24 cells. (−)-Gochnatiolide B induced G1 arrest which associated with SKP2 downregulation, leading to p27/Kip1 accumulation and downregulation of cyclin D1 in T24 cells. Furthermore, in vivo studies showed that (−)-gochnatiolide B remarkably inhibited tumor growth by 81% compared with vehicle control. Taken together, (−)-gochnatiolide B exhibits inhibitory activity against bladder cancer cells both in vitro and in vivo by inducing apoptosis, which suggests that (−)-gochnatiolide B could be an important candidate compound for prevention and treatment of bladder cancer.
Enteric bacteria boost defences against oxidative stress in Entamoeba histolytica
Authors: Varet Hugo , Shaulov Yana , Sismeiro Odile , Trebicz-Geffen Meirav , Legendre Rachel , Coppée Jean-Yves , Ankri Serge , Guillen Nancy
Published: June 2018

Oxidative stress is one of the strongest toxic factors in nature: it can harm or even kill cells. Cellular means of subverting the toxicity of oxidative stress are important for the success of infectious diseases. Many types of bacterium inhabit the intestine, where they can encounter pathogens. During oxidative stress, we analyzed the interplay between an intestinal parasite (the pathogenic amoeba Entamoeba histolytica - the agent of amoebiasis) and enteric bacteria (microbiome residents, pathogens and probiotics). We found that live enteric bacteria protectedE. histolyticaagainst oxidative stress. By high-throughput RNA sequencing, two amoebic regulatory modes were observed with enteric bacteria but not with probiotics. The first controls essential elements of homeostasis, and the second the levels of factors required for amoeba survival. Characteristic genes of both modes have been acquired by the amoebic genome through lateral transfer from the bacterial kingdom (e.g. glycolytic enzymes and leucine-rich proteins). Members of the leucine-rich are homologous to proteins from anti-bacterial innate immune such as Toll-like receptors. The factors identified here suggest that despite its old age in evolutionary terms, the protozoanE. histolyticadisplays key characteristics of higher eukaryotes’ innate immune systems indicating that components of innate immunity existed in the common ancestor of plants and animals.
Facile preparation and adsorption performance of graphene oxide-manganese oxide composite for uranium
Authors: Yang Aili , Zhu Yukuan , Huang C. P.
Published: June 2018

To overcome the limits of low adsorption capacity and the separation difficulty of solid from liquid phase for graphene oxide (GO), a novel nanocomposite graphene oxide-manganese oxide (GOMO) was facilely fabricated under ultrasonic radiation. The structures and micro-morphology of the products were characterized by fourier transform infrared (FT-IR) spectroscopy, raman shift spectroscopy, X-ray diffraction (XRD) pattern and scanning electron microscopy (SEM). The effect of solution pH, adsorbent dose, contact time, initial uranium concentration, ionic strength and temperature on uranium removal efficiency was studied by batch adsorption experiments. The product GOMO was used to examine the feasibility of the removal of high salt content in uranium-containing wastewater. The adsorption results were fitted using the Langmuir and Freundlich isotherm models. The kinetic parameters in the adsorption process were measured and fitted. Five adsorption/desorption cycles were performed using 3 M HNO3 as the regenerant in order to evaluate the reuse of GOMO.
Clinical significance of CCR7+CD8+ T cells in kidney transplant recipients with allograft rejection
Authors: Kim Kyoung Woon , Kim Bo-Mi , Doh Kyoung Chan , Cho Mi-La , Yang Chul Woo , Chung Byung Ha
Published: June 2018

The regulatory function of CCR7+CD8+ T cells against effector T-cells involved in T-cell mediated rejection (TCMR) in kidney transplant recipients was investigated. In vitro experiments explored the ability of CCR7+CD8+ T cells to suppress T-cell proliferation under T-cell activation conditions or during coculture with human renal proximal tubular epithelial cells (HRPTEpiC). In an ex vivo experiment, the proportion of CCR7+/CD8+, FOXP3+/CCR7+CD8+ T and effector T-cell subsets were compared between the normal biopsy control (NC, n = 17) and TCMR group (n = 17). The CCR7+CD8+ T cells significantly suppressed the proliferation of CD4+ T cells and significantly decreased the proportion of IFN-γ+ and IL-17+/CD4+ T cells and inflammatory cytokine levels (all p < 0.05). After coculturing with HRPTEpiC, CCR7+CD8+ T cells also suppressed T-cell differentiation into IL-2+, IFN-γ+, and IL-17+/CD4+ T cells (all p < 0.05). The TCMR group had significantly fewer CCR7+/CD8+ and FOXP3+/CCR7+CD8+ T in comparison with the NC group, but the proportions of all three effector T-cell subsets were increased in the TCMR group (all p < 0.05). The proportion of CCR7+/CD8+ T was inversely correlated with those of effector T-cell subsets. The results indicate that CCR7+CD8+ T cells may regulate effector T-cells involved in TCMR in an in vitro and in an ex vivo transplant model.