bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecosystem Carbon Use Efficiency Is Insensitive to Nitrogen Addition in an Alpine Meadow
Authors: Ma Fangfang , Song Bing , Zhang Fangyue , Quan Quan , Zhou Qingping , Niu Shuli 
Published: July 2018

AbstractCarbon use efficiency (CUE) is an important variable in carbon cycling and a key parameter in biogeochemical models, which is expected to increase with N availability. However, how CUE changes with N input rate remains elusive and lacks field evidence. We implemented a field manipulative experiment to examine effects of N addition with six levels of rate (0, 2, 4, 8, 16, and 32 g·N·m−2·year−1) on canopy CUE (the ratio of net primary productivity [NPP] to gross primary productivity [GPP]) and ecosystem CUE (the ratio of net ecosystem productivity [NEP] to GPP) in an alpine meadow on the Tibetan Plateau in 2014–2016. Over the 3 years, nitrogen addition treatments did not change canopy CUE or ecosystem CUE in comparing with the control, although it significantly increased GPP, NPP, and NEP; those components of CUE had the same response patterns to N addition rates, which shifted from linear responses in the first year to saturation responses thereafter. Moreover, GPP showed a positive linear relationship with NEP, NPP, ecosystem respiration, and autotrophic respiration under each N addition treatment with no changes in slope. The inherent coupling between GPP and ecosystem respiration, as well as GPP and autotrophic respiration, made CUE less sensitive to N addition than carbon fluxes themselves. The conclusions challenge the widely held hypothesis that ecosystem CUE increases with N addition. This study provides the first empirical evidences on the proposition that CUE is insensitive to N availability, which is of importance in model construction and parameterization.
Spatiotemporal Distribution of Microearthquakes and Implications Around the Seismic Gap Between the Wenchuan and Lushan Earthquakes
Authors: Wang Chaoliang , Liang Chuntao , Deng Kai , Huang Yanling , Zhou Lu 
Published: July 2018

AbstractThe mechanism of why the rupture terminated sharply on both sides of the seismic gap between the Wenchuan and Lushan earthquakes is not yet known along the southwestern Longmen Shan fault zone. The accommodation modes of compressional strain and stress are still not known well in the gap subregion. Using the Match and Locate method, we obtained a detailed catalog of background microearthquakes around the seismic gap from May to December 2015. The characteristics of spatiotemporal distribution of the events is highlighted with a complete magnitude of 0.2. These small events tend to concentrate at different depth ranges on two sides of the seismic gap, indicating that the gap serves as a transition zone between the Wenchuan and Lushan source regions. Strain release through microearthquakes is an unlikely candidate for accommodating modes in the gap, because of the sustained deficit of microseismicity. A strong anticorrelation between background seismicity and monthly precipitation variation rate is observed for different magnitude scales. Enhanced seismicity may be activated by the terrestrial water storage reduction next to a precipitation peak with a time lag of 1–2 months during the summer and autumn, indicating a seasonal modulation of seismicity by the water storage cycle. The background microseismicity exhibits prominent responses to precipitation variation due to a short nucleation duration of less than one quarter.
Development of a Pediatric Psychology Practicum for Doctoral Trainees in the Context of Outpatient Pediatric Gastroenterology
Authors: Murphy Lexa K. , Stone Amanda L. , Walker Lynn S. , Acra Sari A. , Hawkins Stacy , Han Gloria T. , McLaughlin F. Joseph 
Published: July 2018

This article demonstrates how the development of a practicum in pediatric psychology in a multidisciplinary clinic provides rich opportunities for doctoral trainees. The process of partnering with a pediatric gastroenterology clinic with limited behavioral health services and developing a practicum that met both clinic needs and trainee goals is described. Initial data assessing utilization, acceptability, and training effectiveness are presented. Medical providers ( N = 11) were asked to complete a brief survey to assess their experience with the trainees; graduates of the training clinic ( N = 3) were asked to retrospectively rate competencies before and after the training practicum. Preliminary data suggest that pediatric psychology services were well utilized and providers reported high levels of acceptability and satisfaction. Graduates of the training practicum reported growth in each competency. This practicum evolved into a tiered 2-year practicum experience that met core competencies in pediatric psychology across multiple domains. Lessons learned are reviewed in order to guide other graduate programs wishing to develop similar pediatric psychology practicum for advanced doctoral students with interests in pediatric psychology. Implications for Impact Statement This article reviews the development of a new clinical psychology training practicum in a pediatric multidisciplinary setting and discusses how this experience addressed core competencies in training in pediatric psychology. The development process is reviewed, initial utilization and acceptability data are presented, and specific lessons learned are provided for training programs interested in developing similar practicum.
Genomic profiling of four cultivated Candidatus Nitrotoga spp. predicts broad metabolic potential and environmental distribution
Authors: Boddicker Andrew M , Mosier Annika C 
Published: July 2018

Abstract
Nitrite-oxidizing bacteria (NOB) play a critical role in the mitigation of nitrogen pollution by metabolizing nitrite to nitrate, which is removed via assimilation, denitrification, or anammox. Recent studies showed that NOB are phylogenetically and metabolically diverse, yet most of our knowledge of NOB comes from only a few cultured representatives. Using cultivation and genomic sequencing, we identified four putative Candidatus Nitrotoga NOB species from freshwater sediments and water column samples in Colorado, USA. Genome analyses indicated highly conserved 16S rRNA gene sequences, but broad metabolic potential including genes for nitrogen, sulfur, hydrogen, and organic carbon metabolism. Genomic predictions suggested that Ca. Nitrotoga can metabolize in low oxygen or anoxic conditions, which may support an expanded environmental niche for Ca. Nitrotoga similar to other NOB. An array of antibiotic and metal resistance genes likely allows Ca. Nitrotoga to withstand environmental pressures in impacted systems. Phylogenetic analyses highlighted a deeply divergent nitrite oxidoreductase alpha subunit (NxrA), suggesting a novel evolutionary trajectory for Ca. Nitrotoga separate from any other NOB and further revealing the complex evolutionary history of nitrite oxidation in the bacterial domain. Ca. Nitrotoga-like 16S rRNA gene sequences were prevalent in globally distributed environments over a range of reported temperatures. This work considerably expands our knowledge of the Ca. Nitrotoga genus and suggests that their contribution to nitrogen cycling should be considered alongside other NOB in wide variety of habitats.
Ricolinostat (ACY-1215) suppresses proliferation and promotes apoptosis in esophageal squamous cell carcinoma via miR-30d/PI3K/AKT/mTOR and ERK pathways
Authors: Cao Jinlin , Lv Wang , Wang Luming , Xu Jinming , Yuan Ping , Huang Sha , He Zhehao , Hu Jian 
Published: July 2018

AbstractRicolinostat (ACY-1215), a first-in-class selective HDAC6 inhibitor, exhibits antitumor effects alone or in combination with other drugs in various cancers. However, its efficacy in esophageal cancer remains unclear. In this study, we found that the high expression of HDAC6 was associated with poor prognosis in esophageal squamous cell carcinoma (ESCC) tissues. Then, we identified that ACY-1215 significantly inhibited cellular proliferation in ESCC, and caused G2/M phase arrest and apoptosis. We further demonstrated that ACY-1215 treatment reduced the expression of PI3K, P-AKT, P-mTOR, and P-ERK1/2 and increased that of Ac-H3K9 and Ac-H4K8. In addition, using miRNA microarray and bioinformatics analysis, we detected that ACY-1215 promoted miR-30d expression, and PI3K regulatory subunit 2 (PIK3R2) was a direct target of miR-30d. Anti-miR-30d partially rescued the G2/M phase arrest and apoptosis caused by ACY-1215 treatment. The reductions in PI3K, P-AKT, and P-mTOR expression were also partially reversed by miR-30d inhibitor. Furthermore, the effects of ACY-1215 inhibited ESCC proliferation were validated in a mouse xenograft model in vivo. In conclusion, our study showed that ACY-1215 suppressed proliferation and promoted apoptosis in ESCC via miR-30d/PI3K/AKT/mTOR and ERK pathways and that ACY-1215 may be a promising antitumor agent in ESCC.
Co-inhibition of mTORC1, HDAC and ESR1α retards the growth of triple-negative breast cancer and suppresses cancer stem cells
Authors: Sulaiman Andrew , McGarry Sarah , Lam Ka Mien , El-Sahli Sara , Chambers Jason , Kaczmarek Shelby , Li Li , Addison Christina , Dimitroulakos Jim , Arnaout Angel , Nessim Carolyn , Yao Zemin , Ji Guang , Song Haiyan , Liu Sheng , Xie Ying , Gadde Suresh , Li Xuguang , Wang Lisheng 
Published: July 2018

AbstractTriple-negative breast cancer (TNBC) is the most refractory subtype of breast cancer. It causes the majority of breast cancer-related deaths, which has been largely associated with the plasticity of tumor cells and persistence of cancer stem cells (CSCs). Conventional chemotherapeutics enrich CSCs and lead to drug resistance and disease relapse. Development of a strategy capable of inhibiting both bulk and CSC populations is an unmet medical need. Inhibitors against estrogen receptor 1, HDACs, or mTOR have been studied in the treatment of TNBC; however, the results are inconsistent. In this work, we found that patient TNBC samples expressed high levels of mTORC1 and HDAC genes in comparison to luminal breast cancer samples. Furthermore, co-inhibition of mTORC1 and HDAC with rapamycin and valproic acid, but neither alone, reproducibly promoted ESR1 expression in TNBC cells. In combination with tamoxifen (inhibiting ESR1), both S6RP phosphorylation and rapamycin-induced 4E-BP1 upregulation in TNBC bulk cells was inhibited. We further showed that fractionated CSCs expressed higher levels of mTORC1 and HDAC than non-CSCs. As a result, co-inhibition of mTORC1, HDAC, and ESR1 was capable of reducing both bulk and CSC subpopulations as well as the conversion of fractionated non-CSC to CSCs in TNBC cells. These observations were partially recapitulated with the cultured tumor fragments from TNBC patients. Furthermore, co-administration of rapamycin, valproic acid, and tamoxifen retarded tumor growth and reduced CD44high/+/CD24low/− CSCs in a human TNBC xenograft model and hampered tumorigenesis after secondary transplantation. Since the drugs tested are commonly used in clinic, this study provides a new therapeutic strategy and a strong rationale for clinical evaluation of these combinations for the treatment of patients with TNBC.
MicroRNA-143 targets ERK5 in granulopoiesis and predicts outcome of patients with acute myeloid leukemia
Authors: Hartmann Jens-Uwe , Bräuer-Hartmann Daniela , Kardosova Miroslava , Wurm Alexander A. , Wilke Franziska , Schödel Cindy , Gerloff Dennis , Katzerke Christiane , Krakowsky Rosanna , Namasu Carolina Yaeko , Bill Marius , Schwind Sebastian , Müller-Tidow Carsten , Niederwieser Dietger , Alberich-Jorda Meritxell , Behre Gerhard 
Published: July 2018

AbstractHematopoiesis, the formation of blood cells from hematopoietic stem cells (HSC), is a highly regulated process. Since the discovery of microRNAs (miRNAs), several studies have shown their significant role in the regulation of the hematopoietic system. Impaired expression of miRNAs leads to disrupted cellular pathways and in particular causes loss of hematopoietic ability. Here, we report a previously unrecognized function of miR-143 in granulopoiesis. Hematopoietic cells undergoing granulocytic differentiation exhibited increased miR-143 expression. Overexpression or ablation of miR-143 expression resulted in accelerated granulocytic differentiation or block of differentiation, respectively. The absence of miR-143 in mice resulted in a reduced number of mature granulocytes in blood and bone marrow. Additionally, we observed an association of high miR-143 expression levels with a higher probability of survival in two different cohorts of patients with acute myeloid leukemia (AML). Overexpression of miR-143 in AML cells impaired cell growth, partially induced differentiation, and caused apoptosis. Argonaute2-RNA-Immunoprecipitation assay revealed ERK5, a member of the MAPK-family, as a target of miR-143 in myeloid cells. Further, we observed an inverse correlation of miR-143 and ERK5 in primary AML patient samples, and in CD34+ HSPCs undergoing granulocytic differentiation and we confirmed functional relevance of ERK5 in myeloid cells. In conclusion, our data describe miR-143 as a relevant factor in granulocyte differentiation, whose expression may be useful as a prognostic and therapeutic factor in AML therapy.
Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson’s disease
Authors: Milanese Chiara , Cerri Silvia , Ulusoy Ayse , Gornati Simona V. , Plat Audrey , Gabriels Sylvia , Blandini Fabio , Di Monte Donato A. , Hoeijmakers Jan H. , Mastroberardino Pier G. 
Published: July 2018

AbstractThe involvement of DNA damage and repair in aging processes is well established. Aging is an unequivocal risk factor for chronic neurodegenerative diseases, underscoring the relevance of investigations into the role that DNA alterations may have in the pathogenesis of these diseases. Consistently, even moderate impairment of DNA repair systems facilitates the onset of pathological features typical of PD that include derangement of the dopaminergic system, mitochondrial dysfunction, and alpha-synuclein stress. The latter establishes a connection between reduced DNA repair capacity and a cardinal feature of PD, alpha-synuclein pathology. It remains to be determined, however, whether alpha-synuclein stress activates in vivo the canonical signaling cascade associated with DNA damage, which is centered on the kinase ATM and substrates such as γH2Ax and 53BP1. Addressing these issues would shed light on age-related mechanisms impinging upon PD pathogenesis and neurodegeneration in particular. We analyzed two different synucleinopathy PD mouse models based either on intranigral delivery of AAV-expressing human alpha-synuclein, or intrastriatal injection of human alpha-synuclein pre-formed fibrils. In both cases, we detected a significant increase in γH2AX and 53BP1 foci, and in phospho-ATM immunoreactivity in dopaminergic neurons, which collectively indicate DNA damage and activation of the DNA damage response. Mechanistic experiments in cell cultures indicate that activation of the DNA damage response is caused, at least in part, by pro-oxidant species because it is prevented by exogenous or endogenous antioxidants, which also rescue mitochondrial anomalies caused by proteotoxic alpha-synuclein. These in vivo and in vitro findings reveal that the cellular stress mediated by alpha-synuclein—a pathological hallmark in PD—elicits DNA damage and activates the DNA damage response. The toxic cascade leading to DNA damage involves oxidant stress and mitochondrial dysfunction The data underscore the importance of DNA quality control for preservation of neuronal integrity and protection against neurodegenerative processes.
A positive feedback loop bi-stably activates fibroblasts
Authors: Yeo So-Young , Lee Keun-Woo , Shin Dongkwan , An Sugyun , Cho Kwang-Hyun , Kim Seok-Hyung 
Published: July 2018

AbstractAlthough fibroblasts are dormant in normal tissue, they exhibit explosive activation during wound healing and perpetual activation in pathologic fibrosis and cancer stroma. The key regulatory network controlling these fibroblast dynamics is still unknown. Here, we report that Twist1, a key regulator of cancer-associated fibroblasts, directly upregulates Prrx1, which, in turn, increases the expression of Tenascin-C (TNC). TNC also increases Twist1 expression, consequently forming a Twist1-Prrx1-TNC positive feedback loop (PFL). Systems biology studies reveal that the Twist1-Prrx1-TNC PFL can function as a bistable ON/OFF switch and regulates fibroblast activation. This PFL can be irreversibly activated under pathologic conditions, leading to perpetual fibroblast activation. Sustained activation of the Twist1-Prrx1-TNC PFL reproduces fibrotic nodules similar to idiopathic pulmonary fibrosis in vivo and is implicated in fibrotic disease and cancer stroma. Considering that this PFL is specific to activated fibroblasts, Twist1-Prrx1-TNC PFL may be a fibroblast-specific therapeutic target to deprogram perpetually activated fibroblasts.
Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury
Authors: Bonizzato Marco , Pidpruzhnykova Galyna , DiGiovanna Jack , Shkorbatova Polina , Pavlova Natalia , Micera Silvestro , Courtine Grégoire 
Published: July 2018

AbstractThe delivery of brain-controlled neuromodulation therapies during motor rehabilitation may augment recovery from neurological disorders. To test this hypothesis, we conceived a brain-controlled neuromodulation therapy that combines the technical and practical features necessary to be deployed daily during gait rehabilitation. Rats received a severe spinal cord contusion that led to leg paralysis. We engineered a proportional brain–spine interface whereby cortical ensemble activity constantly determines the amplitude of spinal cord stimulation protocols promoting leg flexion during swing. After minimal calibration time and without prior training, this neural bypass enables paralyzed rats to walk overground and adjust foot clearance in order to climb a staircase. Compared to continuous spinal cord stimulation, brain-controlled stimulation accelerates and enhances the long-term recovery of locomotion. These results demonstrate the relevance of brain-controlled neuromodulation therapies to augment recovery from motor disorders, establishing important proofs-of-concept that warrant clinical studies.
Transmissive silicon photonic dichroic filters with spectrally selective waveguides
Authors: Magden Emir Salih , Li Nanxi , Raval Manan , Poulton Christopher V. , Ruocco Alfonso , Singh Neetesh , Vermeulen Diedrik , Ippen Erich P. , Kolodziejski Leslie A. , Watts Michael R. 
Published: July 2018

AbstractMany optical systems require broadband filters with sharp roll-offs for efficiently splitting or combining light across wide spectra. While free space dichroic filters can provide broadband selectivity, on-chip integration of these high-performance filters is crucial for the scalability of photonic applications in multi-octave interferometry, spectroscopy, and wideband wavelength-division multiplexing. Here we present the theory, design, and experimental characterization of integrated, transmissive, 1 × 2 port dichroic filters using spectrally selective waveguides. Mode evolution through adiabatic transitions in the demonstrated filters allows for single cutoff and flat-top responses with low insertion losses and octave-wide simulated bandwidths. Filters with cutoffs around 1550 and 2100 nm are fabricated on a silicon-on-insulator platform with standard complementary metal-oxide-semiconductor processes. A filter roll-off of 2.82 dB nm−1 is achieved while maintaining ultra-broadband operation. This new class of nanophotonic dichroic filters can lead to new paradigms in on-chip communications, sensing, imaging, optical synthesis, and display applications.
Linked dimensions of psychopathology and connectivity in functional brain networks
Authors: Xia Cedric Huchuan , Ma Zongming , Ciric Rastko , Gu Shi , Betzel Richard F. , Kaczkurkin Antonia N. , Calkins Monica E. , Cook Philip A. , García de la Garza Angel , Vandekar Simon N. , Cui Zaixu , Moore Tyler M. , Roalf David R. , Ruparel Kosha , Wolf Daniel H. , Davatzikos Christos , Gur Ruben C. , Gur Raquel E. , Shinohara Russell T. , Bassett Danielle S. , Satterthwaite Theodore D. 
Published: July 2018

AbstractNeurobiological abnormalities associated with psychiatric disorders do not map well to existing diagnostic categories. High co-morbidity suggests dimensional circuit-level abnormalities that cross diagnoses. Here we seek to identify brain-based dimensions of psychopathology using sparse canonical correlation analysis in a sample of 663 youths. This analysis reveals correlated patterns of functional connectivity and psychiatric symptoms. We find that four dimensions of psychopathology – mood, psychosis, fear, and externalizing behavior – are associated (r = 0.68–0.71) with distinct patterns of connectivity. Loss of network segregation between the default mode network and executive networks emerges as a common feature across all dimensions. Connectivity linked to mood and psychosis becomes more prominent with development, and sex differences are present for connectivity related to mood and fear. Critically, findings largely replicate in an independent dataset (n = 336). These results delineate connectivity-guided dimensions of psychopathology that cross clinical diagnostic categories, which could serve as a foundation for developing network-based biomarkers in psychiatry.
Tailoring van der Waals dispersion interactions with external electric charges
Authors: Kleshchonok Andrii , Tkatchenko Alexandre 
Published: July 2018

Abstractvan der Waals (vdW) dispersion interactions strongly impact the properties of molecules and materials. Often, the description of vdW interactions should account for the coupling with pervasive electric fields, stemming from membranes, ionic channels, liquids, or nearby charged functional groups. However, this quantum-mechanical effect has been omitted in atomistic simulations, even in widely employed electronic-structure methods. Here, we develop a model and study the effects of an external charge on long-range vdW correlations. We show that a positive external charge stabilizes dispersion interactions, whereas a negative charge has an opposite effect. Our analytical results are benchmarked on a series of (bio)molecular dimers and supported by calculations with high-level correlated quantum-chemical methods, which estimate the induced dispersion to reach up to 35% of intermolecular binding energy (4 kT for amino-acid dimers at room temperature). Our analysis bridges electrostatic and electrodynamic descriptions of intermolecular interactions and may have implications for non-covalent reactions, exfoliation, dissolution, and permeation through biological membranes.
Exploring the role of stromal osmoregulation in cancer and disease using executable modelling
Authors: Shorthouse David , Riedel Angela , Kerr Emma , Pedro Luisa , Bihary Dóra , Samarajiwa Shamith , Martins Carla P. , Shields Jacqueline , Hall Benjamin A. 
Published: July 2018

AbstractOsmotic regulation is a vital homoeostatic process in all cells and tissues. Cells initially respond to osmotic stresses by activating transmembrane transport proteins to move osmotically active ions. Disruption of ion and water transport is frequently observed in cellular transformations such as cancer. We report that genes involved in membrane transport are significantly deregulated in many cancers, and that their expression can distinguish cancer cells from normal cells with a high degree of accuracy. We present an executable model of osmotic regulation and membrane transport in mammalian cells, providing a mechanistic explanation for phenotype change in varied disease states, and accurately predicting behaviour from single cell expression data. We also predict key proteins involved in cellular transformation, SLC4A3 (AE3), and SLC9A1 (NHE1). Furthermore, we predict and verify a synergistic drug combination in vitro, of sodium and chloride channel inhibitors, which target the osmoregulatory network to reduce cancer-associated phenotypes in fibroblasts.