bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tectonics Inversions, Fault Segmentation, and Triggering Mechanisms in the Central Apennines Normal Fault System: Insights From High‐Resolution Velocity Models
Authors: Buttinelli M. , Pezzo G. , Valoroso L. , De Gori P. , Chiarabba C. 
Published: October 2018

AbstractThe potential role of subsequent tectonic phases in reworking inherited geological structures is a key issue to unravel the seismotectonics of an area. This has a direct connection with fault segmentation, earthquakes maximum magnitude, and strong implications for seismic hazard assessment. The central Apennines (Italy) represent an exemplary case, since it developed because of the overprint of different deformational phases, producing potential conditions for episodic tectonic inversions and a very complex structural architecture. In this paper, we show how inherited compressional structures, still dominating the Apennines belt architecture, interfere with the active extension, having a direct connection with active seismotectonics. We present seismicity and new velocity tomograms of an 80‐km‐long section of the normal fault system activated during the 2009 and 2016–2018 seismic sequences. The joint interpretation highlights how the extensional seismic sequences partially reactivated inherited compressive structures, which have not an undisputable relationship with the surficial geological setting. Complexity deriving from the irregular geometry of normal faults and inverted thrust ramps is responsible for the observed intense fragmentation of the extensional system. Fluid overpressure seems to be a viable mechanism behind the partial remobilization of unbroken segments of the fault system.
Disaggregating Soil Moisture to Finer Spatial Resolutions: A Comparison of Alternatives
Authors: Ajami Hoori , Sharma Ashish 
Published: October 2018

AbstractThe spatial and temporal variability in soil moisture modulates runoff generation and the degree of land‐atmosphere coupling. Numerous statistical and modeling approaches have been implemented to characterize soil moisture spatial heterogeneity at fine spatial resolution using data from sparse observational networks or distributed model simulations. This characterization has been subsequently employed to translate coarse model simulations (of the order of a few hundred meters or kilometers) to finer spatial scales for a range of ensuing applications that rely on high‐resolution characterization of soil moisture. One common feature of these disaggregation methods is that the impact of soil moisture memory is ignored. This results in both spatial and temporal persistence being poorly simulated, leading to poorer specifications of cropping and irrigation plans. To overcome this shortcoming, we developed a hybrid disaggregation method that uses the first‐order autoregressive model (AR1) constructed from fine‐resolution (60 m) soil moisture simulations to disaggregate catchment mean soil moisture obtained from remote sensing or semidistributed model simulations. Soil moisture simulations from an integrated land surface‐groundwater model, ParFlow‐Common Land Model in Baldry subcatchment, Australia, are used as virtual observations. We examined the AR1 method performance against topographic wetness index‐based methods and those developed from temporal stability method. Results illustrate that the disaggregation schemes calibrated to a 10‐day fine‐scale model simulation perform better than the topographic‐based methods in approximating soil moisture distribution at a 60‐m resolution in the catchment. Furthermore, the AR1 model is the best model (Nash‐Sutcliffe efficiency [NSE] > 0.45) among various alternatives explored here. Applying the hybrid univariate AR1 model is promising for disaggregating semidistributed models' soil moisture simulations while significantly reducing the computational time.
A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety
Authors: Hommers L. G. , Richter J. , Yang Y. , Raab A. , Baumann C. , Lang K. , Schiele M. A. , Weber H. , Wittmann A. , Wolf C. , Alpers G. W. , Arolt V. , Domschke K. , Fehm L. , Fydrich T. , Gerlach A. , Gloster A. T. , Hamm A. O. , Helbig-Lang S. , Kircher T. , Lang T. , Pané-Farré C. A. , Pauli P. , Pfleiderer B. , Reif A. , Romanos M. , Straube B. , Ströhle A. , Wittchen H.-U. , Frantz S. , Ertl G. , Lohse M. J. , Lueken U. , Deckert J. 
Published: October 2018

AbstractIncreased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.
Advanced smart biomaterials and constructs for hard tissue engineering and regeneration
Authors: Zhang Ke , Wang Suping , Zhou Chenchen , Cheng Lei , Gao Xianling , Xie Xianju , Sun Jirun , Wang Haohao , Weir Michael D. , Reynolds Mark A. , Zhang Ning , Bai Yuxing , Xu Hockin H. K. 
Published: October 2018

AbstractHard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that contain calcium phosphate minerals. Smart biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Smart biomaterials and constructs refer to biomaterials and constructs that possess instructive/inductive or triggering/stimulating effects on cells and tissues by engineering the material’s responsiveness to internal or external stimuli or have intelligently tailored properties and functions that can promote tissue repair and regeneration. The smart material-based approaches include smart scaffolds and stem cell constructs for bone tissue engineering; smart drug delivery systems to enhance bone regeneration; smart dental resins that respond to pH to protect tooth structures; smart pH-sensitive dental materials to selectively inhibit acid-producing bacteria; smart polymers to modulate biofilm species away from a pathogenic composition and shift towards a healthy composition; and smart materials to suppress biofilms and avoid drug resistance. These smart biomaterials can not only deliver and guide stem cells to improve tissue regeneration and deliver drugs and bioactive agents with spatially and temporarily controlled releases but can also modulate/suppress biofilms and combat infections in wound sites. The new generation of smart biomaterials provides exciting potential and is a promising opportunity to substantially enhance hard tissue engineering and regenerative medicine efficacy.
Loss of GRHL3 leads to TARC/CCL17-mediated keratinocyte proliferation in the epidermis
Authors: Goldie Stephen J. , Cottle Denny L. , Tan Fiona H. , Roslan Suraya , Srivastava Seema , Brady Rhys , Partridge Darren D. , Auden Alana , Smyth Ian M. , Jane Stephen M. , Dworkin Sebastian , Darido Charbel 
Published: October 2018

AbstractIdentifying soluble factors that influence epidermal integrity is critical for the development of preventative and therapeutic strategies for disorders such as ichthyosis, psoriasis, dermatitis and epidermal cancers. The transcription factor Grainyhead-like 3 (GRHL3) is essential for maintaining barrier integrity and preventing development of cutaneous squamous cell carcinoma (SCC); however, how loss of this factor, which in the skin is expressed exclusively within suprabasal epidermal layers triggers proliferation of basal keratinocytes, had thus far remained elusive. Our present study identifies thymus and activation-regulated chemokine (TARC) as a novel soluble chemokine mediator of keratinocyte proliferation following loss of GRHL3. Knockdown of GRHL3 in human keratinocytes showed that of 42 cytokines examined, TARC was the only significantly upregulated chemokine. Mouse skin lacking Grhl3 presented an inflammatory response with hallmarks of TARC activation, including heightened induction of blood clotting, increased infiltration of mast cells and pro-inflammatory T cells, increased expression of the pro-proliferative/pro-inflammatory markers CD3 and pSTAT3, and significantly elevated basal keratinocyte proliferation. Treatment of skin cultures lacking Grhl3 with the broad spectrum anti-inflammatory 5-aminosalicylic acid (5ASA) partially restored epidermal differentiation, indicating that abnormal keratinocyte proliferation/differentiation balance is a key driver of barrier dysfunction following loss of Grhl3, and providing a promising therapeutic avenue in the treatment of GRHL3-mediated epidermal disorders.
Targeting enhancer of zeste homolog 2 protects against acute kidney injury
Authors: Zhou X. , Zang X. , Guan Y. , Tolbert T. , Zhao T. C. , Bayliss G. , Zhuang S. 
Published: October 2018

AbstractDespite the established oncogenic and profibrotic functions of enhancer of zeste homolog 2 (EZH2), a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3), its role in acute kidney injury (AKI) remains unclear. In this study, we demonstrated that EZH2 and H3K27me3 were upregulated in the murine kidney with AKI induced by either ischemia-reperfusion (I/R) or folic acid (FA). Pharmacologic inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) prevented tubular injury in both models as demonstrated by reduced renal dysfunction, diminished neutrophil gelatinase-associated lipocalin expression and decreased renal tubular cell death. Injury to the kidney resulted in reduced expression of E-cadherin and ZO-1, whereas EZH2 inhibition largely preserved their expression. Moreover, 3-DZNep was effective in counteracting the increased expression of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the phosphorylation of Raf-1 and ERK1/2 in the injured kidney. Conversely, blocking EZH2 reversed the decrease of tissue inhibitor of metalloproteinase (TIMP)-2 and metalloproteinase (TIMP)-3, and Raf kinase inhibitor protein (RKIP) in the kidney after acute injury. Similarly, oxidant injury to cultured kidney proximal tubular epithelial cells caused a decrease in the expression of E-cadherin, ZO-1, TIMP-2/-3, and RKIP, as well as an increase in the expression of MMP-2/9 and phosphorylation of Raf-1 ERK1/2. Blocking EZH2 with 3-DZNep or SiRNA hindered these responses. Thus, these results suggest that targeting EZH2 protects against AKI through a mechanism associated with the preservation of adhesion/junctions, reduction of matrix metalloproteinases and attenuation of the Raf-1/ERK1/2 pathway.
Diesel exhaust particles induce autophagy and citrullination in Normal Human Bronchial Epithelial cells
Authors: Colasanti Tania , Fiorito Silvana , Alessandri Cristiano , Serafino Annalucia , Andreola Federica , Barbati Cristiana , Morello Francesca , Alfè Michela , Di Blasio Gabriele , Gargiulo Valentina , Vomero Marta , Conti Fabrizio , Valesini Guido 
Published: October 2018

AbstractA variety of environmental agents has been found to influence the development of autoimmune diseases; in particular, the studies investigating the potential association of systemic autoimmune rheumatic diseases with environmental micro and nano-particulate matter are very few and contradictory. In this study, the role of diesel exhaust particles (DEPs), one of the most important components of environment particulate matter, emitted from Euro 4 and Euro 5 engines in altering the Normal Human Bronchial Epithelial (NHBE) cell biological activity was evaluated. NHBE cells were exposed in vitro to Euro 4 and Euro 5 particle carbon core, sampled upstream of the typical emission after-treatment systems (diesel oxidation catalyst and diesel particulate filter), whose surfaces have been washed from well-assessed harmful species, as polycyclic aromatic hydrocarbons (PAHs) to: (1) investigate their specific capacity to affect cell viability (flow cytometry); (2) stimulate the production of the pro-inflammatory cytokine IL-18 (Enzyme-Linked ImmunoSorbent Assay -ELISA-); (3) verify their specific ability to induce autophagy and elicit protein citrullination and peptidyl arginine deiminase (PAD) activity (confocal laser scanning microscopy, immunoprecipitation, Sodium Dodecyl Sulphate-PolyAcrylamide Gel Electrophoresis -SDS-PAGE- and Western blot, ELISA). In this study we demonstrated, for the first time, that both Euro 4 and Euro 5 carbon particles, deprived of PAHs possibly adsorbed on the soot surface, were able to: (1) significantly affect cell viability, inducing autophagy, apoptosis and necrosis; (2) stimulate the release of the pro-inflammatory cytokine IL-18; (3) elicit protein citrullination and PAD activity in NHBE cells. In particular, Euro 5 DEPs seem to have a more marked effect with respect to Euro 4 DEPs.
A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor
Authors: Hewit Kay , Sandilands Emma , Martinez Rafael Sanchez , James Daniel , Leung Hing Y. , Bryant David M. , Shanks Emma , Markert Elke K. 
Published: October 2018

AbstractBased on a molecular classification of prostate cancer using gene expression pathway signatures, we derived a set of 48 genes in critical pathways that significantly predicts clinical outcome in all tested patient cohorts. We tested these genes in a functional genomics screen in a panel of three prostate cancer cell lines (LNCaP, PC3, DU145), using RNA interference. The screen revealed several genes whose knockdown caused strong growth inhibition in all cell lines. Additionally, we tested the gene set in the presence of docetaxel to see whether any gene exhibited additive or synergistic effects with the drug. We observed a strong synergistic effect between DLGAP5 knockdown and docetaxel in the androgen-sensitive line LNCaP, but not in the two other androgen-independent lines. We then tested whether this effect was connected to androgen pathways and found that knockdown of the androgen receptor by si-RNA attenuated the synergy significantly. Similarly, androgen desensitized LNCaP-AI cells had a higher IC50 to docetaxel and did not exhibit the synergistic interaction. Short-term exposure to enzalutamide did not significantly alter the behaviour of parental LNCaP cells. An immunofluorescence analysis in LNCaP cells suggests that under the double insult of DLGAP5 knockdown and docetaxel, cells predominantly arrest in metaphase. In contrast, the knockdown of the androgen receptor by siRNA appears to assist cells to progress through metaphase in to anaphase, even in the presence of docetaxel. Our data suggest that DLGAP5 has a unique function in stabilizing spindle formation and surviving microtubule assault from docetaxel, in an androgen-regulated cell cycle system.
Medial temporal lobe functional connectivity predicts stimulation-induced theta power
Authors: Solomon E. A. , Kragel J. E. , Gross R. , Lega B. , Sperling M. R. , Worrell G. , Sheth S. A. , Zaghloul K. A. , Jobst B. C. , Stein J. M. , Das S. , Gorniak R. , Inman C. S. , Seger S. , Rizzuto D. S. , Kahana M. J. 
Published: October 2018

AbstractFocal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5–13 Hz) spectral coherence predicted stimulation-evoked increases in theta (5–8 Hz) power, particularly when stimulation was applied in or adjacent to white matter. Stimulation tended to decrease power in the high-frequency broadband (HFB; 50–200 Hz) range, and these modulations were correlated with HFB-based networks in a subset of subjects. Our results demonstrate that functional connectivity is predictive of causal changes in the brain, capturing evoked activity across brain regions and frequency bands.
Simultaneous weak measurement of non-commuting observables: a generalized Arthurs-Kelly protocol
Authors: Ochoa Maicol A. , Belzig Wolfgang , Nitzan Abraham 
Published: October 2018

AbstractIn contrast to a projective quantum measurement, in a weak measurement the system is only weakly perturbed while only partial information on the measured observable is obtained. A simultaneous measurement of non-commuting observables cannot be projective, however the strongest possible such measurement can be defined as providing their values at the smallest uncertainty limit. Starting with the Arthurs and Kelly (AK) protocol for such measurement of position and momentum, we derive a systematic extension to a corresponding weak measurement along three steps: First, a plausible form of the weak measurement operator analogous to the Gaussian Kraus operator, often used to model a weak measurement of a single observable, is obtained by projecting a naïve extension (valid for commuting observable) onto the corresponding Gabor space. Second, we show that the so obtained set of measurement operators satisfies the normalization condition for the probability to obtain given values of the position and momentum in the weak measurement operation, namely that this set constitutes a positive operator valued measure (POVM) in the position-momentum space. Finally, we show that the so-obtained measurement operator corresponds to a generalization of the AK measurement protocol in which the initial detector wavefunctions is suitable broadened.
Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer
Authors: Domińska Kamila , Okła Piotr , Kowalska Karolina , Habrowska-Górczyńska Dominika Ewa , Urbanek Kinga Anna , Ochędalski Tomasz , Piastowska-Ciesielska Agnieszka Wanda 
Published: October 2018

AbstractAngiotensin 1–7 (Ang1–7) is an endogenous bioactive component of the renin-angiotensin system (RAS). In addition to its cardiovascular properties, its anti-proliferative and anti-angiogenic traits are believed to play important roles in carcinogenesis. The present study examines the influence of Ang1–7 on processes associated with development and progression of prostate cancer cells. Our findings indicate that while Ang1–7 (1 nM; 48 h) can effectively reduce cell proliferation in DU-145, it can induce a significant decrease in the expression of MKI67 in LNCaP. In both cell lines we also observed a reduction in colony size in soft agar assay. A various changes in gene expression were noted after exposure to Ang1–7: those of anti- and pro-apoptotic agents and the NF-kB family of transcription factors, as well as mesenchymal cell markers and vascular endothelial growth factor A (VEGFA). In addition, Ang1–7 was found to modulate cell adhesion and matrix metallopeptidase (MMP) activity. Changes were also observed in the levels of angiotensin receptors and sex steroid hormone receptors. Ang1–7 reduced the levels of estrogen receptor alpha gene (ESR1) and increased the expression of estrogen receptor beta gene (ESR2) in all prostate cancer cells; it also up-regulated androgen receptor (AR) expression in androgen-sensitive cells but contradictory effect was observed in androgen- irresponsive cell lines. In summary, the results confirm the existence of complex network between the various elements of the local RAS and the molecular and cellular mechanisms of prostate cancerogenesis. The response of cancer cells to Ang1–7 appears to vary dependently on the dose and time of incubation as well as the aggressiveness and the hormonal status of cells.
High expression of WNT7A predicts poor prognosis and promote tumor metastasis in pancreatic ductal adenocarcinoma
Authors: Wu Dong-jin , Jiang Yong-sheng , He Rui-zhe , Tao Ling-ye , Yang Min-wei , Fu Xue-liang , Yang Jiang-yu , Zhu Kun 
Published: October 2018

AbstractDue to the therapy resistance and frequent metastasis, pancreatic ductal adenocarcinoma(PDAC) remains one of the most malignant carcinoma. WNT7A, an important ligand of Wnt/β-catenin signaling pathways, has a controversial role in tumor development. The role of WNT7A in PDAC remains unclear. In this study, we analyzed the expression pattern of WNT7A at mRNA and protein levels. We found pancreatic cancer tissue demonstrated a significant high WNT7A expression compared with the adjacent non-tumor tissue and the expression of WNT7A positively correlates with poor prognosis and lymph node metastasis. Then, we performed transwell assays and wound healing assays in vitro and found that WNT7A promotes the migration capacity of cancer cells. Furthermore, we explored the underlying mechanism of the WNT7A inducing cell migration. Results showed that up-regulated WNT7A expression inducing higher expression of N-cadherin and lower expression of E-cadherin while the contrast result was shown in the WNT7A knock-down group, which suggested that WNT7A might contribute to an epithelial–mesenchymal transition. Finally, we found that the hypoxia culture condition remarkably increased the WNT7A expression. In conclusion, our work demonstrated that hypoxia induced high expression of WNT7A might promote the cell migration via enhancing the epithelial–mesenchymal transition in PDAC.