bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing California Wintertime Precipitation Responses to Various Climate Drivers
Authors: Allen Robert J. , Lamarque Jean‐Francois , Watson‐Parris Duncan , Olivié Dirk 
Published: May 2020

AbstractUnderstanding how drivers of climate change affect precipitation remains an important area of research. Although several robust precipitation responses have been identified under continued increases in greenhouse gases (GHGs), considerable uncertainty remains. This is particularly the case at regional scales, including the West Coast of the United States and California. Here, we exploit idealized, single forcing simulations from the Precipitation Driver Response Model Intercomparison Project (PDRMIP) to address how climate drivers impact California wintertime precipitation. Consistent with recent work, GHGs including carbon dioxide and methane, as well as solar forcing, yield a robust increase in California wintertime precipitation. We also find robust California precipitation responses to aerosols but with opposite responses for sulfate versus black carbon aerosol. Sulfate aerosol increases California wintertime precipitation, whereas black carbon reduces it. Moreover, California precipitation is more sensitive to aerosols, particularly regional emissions from Europe and Asia, than to GHGs. These precipitation responses are consistent with shifts in the jet stream and altered moisture fluxes. Although the idealized nature of PDRMIP simulations precludes a formal attribution, our results suggest that aerosols can perturb precipitation and fresh water resources along the West Coast of the United States.
Analysis of the Thermodynamic Phase Transition of Tracked Convective Clouds Based on Geostationary Satellite Observations
Authors: Coopman Q. , Hoose C. , Stengel M. 
Published: May 2020

AbstractClouds are liquid at temperature greater than 0°C and ice at temperature below −38°C. Between these two thresholds, the temperature of the cloud thermodynamic phase transition from liquid to ice is difficult to predict and the theory and numerical models do not agree: Microphysical, dynamical, and meteorological parameters influence the glaciation temperature. We temporally track optical and microphysical properties of 796 clouds over Europe from 2004 to 2015 with the space‐based instrument Spinning Enhanced Visible and Infrared Imager on board the geostationary METEOSAT second generation satellites. We define the glaciation temperature as the mean between the cloud top temperature of those consecutive images for which a thermodynamic phase change in at least one pixel is observed for a given cloud object. We find that, on average, isolated convective clouds over Europe freeze at −21.6°C. Furthermore, we analyze the temporal evolution of a set of cloud properties and we retrieve glaciation temperatures binned by meteorological and microphysical regimes: For example, the glaciation temperature increases up to 11°C when cloud droplets are large, in line with previous studies. Moreover, the correlations between the parameters characterizing the glaciation temperature are compared and analyzed and a statistical study based on principal component analysis shows that after the cloud top height, the cloud droplet size is the most important parameter to determine the glaciation temperature.
Using Data Assimilation to Reconstruct High‐Latitude Polar Cap Patches
Authors: Negale Michael , Holmes Jeffrey , Parris Richard , Ober Daniel , Dao Eugene , Kelly Ralph , Eccles J. Vincent , Hines Jack , Pedersen Todd 
Published: May 2020

AbstractDiscrete high‐density plasma structures in the Earth's ionosphere that convect across the polar cap from the dayside to nightside are known as polar cap patches. This high‐latitude phenomenon can interfere and disrupt satellite and high‐frequency (HF) communications when the associated sharp electron density gradients are encountered, and therefore, accurate modeling and forecasting of such events would be greatly beneficial. In this study, we have utilized the assimilative Global Positioning System Ionospheric Inversion (GPSII) method to reconstruct the high‐latitude ionosphere utilizing data from Global Navigation Satellite System (GNSS) receivers, vertical ionosondes, the Resolute Bay Incoherent Scatter Radar (RISR‐N), in situ satellite data, and Super Dual Auroral Radar Network (SuperDARN) radars. The novel method of assimilating RISR‐N and SuperDARN ground scatter measurements helps to increase the limited number of observations at high latitudes. The reconstructed polar cap patches are shown to correspond with ground‐ and spaced‐based observations, illustrating the ability of utilizing GPSII to study the complex high‐latitude region.
UHF Propagation Through a Trunk‐Dominated Forest
Authors: Torrico Saúl A. , Utku Cuneyt , Lang Roger H. 
Published: May 2020

AbstractTransport theory is used to calculate the intensity of a wave propagating though a trunk‐dominated forest. The trunks are replaced by parallel infinitely long dielectric cylinders, and a vertically polarized plane wave is normally incident on the layer of these randomly distribution parallel cylinders. The problem can be reduced to a two‐dimensional transport problem that can be solved by the eigenvalue technique for the coherent, incoherent, and total intensity of the propagating wave. Using the assumption that the distribution of trunks is sparse and that the trunks locations are independent from one another, the probability density function (PDF) of the total and incoherent intensity as a function of depth into the layer can be found. To verify these results, a Monte Carlo (MC) simulation is performed in the low frequency limit which takes the effect of multiple scattering into account. The results show that there is a very close correspondence between the transport and MC simulation findings; the coherent, incoherent, and the total intensity for these two methods agree very closely as a function of distance into the slab. In addition, the PDFs for these three quantities also agree with the MC based histograms. One sees that as the wave propagates into the layer, the Rician distribution for the magnitude tends to a Rayleigh PDF as the coherent wave decays.
Comparison of Surface Radio Refractivity Variability in the Northern and Southern Parts of Quebec, Canada
Authors: Bettouche Y. , Obeidat H. A. , Agba B. L. , Kouki A. B. , Mosleh M. F. , AlAbdullah A. M. , Abd‐Alhameed R. A. 
Published: May 2020

AbstractThirty‐nine years of archived meteorological data measured at two stations located in the northern and southern parts of Quebec, Canada are used to estimate the surface refractivity and its dry and wet components. The results of the comparison of the obtained estimates showed that for all months the values of the dry component are higher in the northern part, whereas the values of the wet component are higher in the southern part. Due to this, for several months of the year, the values of the surface refractivity are higher in the northern part and for the remaining months in the southern part. Moreover, in both parts, August is the month where the highest values of the surface refractivity were recorded. In this particular month, the slope of the surface refractivity trend in the northern part is several times higher than that in the southern part. The obtained results show that the performance of the used direct smoothing forecasting technique depends on the deviation between the values of N in the current year and the previous year.
AP-1 controls the p11-dependent antidepressant response
Authors: Chottekalapanda Revathy U. , Kalik Salina , Gresack Jodi , Ayala Alyssa , Gao Melanie , Wang Wei , Meller Sarah , Aly Ammar , Schaefer Anne , Greengard Paul 
Published: May 2020

AbstractSelective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed drugs for mood disorders. While the mechanism of SSRI action is still unknown, SSRIs are thought to exert therapeutic effects by elevating extracellular serotonin levels in the brain, and remodel the structural and functional alterations dysregulated during depression. To determine their precise mode of action, we tested whether such neuroadaptive processes are modulated by regulation of specific gene expression programs. Here we identify a transcriptional program regulated by activator protein-1 (AP-1) complex, formed by c-Fos and c-Jun that is selectively activated prior to the onset of the chronic SSRI response. The AP-1 transcriptional program modulates the expression of key neuronal remodeling genes, including S100a10 (p11), linking neuronal plasticity to the antidepressant response. We find that AP-1 function is required for the antidepressant effect in vivo. Furthermore, we demonstrate how neurochemical pathways of BDNF and FGF2, through the MAPK, PI3K, and JNK cascades, regulate AP-1 function to mediate the beneficial effects of the antidepressant response. Here we put forth a sequential molecular network to track the antidepressant response and provide a new avenue that could be used to accelerate or potentiate antidepressant responses by triggering neuroplasticity.
Target identification of natural medicine with chemical proteomics approach: probe synthesis, target fishing and protein identification
Authors: Chen Xiao , Wang Yutong , Ma Nan , Tian Jing , Shao Yurou , Zhu Bo , Wong Yin Kwan , Liang Zhen , Zou Chang , Wang Jigang 
Published: May 2020

AbstractNatural products are an important source of new drugs for the treatment of various diseases. However, developing natural product-based new medicines through random moiety modification is a lengthy and costly process, due in part to the difficulties associated with comprehensively understanding the mechanism of action and the side effects. Identifying the protein targets of natural products is an effective strategy, but most medicines interact with multiple protein targets, which complicate this process. In recent years, an increasing number of researchers have begun to screen the target proteins of natural products with chemical proteomics approaches, which can provide a more comprehensive array of the protein targets of active small molecules in an unbiased manner. Typically, chemical proteomics experiments for target identification consist of two key steps: (1) chemical probe design and synthesis and (2) target fishing and identification. In recent decades, five different types of chemical proteomic probes and their respective target fishing methods have been developed to screen targets of molecules with different structures, and a variety of protein identification approaches have been invented. Presently, we will classify these chemical proteomics approaches, the application scopes and characteristics of the different types of chemical probes, the different protein identification methods, and the advantages and disadvantages of these strategies.
A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity
Authors: Kostaras Eleftherios , Kaserer Teresa , Lazaro Glorianne , Heuss Sara Farrah , Hussain Aasia , Casado Pedro , Hayes Angela , Yandim Cihangir , Palaskas Nicolaos , Yu Yi , Schwartz Brian , Raynaud Florence , Chung Yuen-Li , Cutillas Pedro R. , Vivanco Igor 
Published: May 2020

Abstract
Background
AKT, a critical effector of the phosphoinositide 3-kinase (PI3K) signalling cascade, is an intensely pursued therapeutic target in oncology. Two distinct classes of AKT inhibitors have been in clinical development, ATP-competitive and allosteric. Class-specific differences in drug activity are likely the result of differential structural and conformational requirements governing efficient target binding, which ultimately determine isoform-specific potency, selectivity profiles and activity against clinically relevant AKT mutant variants.

Methods
We have carried out a systematic evaluation of clinical AKT inhibitors using in vitro pharmacology, molecular profiling and biochemical assays together with structural modelling to better understand the context of drug-specific and drug-class-specific cell-killing activity.

Results
Our data demonstrate clear differences between ATP-competitive and allosteric AKT inhibitors, including differential effects on non-catalytic activity as measured by a novel functional readout. Surprisingly, we found that some mutations can cause drug resistance in an isoform-selective manner despite high structural conservation across AKT isoforms. Finally, we have derived drug-class-specific phosphoproteomic signatures and used them to identify effective drug combinations.

Conclusions
These findings illustrate the utility of individual AKT inhibitors, both as drugs and as chemical probes, and the benefit of AKT inhibitor pharmacological diversity in providing a repertoire of context-specific therapeutic options.
Racial differences in prostate cancer: does timing of puberty play a role?
Authors: Hur Jinhee , Giovannucci Edward 
Published: May 2020

AbstractThe burden of prostate cancer has a remarkably disproportionate distribution across racial groups. For example, in the USA, African Americans are twice as likely as individuals of European ancestry to develop or die from prostate cancer, and have a more aggressive disease nature at diagnosis. In contrast, Asian American men have the lowest incidence and mortality rates of prostate cancer. That considerable racial disparities exist even in the subclinical stage of prostate cancer among young men in their 20–30s suggests that patterns of prostate carcinogenesis start to diverge even earlier, perhaps during puberty, when the prostate matures at its most rapid rate. Mendelian randomisation studies have provided strong population-based evidence supporting the hypothesis that earlier onset of puberty increases the risk of prostate cancer—particularly of high grade—and prostate cancer-specific mortality later in life, observations which correspond to the epidemiology of the disease in African Americans. Notably, African American boys initiate genital development ~1 year earlier and thus go through longer periods of pubertal maturation compared with European American boys. In this perspective, bringing together existing evidence, we point to puberty as a potential critical window of increased susceptibility to prostate carcinogenesis that could account for the marked prevailing racial differences in the burden of prostate cancer.
Omental adipocytes promote peritoneal metastasis of gastric cancer through the CXCL2–VEGFA axis
Authors: Natsume Makoto , Shimura Takaya , Iwasaki Hiroyasu , Okuda Yusuke , Hayashi Kazuki , Takahashi Satoru , Kataoka Hiromi 
Published: May 2020

Abstract
Background
Gastric cancer (GC) patients frequently develop peritoneal metastasis; however, the underlying mechanism remains unknown. We hypothesised that omental adipocytes (OmAd) trigger GC cells towards malignant activity to induce peritoneal metastasis.

Methods
We analysed interactions among human GC cells, endothelial cells and OmAd using a 3D co-culture system. We also employed a multipronged animal study, including subcutaneous and orthotopic tumours, and humanised omental adipose tissue models. Urinary levels of CXCL2 were analysed in human GC patients with and without peritoneal metastasis.

Results
Conditioned media derived from OmAd (OmAd-CM) promoted the proliferation, migration and capacity to induce angiogenesis of GC cells through AKT phosphorylation and VEGFA overexpression, whereas silencing CXCL2 in OmAd cancelled OmAd-induced effects. In an orthotopic tumour model using SCID mice, omentectomy suppressed GC growth and peritoneal dissemination, and reduced serum levels of CXCL2. OmAd promoted GC growth in a humanised omental adipose tissue model using NSG mice, but silencing CXCL2 in OmAd cancelled OmAd-induced tumour growth. Finally, urinary levels of CXCL2 were significantly higher in GC patients with peritoneal metastasis than in those without.

Conclusion
Omental adipocytes trigger GC cells to an aggressive phenotype through CXCL2 secretion, which induces angiogenesis followed by cell growth and peritoneal metastasis.
Defining COMMD4 as an anti-cancer therapeutic target and prognostic factor in non-small cell lung cancer
Authors: Suraweera Amila , Duff Alex , Adams Mark N. , Jekimovs Christian , Duijf Pascal H. G. , Liu Cheng , McTaggart Matthew , Beard Sam , O’Byrne Kenneth J. , Richard Derek J. 
Published: May 2020

Abstract
Background
Non-small cell lung cancers (NSCLC) account for 85–90% of all lung cancers. As drug resistance critically impairs chemotherapy effectiveness, there is great need to identify new therapeutic targets. The aims of this study were to investigate the prognostic and therapeutic potential of the copper-metabolism-domain-protein, COMMD4, in NSCLC.

Methods
The expression of COMMD4 in NSCLC was investigated using bioinformatic analysis, immunoblotting of immortalised human bronchial epithelial (HBEC) and NSCLC cell lines, qRT-PCR and immunohistochemistry of tissue microarrays. COMMD4 function was additionally investigated in HBEC and NSCLC cells depleted of COMMD4, using small interfering RNA sequences.

Results
Bioinformatic analysis and in vitro analysis of COMMD4 transcripts showed that COMMD4 levels were upregulated in NSCLC and elevated COMMD4 was associated with poor prognosis in adenocarcinoma (ADC). Immunoblotting demonstrated that COMMD4 expression was upregulated in NSCLC cells and siRNA-depletion of COMMD4, decreased cell proliferation and reduced cell viability. Cell death was further enhanced after exposure to DNA damaging agents. COMMD4 depletion caused NSCLC cells to undergo mitotic catastrophe and apoptosis.

Conclusions
Our data indicate that COMMD4 may function as a prognostic factor in ADC NSCLC. Additionally, COMMD4 is a potential therapeutic target for NSCLC, as its depletion induces cancer cell death.
Inhibition of soluble epoxide hydrolase attenuates renal tubular mitochondrial dysfunction and ER stress by restoring autophagic flux in diabetic nephropathy
Authors: Jiang Xu-shun , Xiang Xing-yang , Chen Xue-mei , He Jun-ling , Liu Ting , Gan Hua , Du Xiao-gang 
Published: May 2020

AbstractDiabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD), and renal tubular cell dysfunction contributes to the pathogenesis of DN. Soluble epoxide hydrolase (sEH) is an enzyme that can hydrolyze epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFAs) into the less biologically active metabolites. Inhibition of sEH has multiple beneficial effects on renal function, however, the exact role of sEH in hyperglycemia-induced dysfunction of tubular cells is still not fully elucidated. In the present study, we showed that human proximal tubular epithelial (HK-2) cells revealed an upregulation of sEH expression accompanied by the impairment of autophagic flux, mitochondrial dysfunction, ubiquitinated protein accumulation and enhanced endoplasmic reticulum (ER) stress after high glucose (HG) treatment. Furthermore, dysfunctional mitochondria accumulated in the cytoplasm, which resulted in excessive reactive oxygen species (ROS) generation, Bax translocation, cytochrome c release, and apoptosis. However, t-AUCB, an inhibitor of sEH, partially reversed these negative outcomes. Moreover, we also observed increased sEH expression, impaired autophagy flux, mitochondrial dysfunction and enhanced ER stress in the renal proximal tubular cells of db/db diabetic mice. Notably, inhibition of sEH by treatment with t-AUCB attenuated renal injury and partially restored autophagic flux, improved mitochondrial function, and reduced ROS generation and ER stress in the kidneys of db/db mice. Taken together, these results suggest that inhibition of sEH by t-AUCB plays a protective role in hyperglycemia-induced proximal tubular injury and that the potential mechanism of t-AUCB-mediated protective autophagy is involved in modulating mitochondrial function and ER stress. Thus, we provide new evidence linking sEH to the autophagic response during proximal tubular injury in the pathogenesis of DN and suggest that inhibition of sEH can be considered a potential therapeutic strategy for the amelioration of DN.
High glucose mediates NLRP3 inflammasome activation via upregulation of ELF3 expression
Authors: Wang Jing , Shen Xuefang , Liu Jing , Chen Wankun , Wu Fengfeng , Wu Weifei , Meng Zhipeng , Zhu Minmin , Miao Changhong 
Published: May 2020

AbstractMicrotubule affinity regulating kinase 4 (MARK4) plays a crucial role in the regulation of NOD-like receptor pyrin domain 3 (NLRP3) inflammasome activation, which leads to the generation of bioactive interleukin (IL)-1β and IL-18. E74-like ETS transcription factor 3 (ELF3) participates in endothelial inflammatory processes. We hypothesized that ELF3 modulates MARK4 expression in vascular endothelial cells, thus contributing to high glucose-mediated NLRP3 inflammasome activation. Plasma IL-1β, IL-18, NLRP3 inflammasome and MARK4 expression was increased in diabetic patients and rats. An in vitro study indicated that high glucose increased IL-1β and IL-18 expression and activated the NLRP3 inflammasome via upregulation of MARK4 in human umbilical vein endothelial cells (HUVECs). Furthermore, high glucose increased ELF3 expression. ELF3 downregulation reversed the effects of high glucose treatment. Accordingly, the effects of ELF3 overexpression were similar to those of high glucose treatment and were counteracted by siMARK4. Furthermore, ELF3 was found to interact with SET8. High glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. Overexpression of SET8 inhibited high glucose-induced MARK4 expression and NLRP3 inflammasome activation. The effects of shSET8 were similar to those of high glucose treatment and were counteracted by siMARK4. A mechanistic study found that ELF3 and H4K20me1 were enriched in the MARK4 promoter region. si-ELF3 attenuated MARK4 promoter activity and augmented the inhibitory effect of SET8 on MARK4 promoter activity. Furthermore, SET8 downregulation and ELF3 upregulation were confirmed in diabetic patients and rats. In conclusion, ELF3 interacted with SET8 to modulate MARK4 expression, which participated in hyperglycaemia-mediated endothelial NLRP3 inflammasome activation.