bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in pesticide suicide in South Korea, 1983–2014
Authors: Cha Eun Shil , Chang Shu-Sen , Choi Yeongchull , Lee Won Jin
Published: March 2019

Aims

Self-poisoning using pesticides is among the major methods of suicide worldwide, and accounts for one-fifth of suicides in 2006–2010 in South Korea. We investigated long-term trends in pesticide suicide rates in South Korea and factors related to these trends.

Methods

We calculated age-standardised rates of pesticide suicide in South Korea (1983–2014) using registered death data. We used graphical approach and joinpoint regression analysis to examine secular trends in pesticide suicide by sex, age and area, and a time-series analysis to investigate association of pesticide suicide rate with socioeconomic and agriculture-related factors. Age, period and cohort effects were examined using the intrinsic estimator method.

Results

Age-standardised rate of pesticide suicide fluctuated between 1983 and 2000 before it markedly increased in 2000–2003 (annual percent change 29.7%), followed by a gradual fall (annual percent change −6.3%) in 2003–2011. Following the paraquat ban (2011–2012), there was a marked reduction (annual percent change −28.2%) in 2011–2014. Trend in pesticide suicide was associated with divorce rate but not with other factors studied. Declines in pesticide suicide in 2003–2011 were most noticeable in younger groups and metropolises; by contrast, elderly adults aged 70+ living in rural areas showed an upward trend until after the 2011–2012 paraquat ban, when it turned downward. In the age–period–cohort modelling, having been born between 1938 and 1947 was associated with higher pesticide suicide rates.

Conclusions

Pesticide suicide trend changed substantially in South Korea over the last three decades. Effective prevention should include close monitoring of trends and strong regulations of toxic pesticides.
Q10 Coenzyme Supplementation can Improve Oxidative Stress Response to Exercise in Metabolic Syndrome in Rats
Authors: Chis Bogdan Augustin , Chis Ana Florica , Muresan Adriana , Fodor Daniela
Published: March 2019

Abstract. Background: The metabolic syndrome leads to high morbidity and mortality. Almost all pathological states are associated with oxidative stress (OS) disorders. This study evaluates the effects of Coenzyme Q10 (CoQ10) supplementation on different lifestyles, in relation to serum and tissue OS parameters. Materials and methods: Twelve Wistar rat groups (10 rats/group) were equally divided in three types of diets: standard (St), high fat (HF), high sugar (HS); within each diet group there was one sedentary group with CoQ10 supplementation (100 mg/kg body weight), one sedentary without CoQ10, one trained group with CoQ10 and one trained group without CoQ10 supplementation. After 28 days blood samples were collected as follows: after 12 hours of fasting (T0), 1 hour postprandial (T1) and after 1 hour of exercise (T2) or sedentary postprandial time (T3). Thiol groups (SH) and malondialdehyde (MDA) were determined from serum and liver homogenate. Results: Significant changes were observed in fasting MDA for HF (p = 0.024 for training, 0.028 for CoQ10). Postprandial, OS status altered, with highest MDA in HF sedentary non-CoQ10 group (3.92 ± 0.37 vs 2.67 ± 0.41 nmol/ml in St trained CoQ10). At T2 the untrained and non-CoQ10 groups had the highest MDA levels (up to 22.3% vs T1, p < 0.001 in HF) as SH dropped (34.4% decrease vs T1, p < 0.001 in HF). At T3 high MDA levels were observed, correlated with low SH (Pearson r = −0.423 overall), irrespective of the CoQ10 supplementation. CoQ10 improved the liver OS status (MDA and SH decreased), but not the exercise, in all diets. Conclusions: CoQ10 supplementation accompanied by chronic exercise improved the OS serum profile, irrespective of the daily diet. CoQ10 lowered liver MDA and SH concentrations.
Behindertenspezifische Herausforderungen bei der pflegerischen Versorgung von contergangeschädigten Menschen – eine Bedarfsanalyse
Authors: Samel Christina , Albus Christian , Tebest Ralf , Forster Kristin , Lüngen Markus , Niecke Alexander , Pfaff Holger , Peters Klaus M.
Published: March 2019

Zusammenfassung. Hintergrund: Zwischen 1957 und 1962 wurden in Deutschland ca. 5000 sogenannte Contergan-Kinder geboren, deren Mütter während der Schwangerschaft das Beruhigungs- und Schlafmittel Contergan genommen hatten. Fragestellung: Das Ziel der Studie war es, die pflegerische Versorgung, ungedeckte Bedarfe und finanzielle Eigenleistungen vor dem Hintergrund der Conterganschädigung mit ihren spezifischen Ausprägungen bei einzelnen Betroffenen sowie eventuelle zukünftige Herausforderungen zu erheben. Methoden: Es wurde eine Befragung mittels Fragebogen zu der pflegerischen Versorgung, den Bedürfnissen und vorliegenden Pflegestufen durchgeführt. Außerdem gab es eine orthopädische und psychische Untersuchung der Betroffenen hinsichtlich ihrer körperlichen Behinderungen und Beeinträchtigungen sowie psychischer Störungen. Ergebnisse: Die Contergangeschädigten teilen sich bezüglich ihrer pflegerischen Bedürfnisse in zwei Gruppen: Personen mit und ohne Beeinträchtigungen der Extremitäten. Das Vorhandensein des pflegerischen Bedarfes und die dafür aufgewendeten privaten Mittel verlaufen entlang dieser Grenze. Viele der Betroffenen werden nur von ihrem sozialen Umfeld pflegerisch betreut, was eine eigene Problematik darstellt, da das Umfeld der Betroffenen mitaltert und sie teilweise sogar noch von ihren Eltern versorgt werden. Schlussfolgerungen: Die Prävalenz für die Pflege bei Contergangeschädigten ist höher als in der deutschen Allgemeinbevölkerung derselben Altersgruppe, professionelle Pflegedienstleister sind unterrepräsentiert. Diese sollten häufiger in Anspruch genommen werden und dem spezifischen Bedarf der Betroffenen gerecht werden.
An Investigation of Gatekeeper Training and Self-Efficacy for Suicide Intervention Among College/University Faculty
Authors: Sylvara Ashley L. , Mandracchia Jon T.
Published: March 2019

Abstract. Background: Suicide is a major global issue; US college students may be at greater risk and faculty may play a crucial role in prevention. Aims: The primary purpose of the present study was to examine: the level of confidence of college/university faculty in identifying at-risk students, to what extent they believed that their actions might reduce suicide, and their knowledge and experiences of their school's policies regarding intervention with at-risk students. Method: Data from 507 higher education faculty across the US were obtained via an online survey tool. Participants consisted mostly of professors and all had completed some level of graduate school. Results: Most participants reported believing it is the college/university faculty's role to identify students at risk for suicide; however, many reported that their institution did not provide gatekeeper training. Participants who had received gatekeeper training were more confident in identifying and assisting at-risk students. Limitations: The study did not determine participants' actual policy knowledge or the various types and lengths of training received. Conclusion: More widespread gatekeeper training for college/university faculty may provide benefits to faculty's confidence and could promote increased assistance for at-risk students.
On the Timescale of Magma Ocean Solidification and Its Chemical Consequences: 1. Thermodynamic Database for Liquid at High Pressures
Authors: Miyazaki Yoshinori , Korenaga Jun
Published: March 2019

We present a new method to construct an internally consistent thermodynamic model using a compilation of high‐pressure melting experiments. The steepest descent method and Monte Carlo sampling are combined to constrain all model parameters simultaneously instead of determining each parameter sequentially from relevant experiments. Our approach is applied to the published melting experiments on mantle materials to obtain the thermodynamic parameters of the MgO‐FeO‐SiO2 ternary system. Inversion with the subsets of experimental data is conducted as well to investigate the source of discrepancy among existing studies, and the key parameters are found to be the thermal expansivity of SiO2 and the excess volume of mixing between MgO and SiO2. Mixing between FeO and SiO2 is only constrained with large uncertainty, which could also imply that oxides with low concentrations have minimal effects on melting. Constraining the thermodynamics of MgO and SiO2 will be important for a better understanding of mantle melting at high pressures.
Aftershock Patterns in Recent Central Apennines Sequences
Authors: Sebastiani G. , Govoni A. , Pizzino L.
Published: March 2019

During the last 20 years, three seismic sequences affected the Apenninic belt (central Italy): Colfiorito (1997–1998), L'Aquila (2009), and Amatrice Visso‐Norcia Campotosto (2016–2017). They lasted for a long time, with a series of moderate‐to‐large earthquakes distributed over 40‐ to 60‐km‐long Apenninic‐trending segments. Their closeness in space and time suggested to study their aftershock sequences to highlight similarities and differences. Aftershock space migration and the distribution of aftershock interarrival times were studied. Mathematical Morphology and nonparametric statistics were applied to reduce the effect of spatial noise. Parametric analysis in time domain and spectral analysis were performed. Two different types of aftershock sequences were found. The L'Aquila sequence presented a continuous and periodic temporal variation (period ≃120 days) of aftershock activity center along the sequence axis, while the other two sequences showed a piecewise continuous pattern and a shorter duration. We also found two different types of temporal evolution of the mean radial distance between the aftershock hypocenters and the one of a reference event corresponding to the start of a large and fast increase of daily energy release. One type was well described by a simple exponential model, while a power law model was more appropriate for the other one. Furthermore, in the first case, the aftershock interarrival time was very well fitted by an exponential model, while noticeable deviations were present in the other case. A possible explanation was provided in terms of the local geological and hydrogeological properties, which depend on the region location with respect to the Ancona‐Anzio tectonic lineament.
Sea Surface Height and Current Responses to Synoptic Winter Wind in the Bohai, Yellow, and East China Seas: Two Leading Coastal Trapped Waves
Authors: Li Zhiyuan , Huang Daji
Published: March 2019

This study investigates the sea surface height (SSH) and current responses to synoptic winter wind in the Bohai, Yellow, and East China Seas (BYES) using a numerical model. The basin‐scale responses are primarily interpreted as two leading coastal trapped waves (CTWs) identified through the complex empirical orthogonal function analysis of SSH. One CTW is a Kelvin wave (KW) explaining 76% of the total SSH variance; the other is a wind‐forced lowest shelf wave (SW1) explaining 17% of the total SSH variance. The KW dominates the current in the Bohai and Yellow Seas (BYS), and the SW1 dominates the current in the western East China Sea (ECS). The KW is a free relaxation response to large wind‐driven SSH variations and propagates cyclonically in the BYES around one SSH node. The SW1 propagates cyclonically in the semienclosed BYS around two nodes and southward along the western ECS with two nodes on the shelf. The wavelength and e‐folding scale of amplitude vary spatially, producing regionally distinct features and mechanisms. In the semienclosed BYS, the associated geostrophic current is along the cophase line of SSH, and its magnitude is proportional to both wave amplitude and wavenumber. In the western ECS, the associated geostrophic current is perpendicular to the cophase line of SSH, and its magnitude is proportional to the wave amplitude and inversely proportional to the e‐folding scale of amplitude. This study reveals not only the basin‐scale SSH and current variations in the BYES but also new features of CTWs in a semienclosed embayment.
Stochastic Space‐Time Downscaling of Rainfall Using Event‐Based Multiplicative Cascade Simulations
Authors: Raut Bhupendra A. , Reeder Michael J. , Jakob Christian , Seed Alan W.
Published: March 2019

A multiplicative cascade model called High‐resolution Downscaling of Rainfall Using Short‐Term Ensemble Prediction System (HiDRUS) is developed and tested in the greater Melbourne region (Australia) by downscaling coarse‐resolution ERA‐I rainfall to 1‐km horizontal and 6‐min temporal resolutions. The parameters required for the cascade model are computed from radar observations of rain events during 2008–2015, and a library of rainfall events and their associated synoptic conditions created. Each day, the area‐averaged rainfall and synoptic conditions are taken from ERA‐I and compared with the library. From the library, similar days are chosen randomly and downscaled using the cascade model. Ensembles of 100 realizations per day are produced for the period 1995–2004. The downscaled rainfall is compared with 6‐min rain gauges and daily gridded rain gauge data at four locations in the greater Melbourne region. HiDRUS reproduces the monthly variability of rainfall, frequency distribution of daily and 6‐min rainfall, and the autocorrelation function satisfactorily. Changes in heavy rainfall are also captured by HiDRUS but with increasing uncertainty as the intensities increase.
Widespread Warming Before and Elevated Barium Burial During the Paleocene‐Eocene Thermal Maximum: Evidence for Methane Hydrate Release?
Authors: Frieling J. , Peterse F. , Lunt D. J. , Bohaty S. M. , Sinninghe Damsté J. S. , Reichart G. ‐J. , Sluijs A.
Published: March 2019

Current climate change may induce positive carbon cycle feedbacks that amplify anthropogenic warming on time scales of centuries to millennia. Similar feedbacks might have been active during a phase of carbon cycle perturbation and global warming, termed the Paleocene‐Eocene Thermal Maximum (PETM, 56 million years ago). The PETM may help constrain these feedbacks and their sensitivity to warming. We present new high‐resolution carbon isotope and sea surface temperature data from Ocean Drilling Program Site 959 in the Equatorial Atlantic. With these and existing data from the New Jersey Shelf and Maud Rise, Southern Ocean, we quantify the lead‐lag relation between PETM warming and the carbon input that caused the carbon isotope excursion (CIE). We show ~2 °C of global warming preceded the CIE by millennia, strongly implicating CO2‐driven warming triggered a positive carbon cycle feedback. We further compile new and published barium (Ba) records encompassing continental shelf, slope, and deep ocean settings. Based on this compilation, we calculate that average Ba burial rates approximately tripled during the PETM, which may require an additional source of Ba to the ocean. Although the precipitation pathway is not well constrained, dissolved Ba stored in sulfate‐depleted pore waters below methane hydrates could represent an additional source. We speculate the most complete explanation for early warming and rise in Ba supply is that hydrate dissociation acted as a positive feedback and caused the CIE. These results imply hydrates are more temperature sensitive than previously considered, and may warrant reconsideration of the political assignment of 2 °C warming as a safe future scenario.
The Impact of Pre‐Salt Rift Topography on Salt Tectonics: A Discrete‐Element Modeling Approach
Authors: M. Pichel Leonardo , Finch Emma , Gawthorpe Rob L.
Published: March 2019

Gravity‐driven salt tectonics along passive margins is commonly depicted as comprising domains of updip extension and downdip contraction linked by an intermediate, broadly undeformed zone of translation. This study expands on recently published physical models using discrete‐element modeling to demonstrate how salt‐related translation over pre‐salt rift structures produce complex deformation and distribution of structural styles in translational salt provinces. Rift geometries defined by horsts and tilted fault‐blocks generate base‐salt relief affecting salt flow, diapirism and overburden deformation. Models show how flow across pairs of tilted fault‐blocks and variably‐dipping base‐salt ramps associated with pre‐salt faults and footwalls produce abrupt flux variations that result in alternation of contractional and extensional domains. Translation over tilted fault‐blocks defined by basinward‐dipping normal faults results in wide, low amplitude inflation zones above footwalls and abrupt subsidence over steep fault‐scarps, with reactive diapirs that are squeezed and extrude salt as they move over the fault. Translation over tilted‐blocks defined by landward‐dipping faults produces narrow inflation zones over steep fault‐scarps and overall greater contraction and less diapirism. As salt and cover move downdip, structures translate over different structural domains, being inverted and/or growing asymmetrically. Our models allow, for the first time, a detailed evolution of these systems in cross‐section and demonstrate the effects of variable pre‐salt relief, salt sub‐basin connectivity, width and slope of base‐salt ramps. Results are applicable to syn‐ and post‐rift salt basins; ultimately improving understanding of the effects of base‐salt relief on salt tectonics and working as a guide for interpretation of complex salt deformation.
Delineating Facies Spatial Distribution by Integrating Ensemble Data Assimilationand Indicator Geostatistics With Level‐Set Transformation
Authors: Song Xuehang , Chen Xingyuan , Ye Ming , Dai Zhenxue , Hammond Glenn , Zachara John M.
Published: March 2019

The facies‐based approach has been widely adopted to delineate an aquifer into distinct geological units with unique distributions of hydraulic, physical, and/or chemical properties. The recent development in ensemble‐based data assimilation methods allows both the direct and indirect data to be used to improve facies delineation. A major difficulty in those applications is to honor the spatial continuity and avoid overfitting after data assimilation. We introduce a new facies delineation framework to integrate ensemble data assimilation with traditional transition probability‐based geostatistics. A level‐set concept is used to parametrize discrete facies indicators and for updating facies shape. During the iterative data assimilation process, we impose spatial continuity by conditioning facies field generation on points selected adaptively based on their sensitivity to observation data. This reconditioning step is a key step to maintain spatial continuity and overcome overfitting problems in inversion. We selected two examples to evaluate the performance of the new framework in estimating facies‐based permeability field. The first example is a two‐dimensional synthetic system with transient head data induced by pumping tests used for delineating two facies. The second example is a three‐dimensional case with three facies, conceptualized from a field tracer experiment within the Columbia River corridor in Washington State, USA. Both examples demonstrate that the new method can adequately capture the spatial pattern of hydrofacies with reconditioning, which leads to the improved prediction of system behaviors.
Relative Permeability Scaling From Pore‐Scale Flow Regimes
Authors: Picchi D. , Battiato I.
Published: March 2019

Relative permeability measurements are commonly fitted with the Corey and Brooks‐Corey correlations. Despite such correlations fit experimental data generally well, they are mostly of an empirical nature. Here, we propose a semiempirical model to determine relative permeabilities of the wetting and the nonwetting phases in real 3‐D porous media that accounts for pore‐scale flow regimes. The starting point is the homogenization framework proposed by Picchi and Battiato (2018, https://doi.org/10.1029/2018WR023172), where the upscaling is conducted for different spatial distributions of the flowing phases in the capillary tube setting. First, we extend the approach to realistic media by allowing pore‐scale flow regimes to coexist in a complex geometry while accounting for capillary and viscous limits in the dynamics. Then, we discuss the scaling behavior of normalized relative permeabilities in terms of the phases viscosity ratio and identify three classes which govern their scaling. We also derive an analytical expression for the fractional flow. Finally, we provide a detailed validation of the proposed model for both relative permeabilities and fractional flow against data from numerical simulations and experiments available in the literature. The data set used for validation covers a wide range of systems, ranging from brine‐CO2 to oil‐water flows. The equations derived capture well the trend of both numerical and experimental data.
Podcast: Toxic City Under the Ice
Authors: Lipuma Lauren
Published: March 2019

In the latest episode of its Centennial series, AGU’s Third Pod from the Sun recounts the history of a top-secret military project with unintended environmental consequences.
Revisiting the Circulation of Hudson Bay: Evidence for a Seasonal Pattern
Authors: Ridenour Natasha A. , Hu Xianmin , Sydor Kevin , Myers Paul G. , Barber David G.
Published: March 2019

The Hudson Bay Complex is the outlet for many Canadian rivers, receiving roughly 900 km3/year of river runoff. Historically, studies found a consistent cyclonic flow year‐round in Hudson Bay, due to the geostrophic boundary current induced by river discharge and cyclonic wind forcing that was supported by available observations at that time. Using a high‐resolution ocean general circulation model, we show that in summer, the mean circulation is not cyclonic but consists of multiple small cyclonic and anticyclonic features, with the mean flow directed through the center of the bay. Absolute Dynamic Topography and velocity observations also show this seasonal flow pattern. We find that this summer circulation is driven by geostrophic currents, generated by steric height gradients, which are induced by increased river discharge during the spring freshet, and reinforced by anticyclonic seasonal wind patterns.
Forfeiting the priority effect: turnover defines biofilm community succession
Authors: Brislawn Colin J , Graham Emily B , Dana Karl , Ihardt Peter , Fansler Sarah J , Chrisler William B , Cliff John B , Stegen James C , Moran James J , Bernstein Hans C
Published: March 2019

Microbial community succession is a fundamental process that affects underlying functions of almost all ecosystems; yet the roles and fates of the most abundant colonizers are often poorly understood. Does early abundance spur long term persistence? How do deterministic and stochastic processes influence the ecological contribution of colonizers? We performed a succession experiment within a hypersaline ecosystem to investigate how different processes contributed to the turnover of founder species. Bacterial and eukaryotic colonizers were identified during primary succession and tracked through a defined, 79-day biofilm maturation period using 16S and 18S rRNA gene sequencing in combination with high resolution imaging that utilized stable isotope tracers to evaluate successional patterns of primary producers and nitrogen fixers. The majority of the founder species did not maintain high abundance throughout succession. Species replacement (versus loss) was the dominant process shaping community succession. We also asked if different ecological processes acted on bacteria versus Eukaryotes during succession and found deterministic and stochastic forces corresponded more with microeukaryote and bacterial colonization, respectively. Our results show that taxa and functions belonging to different kingdoms, which share habitat in the tight spatial confines of a biofilm, were influenced by different ecological processes and time scales of succession.
Pilot study of DNA methylation, molecular aging markers and measures of health and well-being in aging
Authors: Vyas Chirag M. , Hazra Aditi , Chang Shun-Chiao , Qiu Weiliang , Reynolds Charles F. , Mischoulon David , Chang Grace , Manson JoAnn E. , De Vivo Immaculata , Okereke Olivia I.
Published: March 2019

Relations of DNA methylation markers to other biological aging markers and to psychosocial, behavioral, and health measures remain unclear. The sample included 23 participants (n = 11 cases with psychiatric diagnoses andn = 12 controls without current or lifetime psychiatric disorder), balanced by age and sex. Genomic DNA was extracted from blood samples; the following were performed: genome-wide DNA methylation assay using Illumina 850k methylationEPIC; PCR assays for relative telomere length (RTL) and mitochondrial DNA copy number (mtCN). Exposures were: case status; depression and anxiety symptoms; psychosocial support; subjective and objective cognition. Outcomes were: DNA methylation age (DNAm age); RTL; mtCN; extrinsic and intrinsic epigenetic age acceleration (EEAA and IEAA). Stronger correlation with chronological age was observed for DNAm age (ρ = 0.86;p < 0.0001) compared to RTL (ρ = −0.53;p < 0.01); mtCN was not correlated with age. DNAm age was more strongly correlated with behavioral and health variables than RTL or mtCN; e.g., correlations with DNAm age: body mass index (ρ = 0.36;p = 0.10); smoking pack-years (ρ = 0.37;p = 0.08); physical activity (ρ = −0.56;p = 0.01); alcohol intake (ρ = 0.56;p = 0.01). DNAm age was inversely correlated with psychosocial support (ρ = −0.42;p = 0.048) and Modified Mini-Mental State score (ρ = −0.44;p = 0.01). Anxiety, psychosocial support, and objective cognition were significantly related to accelerated aging; depression and subjective cognition were not. In conclusion, DNAm age correlated more strongly with chronological age and key psychosocial, behavioral, and health variables than RTL or mtCN. Signals for associations with epigenetic aging were observed for psychosocial and neurobehavioral variables.
Akirin2 is modulated by miR-490-3p and facilitates angiogenesis in cholangiocarcinoma through the IL-6/STAT3/VEGFA signaling pathway
Authors: Leng Kaiming , Xu Yi , Kang Pengcheng , Qin Wei , Cai Hailong , Wang Hao , Ji Daolin , Jiang Xingming , Li Jinglin , Li Zhenglong , Huang Lining , Zhong Xiangyu , Sun Xueying , Wang Zhidong , Cui Yunfu
Published: March 2019

Akirin2 is a key regulator of embryonic development and the innate immunity response. However, this regulator’s role in tumorigenesis especially in cholangiocarcinoma (CCA) development has not been thoroughly elucidated to date. In the current work, we used RT-qPCR, western blot analysis, and immunohistochemistry (IHC) to explore the expression level of Akirin2, and the relationship between Akirin2 levels and clinicopathological characteristics was evaluated. The biological functions of Akirin2 were examined in vitro and in vivo by using a lentiviral vector system. Luciferase reporter assays were applied to detect the direct binding relationship between the 3′-UTR of Akirin2 mRNA and miR-490-3p. The results showed that Akirin2 was overexpressed in CCA and this upregulation was associated with a shorter overall survival. Silencing or overexpressing Akirin2 by lentiviral approaches significantly influenced CCA cell proliferation, migration, invasion, and angiogenesis. An in vivo tumor model further validated the oncogenic effect of Akirin2 on CCA cell growth, metastasis, and angiogenesis. Mechanistic studies demonstrated that Akirin2 induced angiogenesis by increasing the expression of VEGFA by activating the IL-6/STAT3 signaling pathway. Akirin2 promoted cell migratory and invasive potential by affecting the epithelial–mesenchymal transition (EMT) process. In addition, Akirin2 expression was negatively controlled by miR-490-3p in CCA cells, and miR-490-3p attenuated cell migration and angiogenesis in CCA cells by silencing Akirin2. Taken together, the data indicated that Akirin2 could be regulated by miR-490-3p at the posttranscriptional level and facilitate CCA cell progression via the IL-6/STAT3/VEGFA signaling pathway. The present study may expedite the development of novel therapeutic strategies for CCA.
Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression via CCR5
Authors: Nishikawa Gen , Kawada Kenji , Nakagawa Jun , Toda Kosuke , Ogawa Ryotaro , Inamoto Susumu , Mizuno Rei , Itatani Yoshiro , Sakai Yoshiharu
Published: March 2019

Mesenchymal stem cells (MSCs) are recruited from BM to the stroma of developing tumors, where they serve as critical components of the tumor microenvironment by secreting growth factors, cytokines, and chemokines. The role of MSCs in colorectal cancer (CRC) progression was controversial. In this study, we found that C-C chemokine receptor type 5 (CCR5) ligands (i.e., C-C motif chemokine ligand 3 (CCL3), CCL4, and CCL5) were highly produced from MSCs using a chemokine array screening with conditioned media from the cultured human MSCs. A relatively strong CCR5 expression could be detected within the cytoplasm of several CRC cell lines. Regarding the effect of MSC, we found that the xenografts in which CCR5-overexpressing HCT116 cells were inoculated into immunocompromised mice were highly promoted in vivo by a mixture with MSCs. Notably, the CCR5 inhibitor, maraviroc, significantly abolished the MSC-induced tumor growth in vivo. In human clinical specimens (n = 89), 20 cases (29%) were high for CCR5, whereas 69 cases (71%) were low. Statistical analyses indicated that CCR5 expression in primary CRC was associated with CRC patients’ prognosis. Especially, stage III/IV patients with CCR5-high CRCs exhibited a significantly poorer prognosis than those with CCR5-low CRCs. Furthermore, we investigated the effects of preoperative serum CCR5 ligands on patients’ prognosis (n = 114), and found that CRC patients with high serum levels of CCL3 and CCL4 exhibited a poorer prognosis compared to those with low levels of CCL3 and CCL4, while there was no association between CCL5 and prognosis. These results suggest that the inhibition of MSC–CRC interaction by a CCR5 inhibitor could provide the possibility of a novel therapeutic strategy for CRC, and that serum levels of CCL3 and CCL4 could be predictive biomarkers for the prognosis of CRC patients.
Polymicrobial synergy within oral biofilm promotes invasion of dendritic cells and survival of consortia members
Authors: El-Awady Ahmed , de Sousa Rabelo Mariana , Meghil Mohamed M. , Rajendran Mythilypriya , Elashiry Mahmoud , Stadler Amanda Finger , Foz Adriana Moura , Susin Cristiano , Romito Giuseppe Alexandre , Arce Roger M. , Cutler Christopher W.
Published: March 2019

Years of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses.
Novel Peptide Inhibitors for Lactate Dehydrogenase A (LDHA): A Survey to Inhibit LDHA Activity via Disruption of Protein-Protein Interaction
Authors: Jafary Farzaneh , Ganjalikhany Mohamad Reza , Moradi Ali , Hemati Mahdie , Jafari Sepideh
Published: March 2019

Lactate dehydrogenase A (LDHA) is a critical metabolic enzyme belonging to a family of 2-hydroxy acid oxidoreductases that plays a key role in anaerobic metabolism in the cells. In hypoxia condition, the overexpression of LDHA shifts the metabolic pathway of ATP synthesis from oxidative phosphorylation to aerobic glycolysis and the hypoxia condition is a common phenomenon occurred in the microenvironment of tumor cells; therefore, the inhibition of LDHA is considered to be an excellent strategy for cancer therapy. In this study, we employed in silico methods to design inhibitory peptides for lactate dehydrogenase through the disturbance in tetramerization of the enzyme. Using peptide as an anti-cancer agent is a novel approach for cancer therapy possessing some advantages with respect to the chemotherapeutic drugs such as low toxicity, ease of synthesis, and high target specificity. So peptides can act as appropriate enzyme inhibitor in parallel to chemical compounds. In this study, several computational techniques such as molecular dynamics (MD) simulation, docking and MM-PBSA calculation have been employed to investigate the structural characteristics of the monomer, dimer, and tetramer forms of the enzyme. Analysis of MD simulation and protein-protein interaction showed that the N-terminal arms of each subunit have an important role in enzyme tetramerization to establish active form of the enzyme. Hence, N-terminal arm can be used as a template for peptide design. Then, peptides were designed and evaluated to obtain best binders based on the affinity and physicochemical properties. Finally, the inhibitory effect of the peptides on subunit association was measured by dynamic light scattering (DLS) technique. Our results showed that the designed peptides which mimic the N-terminal arm of the enzyme can successfully target the C-terminal domain and interrupt the bona fide form of the enzyme subunits. The result of this study makes a new avenue to disrupt the assembly process and thereby oppress the function of the LDHA.
Deferiprone: Pan-selective Histone Lysine Demethylase Inhibition Activity and Structure Activity Relationship Study
Authors: Khodaverdian Verjine , Tapadar Subhasish , MacDonald Ian A. , Xu Yuan , Ho Po-Yi , Bridges Allison , Rajpurohit Pragya , Sanghani Bhakti A. , Fan Yuhong , Thangaraju Muthusamy , Hathaway Nathaniel A. , Oyelere Adegboyega K.
Published: March 2019

Deferiprone (DFP) is a hydroxypyridinone-derived iron chelator currently in clinical use for iron chelation therapy. DFP has also been known to elicit antiproliferative activities, yet the mechanism of this effect has remained elusive. We herein report that DFP chelates the Fe2+ion at the active sites of selected iron-dependent histone lysine demethylases (KDMs), resulting in pan inhibition of a subfamily of KDMs. Specifically, DFP inhibits the demethylase activities of six KDMs - 2A, 2B, 5C, 6A, 7A and 7B - with low micromolar IC50s while considerably less active or inactive against eleven KDMs - 1A, 3A, 3B, 4A-E, 5A, 5B and 6B. The KDM that is most sensitive to DFP, KDM6A, has an IC50that is between 7- and 70-fold lower than the iron binding equivalence concentrations at which DFP inhibits ribonucleotide reductase (RNR) activities and/or reduces the labile intracellular zinc ion pool. In breast cancer cell lines, DFP potently inhibits the demethylation of H3K4me3 and H3K27me3, two chromatin posttranslational marks that are subject to removal by several KDM subfamilies which are inhibited by DFP in cell-free assay. These data strongly suggest that DFP derives its anti-proliferative activity largely from the inhibition of a sub-set of KDMs. The docked poses adopted by DFP at the KDM active sites enabled identification of new DFP-based KDM inhibitors which are more cytotoxic to cancer cell lines. We also found that a cohort of these agents inhibited HP1-mediated gene silencing and one lead compound potently inhibited breast tumor growth in murine xenograft models. Overall, this study identified a new chemical scaffold capable of inhibiting KDM enzymes, globally changing histone modification profiles, and with specific anti-tumor activities.
Prevention of respiratory syncytial virus infection with probiotic lactic acid bacterium Lactobacillus gasseri SBT2055
Authors: Eguchi Kei , Fujitani Naoki , Nakagawa Hisako , Miyazaki Tadaaki
Published: March 2019

Lactobacillus gasseri SBT2055 (LG2055) is a probiotic lactic acid bacterium with multifunctional effects, including the prevention of influenza A virus infection in mice, reduction of adipocyte size in mice, and increased lifespan in C. elegans. We investigated whether LG2055 exhibits antiviral activity against respiratory syncytial virus (RSV), a global pathogen for which a preventive strategy is required. Following oral administration of LG2055 in mice, the RSV titre in the lung was significantly decreased, while body weight was not decreased after virus infection. Additionally, the elevated expression of pro-inflammatory cytokines in the lung upon RSV infection decreased after LG2055 administration. Moreover, interferon and interferon stimulated genes were upregulated by LG2055 treatment. Comparative cellular proteomic analysis revealed that SWI2/SNF2-related CREB-binding protein activator protein (SRCAP) was a candidate for the antiviral activity of LG2055 against RSV. There was a positive correlation between the inhibition of RSV replication and the suppression of SRCAP expression and RSV replication was suppressed by SRCAP silencing. Since SRCAP is a scaffold protein to which viral non-structural proteins bind, the downregulation of SRCAP induced by LG2055 could provide new insights about the inhibition of RSV replication. In summary, our study demonstrated that LG2055 has prophylactic potential against RSV infection.
Positive selection in Europeans and East-Asians at the ABCA12 gene
Authors: Sirica Roberto , Buonaiuto Marianna , Petrella Valeria , Sticco Lucia , Tramontano Donatella , Antonini Dario , Missero Caterina , Guardiola Ombretta , Andolfi Gennaro , Kumar Heerman , Ayub Qasim , Xue Yali , Tyler-Smith Chris , Salvemini Marco , D’Angelo Giovanni , Colonna Vincenza
Published: March 2019

Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of theABCA12gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation. We confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site ofABCA12. We found no obvious effect of rs10180970 alleles onABCA12gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and present in non-Africans 45,000 years ago.
The association of genetically controlled CpG methylation (cg158269415) of protein tyrosine phosphatase, receptor type N2 (PTPRN2) with childhood obesity
Authors: Lee Suman
Published: March 2019

Protein tyrosine phosphatase, receptor type N2 (PTPRN2) encodes a major islet autoantigen in type-1 diabetes. Previous genetic studies have shown its significant association with obesity. PTPRN2 plays an important role in epigenetic regulation of metabolic diseases and cancers. We investigated CpG methylations (cg17429772 and cg158269415) in PTPRN2 by pyrosequencing from blood samples of childhood obesity (n = 638). cg158269415 had significant positive correlations with body mass index (BMI) and waist-hip ratio (WHR). Case-control analysis showed that cg158269415 methylation in blood sample was significantly more hypermethylated in obese cases (n = 252), an average of 2.93% more than that that in controls (n = 386). The cg158269415 methylation has a trimodal distribution pattern with strong dependency on nearby located rs1670344 G > A genotype. Correlations of cg158269415 with BMI and WHR were significant and strong in major G allele carriers (GG + GA). Our study showed that an epigenetic association of PTPRN2 gene with childhood obesity was under certain genetic background. The genetic and epigenetic interplay of PTPRN2 gene may implicate a mechanism of childhood obesity. Whether these small changes in DNA methylation from whole blood are causally or consequently related to childhood obesity outcome and their clinical relevance remains to be determined. However, this study presents a promising obesity risk marker that warrants further investigation.
Re-localization of hormone effectors is associated with dormancy alleviation by temperature and after-ripening in sunflower seeds
Authors: Xia Qiong , Ponnaiah Maharajah , Thanikathansubramanian Kaviya , Corbineau Françoise , Bailly Christophe , Nambara Eiji , Meimoun Patrice , El-Maarouf-Bouteau Hayat
Published: March 2019

Temperature is the primary factor that affects seed dormancy and germination. However, the molecular mechanism that underlies its effect on dormancy alleviation remained largely unknown. In this study, we investigate hormone involvement in temperature induced germination as compared to that caused by after-ripening. Dormant (D) sunflower seeds cannot germinate at 10 °C but fully germinate at 20 °C. After-ripened seeds become non-dormant (ND), i.e. able to germinate at 10 °C. Pharmacological experiments showed the importance of abscisic acid (ABA), gibberellins (GAs) and ethylene in temperature- and after-ripening-induced germination of sunflower seeds. Hormone quantification showed that after-ripening is mediated by a decline in both ABA content and sensitivity while ABA content is increased in D seeds treated at 10 or 20 °C, suggesting that ABA decrease is not a prerequisite for temperature induced dormancy alleviation. GAs and ethylene contents were in accordance with germination potential of the three conditions (GA1 was higher in D 20 °C and ND 10 °C than in D 10 °C). Transcripts analysis showed that the major change concerns ABA and GAs metabolism genes, while ABA signalling gene expression was significantly unchanged. Moreover, another level of hormonal regulation at the subcellular localization has been revealed by immunocytolocalization study. Indeed, ABA, protein Abscisic acid-Insensitive 5 (ABI5), involved in ABA-regulated gene expression and DELLA protein RGL2, a repressor of the gibberellins signalling pathway, localized mainly in the nucleus in non-germinating seeds while they localized in the cytosol in germinating seeds. Furthermore, ACC-oxidase (ACO) protein, the key ethylene biosynthesis enzyme, was detected in the meristem only in germinating seeds. Our results reveal the importance of hormone actors trafficking in the cell and their regulation in specialized tissue such as the meristem in dormancy alleviation and germination.
Human electrocortical dynamics while stepping over obstacles
Authors: Nordin Andrew D. , Hairston W. David , Ferris Daniel P.
Published: March 2019

To better understand human brain dynamics during visually guided locomotion, we developed a method of removing motion artifacts from mobile electroencephalography (EEG) and studied human subjects walking and running over obstacles on a treadmill. We constructed a novel dual-layer EEG electrode system to isolate electrocortical signals, and then validated the system using an electrical head phantom and robotic motion platform. We collected data from young healthy subjects walking and running on a treadmill while they encountered unexpected obstacles to step over. Supplementary motor area and premotor cortex had spectral power increases within ~200 ms after object appearance in delta, theta, and alpha frequency bands (3–13 Hz). That activity was followed by similar posterior parietal cortex spectral power increase that decreased in lag time with increasing locomotion speed. The sequence of activation suggests that supplementary motor area and premotor cortex interrupted the gait cycle, while posterior parietal cortex tracked obstacle location for planning foot placement nearly two steps ahead of reaching the obstacle. Together, these results highlight advantages of adopting dual-layer mobile EEG, which should greatly facilitate the study of human brain dynamics in physically active real-world settings and tasks.
Effect of feed restriction and refeeding on performance and metabolism of European and Caribbean growing pigs in a tropical climate
Authors: Poullet Nausicaa , Bambou Jean-Christophe , Loyau Thomas , Trefeu Christine , Feuillet Dalila , Beramice David , Bocage Bruno , Renaudeau David , Gourdine Jean-Luc
Published: March 2019

Reduction in feed intake is a common physiological response of growing pigs facing stressful environmental conditions. The present experiment aims to study (1) the effects of a short-term feed restriction and refeeding on pig performance and metabolism and (2) the differential response between two breeds, Large White (LW), which has been selected for high performance, and Creole (CR), which is adapted to tropical conditions. A trial of 36 castrated male pigs (18 LW and 18 CR) was carried out. For each breed, half of the animals were restrictively fed at 50% of the standard feed allowance for 6 days and then fed normally for the next 14 days. Growth performance, thermoregulatory responses, plasma hormones and metabolites were measured. Results showed that, for all traits, the difference in response between the two breeds was small and rarely significant, which may be due to the short duration of the feed restriction. Irrespective of breed, feed restriction induced a reduction of growth rate and feed efficiency that was rapidly compensated for upon refeeding. Feed restriction also reduced skin temperature, rectal temperature and respiratory rate, as well as blood urea and cholesterol, which are of interest as potential biomarkers for feed restriction.