bluuebunny/crossref_metadata_2025 huggingface dataset:
An Improved Ionosonde‐Based Parameter to Assess Sporadic E Layer Intensities: A Simple Idea and an Algorithm
Authors: Haldoupis Christos
Published: February 2019

In the long era of sporadic E layer (Es) ionosonde research, the ordinary wave critical frequency foEs is used as a measure of Es layer occurrence and intensity. This practice, however, undermines that sporadic E layers are in fact metal ion layers, whereas foEs relates inherently to the sum of both the layer metal and the regular E region plasma densities. This means that foEs acts as an overestimate of Es intensity, a fact that somehow has been overlooked and escaped attention. To deal with this deficiency, an algorithm is introduced which combines the ionosonde‐measured foEs and virtual height h'Es parameters with International Reference Ionosphere model predictions of E region electron densities, to arrive at a new critical frequency which depends on sporadic E metal plasma density only; therefore, it represents an unbiased estimate of Es layer intensity. The extensive use of foEs in numerous sporadic E studies must have introduced errors in various results in relation with the Es variability in the time, frequency, and space domains. It is therefore important that this new parameter, notated as foμEs, is now adopted and used instead of foEs in the evaluation of sporadic E. The same methodology applies also for the sporadic E blanketing critical frequency fbEs, which at times is taken as an alternative estimate of Es intensity; similarly, a new parameter, notated as fbμEs, should be used instead of fbEs.
Estimate of Turbulent Energy Dissipation Rate From the VHF Radar and Radiosonde Observations in the Antarctic
Authors: Kohma M. , Sato K. , Tomikawa Y. , Nishimura K. , Sato T.
Published: February 2019

This study estimated the turbulent kinetic energy dissipation rates (TKEDRs) from 1‐year observations of the Program of the Antarctic Syowa Mesosphere‐Stratosphere‐Troposphere/Incoherent Scatter radar (PANSY radar) from October 2015 to September 2016 and compared the results with estimates from radiosonde measurements based on Thorpe's method. The radar‐based estimates showed that the TKEDR at Syowa Station was on the order of 10−5–10−3 m2/s3 in the altitude range of 1.5–19 km. Taking the proportional constant for Thorpe's method (the ratio of the Thorpe scale to Ozmidov scale) as unity, the radiosonde‐based measurements show values of TKEDR larger than radar‐based estimates by a factor of 2–5. The difference in the TKEDR between radiosonde‐ and radar‐based estimates is larger in the middle and upper troposphere than in the stratosphere. According to previous observational and numerical studies, Thorpe's method tends to overestimate the TKEDR for deep overturning layers. It is confirmed that the depth of the overturning layer is negatively correlated with the difference between radiosonde‐ and radar‐based estimates. The seasonal variation was also examined. An analysis using the distance from the local tropopause level showed that the local maximum in the TKEDR around the tropopause is particularly clear in austral summer. This is likely connected to the seasonality in the gravity wave activity in the Antarctic stratosphere.
The Importance of the One‐Dimensional Assumption in Soil Moisture ‐ Rainfall Depth Correlation at Varying Spatial Scales
Authors: Holgate C. M. , Van Dijk A. I. J. M. , Evans J. P. , Pitman A. J.
Published: February 2019

Inferring local land‐atmosphere coupling through correlation of colocated soil moisture and future rainfall inherently assumes a one‐dimensional (1‐D) framing of the coupling mechanism. For the first time we demonstrate the importance of upholding this assumption by examining the statistical relationship between daily soil moisture and rainfall depths over Australia, specifying spatial scales (0.05°, 0.5°, 1°, and 2.5°) to constrain the relationship to local‐only physical processes. At small scales, without consideration of the 1‐D assumption, strong land‐atmosphere coupling is suggested across much of the country. However, when adhering to a 1‐D framework, small sample sizes make correlation unsuitable for assessing local coupling at these small scales. When adhering to a 1‐D framework, at scales of 0.5° and above, we find positive correlations in northern Australia in the wet and transition seasons and negative correlations in southern Australia in austral winter. The correlation is scale dependent, suggesting that as spatial resolutions increase in the future and land‐atmosphere coupling heterogeneity is resolved, spatial distributions of local coupling may differ from larger‐scale estimates characteristic of current coarse resolution climate models.
Nitrate Pathways, Processes, and Timing in an Agricultural Karst System: Development and Application of a Numerical Model
Authors: Husic A. , Fox J. , Adams E. , Ford W. , Agouridis C. , Currens J. , Backus J.
Published: February 2019

Nitrogen (N) contamination within agricultural‐karst landscapes and aquifers is widely reported; however, the complex hydrological pathways of karst make N fate difficult to ascertain. We developed a hydrologic and N numerical model for agricultural‐karst, including simulation of soil, epikarst, phreatic, and quick flow pathways as well as biochemical processes such as nitrification, mineralization, and denitrification. We tested the model on four years of nitrate (NO3−) data collected from a phreatic conduit and an overlying surface channel in the Cane Run watershed, Kentucky, USA. Model results indicate that slow to moderate flow pathways (phreatic and epikarst) dominate the N load and account for nearly 90% of downstream NO3− delivery. Further, quick flow pathways dilute NO3− concentrations relative to background aquifer levels. Net denitrification distributed across soil, epikarst, and phreatic water removes approximately 36% of the N inputs to the system at rates comparable to nonkarst systems. Evidence is provided by numerical modeling that NO3− accumulation via evapotranspiration in the soil followed by leaching through the epikarst acts as a control on spring NO3− concentration and loading. Compared to a fluvial‐dominated immature karst system, mature‐karst systems behave as natural detention basins for NO3−, temporarily delaying NO3− delivery to downstream waters and maintaining elevated NO3− concentrations for days to weeks after hydrologic activity ends. This study shows the efficacy of numerical modeling to elucidate complex pathways, processes, and timing of N in karst systems.
Socio‐Hydrology in Perspective—Circa 2018
Authors: Hall Jim W.
Published: February 2019

The special section on socio‐hydrology is one of most successful in Water Resources Research, containing more than 30 articles, with many more submitted. As we would hope for a special section, this is just the start, and we continue to receive a flow of papers that either explicitly describe themselves as socio‐hydrology or are addressing the challenges of coupled human and water systems. In this Editorial, we reflect upon the scope and nature of those articles and make some tentative suggestions about future directions and the realistic ambition for socio‐hydrology.
Assessment of Functional Outcomes of an Interdisciplinary Inpatient Pediatric Pain Rehabilitation Program
Authors: Robinson Merideth , Ward Cynthia M. , Shieh Beverly S. , Armstrong Bridget , Docimo Marissa A. , Celedon Ximena , Rybczynski Suzanne , Levey Eric , Slifer Keith J.
Published: February 2019

Objective: The aim of the current study was to replicate and extend the program outcome analysis previously reported by Maynard, Amari, Wieczorek, Christensen, and Slifer (2010) by evaluating and describing the effectiveness of the same inpatient interdisciplinary pain rehabilitation program using standardized measures not included in the original study. The current study examined functional ability; subjective pain experience; school status; social functioning; mood; and anxiety at admission, discharge, and follow-up. Additionally, the study examined differences in treatment response across pain diagnoses. Method: A retrospective chart review of 59 patients, aged 9–20 years, was conducted. Pain-related disability, depression, anxiety, social functioning, and school attendance were assessed at admission, discharge and at 3, 12, and 24 months of follow-up. Results: Patients showed statistically significant improvements in pain-related disability (youth and parent report), depression, anxiety, social functioning, and school attendance. As expected based on prior research, the study did not find significant differences in self-reported pain severity between admission and discharge. Additionally, participants with head pain showed less change in parent-reported functional disability than participants with musculoskeletal, abdominal, or other types of pain. Preliminary follow-up data showed maintenance or improvement in school attendance and community participation despite intermittent emergency room (ER)/hospital visits. Conclusion: The inpatient interdisciplinary rehabilitation approach is effective in improving pain-related disability, depression, anxiety, social functioning, school attendance, and community participation, which adds to the body of literature supporting intensive interdisciplinary treatment for children and adolescents with chronic pain. The current study suggests that an intensive interdisciplinary approach may be effective for a wide variety of chronic pain conditions.

Implications for Impact Statement

This study examines the effectiveness of an inpatient interdisciplinary rehabilitation approach to treatment of chronic pain. The study found that participants showed significant improvements in pain-related disability, depression, anxiety, social functioning, and school attendance, although participants with head pain showed less improvement in parent-reported functional disability than other diagnoses. Preliminary data also suggest maintenance or improvement in functional outcomes after discharge.
Effectiveness of Family-Based Treatment for Pediatric Eating Disorders in a Tertiary Care Setting
Authors: Coelho Jennifer S. , Beach Barbara , O’Brien Karina , Marshall Sheila , Lam Pei-Yoong
Published: February 2019

Objective: A retrospective chart review was conducted to investigate outcomes in children and adolescents who entered family-based treatment (FBT) in a tertiary eating disorders treatment setting that offers treatment across the continuum of care (i.e., outpatient, day treatment, and inpatient services). Method: Chart data were extracted for children and adolescents who received FBT during the study period (2010–2016). Results: A total of 62 individuals were included in the database, 51 of whom (82.3%) were underweight (i.e., less than 95% median body mass index) at FBT start. The majority of the sample (84.3%) who were underweight at FBT admission achieved at least partial weight restoration. A portion of the sample (21%) was discharged to a more intensive treatment (i.e., day treatment or inpatient care). Weight at FBT start was examined as a potential predictor of outcomes; however, those starting FBT at a lower weight were not more likely to require intensive treatment services. Conclusions: Overall, the study supports the effectiveness of FBT in a tertiary care setting, including for those starting FBT at a very low initial body weight (that is, less than 78% median body mass index). Implications for outpatient clinical care of pediatric eating disorders will be discussed.

Implications for Impact Statement

Family-based treatment (FBT) for pediatric eating disorders appears to be effective in real-world settings outside of controlled research trials. Children and adolescents who start FBT at a very low initial body weight are not more likely than those who start FBT at a higher body weight to require more intensive treatment (e.g., day treatment or inpatient admission). Initial body weight at FBT start does not appear to be a pertinent criterion for determination of FBT suitability.
Cell division cycle associated 5 promotes colorectal cancer progression by activating the ERK signaling pathway
Authors: Shen Aling , Liu Liya , Chen Hongwei , Qi Fei , Huang Yue , Lin Jiumao , Sferra Thomas Joseph , Sankararaman Senthilkumar , Wei Lihui , Chu Jianfeng , Chen Youqin , Peng Jun
Published: February 2019

Cell division cycle associated 5 (CDCA5) is implicated in the development and progression of a variety of human cancers. Functional significance of CDCA5 in colorectal cancer (CRC), however, has not been investigated. Using a combination of on-line data mining, biochemistry, and molecular biology, we examined the potential oncogenic activity of CDCA5 and the underlying mechanisms. Experiments with human tissue sample showed increased CDCA5 expression in CRC vs. in noncancerous adjacent tissue, and association of CDCA5 upregulation in CRC tissues with shorter patient survival. Also, representative CRC cell-lines had higher CDCA5 expression vs. fetal colonic mucosal cells. CDCA5 knockdown using lentivirus-mediated shRNA inhibited the proliferation and induced apoptosis in cultured HCT116 and HT-29 cells, and suppressed the growth of xenograft in nude mice. CDCA5 knockdown decreased the expression of CDK1 and CyclinB1, increased caspase-3 activity, cleaved PARP and the Bax/Bcl-2 ratio. CDCA5 knockdown also significantly decreased phosphorylation of ERK1/2 and expression of c-jun. Taken together, these findings suggest a significant role in CRC progression of CRC, likely by activating the ERK signaling pathway.
Endogenous arginase 2 as a potential biomarker for PEGylated arginase 1 treatment in xenograft models of squamous cell lung carcinoma
Authors: Lam Sze-Kwan , Yan Sheng , Xu Shi , U Kin-Pong , Cheng Paul Ning-Man , Ho James Chung-Man
Published: February 2019

Depletion of arginine induced by PEGylated arginase 1 (ARG1) (BCT-100) has shown anticancer effects in arginine auxotrophic cancers that lack argininosuccinate synthetase (ASS1) and ornithine transcarbamylase (OTC). High levels of endogenous arginase 2 (ARG2) have been previously reported in human lung cancers. Although a high-ARG2 level neither causes immunosuppression nor affects disease progression, it may theoretically affect the efficacy of PEGylated ARG1 treatment. ARG2 was shown to be highly expressed in H520 squamous cell lung carcinoma (lung SCC) xenografts but undetectable in SK-MES-1 and SW900 lung SCC xenografts. We propose that high-endogenous expression of ARG2 could impede the anti-tumor effect of PEGylated ARG1 in lung SCC. The in vivo effect of PEGylated ARG1 was investigated using three xenograft models of lung SCC. PEGylated ARG1 (60 mg/kg) suppressed tumor growth in SK-MES-1 and SW900 but not H520 xenografts. ASS1 was expressed in SK-MES-1 and SW900 xenografts while OTC expression remained low in all xenografts. A high-endogenous ARG2 level was detected only in H520 xenografts. Serum arginine level was decreased significantly by PEGylated ARG1 in all xenografts. Nonetheless intratumoral arginine level was decreased by PEGylated ARG1 in SK-MES-1 and SW900, not H520 xenografts. In SK-MES-1 xenografts, PEGylated ARG1 treatment induced G1 arrest, downregulation of Ki67 and Mcl-1 and activation of apoptosis. In SW900 xenografts, upregulation of Bim and activation of apoptosis were observed upon PEGylated ARG1 treatment. Silencing of ARG2 re-sensitized the H520 xenografts to PEGylated ARG1 treatment, partially mediated through arginine depletion via G1 arrest and apoptosis. PEGylated ARG1 treatment (BCT-100) was effective in lung SCC xenografts with low-endogenous levels of ASS1/OTC and ARG2. High-endogenous ARG2 expression may cause resistance to PEGylated ARG1 treatment in lung SCC xenografts. ARG2 may serve as a third predictive biomarker in PEGylated ARG1 treatment in lung SCC.
Management of cardiovascular risk in patients with multiple myeloma
Authors: Plummer Chris , Driessen Christoph , Szabo Zsolt , Mateos María-Victoria
Published: February 2019

Multiple myeloma (MM) is a plasma cell malignancy that accounts for 10% of hematological cancers. It predominantly affects elderly people; median age at diagnosis is 70 years. Consequently, many patients with MM have cardiovascular comorbidities or risk factors. MM can cause cardiac comorbidities such as cardiomyopathy and heart failure caused by cardiac amyloidosis and/or anemia. Some of the treatments used in MM can also affect cardiovascular health. Advances in pharmacotherapy for MM, such as the introduction of immunomodulators, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies, have dramatically improved progression-free survival and life expectancy, but new agent classes are associated with adverse events that were not previously observed on a regular basis, including cardiovascular events. However, with careful risk assessment, monitoring, and prophylactic therapy, many of these cardiovascular complications can be managed or treated successfully. Most routine cardiovascular surveillance is undertaken by the treating hemato-oncologist, but a multidisciplinary approach involving cardiologists may help to optimize patient outcomes. In this review, we survey the cardiac complications commonly reported in patients with MM, discuss how they can be prevented and managed, and summarize the role cardiologists can play in delivering the best possible outcomes for patients with MM and cardiovascular comorbidities.
A snapshot of biodiversity protection in Antarctica
Authors: Wauchope Hannah S. , Shaw Justine D. , Terauds Aleks
Published: February 2019

Threats to Antarctic biodiversity are escalating, despite its remoteness and protection under the Antarctic Treaty. Increasing human activity, pollution, biological invasions and the omnipresent impacts of climate change all contribute, and often combine, to exert pressure on Antarctic ecosystems and environments. Here we present a continent-wide assessment of terrestrial biodiversity protection in Antarctica. Despite Antarctic Specially Protected Areas covering less than 2% of Antarctica, 44% of species (including seabirds, plants, lichens and invertebrates) are found in one or more protected areas. However, protection is regionally uneven and biased towards easily detectable and charismatic species like seabirds. Systematic processes to prioritize area protection using the best available data will maximize the likelihood of ensuring long-term protection and conservation of Antarctic biodiversity.
Validation of vessel size imaging (VSI) in high-grade human gliomas using magnetic resonance imaging, image-guided biopsies, and quantitative immunohistochemistry
Authors: Chakhoyan Ararat , Yao Jingwen , Leu Kevin , Pope Whitney B. , Salamon Noriko , Yong William , Lai Albert , Nghiemphu Phioanh L. , Everson Richard G. , Prins Robert M. , Liau Linda M. , Nathanson David A. , Cloughesy Timothy F. , Ellingson Benjamin M.
Published: February 2019

To evaluate the association between a vessel size index (VSIMRI) derived from dynamic susceptibility contrast (DSC) perfusion imaging using a custom spin-and-gradient echo echoplanar imaging (SAGE-EPI) sequence and quantitative estimates of vessel morphometry based on immunohistochemistry from image-guided biopsy samples. The current study evaluated both relative cerebral blood volume (rCBV) and VSIMRI in eleven patients with high-grade glioma (7 WHO grade III and 4 WHO grade IV). Following 26 MRI-guided glioma biopsies in these 11 patients, we evaluated tissue morphometry, including vessel density and average radius, using an automated procedure based on the endothelial cell marker CD31 to highlight tumor vasculature. Measures of rCBV and VSIMRI were then compared to histological measures. We demonstrate good agreement between VSI measured by MRI and histology; VSIMRI = 13.67 μm and VSIHistology = 12.60 μm, with slight overestimation of VSIMRI in grade III patients compared to histology. rCBV showed a moderate but significant correlation with vessel density (r = 0.42, p = 0.03), and a correlation was also observed between VSIMRI and VSIHistology (r = 0.49, p = 0.01). The current study supports the hypothesis that vessel size measures using MRI accurately reflect vessel caliber within high-grade gliomas, while traditional measures of rCBV are correlated with vessel density and not vessel caliber.
Natural enamel caries, dentine reactions, dentinal fluid and biofilm
Authors: de Barros Pinto Laryssa , Lira Maria Luiza Lima Alves , Cavalcanti Yuri Wanderley , Dantas Eugênia Livia de Andrade , Vieira Maria Lúcia Oliveira , de Carvalho Gabriel Garcia , de Sousa Frederico Barbosa
Published: February 2019

It is believed that penetration of dentinal fluid into natural enamel caries (NEC) is negligible because of the barrier created by underlying sclerotic dentine, but there are conflicting evidences on whether dentine subjacent to NEC is sclerotic or demineralized. This study aimed at investigating the relationship between NEC, subjacent dentine reactions, modification of dentinal fluid, and composition of cariogenic biofilm formed on the NEC surface. Proximal NEC (PNEC) lesions of human permanent posterior teeth were included in five experiments. Histologically, microradiographic analysis with contrast solution (MRC) in dentine revealed a decreased proportion of sclerotic dentine and an increased proportion of deep dentine demineralization compared to the classical stereomicroscopic histological analysis based on dentin color and translucency. Real-time MRC and 3D optical profilometry, and 3D microtomographic analysis evidenced a facilitated transport of modified dentinal fluid towards PNEC lesions. Cariogenic biofilm formed in vitro on the PNEC surface presented lower amounts of insoluble and soluble matrix polysaccharides when 2% chlorexidine was inserted in the pulp chamber. In conclusion, this study evidenced that dentine subjacent to PNEC is mostly demineralized, providing facilitated pathway for dentinal fluid to penetrate into PNEC and alter the composition of the biofilm formed on the PNEC surface.
Hyperactivation of mTORC1 disrupts cellular homeostasis in cerebellar Purkinje cells
Authors: Sakai Yusuke , Kassai Hidetoshi , Nakayama Hisako , Fukaya Masahiro , Maeda Tatsuya , Nakao Kazuki , Hashimoto Kouichi , Sakagami Hiroyuki , Kano Masanobu , Aiba Atsu
Published: February 2019

Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolism. The importance of mTORC1 signaling in neuronal development and functions has been highlighted by its strong relationship with many neurological and neuropsychiatric diseases. Previous studies demonstrated that hyperactivation of mTORC1 in forebrain recapitulates tuberous sclerosis and neurodegeneration. In the mouse cerebellum, Purkinje cell-specific knockout of Tsc1/2 has been implicated in autistic-like behaviors. However, since TSC1/2 activity does not always correlate with clinical manifestations as evident in some cases of tuberous sclerosis, the intriguing possibility is raised that phenotypes observed in Tsc1/2 knockout mice cannot be attributable solely to mTORC1 hyperactivation. Here we generated transgenic mice in which mTORC1 signaling is directly hyperactivated in Purkinje cells. The transgenic mice exhibited impaired synapse elimination of climbing fibers and motor discoordination without affecting social behaviors. Furthermore, mTORC1 hyperactivation induced prominent apoptosis of Purkinje cells, accompanied with dysregulated cellular homeostasis including cell enlargement, increased mitochondrial respiratory activity, and activation of pseudohypoxic response. These findings suggest the different contributions between hyperactivated mTORC1 and Tsc1/2 knockout in social behaviors, and reveal the perturbations of cellular homeostasis by hyperactivated mTORC1 as possible underlying mechanisms of neuronal dysfunctions and death in tuberous sclerosis and neurodegenerative diseases.
Recording single- and multi-unit neuronal action potentials from the surface of the dorsal root ganglion
Authors: Kashkoush Ahmed I. , Gaunt Robert A. , Fisher Lee E. , Bruns Tim M. , Weber Douglas J.
Published: February 2019

The dorsal root ganglia (DRG) contain cell bodies of primary afferent neurons, which are frequently studied by recording extracellularly with penetrating microelectrodes inserted into the DRG. We aimed to isolate single- and multi-unit activity from primary afferents in the lumbar DRG using non-penetrating electrode arrays and to characterize the relationship of that activity with limb position and movement. The left sixth and seventh lumbar DRG (L6-L7) were instrumented with penetrating and non-penetrating electrode arrays to record neural activity during passive hindlimb movement in 7 anesthetized cats. We found that the non-penetrating arrays could record both multi-unit and well-isolated single-unit activity from the surface of the DRG, although with smaller signal to noise ratios (SNRs) compared to penetrating electrodes. Across all recorded units, the median SNR was 1.1 for non-penetrating electrodes and 1.6 for penetrating electrodes. Although the non-penetrating arrays were not anchored to the DRG or surrounding tissues, the spike amplitudes did not change (<1% change from baseline spike amplitude) when the limb was moved passively over a limited range of motion (~20 degrees at the hip). Units of various sensory fiber types were recorded, with 20% of units identified as primary muscle spindles, 37% as secondary muscle spindles, and 24% as cutaneous afferents. Our study suggests that non-penetrating electrode arrays can record modulated single- and multi-unit neural activity of various sensory fiber types from the DRG surface.
Defining Optimal Soybean Sowing Dates across the US
Authors: Mourtzinis Spyridon , Specht James E. , Conley Shawn P.
Published: February 2019

Global crop demand is expected to increase by 60–110% by 2050. Climate change has already affected crop yields in some countries, and these effects are expected to continue. Identification of weather-related yield-limiting conditions and development of strategies for agricultural adaptation to climate change is essential to mitigate food security concerns. Here we used machine learning on US soybean yield data, collected from cultivar trials conducted in 27 states from 2007 to 2016, to examine crop sensitivity to varying in-season weather conditions. We identified the month-specific negative effect of drought via increased water vapor pressure deficit. Excluding Texas and Mississippi, where later sowing increased yield, sowing 12 days earlier than what was practiced during this decade across the US would have resulted in 10% greater total yield and a cumulative monetary gain of ca. US$9 billion. Our data show the substantial nation- and region-specific yield and monetary effects of adjusting sowing timing and highlight the importance of continuously quantifying and adapting to climate change. The magnitude of impact estimated in our study suggest that policy makers (e.g., federal crop insurance) and laggards (farmers that are slow to adopt) that fail to acknowledge and adapt to climate change will impact the national food security and economy of the US.
G6Pase location in the endoplasmic reticulum: Implications on compartmental analysis of FDG uptake in cancer cells
Authors: Scussolini Mara , Bauckneht Matteo , Cossu Vanessa , Bruno Silvia , Orengo Anna Maria , Piccioli Patrizia , Capitanio Selene , Yosifov Nikola , Ravera Silvia , Morbelli Silvia , Piana Michele , Sambuceti Gianmario , Caviglia Giacomo , Marini Cecilia
Published: February 2019

The favourable kinetics of 18F-fluoro-2-deoxyglucose (FDG) permits to depict cancer glucose consumption by a single evaluation of late tracer uptake. This standard procedure relies on the slow radioactivity loss, usually attributed to the limited tumour expression of G6P-phosphatase (G6Pase). However, this classical interpretation intrinsically represents an approximation since, as in all tissues, cancer G6Pase activity is remarkable and is confined to the endoplasmic reticulum (ER), whose lumen must be reached by phosphorylated FDG to explain its hydrolysis and radioactivity release. The present study tested the impact of G6Pase sequestration on the mathematical description of FDG trafficking and handling in cultured cancer cells. Our data show that accounting for tracer access to the ER configures this compartment as the preferential site of FDG accumulation. This is confirmed by the reticular localization of fluorescent FDG analogues. Remarkably enough, reticular accumulation rate of FDG is dependent upon extracellular glucose availability, thus configuring the same ER as a significant determinant of cancer glucose metabolism.
New risk prediction model of coronary heart disease in participants with and without diabetes: Assessments of the Framingham risk and Suita scores in 3-year longitudinal database in a Japanese population
Authors: Hirai Hiroyuki , Asahi Koichi , Yamaguchi Satoshi , Mori Hirotaka , Satoh Hiroaki , Iseki Kunitoshi , Moriyama Toshiki , Yamagata Kunihiro , Tsuruya Kazuhiko , Fujimoto Shouichi , Narita Ichiei , Konta Tsuneo , Kondo Masahide , Shibagaki Yugo , Kasahara Masato , Watanabe Tsuyoshi , Shimabukuro Michio
Published: February 2019

The Framingham Risk Score (FRS) has been reported to predict coronary heart disease (CHD), but its assessment has been unsuccessful in Asian population. We aimed to assess FRS and Suita score (a Japanese CHD prediction model) in a Japanese nation-wide annual health check program, participants aged 40–79 years were followed up longitudinally from 2008 to 2011. Of 35,379 participants analyzed, 1,234 had new-onset CHD. New-onset CHD was observed in diabetic men [6.00%], non-diabetic men [3.96%], diabetic women [5.51%], and non-diabetic women [2.86%], respectively. Area under the curve (AUC) of receiver operating characteristic (ROC) curve for CHD prediction were consistently low in Suita score (TC), FRS (TC) and NCEP-ATPIII FRS (TC), suggesting that these scores have only a limited power. ROC, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) and Hosmer–Lemeshow goodness-of-fit test did not show clear differences between Suita score (TC) and FRS (TC). New models combining waist circumference ≥85 cm in men or proteinuria ≥1+ in women to Suita score (TC) was superior in diabetic men and women. New models could be useful to predict 3-year risk of CHD at least in Japanese population especially in diabetic population.
Constructing Supported Cell Membranes with Controllable Orientation
Authors: Lyu Shao-Wei , Wang Jou-Fang , Chao Ling
Published: February 2019

Membrane proteins play important roles in various cellular processes. Methods that can retain their structure and membrane topology information during their characterization are desirable for understanding their structure-function behavior. Here, we use giant plasma membrane vesicles (GPMVs) to form the supported cell membrane and develop a blotting method to control the orientation of the deposited cell membrane in order to study membrane proteins from either the extracellular or the cytoplasmic sides. We show that the membrane orientation can be retained in the directly-deposited membrane and the deposited membrane on mica can be blotted onto glass to reverse the membrane orientation. We used Aquaporin 3 (AQP3), an abundant native transmembrane protein in Hela cells, as a target to examine the cell membrane orientation in the directly-deposited and reversed membrane platforms. The immunostaining of antibodies targeting either the cyto-domain or ecto-domain of AQP3 shows that the intracellular side of the cell membrane faced the bulk aqueous environment when the GPMVs spontaneously ruptured on the support and that the membrane orientation was reversed after blotting. With this blotting method, we can thus control the orientation of the supported cell membrane to study membrane protein functions and structures from either side of the cell plasma membrane.
Behçet’s disease and genetic interactions between HLA-B*51 and variants in genes of autoinflammatory syndromes
Authors: Burillo-Sanz Sergio , Montes-Cano Marco-Antonio , García-Lozano José-Raúl , Olivas-Martínez Israel , Ortego-Centeno Norberto , García-Hernández Francisco-José , Espinosa Gerard , Graña-Gil Genaro , Sánchez-Bursón Juan , Juliá María Rosa , Solans Roser , Blanco Ricardo , Barnosi-Marín Ana-Celia , Gómez de la Torre Ricardo , Fanlo Patricia , Rodríguez-Carballeira Mónica , Rodríguez-Rodríguez Luis , Camps Teresa , Castañeda Santos , Alegre-Sancho Juan-Jose , Martín Javier , González-Escribano María Francisca
Published: February 2019

Behçet’s disease (BD) is an immune-mediated systemic disorder with a well-established genetic base. In a previous study, using a next generation sequencing approach, we found many rare variants and some functional polymorphisms in genes related to autoinflammatory syndromes (AID): CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A in our BD cohort. Our strategy did not allow us to establish either number of patients with variants, proportion of individuals accumulating them or relationship with other genetic factors. With the goal to answer these questions, the individual samples were sequenced. Additionally, three functional polymorphisms: NLRP3 p.Gln703Lys, NOD2 p.Arg702Trp and p.Val955Ile were genotyped using TaqMan assays. A total of 98 patients (27.6%) carried at least one rare variant and 13 of them (3.7%) accumulated two or three. Functional regression model analysis suggests epistatic interaction between B51 and MEFV (P = 0.003). A suggestive protective association of the minor allele of NOD2 p.Arg702Trp (P = 0.01) was found in both, B51 positive and negative individuals. Therefore, a high percentage of patients with BD have rare variants in AID genes. Our results suggest that the association of MEFV with BD could be modulated by the HLA molecules; whereas the protective effect of NOD2 p.Arg702Trp would be independent of HLA.
Distributions of soil branched glycerol dialkyl glycerol tetraethers from different climate regions of China
Authors: Wang M. , Zheng Z. , Zong Y. , Man M. , Tian L.
Published: February 2019

Distributions of branched glycerol dialkyl glycerol tetraethers (brGDGTs) from soil bacteria have been recently used for reconstructions of past soil pH and air temperature history. Here, we report the brGDGTs distribution patterns from different climate regions of China, using 42 novel brGDGT data from sub-tropical Chinese soils, compiled alongside previously-published data encompassing different environmental conditions across China. These patterns show high abundance of Ia fraction in soils from humid areas, and high abundance of IIa′ and IIIa′ fractions corresponds to semi-humid or semi-arid conditions, implying a possible relationship with precipitation. The abundance of IIa fraction appears negatively correlated with air temperature. Statistically, the soil pH and temperature factors represent 62% and 30% variations of the total variance respectively. For soils from humid and semi-humid regions, strong correlations between cyclization of branched tetraethers (CBT′) index and soil pH (R2 = 0.89) and between methylation of branched tetraethers (MBT′5ME) index and mean annual temperature (MAT)(R2 = 0.82) exist. When soils from semi-arid regions are included, the correlations become slightly stronger with pH and significantly weaker with MAT. Our study confirms the usefulness of soil brGDGTs distributions for Quaternary palaeo-climate reconstructions.
Personality traits influence contest outcome, and vice versa, in a territorial butterfly
Authors: Kaiser Aurélien , Merckx Thomas , Van Dyck Hans
Published: February 2019

Holding a territory is often crucial in order to acquire key resources, including mating partners. However, few studies have investigated the role of animal personality in the context of territorial conflicts and how the contest outcome itself may influence personality traits. We studied personality in male Speckled wood butterflies, Pararge aegeria, before and after territorial contests for sunspot territories. Before interactions, boldness decreased with age, while activity and exploration were only influenced by ambient conditions. Neither age nor morphology did influence the probability to win contests, but winners were more active and more explorative than losers and, moreover, males that received a red wing mark were more likely to be winners. Butterflies that lost a contest showed pronounced behavioural changes. Mean boldness increased and its repeatability was disrupted, while no such change was detected in winners. The observed boldness increase in losers may be explained by a ‘desperado effect’, though its implication for successive contests remains unknown. Given that territoriality is expected to have important consequences for reproductive success, our results suggest that personality traits may indirectly contribute to individual fitness by influencing the ability to gain access to mate-location patches.
Host plant and population source drive diversity of microbial gut communities in two polyphagous insects
Authors: Jones Asher G. , Mason Charles J. , Felton Gary W. , Hoover Kelli
Published: February 2019

Symbioses between insects and microbes are ubiquitous, but vary greatly in terms of function, transmission mechanism, and location in the insect. Lepidoptera (butterflies and moths) are one of the largest and most economically important insect orders; yet, in many cases, the ecology and functions of their gut microbiomes are unresolved. We used high-throughput sequencing to determine factors that influence gut microbiomes of field-collected fall armyworm (Spodoptera frugiperda) and corn earworm (Helicoverpa zea). Fall armyworm midgut bacterial communities differed from those of corn earworm collected from the same host plant species at the same site. However, corn earworm bacterial communities differed between collection sites. Subsequent experiments using fall armyworm evaluating the influence of egg source and diet indicated that that host plant had a greater impact on gut communities. We also observed differences between regurgitant (foregut) and midgut bacterial communities of the same insect host, suggesting differential colonization. Our findings indicate that host plant is a major driver shaping gut microbiota, but differences in insect physiology, gut region, and local factors can also contribute to variation in microbiomes. Additional studies are needed to assess the mechanisms that affect variation in insect microbiomes, as well as the ecological implications of this variability in caterpillars.
Mutations in the dimer interfaces of the dengue virus capsid protein affect structural stability and impair RNA-capsid interaction
Authors: Figueira-Mansur Janaina , Aguilera Estefania A. , Stoque Rafael M. , Ventura Gustavo T. , Mohana-Borges Ronaldo
Published: February 2019

The dengue virus 2 capsid protein (DENV2C) plays a primary structural role in the protection of the viral genome and is crucial for nucleocapsid assembly. In this study, we generated single mutants of DENV2C at L50 and L54 residues of the α2 helix, which was shown to interfere with the integration of the capsid into lipid droplets, and at residues L81 and I88 located in the α4 helix, which was shown to affect viral assembly. We demonstrated that the oligomeric states of DENV2C and its mutants exist primarily in the dimeric state in solution. All single-point mutations introduced in DENV2C promoted reduction in protein stability, an effect that was more pronounced for the L81N and I88N mutants, but not protein unfolding. All the single-point mutations affected the ability of DEN2C to interact with RNA. We concluded that mutations in the α2-α2′ and α4-α4′ dimer interfaces of DENV2C affect the structural stability of the protein and impair RNA-capsid interaction. These effects were more pronounced for mutations at the L81 and I88 residues in the α4 helix. These results indicate the importance of the α4-α4′ dimer interface, which could be studied as a potential target for drug design in the future.
Surface chemical defence of the eelgrass Zostera marina against microbial foulers
Authors: Papazian Stefano , Parrot Delphine , Burýšková Barbora , Weinberger Florian , Tasdemir Deniz
Published: February 2019

Plants rely on both mechanical and chemical defence mechanisms to protect their surfaces against microorganisms. The recently completed genome of the eelgrass Zostera marina, a marine angiosperm with fundamental importance for coastal ecosystems, showed that its re-adaptation from land to the sea has led to the loss of essential genes (for chemical communication and defence) and structural features (stomata and thick cuticle) that are typical of terrestrial plants. This study was designed to understand the molecular nature of surface protection and fouling-control strategy of eelgrass against marine epiphytic yeasts. Different surface extraction methods and comparative metabolomics by tandem mass spectrometry (LC-MS/MS) were used for targeted and untargeted identification of the metabolite profiles of the leaf surface and the whole tissue extracts. Desorption electrospray ionization-imaging mass spectrometry (DESI-IMS) coupled with traditional bioassays revealed, for the first time, the unique spatial distribution of the eelgrass surface-associated phenolics and fatty acids, as well as their differential bioactivity against the growth and settlement of epiphytic yeasts. This study provides insights into the complex chemical defence system of the eelgrass leaf surface. It suggests that surface-associated metabolites modulate biotic interactions and provide chemical defence and structural protection to eelgrass in its marine environment.
Imbalance in the Expression of Genes Associated with Purinergic Signalling in the Lung and Systemic Arteries of COPD Patients
Authors: Careta Oriol , Cuevas Ester , Muñoz-Esquerre Mariana , López-Sánchez Marta , Pascual-González Yuliana , Dorca Jordi , Aliagas Elisabet , Santos Salud
Published: February 2019

Growing evidence indicates that purinergic signalling is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the vascular remodelling that occurs in other disorders; however, its role in initial vascular changes of COPD is not entirely known. We hypothesised that expression of genes regulating extracellular ATP and adenosine levels would be altered in the lung and systemic arteries of COPD patients. Quantitative real-time PCR was performed to analyse the relative expression of 17 genes associated with purinergic signalling and inflammation in lungs and intercostal arteries of never smokers (NS) (n = 16), non-obstructed smokers (NOS) (n = 17) and COPD patients (n = 21). Gene expression of ATP-degrading enzymes was decreased in both tissues of NOS and COPD patients compared to NS. NT5E expression (gene transcribing for an AMP hydrolyzing ectonucleotidase) was increased in both tissues in NOS compared to the other groups. P1 and P2 receptors did not show changes in expression. Expression of genes associated with inflammation (interleukin-13) was upregulated only in lung tissues of COPD. These findings suggest that the expression of different extracellular ATP-degrading enzymes is altered in smokers (NOS and COPD patients), promoting inflammation. However, the high NT5E expression found only in NOS could compensate this inflammatory environment.
Untargeted metabolomics by high resolution mass spectrometry coupled to normal and reversed phase liquid chromatography as a tool to study the in vitro biotransformation of new psychoactive substances
Authors: Manier Sascha K. , Keller Andreas , Schäper Jan , Meyer Markus R.
Published: February 2019

In 2016, several synthetic cathinones were seized by the State Bureau of Criminal Investigation Bavaria in Germany. Due to their previous appearances in other countries their metabolism was already investigated in human urine as well as differentin vitromodels. These investigations were conducted using ordinary metabolism studies for drugs of abuse by using general knowledge about drug metabolism and visual comparison of mass spectra. The present study aimed to use untargeted metabolomics to support and improve those methods that highly depend on the investigators experience. Incubations were conducted using pooled human liver microsomes (pHLM) and the two cathinones 1-phenyl-2-(1-pyrrolidinyl)-1-butanone and 1-phenyl-2-(1-pyrrolidinyl)-1-heptanone. Samples were analyzed by LC-HRMS/MS using a metabolomics workflow consisting of a reversed phase or normal phase separation followed by electrospray ionization and full scan in positive or negative mode. LC-MS data was afterwards statistically evaluated using principal component analysis, t-distributed stochastic neighborhood embedding, and hierarchical clustering. Significant features were then identified using MS/MS. The workflow revealed 24 significant features after 1-phenyl-2-(1-pyrrolidinyl)-1-butanone and 39 after 1-phenyl-2-(1-pyrrolidinyl)-1-heptanone incubation, consisting of adducts, artifacts, isomers, and metabolites. The applied untargeted metabolomics strategy was able to find almost all of the metabolites that were previously described for 1-phenyl-2-(1-pyrrolidinyl)-1-butanone in literature as well as three additional metabolites. Concerning 1-phenyl-2-(1-pyrrolidinyl)-1-heptanone biotransformation in pHLM, merely four metabolites described in primary human hepatocytes and human urine were not found. This study revealed that untargeted metabolomics workflows are well suited to support biotransformation studies at least of the investigated compounds in pHLM.
High degree of circular polarization in WS2 spiral nanostructures induced by broken symmetry
Authors: Barman Prahalad Kanti , Sarma Prasad V. , Shaijumon M. M. , Kini R. N.
Published: February 2019

We present helicity resolved photoluminescence (PL) measurements of WS2 spiral (SPI) nanostructures. We show that very high degree of circular polarization (DCP) (~94 ± 4%) is obtained from multilayer SPI samples at room temperature upon excitation with a circularly polarized laser at a wavelength near-resonant with the A-exciton (633 nm). TEM analysis showed that these SPI nanostructures have AB stacking in which the inversion symmetry is broken, and hence this leads to very high DCP. Comparison with PL from monolayer and bi-layer WS2 samples, along with polarization resolved PL studies provide evidence for suppression of interlayer/intravalley scattering in the multilayer SPI samples.
Diterpenoid compounds from Wedelia trilobata induce resistance to Tomato spotted wilt virus via the JA signal pathway in tobacco plants
Authors: Zhao Lihua , Hu Zhonghui , Li Shunlin , Zhou Xueping , Li Jing , Su Xiaoxia , Zhang Lizhen , Zhang Zhongkai , Dong Jiahong
Published: February 2019

Tomato spotted wilt virus (TSWV) causes major losses of many crops worldwide. Several strategies have been attempted to control disease caused by TSWV. However, many challenges for the effective control of this disease remain. A promising approach is the use of abiotic or biotic inducers to enhance plant resistance to pathogens. We screened a diterpenoid compound from Wedelia trilobata, 3α-Angeloyloxy-9β-hydroxy-ent-kaur-16-en-19-oic acid (AHK), which had higher curative and protective effects against TSWV than the ningnanmycin control. The rapid initiation of the expression of all the TSWV genes was delayed by more than 1d in the curative assay, and the expression of the NSs, NSm and RdRp genes was inhibited. In addition, the replication of all TSWV genes in systemic leaves was inhibited in the protective assay, with an inhibition rate of more than 90%. The concentrations of jasmonic acid (JA) and jasmonic acid isoleucine (JA-ILE) in the AHK-treated and systemic leaves of the treated plants were significantly higher than those observed in the control. The results suggested that AHK can induce systemic resistance in treated plants. The transcription of the NtCOI1 gene, a key gene in the JA pathway, was significantly higher in both the inoculated and systemic leaves of the AHK-treated plants compared to the control. The AHK-induced resistance to TSWV in Nicotiana benthamiana could be eliminated by VIGS-mediated silencing of the NtCOI1 gene. These results indicated that AHK can activate the JA pathway and induce systemic resistance to TSWV infection.