bluuebunny/crossref_metadata_2025 huggingface dataset:
CerS6 regulates cisplatin resistance in oral squamous cell carcinoma by altering mitochondrial fission and autophagy
Authors: Li Shengjiao , Wu Yangou , Ding Yunpeng , Yu Miao , Ai Zexin
Published: July 2018

Chemoresistance remains a challenge in the effective treatment of solid tumors, including oral squamous cell carcinoma (OSCC). Mitochondrial dynamics and autophagy have recently been implicated in the chemoresistance of cancer cells. The neutralization of ceramide is also associated with multidrug resistance, and ceramide synthase 6 (CerS6) is known to induce apoptosis. However, whether CerS6 regulates chemoresistance in OSCC is not clearly understood. Therefore, we investigated the role of CerS6 in the susceptibility of OSCC cells to cisplatin. In this study, we observed that cisplatin‐resistant OSCC cells process lower levels of fission‐state mitochondria and cell apoptosis than cisplatin‐sensitive cells, and autophagy was activated in cisplatin‐resistant OSCC cells. We found lower CerS6 expression in cisplatin‐resistant OSCC cells. Overexpression of CerS6 with lentivirus‐encoded CerS6 complementary DNA in cisplatin‐resistant OSCC cells increased cisplatin sensitivity. Overexpression of CerS6 enhanced mitochondrial fission and apoptosis and attenuated cisplatin‐induced autophagy in cisplatin‐resistant OSCC cells. Further investigation indicated that CerS6 might function through altering calpain expression to enhance cisplatin sensitivity. Cisplatin‐resistant OSCC cells xenografted onto a nude mouse model confirmed that CerS6 enhanced cisplatin chemotherapy sensitivity to reduce tumor volume. These data indicate that CerS6 could mediate an effective response to cisplatin in chemoresistant OSCC.
Deficiency of fibroblast growth factor 2 (FGF‐2) leads to abnormal spermatogenesis and altered sperm physiology
Authors: Saucedo Lucía , Rumpel Regina , Sobarzo Cristian , Schreiner Dietmar , Brandes Gudrun , Lustig Livia , Vazquez‐Levin Mónica Hebe , Grothe Claudia , Marín‐Briggiler Clara
Published: July 2018

In previous studies, we described the presence of fibroblast growth factor 2 (FGF‐2) and its receptors (FGFRs) in human testis and sperm, which are involved in spermatogenesis and in motility regulation. The aim of the present study was to analyze the role of FGF‐2 in the maintenance of sperm physiology using FGF‐2 knockout (KO) mice. Our results showed that in wild‐type (WT) animals, FGF‐2 is expressed in germ cells of the seminiferous epithelium, in epithelial cells of the epididymis, and in the flagellum and acrosomal region of epididymal sperm. In the FGF‐2 KO mice, we found alterations in spermatogenesis kinetics, higher numbers of spermatids per testis, and enhanced daily sperm production compared with the WT males. No difference in the percentage of sperm motility was detected, but a significant increase in sperm concentration and in sperm head abnormalities was observed in FGF‐2 KO animals. Sperm from KO mice depicted reduced phosphorylation on tyrosine residues (a phenomenon that was associated with sperm capacitation) and increased acrosomal loss after incubation under capacitating conditions. However, the FGF‐2 KO males displayed no apparent fertility defects, since their mating with WT females showed no differences in the time to delivery, litter size, and pup weight in comparison with WT males. Overall, our findings suggest that FGF‐2 exerts a role in mammalian spermatogenesis and that the lack of FGF‐2 leads to dysregulated sperm production and altered sperm morphology and function. FGF‐2‐deficient mice constitute a model for the study of the complex mechanisms underlying mammalian spermatogenesis.
Circular RNA circRNA_15698 aggravates the extracellular matrix of diabetic nephropathy mesangial cells via miR‐185/TGF‐β1
Authors: Hu Wei , Han Qing , Zhao Lei , Wang Li
Published: July 2018

Circular RNAs (circRNAs) are a novel type of noncoding RNAs that modulate the pathogenesis of multiple diseases. Nevertheless, the role of circRNAs in diabetic nephropathy (DN) pathogenesis is still ambiguous. In the current study, our team aims to investigate the expression profiles of circRNAs in DN and identify the function of circRNA on mesangial cells. CircRNAs microarray analysis revealed dysregulated circRNA in db/db DN mice, and circRNA_15698 was validated to be upregulated in both db/db mice and mouse mesangial cells (SV40‐MES13) that were exposed to high glucose (25 mM) using real‐time polymerase chain reaction. Loss‐of‐functional experiments showed that circRNA_15698 knockdown significantly inhibited the expression levels of collagen type I (Col. I), collagen type IV (Col. IV), and fibronectin. Moreover, the cellular localization of circRNA_15698 was mainly in the cytoplasm. Bioinformatics tools and luciferase reporter assay confirmed that circRNA_15698 acted as a ‘sponge’ of miR‐185, and then positively regulated the transforming growth factor‐β1 (TGF‐β1) protein expression, suggesting a circRNA_15698/miR‐185/TGF‐β1 pathway. Further validation experiments validated that circRNA_15698/miR‐185/TGF‐β1 promoted extracellular matrix (ECM)‐related protein synthesis. In summary, our study preliminarily investigates the role of circRNAs in mesangial cells and ECM accumulation, providing a novel insight for DN pathogenesis.
Prolonged lipopolysaccharide exposure induces transient immunosuppression in BV2 microglia
Authors: Twayana Krishna Sundar , Chaudhari Namrata , Ravanan Palaniyandi
Published: July 2018

Continuous pre‐exposure of immune cells to low level of inflammatory stimuli makes them hyporesponsive to subsequent exposure. This pathophysiological adaptation; known as endotoxin tolerance is a general paradigm behind several disease pathogenesis. Current study deals with this immunosuppression with respect to BV2 microglia. We attempted to investigate their immune response under prolonged endotoxin exposure and monitor the same upon withdrawal of the stimuli. BV2 microglia cells were maintained under continual exposure of lipopolysaccharide (LPS) for weeks with regular passage after 72 hr (prolonged LPS exposed cells [PLECs]). PLECs were found to be immunosuppressed with diminished expression of proinflammatory cytokines (IL6, IL1β, TNF‐α, and iNOS) and production of nitric oxide, as compared to once LPS exposed cells. Upon remaintenance of cells in normal media without LPS exposure (LPS withdrawal cells [LWCs]), the induced immunosuppression reversed and cells started responding to inflammatory stimuli; revealed by significant expression of proinflammatory cytokines. LWCs showed functional similarities to never LPS exposed cells (NLECs) in phagocytosis activity and their response to anti‐inflammatory agents like dexamethasone. Despite their immunoresponsiveness, PLECs were inflamed and showed higher autophagy rate than NLECs. Additionally, we investigated the role of inhibitor of apoptotic proteins (IAPs) in PLECs to understand whether IAPs aids in the survival of microglial cells under stress conditions. Our results revealed that cIAP1 and cIAP2 are induced in PLECs which might play a role in retaining the viability. Furthermore, antagonism of IAPs has significantly induced cell death in PLECs suggesting the role of IAPs in microglial survival under stress condition. Conclusively, our data suggest that continuous exposure of BV2 microglia cells to LPS results in transient immunosuppression and indicates the involvement of IAPs in retaining their viability under inflammatory stress.
Assessment of food quality and microbial safety of brown macroalgae (Alaria esculenta and Saccharina latissima)
Authors: Blikra Marthe J , Løvdal Trond , Vaka Mette R , Roiha Irja S , Lunestad Bjørn Tore , Lindseth Cecilie , Skipnes Dagbjørn
Published: July 2018

Background

There has been a rapid increase in the number of seaweed farms in the Western world, and it is crucial for these companies and their customers to have standardized methods for quality assessment and optimization. The aim of this study was to adapt known methods for food‐quality determination for the analysis of seaweed quality, including color, texture, and microbiology, and to discuss optimal heat treatments for the popular macroalgae Saccharina latissima and Alaria esculenta.

Results

The development of an attractive, green color during heating was highly specific to species, freezing history, and part of the thallus. Resilience and thermostability were also species dependent. Low microbial numbers (1–3 log cfu/g) for total aerobic count, psychrotrophic bacteria, and spore‐forming bacteria were found, but Bacillus spp. were isolated. No enterococci, coliforms, pathogenic vibrios, or Listeria monocytogenes were detected.

Conclusion

The methods employed were able to describe clearly the physical and microbial qualities of A. esculenta and S. latissima, and quality changes during processing. Based on the results, optimal cooking for a minimum of 15 min at 95 °C was suggested for S. latissima. Fresh and frozen A. esculenta showed the greenest color after heating for 5–9 s at a high temperature (> 85 °C). If a higher heat load is needed to achieve safe and stable food products, using fresh and not frozen A. esculenta is highly recommended, as fresh specimens remain green even after 15 min at 95 °C. © 2018 Society of Chemical Industry
In‐capillary derivatization with fluorescamine for the rapid determination of adamantane drugs by capillary electrophoresis with UV detection
Authors: Prapatpong Pornpan , Nuchtavorn Nantana , Macka Mirek , Suntornsuk Leena
Published: July 2018

In‐capillary derivatization using fluorescamine as the labeling reagent was proposed to enhance the detectability of adamantine drugs (memantine, amantadine and rimantadine) by spectrophotometric detection. Fluorescamine and the drugs were delivered to the capillary electrophoresis instrument at a ratio of 10:1 by zone injection. The derivatization reaction occurred following the application of voltage (20 kV). The derivatized products, hydrolyzed‐ fluorescamine and excess fluorescamine were separated in 7 min using 100 mM borate buffer (pH 10.0) containing 0.1% w/v of Brij®‐35 and 20% v/v of acetonitrile. Validation data showed good linearity (r2 > 0.98), precision (%RSDs < 3.4), and accuracy (recoveries ranging from 98.0 to 102.0%). The detection and quantitation limits are in the range of 6.0–8.5 and 18–25 μM, respectively. The validation data is comparable to reported methods, however, the current method offers better precision with enhanced sensitivity (up to six times). Applications of the method show percent labeled amounts found in the studied samples within 100.6–109.3%, which complied with the United States Pharmacopeia limit (90.0–110.0%). The method was simple, rapid and, automated, which required no extra instrumentation or skillful operators.
Active microbiome structure and its association with environmental factors and viruses at different aquatic sites of a high‐altitude wetland
Authors: Eissler Yoanna , Gálvez María‐Jesús , Dorador Cristina , Hengst Martha , Molina Verónica
Published: July 2018

Salar de Huasco is a high‐altitude wetland characterized by a highly diverse microbial life adapted to extreme climatic and environmental conditions. Our study aims to determine active microbial community structure changes within different aquatic sites and its relationship with environmental factors and viruses as potential drivers of diversification in different aquatic areas of this ecosystem. In this study, bacteria and archaea composition (16S rRNA subunit pyrolibraries) and picoplankton and viral abundance were determined at ponds, springs and lagoon sites of the wetland during wet and dry seasons (February and July 2012, respectively). In general, mixosaline waters (1,400–51,000 μS/cm) usually found in ponds and lagoon presented higher picoplanktonic abundances compared to freshwater (<800 μS/cm) spring sites, ranging from 1.07 × 105 to 1.83 × 107 cells/ml. Viral abundance and viral to picoplankton ratio (VPR) also presented greater values at ponds compared to spring sites, reaching up to 4.78 × 108 viruses‐like particles and up to 351 for VPR. In general, ponds hold a higher microbial diversity and complexity associated also with the presence of microbial mats compared with water sources or lagoon (Shannon index H′ 2.6–3.9 vs. <2.0). A greater richness of archaea was also detected in ponds characterized by functional groups such as known methanogens and ammonia oxidizers, and uncultured groups. In total, our results indicate that among the different aquatic sites of the wetland, ponds presented a great microbial community diversification associated to a higher top‐down control by viruses which may influence nutrient and greenhouse gases cycling.
High temperature accelerates growth of aerobic anoxygenic phototrophic bacteria in seawater
Authors: Sato‐Takabe Yuki , Hamasaki Koji , Suzuki Satoru
Published: July 2018

Temperature is an important controlling factor in the growth activity of all microorganisms. Aerobic anoxygenic phototrophic (AAP) bacteria actively grow in the ocean and are known as one of the main driving forces in organic matter cycling in surface seawater environments. Whether temperature change affects AAP bacteria activity from an ecological viewpoint remains an open question. To date, no known studies have reported the effect of temperature change on AAP bacteria growth in the ocean. We here show that the growth rate of AAP bacteria exceeded that of other bacterial types at high water temperatures in the absence of grazers. The slope of the regression line of the net growth rate of AAP bacteria as a function of water temperature was the same as that for non‐AAP bacteria at all temperatures (10, 20, and 30°C); however, when grazers were eliminated, it was 4.7 times higher than that of non‐AAP bacteria. This result suggests that AAP bacteria are more responsive to water temperature increases than other bacteria and that AAP bacteria might become more dominant than other bacteria under elevated water temperatures.
ADCK3‐related Coenzyme Q10 Deficiency: A Potentially Treatable Genetic Disease
Authors: Chang Anna , Ruiz‐Lopez Marta , Slow Elizabeth , Tarnopolsky Mark , Lang Anthony E. , Munhoz Renato P
Published: July 2018

Background

Disorders related to dysfunction of coenzyme (CoQ10) metabolism, including AarF domain containing kinase 3 gene (ADCK3) mutations, have received attention due to the potential for response to CoQ10 supplementation.

Methods

We describe two new cases of neurological syndromes due to ADCK3 mutations that obtained striking benefit from CoQ10, and a third who did not. We also review 20 cases from the literature in which responses to CoQ10 were documented out of all 38 previously reported cases.

Results

Despite the remarkable responses in some cases with ataxia and movement disorders (myoclonus, dystonia, tremor), overall, we were not able to identify variables that predicted response to CoQ10 supplementation.

Conclusions

Based on our experience and data from the literature, we recommend a minimum of 10 mg/kg/day of ubiquinone with titration up to 15 mg/kg/day, maintained at least for 6 months in order to obtain or exclude potential benefit from therapy.
Repeat periods of electrical stimulation prolong the modulation of the micturition reflex in the rat
Authors: Chen Hui , Zeng Jianwen , Zeng Peng , Jiang Chonghe , Xie Keji , Lindström Sivert
Published: July 2018

Aims

The aim of this study was to determine if the duration of the micturition reflex modulation could be prolonged by repeated periods of afferent stimulation in the decorticated rat.

Methods

Eighteen female Sprague‐Dawley rats were used for the study, 10 for intravesical electrical stimulation (IVES), and 8 for Ano‐genital pudendal afferents stimulation. Repeated constant flow cystometries were performed with body‐warm saline (0.06‐0.1 mL/min) at about 10 min interval. The selected afferents were stimulated continuously for 5 min at maximal intensity. The same stimulation was repeated six times with a pause of 5 min between the stimulations. The mean threshold volume of cystometries performed during one hour before and each hour after the stimulation were compared.

Results

After six periods of IVES, the micturition threshold volume decreased to its lowest value (62% of control) during the first hour and remained at 80% 4 h later (n = 10, P < 0.01). Ano‐genital afferent stimulation produced a corresponding increase in the micturition threshold volume. The long‐lasting poststimulation effect was again observed for more than 5 h. During the first hour the mean threshold volume increased to 211% of controls and it remained at about this level for the entire observation period (n = 8, P < 0.01).

Conclusions

Repeated short periods of stimulation prolonged the modulatory effect well beyond the stimulation period. The findings provide experimental evidence supporting the clinical application of IVES and ano‐genital stimulation for treatment of neurogenic urinary bladder dysfunction.
Prevalence and associated factors of urinary leakage among women participating in the 45 and Up Study
Authors: Concepcion Kristine , Cheng Yan , McGeechan Kevin , Robertson Sarah , Stewart Mary , Bateson Deborah , Estoesta Jane , Chiarelli Pauline
Published: July 2018

Aims

The study was undertaken to investigate the prevalence of urinary leakage and its associated factors among a sample of females aged 45 years and over in New South Wales.

Methods

Data were obtained from the 45 and Up Study wherein urinary leakage is identified as women who reported being troubled by leaking urine. At baseline, 143 096 females (2006‐2009) and 59 060 females in the follow‐up survey (2012‐2015) were included in the analysis. We estimated the prevalence, and identified the factors associated with urinary leakage using logistic regression models.

Results

The prevalence of urinary leakage was 44.0% at baseline and 44.6% at the first follow‐up survey. Among women who reported urinary leakage at baseline, 21.2% reported urine leakage once a week or less and 13.1% four or more times per week. Increasing age, abnormal BMI, back pain, anxiety, depression, and psychological distress were associated with greater odds of women reporting urinary leakage. Asian ancestry and being unemployed was associated with a lower risk for urinary incontinence.

Conclusion

Findings from this analysis estimate that approximately one in two women aged 45 years and older will most likely experience urinary leakage. The associated factors could serve as screening indicators for urinary leakage.
Circulating Candidate Biomarkers in Giant Cell Tumors of Bone
Authors: Conti Amalia , Luchini Alessandra , Benassi Maria Serena , Magagnoli Giovanna , Pierini Michela , Piccinni‐Leopardi Martina , Quattrini Irene , Pollino Serena , Picci Piero , Liotta Lance A. , Pazzaglia Laura
Published: July 2018

Purpose

Approximately 5% of giant cell tumors (GCT) of bone develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict malignant progression.

Experimental design

The hydrogel nanoparticle technique followed by MS was used to detect low molecular weight serum proteins or protein fragments in serum of 20 GCT patients with different clinical course and in ten healthy sera used as control. The most representative low‐abundant de novo or differentially abundant proteins were submitted to String database that recognized interconnected activated pathways including protein activation cascade, wound healing, cell‐substrate adhesion, and response to stress. Statistics were performed for identification of candidate prognostic factors.

Results

Proteome cluster analysis separated metastasis‐free from metastatic GCT patients in two well‐defined groups where serum levels of signaling transduction mediators and regulators of kinase activity presented a high discriminatory power. Increased expression of proteins STAT5B, GRB2, and OXSR1 was related to a higher probability of metastasis. Multivariate analysis demonstrated that tumor grade and STAT5B were independent prognostic factors.

Conclusions and clinical relevance

By using a noninvasive technique, we identified differentially abundant serum candidate biomarkers, also providing prognostic information in patients with GCT of bone.
Utilities for Mass Spectrometry Analysis of Proteins (UMSAP): Fast post‐processing of mass spectrometry data
Authors: Bravo‐Rodriguez Kenny , Hagemeier Birte , Drescher Lea , Lorenz Marian , Rey Juliana , Meltzer Michael , Kaschani Farnusch , Kaiser Markus , Ehrmann Michael
Published: July 2018

Rationale

Mass spectrometry (MS) is an invaluable tool for the analysis of proteins. However, the sheer amount of data generated in MS studies demands dedicated data‐processing tools that are efficient and require minimal user intervention.

Methods

Utilities for Mass Spectrometry Analysis of Proteins (UMSAP) is a graphical user interface designed for efficient post‐processing of MS result files. The software is written in Tcl/Tk and can be used in Windows, OS X or Linux. No third party programs or libraries are required. Currently, UMSAP can process data obtained from proteolytic degradation experiments and generates graphical outputs allowing a straightforward interpretation of statistically relevant results.

Results

UMSAP is used here to analyze the proteolytic degradation of glycerophosphoryl diester phosphodiesterase GlpQ by the protein quality control protease DegP. Mass spectrometry was used to monitor proteolysis over time in the absence and presence of a peptidic allosteric activator of DegP. The software's output clearly shows the increased proteolytic activity of DegP in the presence of the activating peptide, identifies statistically significant products of the proteolysis and offers valuable insights into substrate specificity.

Conclusions

Utilities for Mass Spectrometry Analysis of Proteins is an open‐source software designed for efficient post‐processing of large datasets obtained by MS analyses of proteins. In addition, the modular architecture of the software allows easy incorporation of new modules to analyze various experimental mass spectrometry setups.
Pay inequality and corporate divestitures
Authors: Feldman Emilie R. , Gartenberg Claudine , Wulf Julie
Published: July 2018

Research Summary: This paper analyzes how pay inequality influences divestiture decisions. Using detailed data on division manager compensation and divestiture activity, this study documents that firms are more likely to divest divisions when pay inequality among division managers is higher. To address potential bias in the measurement of pay inequality, we construct a “synthetic” measure that varies with regional and industry pay shocks that differentially affect division managers within firms. Post hoc analyses reveal that social comparison appears to explain, at least partially, the relationship between unequal pay and divestiture. These findings support the notion that pay inequality can be an important predictor of firm boundaries. More generally, they suggest that unequal pay may have significant strategic consequences as firms increasingly adopt performance‐based compensation to motivate employees.

Managerial Summary: This paper analyzes the link between the degree of inequality in division manager compensation and the likelihood that companies divest businesses. We find that companies are more likely to divest when the pay of their division managers is more widely dispersed. Supplementary analyses show that this relationship is stronger when division managers are more likely to compare their pay to that of their peers, for example, within companies whose divisions operate in more closely related industries or in more proximate geographic regions. These findings show that pay inequality can predict when companies choose to exit businesses. As such, it is relevant for understanding how corporate strategy is influenced by performance‐based compensation policies, particularly as these policies become the norm in companies around the world.
The dark side of institutional intermediaries: Junior stock exchanges and entrepreneurship
Authors: Eberhart Robert N. , Eesley Charles E.
Published: July 2018

Research Summary: Our study shows how institutional intermediaries established to foster the creation of new firms might hinder new firm growth instead. We show that intermediaries can reduce new firm growth rates due to institutional conflict. To analyze this idea, we examine the setting of junior stock exchanges, which are commonly formed to facilitate entrepreneurial growth. The introduction of these exchanges focused investment into new technology firms, reduced investment in other sectors, and led to diminishing new firm growth. Our findings demonstrate how institutional conflict causes unintended effects and reveals the complexity of influencing entrepreneurship with institutional intermediaries.

Managerial Summary: Investors and entrepreneurs face uncertainty when deciding what firms to start and fund. We show that an intermediation effort to make entry easier for entrepreneurs increases the uncertainty that entrepreneurs and investors face. For investors, the enthusiasm for technology firms engendered by the new exchange can motivate investment in marginal firms to maintain as desired deal flow. However, lower firm growth and less liquidity in the future is likely. For entrepreneurs, our results indicate that it is more challenging to manage technology firm growth as well as there is potential opportunity to investigate other industries. Finally, for policy‐makers and supporters of the new exchanges, our results imply that investment flows are altered as intended, but unless listing standards remain high, the virtuous cycle of investment upon which a healthy entrepreneurial climate rests may be disrupted, muting the intended effects of the new exchange.
Graphene Oxide Sieving Membrane for Improved Cycle Life in High‐Efficiency Redox‐Mediated Li–O2 batteries
Authors: Park Se Hwan , Lee Tae Hoon , Lee Young Joo , Park Ho Bum , Lee Yun Jung
Published: July 2018

As soluble catalysts, redox‐mediators (RMs) endow mobility to catalysts for unconstrained access to tethered solid discharge products, lowering the energy barrier for Li2O2 formation/decomposition; however, this desired mobility is accompanied by the undesirable side effect of RM migration to the Li metal anode. The reaction between RMs and Li metal degrades both the Li metal and the RMs, leading to cell deterioration within a few cycles. To extend the cycle life of redox‐mediated Li–O2 batteries, herein graphene oxide (GO) membranes are reported as RM‐blocking separators. It is revealed that the size of GO nanochannels is narrow enough to reject 5,10‐dihydro‐5,10‐dimethylphenazine (DMPZ) while selectively allowing the transport of smaller Li+ ions. The negative surface charges of GO further repel negative ions via Donnan exclusion, greatly improving the lithium ion transference number. The Li–O2 cells with GO membranes efficiently harness the redox‐mediation activity of DMPZ for improved performance, achieving energy efficiency of above 80% for more than 25 cycles, and 90% for 78 cycles when the capacity limits were 0.75 and 0.5 mAh cm‐2, respectively. Considering the facile preparation of GO membranes, RM‐sieving GO membranes can be cost‐effective and processable functional separators in Li–O2 batteries.
Improving stress tolerance and cell integrity ofRhodococcus ruberby overexpressing small-shock-protein Hsp16 ofRhodococcus
Authors: Wang Miaomiao , Chen Jie , Yu Huimin , Shen Zhongyao
Published: July 2018

Rhodococcus species have been successfully used as cell catalysts for valuable chemicals production due to their well-characterized resistance to harmful factors. An understanding of how they respond to stress is of great interest, which will enable the identification of engineering strategies for further improving their resistance and maintaining cell integrity and viability. Here, we assessed the transcriptome response of R. ruber TH3 to heat shock. Approximately, 376 genes were up-regulated in heat-shocked TH3. Among all the up-regulated functional genes, the small heat-shock-protein (Hsp16) with maximal enhanced transcript (463-fold) was identified, and its function was investigated. Results showed that overexpressed Hsp16 has no significant promotive effect on stress tolerance of in-cell enzyme. Interestingly, compared to the control TH3, a little fewer pores and folds on the surface of TH3(Hsp16) and more intact TH3(Hsp-GFP) cells under AM treatment were observed by SEM and LCSM, respectively. Moreover, survival test showed that more (about 501–700) TH3(Hsp16) colonies were observed while only 1–100 TH3 colonies after 50% AM treatment, and this trend is also found in high-temperature cultivation experiments. These results indicate that Hsp16 does great contributions to preventing cell leakage, maintaining cell integrity and viability of R. ruber under stress conditions.
Combination treatment of cancer cells with pan-Akt and pan-mTOR inhibitors: effects on cell cycle distribution, p-Akt expression level and radiolabelled-choline incorporation
Authors: Phyu Su Myat , Smith Tim A. D.
Published: July 2018

Signal transduction pathways, which regulate cell growth and survival, are up-regulated in many cancers and there is considerable interest in their pharmaceutical modulation for cancer treatment. However inhibitors of single pathway components induce feedback mechanisms that overcome the growth moderating effect of the inhibitor. Combination treatments have been proposed to provide a more complete pathway inhibition. Here the effect of dual treatment of cancer cells with a pan-Akt and a pan-mTOR inhibitor was explored. Breast (SKBr3 and MDA-MB-468) and colorectal (HCT8) cancer cells were treated with the pan-Akt inhibitor MK2206 and pan-mTOR inhibitor AZD8055. Cytotoxic effect of the two drugs were determined using the MTT assay and the Combination Index and isobolomic analysis used to determine the nature of the interaction of the two drugs. Flow cytometry and western blot were employed to demonstrate drug effects on cell cycle distribution and phosph-Aktser473 expression. Radiolabelled ([methyl-3H]) Choline uptake was measured in control and drug-treated cells to determine the modulatory effects of the drugs on choline incorporation. The two drugs acted synergistically to inhibit the growth rate of each cancer cell line. Flow cytometry demonstrated G0/G1 blockade with MK2206 and AZD8055 which was greater when cells were treated with both drugs. The incorporation of [methyl-3H] choline was found be decreased to a greater extent in cells treated with both drugs compared with cells treated with either drug alone. Conclusions Pan-mTOR and pan-Akt inhibition may be highly effective in cancer treatment and measuring changes in choline uptake could be useful in detecting efficacious drug combinations.
Plant breeding selection tools built on factor analytic mixed models for multi-environment trial data
Authors: Smith Alison B. , Cullis Brian R.
Published: July 2018

An advanced and widely used method of analysis for multi-environment trial data involves a linear mixed model with factor analytic (FA) variance structures for the variety by environment effects. This model can accommodate unbalanced data, that is, not all varieties in all environments, it allows the use of pedigree information and appropriate accommodation of individual trial experimental designs, and most importantly the FA structure for the variety by environment effects is parsimonious and regularly results in a good fit to the data. The model provides accurate predictions of the variety effects for every environment in the data-set but this constitutes a large and unwieldly amount of information to process for the purpose of variety selection. We address this issue in the current paper by proposing factor analytic selection tools to summarise the predictions in a concise yet informative manner. The tools, which are natural derivatives of the FA structure, result in measures of overall performance and stability across the environments in the data-set. All measures are expressed on the same scale as the trait under consideration and can easily be combined to form an index for selection.
Recent Progresses in Electrocatalysts for Water Electrolysis
Authors: Khan Muhammad Arif , Zhao Hongbin , Zou Wenwen , Chen Zhe , Cao Wenjuan , Fang Jianhui , Xu Jiaqiang , Zhang Lei , Zhang Jiujun
Published: July 2018

The study of hydrogen evolution reaction and oxygen evolution reaction electrocatalysts for water electrolysis is a developing field in which noble metal-based materials are commonly used. However, the associated high cost and low abundance of noble metals limit their practical application. Non-noble metal catalysts, aside from being inexpensive, highly abundant and environmental friendly, can possess high electrical conductivity, good structural tunability and comparable electrocatalytic performances to state-of-the-art noble metals, particularly in alkaline media, making them desirable candidates to reduce or replace noble metals as promising electrocatalysts for water electrolysis. This article will review and provide an overview of the fundamental knowledge related to water electrolysis with a focus on the development and progress of non-noble metal-based electrocatalysts in alkaline, polymer exchange membrane and solid oxide electrolysis. A critical analysis of the various catalysts currently available is also provided with discussions on current challenges and future perspectives. In addition, to facilitate future research and development, several possible research directions to overcome these challenges are provided in this article.

Graphical Abstract
Interdisciplinary Pain Management Improves Pain and Function in Pediatric Patients with Chronic Pain Associated with Joint Hypermobility Syndrome
Authors: Revivo Gadi , Amstutz Diane K. , Gagnon Christine M. , McCormick Zachary L.
Published: July 2018

Background

The relation between chronic musculoskeletal pain and joint hypermobility in a small percentage of the pediatric population is well described. However, literature discussing the treatment of chronic pain associated with joint hypermobility in pediatrics is limited. The present study examines the impact of interdisciplinary treatment on chronic pain in pediatrics with joint hypermobility syndrome.

Objective

To determine if pediatric patients with chronic pain related to joint hypermobility can be effectively treated with an intensive, interdisciplinary pain management program, as measured by changes in pain, psychosocial and physical functioning, as well as parental coping.

Design

Retrospective cohort study.

Setting

Urban academic tertiary intensive outpatient interdisciplinary pain management clinic.

Participants

The study involved 30 patients who met the criteria for a diagnosis of joint hypermobility and chronic pain and completed an interdisciplinary pain management program.

Intervention

All patients were treated in an intensive pediatric interdisciplinary pain management program for a duration of 6 to 8 weeks. The program provided physical therapy, occupational therapy, psychological counseling, and weekly pediatric rehabilitation medicine follow‐up.

Main Outcome Measures

Outcome measures included numeric rating scale pain scores, the Bath Adolescent Pain Questionnaire, and the Bath Adolescent Pain‐Parent Impact Questionnaire. Changes from pre‐ to post‐treatment were analyzed using paired‐samples t tests.

Results

Patients endorsed pre‐ to post‐treatment improvements in pain, depression, general anxiety, pain‐related anxiety, social functioning, and physical functioning (P < .05). The patients' parents showed significant improvements in depression, anxiety, catastrophic thinking, self‐blame and helplessness, leisure functioning, and parental behavior (P < .05).

Conclusion

The present findings suggest that an intensive interdisciplinary rehabilitation pain management program yields short‐term improvements in pain, emotional and physical function, and daily activity in a pediatric population diagnosed with joint hypermobility. Parents also experienced benefits from the program. A larger prospective study with longer‐term follow‐up is needed.

Level of Evidence

III
Miracles
Authors: Basinger David
Published: July 2018

This book is a critical overview of the manner in which the concept of miracle is understood and discussed in contemporary analytic philosophy of religion. In its most basic sense, a miracle is an unusual, unexpected, observable event brought about by direct divine intervention. The focus of this study is on the key conceptual, epistemological, and theological issues that this definition of the miraculous continues to raise. As this topic is of existential as well as theoretical interest to many, there is no reason to believe the concept of miracle won't continue to be of ongoing interest to philosophers.
Gendered Citation Patterns across Political Science and Social Science Methodology Fields
Authors: Dion Michelle L. , Sumner Jane Lawrence , Mitchell Sara McLaughlin
Published: July 2018

Accumulated evidence identifies discernible gender gaps across many dimensions of professional academic careers including salaries, publication rates, journal placement, career progress, and academic service. Recent work in political science also reveals gender gaps in citations, with articles written by men citing work by other male scholars more often than work by female scholars. This study estimates the gender gap in citations across political science subfields and across methodological subfields within political science, sociology, and economics. The research design captures variance across research areas in terms of the underlying distribution of female scholars. We expect that subfields within political science and social science disciplines with more women will have smaller gender citation gaps, a reduction of the “Matthew effect” where men’s research is viewed as the most central and important in a field. However, gender citation gaps may persist if a “Matilda effect” occurs whereby women’s research is viewed as less important or their ideas are attributed to male scholars, even as a field becomes more diverse. Analysing all articles published from 2007–2016 in several journals, we find that female scholars are significantly more likely than mixed gender or male author teams to cite research by their female peers, but that these citation rates vary depending on the overall distribution of women in their field. More gender diverse subfields and disciplines produce smaller gender citation gaps, consistent with a reduction in the “Matthew effect”. However, we also observe undercitation of work by women, even in journals that publish mostly female authors. While improvements in gender diversity in academia increase the visibility and impact of scholarly work by women, implicit biases in citation practices in the social sciences persist.
Are Papers Written by Women Authors Cited Less Frequently?
Authors: Esarey Justin , Bryant Kristin
Published: July 2018

Dion, Sumner, and Mitchell (2018) find that a published article is more likely to cite at least one female-authored paper if that article is itself authored by women. To complement their work, we study the number of times that an article in their data set is cited given that it has at least one female author. We find that articles with at least one female author are cited no more or less often than male-authored articles once we control for the publishing journal and the number of authors. The importance of controlling for author count in our model suggests that spurious correlation and/or self-citation might explain at least some of the gender differences found by Dion, Sumner, and Mitchell (2018).
Association of left atrial pressure with left atrial volume and N-terminal prohormone brain natriuretic peptide in children with cardiomyopathy
Authors: Agarwal Arpit , Lam Suying , Li Hua , Gorla Sudheer R. , Sasaki Nao , Rusconi Paolo G. , Swaminathan Sethuraman
Published: July 2018

Background

Enlargement of the left atrium is a non-invasive marker of diastolic dysfunction of the left ventricle, a determinant of prognosis in children with cardiomyopathy. Similarly, N-terminal prohormone brain natriuretic peptide is a useful marker in the management of children with cardiomyopathy and heart failure. The aim of this study is to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide in children with cardiomyopathy.

Methods

This was a retrospective study reviewing the medical records of patients <18 years of age, who were diagnosed with cardiomyopathy or acute myocarditis with eventual development of cardiomyopathy. Left atrial volume by transthoracic echocardiogram and pulmonary capillary wedge pressure, a surrogate of left atrial pressure, obtained by means of cardiac catheterisation were analysed. In addition, N-terminal prohormone brain natriuretic peptide levels obtained at the time of the cardiac catheterisation were also reviewed. Statistical analysis was performed to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide levels.

Results

There was a linear correlation of left atrial pressure estimated in the cardiac catheterisation with indexed left atrial volume (r=0.63; p<0.001) and left atrial volume z-scores (r=0.59; p<0.001). We found no statistically significant association between the left atrial pressure and N-terminal prohormone brain natriuretic peptide levels.

Conclusions

Left atrial volume measured non-invasively by echocardiography can be used as a surrogate for left atrial pressure in assessing diastolic dysfunction of the left ventricle in children with cardiomyopathy. The larger the size of the left atrium, worse is the diastolic function of the left ventricle.
At-Sea Workshop Advances Subduction Zone Research
Authors: Regalla Christine , Lymer Gael , Fukuchi Rina
Published: July 2018

International Ocean Discovery Program Core-Log-Seismic integration at Sea (CLSI@Sea) workshop; Nankai Trough, Philippine Sea, off the coast of southwest Japan, January–February 2018
Four Ways Kīlauea Is Redrawing the Map
Authors: Loomis Ilima
Published: July 2018

From burying communities to building new land, this historic eruption is changing the landscape of Hawai‘i Island.
Precipitation of Hydrogen Energetic Neutral Atoms at the Upper Atmosphere of Mars
Authors: Wang X.‐D. , Alho M. , Jarvinen R. , Kallio E. , Barabash S. , Futaana Y.
Published: July 2018

We study the properties of neutral hydrogen atoms precipitating onto the upper atmosphere of Mars. Energetic neutral atoms (ENAs) are produced by the charge exchange process between protons of solar wind (both upstream and shocked) as well as planetary origins and the Martian exospheric neutrals. Using a global hybrid plasma model for Mars‐solar wind interaction combined with an up‐to‐date exosphere model of Mars, we calculate the fluxes, spatial distributions, energy spectra, and direction distributions of hydrogen ENAs (H‐ENAs) at the Martian exobase for each source proton population. H‐ENAs originating from the upstream solar wind region and the magnetosheath dominate the precipitation. Two percent of the solar wind flux penetrates through the magnetic barrier as H‐ENAs under solar minimum conditions. The precipitating solar wind H‐ENA flux is axially symmetric about Sun‐Mars line, while the magnetosheath and planetary H‐ENAs have higher fluxes and a more‐extended precipitation area in the hemisphere where the convection electric field is pointing away from the planet, causing a significant precipitation beyond the terminator. The observed asymmetry is consistently explained by an asymmetric plasma flow in the dayside magnetosheath. The solar wind dynamic pressure increases the solar wind H‐ENA precipitation normalized by the upstream proton flux, due to a closer bow shock position and thus a higher exospheric column density for charge exchange. The spatial distribution of the magnetosheath solar wind and planetary H‐ENAs becomes more axially symmetric with increased dynamic pressure. The solar wind interaction with Mars exhibits more gas‐dynamic‐like signatures for higher dynamic pressure.
Investigating High‐Latitude Energy Deposition Events Occurring During the 17 January 2005 Geomagnetic Storm
Authors: Horvath Ildiko , Lovell Brian C.
Published: July 2018

This study investigates the coupled ionosphere‐thermosphere system during the 17 January 2005 geomagnetic storm. Multiinstrument satellite data are utilized to track polar convection and flow channels (FCs) in the topside ionosphere to compute Poynting flux values approximating electromagnetic energy and to detect localized neutral density increases and also to signal FC signatures in the thermosphere. Our main aim is to identify energy input regions during various events when localized neutral density increases developed. Such events are illustrated in five scenarios covering both hemispheres. These scenarios demonstrate the development of a cusp enhancement above/within FC‐1 associated with newly open field lines and polar cap enhancements above/within FC‐2, FC‐3, and FC‐4 commonly associated with old open field lines. Localized Poynting flux intensifications within these FCs demonstrate energy deposition continuing along old open field lines in the polar cap. The close correlation of these Poynting flux intensifications with their respective cusp and polar cap enhancements, via their underlying FCs through which the electromagnetic energy was deposited, provide observational evidence that these enhancements were generated by their associated energy inputs. These observational results lead to the conclusions that a main region of high‐latitude energy deposition was (i) the polar cap (>78° magnetic latitude) producing polar cap enhancements (scenarios 1–3), (ii) the prenoon auroral zone producing a cusp enhancement (scenario 4), and (iii) both the polar cap producing a polar cap enhancement and the auroral zone (scenario 5).
Three‐Dimensional Electrical Resistivity Modeling to Elucidate the Crustal Magma Supply System Beneath Aso Caldera, Japan
Authors: Hata M. , Matsushima N. , Takakura S. , Utsugi M. , Hashimoto T. , Uyeshima M.
Published: July 2018

A magma supply system is identified in the upper crust beneath Aso caldera, Japan, appearing as a conductive anomaly via three‐dimensional electrical resistivity modeling. Aso caldera contains numerous postcaldera volcanoes, with Naka‐dake cone recently experiencing eruptions at the first crater, including an explosive eruption that ejected volcanic ash 11,000 m into the air in October 2016. The magma supply system imaged by the resistivity model consists of four key components: a magma reservoir at ~17 km depth that corresponds to the Conrad discontinuity, a magma‐filled crack‐propagation zone that extends obliquely from the magma reservoir, another magma reservoir centered at 6 km depth, and an upright crack‐intrusion zone at 2–4 km depth. The shape of the conductive anomaly is consistent with the regional stress regime, with the locations of the low‐velocity anomalies and a deformation source found beneath the caldera. This anomaly is therefore defined as the magma supply system, which feeds magma to the first crater of the Naka‐dake eruptions. The averaged melt fractions of the upper magma reservoir are estimated to be 3%–4% for 89.3 km3 of the reservoir and 96%–99% for 6.3 km3, with resistivity thresholds of <40 and <1 Ωm, respectively. Furthermore, the resistivity model detects three conductive anomalies in Aso caldera that are associated with an aqueous fluid‐flow system in the region. The resistivity model also suggests that the resistivity distribution can play an important role in characterizing the stress regime based on the distribution of earthquake clusters in the upper crust beneath the caldera.