bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Isoforms of the Guanine Nucleotide Exchange Factor, Daple/CCDC88C Cooperate as Tumor Suppressors
Authors: Dunkel Ying , Ear Jason , Mittal Yash , Lim Blaze B. C. , Liu Lawrence , Holda Magda K. , Nitsche Ulrich , Barbazán Jorge , Goel Ajay , Janssen Klaus-Peter , Aznar Nicolas , Ghosh Pradipta 
Published: May 2018

ABSTRACTPreviously Aznar et al., showed that Daple enables Wnt/Frizzled receptors to transactivate trimeric G proteins during non-canonical Wnt signaling via a novel G-protein binding and activating (GBA) motif. By doing so, Daple serves as a double-edged sword; earlier during oncogenesis it suppresses neoplastic transformation and tumor growth, but later it triggers epithelial messenchymal transition (EMT). We have identified and characterized two isoforms of the human Daple/CCDC88c gene. While both isoforms cooperatively suppress tumor growth via their GBA motif, only the full-length transcript triggers EMT and invasion. Aspirin suppresses the full-length transcript and protein but upregulates the short isoform. Both isoforms are suppressed during colon cancer progression, and their reduced expression carries additive prognostic significance. These findings provide insights into the opposing roles of Daple during cancer progression and define the G protein regulatory GBA motif as one of the minimal modules essential for Daple’s role as a tumor suppressor.
Perceived threat bias and reduced hippocampal volume in combat veterans
Authors: Grupe Daniel W. , Hushek Benjamin A. , Ellis Kaley , Schoen Andrew J. , Wielgosz Joseph , Nitschke Jack B. , Davidson Richard J. 
Published: May 2018

AbstractBackgroundReduced hippocampal volume is frequently observed in posttraumatic stress disorder (PTSD), but the exact psychological processes associated with these alterations remain unclear. Given the role of the hippocampus in contextual representations of threat and memory, we investigated relationships between retrospectively reported combat exposure, perceived threat, and hippocampal volume in trauma-exposed veterans.MethodsT1-weighted anatomical MRI scans were obtained from 52 male veterans with a broad range of PTSD symptoms. Hippocampal volume was estimated using automatic segmentation tools in FreeSurfer. An index of perceived threat bias was calculated, reflecting the degree of discordance between subjective perceptions of threat while deployed and self-reported combat exposure. Hippocampal volume was regressed on perceived threat bias and PTSD symptoms on the Clinician-Administered PTSD Scale (CAPS).ResultsPerceived threat bias was unrelated to overall CAPS symptoms, but was positively correlated with CAPS avoidance/numbing symptoms and symptoms of depression, anxiety, and worry. The degree of perceived threat bias was inversely correlated with hippocampal volume. Hippocampal volume was also inversely related to avoidance/numbing CAPS symptoms.ConclusionsThese results indicate that volume of the hippocampus, a region involved in contextual threat processing and memory, is related to recalled associations between traumatic events and accompanying subjective threat appraisals. Future research should clarify the precise temporal milieu of these effects and investigate whether individual differences in hippocampal structure and function contribute to exaggerated threat appraisal at the time of trauma, or in subsequently biased memories or appraisals of traumatic events.
Autophagy is essential for optimal Fe translocation to seeds in Arabidopsis
Authors: Pottier Mathieu , Dumont Jean , Masclaux-Daubresse Céline , Thomine Sébastien 
Published: May 2018

AbstractMicronutrient deficiencies affect a large part of the world population. They are mostly due to the consumption of grains with insufficient content of Fe or Zn. Both de novo uptake by roots and recycling from leaves may provide seeds with nutrients. Autophagy, which is a conserved mechanism for nutrient recycling in eukaryotes, was shown to be involved in nitrogen remobilization to seeds. Here, we have investigated the role of this mechanism in micronutrient translocation to seeds. We found that several Arabidopsis thaliana plants impaired in autophagy display defects in nutrient remobilization to seeds. In atg5-1 mutant, which is completely defective in autophagy, the efficiency of Fe translocation from vegetative organs to seeds was severely decreased even when Fe was provided during seed formation. Combining atg5-1 with sid2 mutation that counteracts premature senescence associated to autophagy deficiency and using 57Fe pulse labeling, we could propose a two-step mechanism in which iron taken up de novo during seed formation is first accumulated in vegetative organs and subsequently remobilized to seeds. Finally, we showed that translocations of zinc and manganese to seeds are also dependent on autophagy. Fine tuning autophagy during seed formation opens therefore new possibilities to improve micronutrient remobilization to seeds.
Opsonin-free, real-time imaging of Cryptococcus neoformans capsule during budding
Authors: Paes Hugo Costa , Frazão Stefânia de Oliveira , Rosa Camila Pereira , Albuquerque Patrícia , Casadevall Arturo , Soares Felipe Maria Sueli , Nicola André Moraes 
Published: May 2018

AbstractCryptococcus neoformans is a unicellular fungal pathogen that causes meningoencephalitis, killing hundreds of thousands of patients each year. Its most distinctive characteristic is a polysaccharide capsule that envelops the whole cell. It is the major virulence attribute and the antigen for serologic diagnosis. We have developed a method for easy observation of the capsule and its growth dynamics using the cell-separation reagent Percoll and differential interference contrast (DIC) microscopy. Percoll suspension is far less disruptive of cell physiology than methods relying on antibody binding to the capsule, and measurements made with it are equivalent with India ink. Time-lapse microscopy observations using this method suggest that during budding, a dividing cell can regulate whether the capsule polysaccharide it produces is deposited on the capsule of the bud or on its own. This observation has important implications for our understanding of the C. neoformans capsule induction process during budding.List of abbreviations and acronymsCSFCerebrospinal fluidDICDifferential interference microscopyNANumerical apertureCCDCharge-coupled deviceMMMinimal mediumCIMCO2-independent mediumMOPS3-Morpholinopropane-1-sulfonic acidSDStandard deviation
Identification of reference genes for real-time PCR gene expression studies during seed development and under abiotic stresses in Cyamopsis tetragonoloba (L.) Taub
Authors: Jaiswal Poonam Subhash , Kaur Navneet , Randhawa Gursharn Singh 
Published: May 2018

AbstractGuar (Cyamopsis tetragonoloba) is an important industrial crop. The knowledge about genes of guar involved in various processes can help in developing improved varieties of this crop. qRT-PCR is a preferred technique for accurate quantification of gene expression data. This technique requires the use of appropriate reference genes from the crop to be studied. Such genes have not been yet identified in guar. The expression stabilities of the 10 candidate reference genes, viz., CYP, ACT 11, EF-1α, TUA, TUB, ACT 7, UBQ 10, UBC 2, GAPDH and 18S rRNA were evaluated in various tissues of guar under normal and abiotic stress conditions. Four different algorithms, geNorm, NormFinder, BestKeeper and ∆Ct approach, were used to assess the expression stabilities and the results obtained were integrated into comprehensive stability rankings. The most stable reference genes were found to be CYP and ACT 11(tissues), ACT 11, UBC 2 and ACT 7 (seed development), ACT 7 and TUB (drought stress), TUA, UBC 2 and CYP (nitrogen stress), TUA and UBC 2 (cold stress), GAPDH and ACT 7 (heat stress) and GAPDH and EF-1a (salt stress). These results indicated the necessity of identifying a suitable reference gene for each experimental condition. Four selected reference genes were validated by normalizing the expression of CtMT1 gene. To the best of our knowledge this is the first report on the identification of reference genes in guar. These findings are likely to provide a boost to the gene expression studies in this important crop.
The Pseudomonas aeruginosa complement of lactate dehydrogenases enables use of D- and L-lactate and metabolic crossfeeding
Authors: Lin Yu-Cheng , Cornell William-Cole , Price-Whelan Alexa , Dietrich Lars E.P. 
Published: May 2018

ABSTRACTPseudomonas aeruginosa is the most common cause of chronic, biofilm-based lung infections in patients with cystic fibrosis (CF). Sputum from patients with CF has been shown to contain oxic and hypoxic subzones as well as millimolar concentrations of lactate. Here, we describe the physiological roles and expression patterns of P. aeruginosa lactate dehydrogenases in the contexts of different growth regimes. P. aeruginosa produces four enzymes annotated as lactate dehydrogenases, three of which are known to contribute to anaerobic or aerobic metabolism in liquid cultures. These three are LdhA, which reduces pyruvate to D-lactate during anaerobic survival, and LldE and LldD, which oxidize D-lactate and L-lactate, respectively, during aerobic growth. We demonstrate that the fourth enzyme, LldA, performs redundant L-lactate oxidation during growth in aerobic cultures in both a defined MOPS-based medium and synthetic CF sputum medium. However, LldA differs from LldD in that its expression is induced specifically by the L-enantiomer of lactate. We also show that all four enzymes perform functions in colony biofilms that are similar to their functions in liquid cultures. Finally, we provide evidence that the enzymes LdhA and LldE have the potential to support metabolic cross-feeding in biofilms, where LdhA can catalyze the production of D-lactate in the anaerobic zone that is then used as a substrate in the aerobic zone. Together, these observations further our understanding of the metabolic pathways that can contribute to P. aeruginosa growth and survival during CF lung infection.IMPORTANCELactate is thought to serve as a carbon and energy source during chronic infections. Sites of bacterial colonization can contain two enantiomers of lactate: the L-form, generally produced by the host, and the D-form, which is usually produced by bacteria including the pulmonary pathogen Pseudomonas aeruginosa. Here, we characterize P. aeruginosa’s set of four enzymes that it can use to interconvert pyruvate and lactate, the functions of which depend on the availability of oxygen and specific enantiomers of lactate. We also show that anaerobic pyruvate fermentation triggers production of the aerobic D-lactate dehydrogenase in both liquid cultures and biofilms, thereby enabling metabolic cross-feeding of lactate over time and space between subpopulations of cells. These metabolic pathways could contribute to P. aeruginosa growth and survival in the lung.
Switch costs in inhibitory control and voluntary behavior: A computational study of the antisaccade task
Authors: Aponte Eduardo A. , Stephan Klaas E. , Heinzle Jakob 
Published: May 2018

AbstractAn integral aspect of human cognition is the ability to inhibit habitual responses in order to initiate complex, rule-guided actions. Moreover, humans have also the ability to alternate between different sets of rules or tasks, at the cost of degraded performance when compared to repeating the same task, a phenomenon called the ‘task switch cost’. While it is recognized that switching between tasks requires often to inhibit habitual responses, the interaction between these two forms of cognitive control has been much less studied than each of them separately. Here, we use a computational model to draw a bridge between inhibitory control and voluntary action generation and thereby provide a novel account of seemingly paradoxical findings in the task switch literature. We investigated task switching in the mixed antisaccade task, in which participants are cued to saccade either in the same or in the opposite direction to a peripheral stimulus. Our model demonstrates that stopping a habitual action leads to increased inhibitory control that persists on the next trial. However, enhanced inhibition affects only the probability of generating habitual responses, and, contrary to previous accounts, cannot be characterized as proactive task interference. In addition, our model demonstrates that voluntary actions (but not habitual responses) are slower and more prompt to errors on switch trials compared to repeat trials. We conclude that precisely the interaction between these two effects explains a variety of contradictory findings reported in the literature.
Substrate binding allosterically relieves autoinhibition of the TRIB1 pseudokinase
Authors: Jamieson Sam A. , Ruan Zheng , Burgess Abigail E. , Curry Jack R. , McMillan Hamish D. , Brewster Jodi L. , Dunbier Anita K. , Axtman Alison D. , Kannan Natarajan , Mace Peter D. 
Published: May 2018

One Sentence SummarySubstrate binding to Tribbles-homolog 1 (TRIB1) pseudokinase induces allosteric changes that allow formation of a complex with the COP1 ubiquitin ligase.AbstractThe Tribbles family of pseudokinases recruit substrates to the COP1 ubiquitin ligase for ubiquitination. CCAAT-enhancer binding protein (C/EBP) family transcription factors are crucial Tribbles substrates in adipocyte and myeloid development. Here we show that the TRIB1 pseudokinase can recruit various C/EBP family members, with binding of C/EBPβ attenuated by phosphorylation. To explain the mechanism of substrate recruitment, we solved the crystal structure of TRIB1 in complex with C/EBPα. TRIB1 undergoes a significant conformational change relative to its substrate-free structure, to bind C/EBPα in a pseudo-substrate-like manner. Crucially, substrate binding triggers allosteric changes that link substrate recruitment to COP1 binding, which is consistent with molecular dynamics and biochemical studies. These findings offer a view of pseudokinase regulation with striking parallels to bona fide kinase regulation— via the activation loop and αC-helix—and raise the possibility of small molecules targeting either the activation loop-in, or loop-out, conformations of Tribbles pseudokinases.
Corporate social responsibility and financial performance in Saudi Arabia
Authors: Al-Malkawi Husam-Aldin Nizar , Javaid Saima 
Published: May 2018

Purpose
The purpose of this paper is to investigate the impact of corporate social responsibility (CSR) on corporate financial performance (CFP) using Zakat as a measure for CSR.

Design/methodology/approach
The study examines a sample of 107 non-financial firms listed on the Saudi Arabia stock market over a ten-year period from 2004 to 2013. The authors use the generalized method of moments framework developed by Arellano and Bover (1995) and Blundell and Bond (1998). In addition, for comparison purpose and as a robustness check, the present study uses other panel data techniques including fixed effects model, random effects model (and pooled ordinary least squares.

Findings
The results reveal that there is a strong positive relationship between CSR (Zakat) and CFP. This suggests that Zakat contribute positively to both firm’s profitability and value and can be considered as a win-win strategy to maximize returns and improve performance while considering the society as a whole. The results are robust to alternative econometric estimation methods.

Practical implications
The companies in Islamic economies can effectively and efficiently implement the basic Shari’a Law of paying Zakat, as a successful measure to implement CSR program, thus benefiting the society by narrowing the gap between the haves and have-nots, that, in turn, leads the company to achieve successfully its short-term as well as long-term goals and enhances the value of the firm in the market. Moreover, corporations are generally encouraged to adopt CSR because of its perceived benefits to both macro- and micro-performances.

Originality/value
To the best of the author’s knowledge, this is the first empirical study attempting to examine CSR-CFP relationship within Saudi context employing Zakat as a proxy for CSR. Additionally, the paper provides support for the stakeholder theory from an Islamic perspective.
Comparative study of the bactericidal effects of indocyanine green‐ and methyl aminolevulinate‐based photodynamic therapy on Propionibacterium acnes as a new treatment for acne
Authors: Choi Seung‐Hwan , Seo Jeong‐Wan , Kim Ki‐Ho 
Published: May 2018

AbstractAcne vulgaris is one of the most common dermatological problems, and its therapeutic options include topical and systemic retinoids and antibiotics. However, increase in problems associated with acne treatment, such as side‐effects from conventional agents and bacterial resistance to antibiotics, has led to greater use of photodynamic therapy. The purpose of this study was to compare the bactericidal effects of indocyanine green‐ and methyl aminolevulinate‐based photodynamic therapy on Propionibacterium acnes. P. acnes were cultured under anaerobic conditions; then they were divided into three groups (control, treated with indocyanine green and treated with methyl aminolevulinate) and illuminated with different lights (630‐nm light‐emitting diode, 805‐nm diode laser and 830‐nm light‐emitting diode). The bactericidal effects were evaluated by comparing each group's colony‐forming units. The cultured P. acnes were killed with an 805‐nm diode laser and 830‐nm light‐emitting diode in the indocyanine green group. No bactericidal effects of methyl aminolevulinate‐based photodynamic therapy were identified. The clinical efficacy of indocyanine green‐based photodynamic therapy in 21 patients was retrospectively analyzed. The Korean Acne Grading System was used to evaluate treatment efficacy, which was significantly decreased after treatment. The difference in the efficacy of the 805‐nm diode laser and 830‐nm light‐emitting diode was not statistically significant. Although the methyl aminolevulinate‐based photodynamic therapy showed no bactericidal effect, the indocyanine green‐based photodynamic therapy has bactericidal effect and clinical efficacy.
Vertical seismic profiling using a daisy‐chained deployment of fibre‐optic cables in four wells simultaneously – Case study at the Ketzin carbon dioxide storage site
Authors: Götz Julia , Lüth Stefan , Henninges Jan , Reinsch Thomas 
Published: May 2018

ABSTRACTThe geological storage of carbon dioxide is considered as one of the measures to reduce greenhouse gas emissions and to mitigate global warming. Operators of storage sites are required to demonstrate safe containment and stable behaviour of the storage complex that is achieved by geophysical and geochemical monitoring, combined with reservoir simulations. For site characterization, as well as for imaging the carbon dioxide plume in the reservoir complex and detecting potential leakage, surface and surface‐borehole time‐lapse seismic monitoring surveys are the most widespread and established tools. At the Ketzin pilot site for carbon dioxide storage, permanently installed fibre‐optic cables, initially deployed for distributed temperature sensing, were used as seismic receiver arrays, demonstrating their ability to provide high‐resolution images of the storage formation. A vertical seismic profiling experiment was acquired using 23 source point locations and the daisy‐chained deployment of a fibre‐optic cable in four wells as a receiver array. The data were used to generate a 3D vertical seismic profiling cube, complementing the large‐scale 3D surface seismic measurements by a high resolution image of the reservoir close to the injection well. Stacking long vibro‐sweeps at each source location resulted in vertical seismic profiling shot gathers characterized by a signal‐to‐noise ratio similar to gathers acquired using geophones. A detailed data analysis shows strong dependency of data quality on borehole conditions with significantly better signal‐to‐noise ratio in regions with good coupling conditions.
Esophageal squamous cell carcinomas in a Malaysian cohort show a lack of association with human papillomavirus
Authors: Cheah Phaik‐Leng , Koh Cing‐Chai , Khang Tsung Fei , Goh Khean‐Lee , Lau Peng‐Choong , Chin Kin‐Fah , Teoh Kean‐Hooi , Toh Yen‐Fa , Looi Lai‐Meng 
Published: May 2018

OBJECTIVEWith an age‐standardized incidence rate of 2 per 100 000, esophageal cancer is not common among Malaysians, but they are nevertheless important due to its poor prognosis. The study is to clarify whether the human papillomavirus (HPV) is associated with esophageal cancer in Malaysians as there has been no report to date on this in Malaysians and other South East Asians.METHODSAltogether 67 esophageal squamous cell carcinomas histologically diagnosed between 1 January 2004 and 31 December 2014 at the Department of Pathology, University of Malaya Medical Center, Malaysia were considered for HPV analysis using two commercially available methods, polymerase chain reaction with flow‐through hybridization (21 HPV GenoArray Diagnostic Kit) and multiplex real‐time polymerase chain reaction (Anyplex II HPV28 Detection). The DNA amplifiability of the formalin‐fixed, paraffin‐embedded tumor was checked by amplification of a 268 bp segment of the human β‐globin gene (GH20/PC04) prior to HPV detection.RESULTSHPV detection was finally carried out in 51 patients. HPV16 was detected in the moderately differentiated, stage IV lower esophageal tumor of a 32‐year‐old Malaysian‐born Chinese woman by both methods. Except for a predilection for Indians, the clinical characteristics of esophageal squamous cell carcinomas in this Malaysian cohort were generally similar to those of other populations.CONCLUSIONIt appears that HPV is rare and an unlikely oncovirus in esophageal squamous cell carcinomas of Malaysians.
High levels of CCL2 or CCL4 in the tumor microenvironment predict unfavorable survival in lung adenocarcinoma
Authors: Li Lei , Liu Yong‐Dong , Zhan Yu‐Ting , Zhu Ying‐Hui , Li Yan , Xie Dan , Guan Xin‐Yuan 
Published: May 2018

BackgroundTumor‐associated immune factors are heterogeneous and play an important role in determining outcome in cancer patients. In this study, the expression levels of immune factors in tumor tissue‐conditioned media from lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) were analyzed.MethodsLUAD and LUSC tissue specimens were collected immediately after surgery for antibody array analysis and real‐time quantitative PCR.ResultsHigher levels of chemokines MCP1/CCL2 (21.11‐fold increase) and MIP‐1β/CCL4 (19.33‐fold increase) were identified in LUAD than in LUSC. Western blot and quantitative real‐time PCR analyses showed higher co‐expression of CCL2 and CCL4 in LUAD tissues compared to LUSC (P < 0.0001). Immunofluorescent co‐staining showed a high percentage of CCL2+/CD68+ and CCL4+/CD68+ tumor‐associated macrophages in LUAD compared to LUSC tissues, which might be responsible for the higher expression of CCL2 and CCL4 in LUAD samples. Kaplan–Meier curves showed that CCL2 overexpression in patients with LUSC was associated with beneficial overall survival (OS; P = 0.048) and progression‐free survival (PFS; P = 0.012); however, LUAD patients with higher CCL2 expression had unfavorable OS (P = 6.7e−08) and PFS (P = 0.00098). Similarly, CCL4 overexpression predicted favorable PFS (P = 0.021) in patients with LUSC, but patients with high CCL4 levels in LUAD had shorter OS (P = 0.013).ConclusionOur study revealed that CCL2 and CCL4 expression levels could serve as potential prognostic biomarkers and therapeutic targets for NSCLC patients.