bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of an engineered biocatalyst system for the production of medium‐chain α,ω‐dicarboxylic acids from medium‐chain ω‐hydroxycarboxylic acids
Authors: Kim Tae‐Hun , Kang Su‐Hwan , Park Jin‐Byung , Oh Deok‐Kun 
Published: May 2020

AbstractMedium‐chain α,ω‐dicarboxylic acids produced from renewable long‐chain fatty acids are valuable as precursors in the chemical industry. However, they are difficult to produce biologically at high concentrations. Although improved biocatalyst systems consisting of engineering of Baeyer–Villiger monooxygenases are used in the production of ω‐hydroxycarboxylic acids from long‐chain fatty acids, the engineering of biocatalysts involved in the production of α,ω‐dicarboxylic acids from ω‐hydroxycarboxylic acids has been rarely attempted. Here, we used highly active bacterial enzymes, Micrococcus luteus alcohol dehydrogenase and Archangium violaceum aldehyde dehydrogenase, for the efficient production of α,ω‐dicarboxylic acids from ω‐hydroxycarboxylic acids and constructed a biocatalyst with cofactor regeneration system by introducing NAD(P)H flavin oxidoreductase as the NAD(P)H oxidase. The inhibition of the biocatalyst by hydrophobic substrates was attenuated by engineering a biocatalyst system with an adsorbent resin, which allowed us to obtain 196 mM decanedioic, 145 mM undecanedioic, and 114 mM dodecanedioic acid from 200 mM of C10, C11, and C12 hydroxyl saturated carboxylic acids, respectively, and 141 mM undecanedioic acid from 150 mM C11 unsaturated carboxylic acids, with molar conversions of 98%, 97%, 95%, and 94%, respectively. The concentration of undecanedioic acid obtained was approximately 40‐fold higher than that in the previously highest results. Our results from this study can be applied for the industrial production of medium‐chain α,ω‐dicarboxylic acids from renewable long‐chain fatty acids.
HIF‐1α interacts with Kindlin‐2 and influences breast cancer elasticity: A study based on shear wave elastography imaging
Authors: Xue Xiaowei , Xue Shaowei , Wan Wenbo , Li Junlai , Shi Huaiyin 
Published: May 2020

AbstractBreast cancer was the most frequent and the second most deadly cancer in women in 2018 in China; thus, early diagnosis of breast cancer is important. Studies have reported that tissue stiffness promotes cancer progression through increased collagen or fibrosis. Shear wave elastography (SWE) is a technique for measuring tissue stiffness. However, the mechanisms underlying cancer tissue stiffness or fibrosis are not entirely clear. Hypoxia‐inducible factor 1 (HIF‐1α) is expressed in response to hypoxia and contributes to tumor progression and metastasis. Kindlin‐2 is an important co‐activator of integrin. We have reported that Kindlin‐2 influences breast cancer stiffness and metastasis. In this study, SWE was used to determine the maximum elasticity (Emax) of patients before operation or core needle biopsy. The specimens were used for staining. Knockdown, overexpression, co‐immunoprecipitation, and immunofluorescence assays were used to explore the relationship between HIF‐1α and Kindlin‐2. We found that HIF‐1α and Kindlin‐2 were highly expressed in invasive breast cancer and that the expression levels of HIF‐1α and Kindlin‐2 were correlated with Emax. HIF‐1α interacts with Kindlin‐2. Besides, HIF‐1α and Kindlin‐2 influence the expression of P4HA1, an important protein in collagen biogenesis through the integrin/FAK pathway. Our study first identified a new mechanism of invasive breast cancer stiffness by linking HIF‐1α and Kindlin‐2 to collagen biogenesis. Therefore, based on SWE, Emax could be a physical biomarker of invasive breast cancer for early, noninvasive diagnosis, and HIF‐1α and Kindlin‐2 could be pathological markers for early diagnosis and targeted therapy.
Epidermal growth factor and three‐dimensional scaffolds provide conducive environment for differentiation of mouse embryonic stem cells into oocyte‐like cells
Authors: Soleimani Azam , Fard Nehleh Zarei , Talaei‐Khozani Tahereh , Bahmanpour Soghra 
Published: May 2020

AbstractThree‐dimensional (3D) culture provides a biomimicry of the naive microenvironment that can support cell proliferation, differentiation, and regeneration. Some growth factors, such as epidermal growth factor (EGF), facilitate normal meiosis during oocyte maturation in vivo. In this study, a scaffold‐based 3D coculture system using purified alginate was applied to induce oocyte differentiation from mouse embryonic stem cells (mESCs). mESCs were induced to differentiate into oocyte‐like cells using embryoid body protocol in the two‐dimensional or 3D microenvironment in vitro. To increase the efficiency of the oocyte‐like cell differentiation from mESCs, we employed a coculture system using ovarian granulosa cells in the presence or absence of epidermal growth factor (+EGF or −EGF) for 14 days and then the cells were assessed for germ cell differentiation, meiotic progression, and oocyte maturation markers. The cultures exposed to EGF in the alginate‐based 3D microenvironment showed the highest level of premeiotic (Oct4 and Mvh), meiotic (Scp1, Scp3, Stra8, and Rec8), and oocyte maturation (Gdf9, Cx37, and Zp2) marker genes (p < .05) in comparison to other groups. According to the gene‐expression patterns, we can conclude that alginate‐based 3D coculture system provided a highly efficient protocol for oocyte‐like cell differentiation from mESCs. The data showed that this culture system along with EGF improved the rate of in vitro oocyte‐like cell differentiation.
Tumor‐suppressor Fbxw7 targets SIK2 for degradation to interfere with TORC2‐AKT signaling in pancreatic cancer
Authors: Zhang Ming‐xia , Wang Hao , Sun Guo‐ping 
Published: May 2020

AbstractThe tumor suppressor F‐box/WD repeat‐containing protein 7 (Fbxw7) is a substrate‐recognition subunit of a ubiquitin ligase complex. We have previously proposed that Fbxw7 inhibited pancreatic cancer cell proliferation and invasion by targeting β‐catenin. To identify other targets of Fbxw7 involved in pancreatic carcinogenesis, we screened the human protein database for Fbxw7 target candidates using the conserved Fbxw7‐recognizing sequences. Twenty‐three candidates are identified, including five known Fbxw7 targets and two cancer‐related genes (salt inducible kinase 2 [SIK2] and ZMIZ1). We identified SIK2 as an Fbxw7 target for degradation by binding to the “TPPPS” motif of SIK2 in pancreatic cancer cells. We also demonstrated that SIK2 promoted proliferation and mitotic progression of pancreatic cancer cells. Moreover, endogenous Fbxw7 downregulates SIK2 protein level for controlling cell cycle progression, possibly by interfering the SIK2/TORC2/AKT signaling pathway to modulate p21 expression. Collectively, these data demonstrate that Fbxw7 targets the cell cycle controller, SIK2, for degradation, thereby leading to the disruption of downstream TORC2/AKT signaling to inhibit pancreatic cancer cell proliferation and cell cycle progression.
G‐CSF‐dependent neutrophil differentiation requires downregulation of MAPK activities through the Gab2 signaling pathway
Authors: Zhao Xianglin , Kawano Shun‐ichiro , Masuda Junko , Murakami Hiroshi 
Published: May 2020

AbstractGranulocyte colony‐stimulating factor (G‐CSF) stimulation of myeloid cells induced tyrosine‐phosphorylation of cellular proteins. One of the tyrosine‐phosphorylated proteins was found to be a scaffold protein, Grb2‐associated binding protein 2 (Gab2). Another member of Gab family protein, Gab3, was exogenously overexpressed in neutrophil progenitor cells to make the Gab3 protein to compete with the endogenous Gab2 for the G‐CSF‐dependent signaling. In Gab3‐overexpressed cells, the level of tyrosine phosphorylation of endogenous Gab2 by G‐CSF stimulation was markedly downregulated, while the phosphorylation of Gab3 was significantly enhanced. The Gab3‐overexpressed cells continuously proliferated in the medium containing G‐CSF and lost the ability to differentiate to the mature neutrophil, characterized by the lobulated nucleus. The G‐CSF stimulation‐dependent tyrosine phosphorylation of Gab3, the association of SHP2 to Gab3 and the following mitogen‐activated protein kinase (MAPK) activation were prolonged in the Gab3‐overexpressed cells, compared to the parental cells, where the binding of SHP2 to Gab2 protein and thereby the activation of MAPK were not sustained after G‐CSF stimulation. Inhibition of MAPK by pharmaceutical inhibitor restored the Gab3‐overexpressed cells to the ability to differentiate to mature neutrophil. Therefore, G‐CSF‐dependent Gab2 phosphorylation and following its downregulation led the short‐term MAPK activation. The downregulation of MAPK after transient Gab2 phosphorylation was necessary for the consequent neutrophil differentiation induced by G‐CSF stimulation.
Accuracy of the PARIS score and PCI complexity to predict ischemic events in patients treated with very thin stents in unprotected left main or coronary bifurcations
Authors: Gallone Guglielmo , D'Ascenzo Fabrizio , Conrotto Federico , Costa Francesco , Capodanno Davide , Muscoli Saverio , Chieffo Alaide , Yoichi Imori , Pennacchi Mauro , Quadri Giorgio , Nuñez‐Gil Ivan , Bocchino Pier Paolo , Piroli Francesco , De Filippo Ovidio , Rolfo Cristina , Wojakowski Wojciech , Trabattoni Daniela , Huczek Zenon , Venuti Giuseppe , Montabone Andrea , Rognoni Andrea , Parma Radoslaw , Figini Filippo , Mitomo Satoru , Boccuzzi Giacomo , Mattesini Alessio , Cerrato Enrico , Wańha Wojciech , Smolka Grzegorz , Cortese Bernardo , Ryan Nicola , Bo Mario , di Mario Carlo , Varbella Ferdinando , Burzotta Francesco , Sheiban Imad , Escaned Javier , Helft Gerard , De Ferrari Gaetano Maria 
Published: May 2020

AbstractBackgroundThe PARIS risk score (PARIS‐rs) and percutaneous coronary intervention complexity (PCI‐c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed.MethodsThe predictive performances of the PARIS‐rs (categorized as low, intermediate, and high) and PCI‐c (according to guideline‐endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents.ResultsAfter 16 (12–22) months, increasing PARIS‐rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI‐c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS‐rs and target lesion revascularization/stent thrombosis for PCI‐c (area under the curves for MACE: PARIS‐rs 0.60 vs. PCI‐c 0.52, p‐for‐difference < .001). PCI‐c accuracy for MACE was higher in low‐clinical‐risk patients; while PARIS‐rs was more accurate in low‐procedural‐risk patients. ≥12‐month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS‐rs patients, (adjusted‐hazard ratio 0.42 [95% CI: 0.22–0.83], p = .012), with no benefit in low to intermediate PARIS‐rs patients. No incremental benefit with longer DAPT was observed in complex PCI.ConclusionsIn the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure‐related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.
Generation of 3D Tumor Spheroids with Encapsulating Basement Membranes for Invasion Studies
Authors: Nazari Shayan S. 
Published: May 2020

AbstractIn the past, in vitro studies of invasion and tumor progression were performed primarily using cancer cells cultured on a flat, two‐dimensional (2D) surface in a monolayer. In recent years, however, many studies have demonstrated differences in cell signaling and cell migration between 2D and 3D cell cultures. Traditional 2D monolayer cancer cell invasion models do not fully recapitulate 3D cell‐to‐cell and cell−to−extracellular matrix interactions that in vivo models can provide. Moreover, although in vivo animal models are irreplaceable for studying tumor biology and metastasis, they are costly, time‐consuming, and impractical for answering preliminary questions. Thus, emergent and evolving 3D spheroid cell culture models have changed the way we study tumors and their interactions with their surrounding extracellular matrix. In the case of breast cancer, metastasis of breast cancer tumors results in high mortality rates, and thus development of robust cell culture models that are reproducible and practical for studying breast cancer progression is important for ultimately developing preventatives for cancer metastasis. This article provides a set of protocols for generating uniform spheroids with a thin sheet of basement membrane for studying the initial invasion of mammary epithelial cells into a surrounding collagen‐rich extracellular matrix. Details are provided for generating 3D spheroids with a basement membrane, polymerizing collagen I, embedding the spheroids in the 3D collagen gel, and immunostaining the spheroids for invasion studies. Published 2020. U.S. Government.Basic Protocol 1: Growth of uniformly sized tumor spheroids with an encapsulating basement membraneBasic Protocol 2: Polymerization and embedding of tumor spheroids in a 3D type I collagen gelAlternate Protocol: Embedding of tumor spheroids in collagen gels using a sandwich methodBasic Protocol 3: Fixing and immunostaining of tumor spheroids embedded in 3D collagen gels
Women in management and sustainable development of SMEs: Do relational environmental management instruments matter?
Authors: Graafland Johan 
Published: May 2020

AbstractScientific literature on the relationship between gender diversity in management and sustainability of large companies has produced mixed results. Whether and how gender diversity stimulates the sustainable development of small and medium sized enterprises (SMEs) has not yet been researched. We hypothesize that having more women in management positions improves the sustainability of SMEs, because this encourages the use of relational environmental management instruments. Small business literature has shown this type of instrument to be more effective in improving the sustainability of SMEs than bureaucratic management instruments. We test the model on a sample of 3,663 European SMEs and find support for this hypothesis. However, the effect is nonlinear and sustainability reaches its maximum when the proportion of women managers is 54%. The management implication is that SMEs can improve their sustainability by a gender balanced management team.
Unmasking features of the auto‐epitope essential for β1‐adrenoceptor activation by autoantibodies in chronic heart failure
Authors: Wölfel Angela , Sättele Mathias , Zechmeister Christina , Nikolaev Viacheslav O. , Lohse Martin J. , Boege Fritz , Jahns Roland , Boivin‐Jahns Valérie 
Published: May 2020

AbstractAimsChronic heart failure (CHF) can be caused by autoantibodies stimulating the heart via binding to first and/or second extracellular loops of cardiac β1‐adrenoceptors. Allosteric receptor activation depends on conformational features of the autoantibody binding site. Elucidating these features will pave the way for the development of specific diagnostics and therapeutics. Our aim was (i) to fine‐map the conformational epitope within the second extracellular loop of the human β1‐adrenoceptor (β1ECII) that is targeted by stimulating β1‐receptor (auto)antibodies and (ii) to generate competitive cyclopeptide inhibitors of allosteric receptor activation, which faithfully conserve the conformational auto‐epitope.Methods and resultsNon‐conserved amino acids within the β1ECII loop (compared with the amino acids constituting the ECII loop of the β2‐adrenoceptor) were one by one replaced with alanine; potential intra‐loop disulfide bridges were probed by cysteine–serine exchanges. Effects on antibody binding and allosteric receptor activation were assessed (i) by (auto)antibody neutralization using cyclopeptides mimicking β1ECII ± the above replacements, and (ii) by (auto)antibody stimulation of human β1‐adrenoceptors bearing corresponding point mutations. With the use of stimulating β1‐receptor (auto)antibodies raised in mice, rats, or rabbits and isolated from exemplary dilated cardiomyopathy patients, our series of experiments unmasked two features of the β1ECII loop essential for (auto)antibody binding and allosteric receptor activation: (i) the NDPK211–214 motif and (ii) the intra‐loop disulfide bond C209↔C215. Of note, aberrant intra‐loop disulfide bond C209↔C216 almost fully disrupted the functional auto‐epitope in cyclopeptides.ConclusionsThe conformational auto‐epitope targeted by cardio‐pathogenic β1‐receptor autoantibodies is faithfully conserved in cyclopeptide homologues of the β1ECII loop bearing the NDPK211–214 motif and the C209↔C215 bridge while lacking cysteine C216. Such molecules provide promising tools for novel diagnostic and therapeutic approaches in β1‐autoantibody‐positive CHF.
Vitamin E (α‐, β + γ‐ and δ‐tocopherol) levels in plant oils
Authors: Aksoz Elif , Korkut Oguzhan , Aksit Dilek , Gokbulut Cengiz 
Published: May 2020

AbstractVitamin E is the most potent lipid‐soluble antioxidant in human plasma. The richest sources of vitamin E are plant oils. This study aims to determine the concentrations of alpha, beta + gamma and delta‐tocopherols (α‐T, β + γ‐T and δ‐T) in various plant or seed oils commonly used in food, pharmaceutics or cosmetics. Forty‐one different plant or seed oil samples were purchased and kept at +4°C in the dark until the chromatographic analysis. Analyses were performed using high‐performance liquid chromatography (HPLC) following the dilution of the oil samples with 2‐propanol in a 1:3 ratio, without further processing. Total tocopherol levels in the oils analysed ranged from 11 to 3468 mg/kg. When the highest total tocopherol levels were taken into consideration, the first five plant oils were pomegranate seeds, wheat germ, fig seed, hippophae rhamnoides and corn oils. Moreover, the wheat germ, fig seed, safflower, sunflower and hazelnut oils had highest α‐tocopherol concentration in the oils analysed. These plant or seed oils have a high potential for using in the food, pharmaceutical and cosmetic industries due to their high tocopherol contents.
Different drying methods of Pistacia Atlantica seeds: Impact on drying kinetics and selected quality properties
Authors: Yarahmadi Negar , Hojjatoleslamy Mohammad , Sedaghat Boroujeni Leila 
Published: May 2020

AbstractThe effect of different drying procedures on the quality characteristics of Pistacia atlantica subsp. kurdica is addressed in this work. Using five different drying methods include microwave, oven (40 and 60°C), sun, and shade, P. atlantica were dried. The variations in moisture content, drying rate, major components of essential oil, and texture property were assessed at the start and at the end points of the drying process. Comparison of the drying methods indicated that microwave drying to be most effective in lowering moisture content, while the shade drying had the lowest rate among methods. In the case of microwave, the dried seeds had highest brittleness, while the highest score for the penetration force was observed in oven 40°C. Regarding major elements of the essential oil (α‐pinene, α‐terpinen‐4‐ol, myrcene, β‐ocimene, β‐caryophyllene, and limonene), there were no significant differences between the five drying techniques, nor compared to the fresh sample. To model the drying process, six thin‐layer drying kinetic models were chosen. It was found that the Midilli–Kucuk model was the most suitable for explaining the drying curve of oven 40 and 60°C, microwave, and sun methods; Wang and Singh model was excellent to explain thin‐layer shade drying behavior of the P. atlantica seeds. In conclusion, in this study, an opportunity is represented to apply the most effective procedures to decrease the drying period and to achieve a product with appropriate safety and quality features.
Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA‐CREB pathway in oral squamous cell carcinoma
Authors: Lin Chong‐Xiang , Tu Cheng‐Wei , Ma Yi‐Ke , Ye Peng‐Cheng , Shao Xia , Yang Zhao‐An , Fang Yi‐Ming 
Published: May 2020

AbstractBackground/AimNobiletin is a polymethoxylated flavone enriched in Citrus and is used as an important drug in traditional Chinese medicine for various kinds of diseases. Among its multiple functions, it has shown that nobiletin inhibits proliferation of various cancer cells. However, it is unclear whether nobiletin inhibits the growth of oral squamous cell carcinoma (OSCC) cells.Materials and MethodsWe explored the antitumor effects of nobiletin in TCA‐8113 and CAL‐27 oral squamous cells. The Cell Counting Kit‐8 (CCK8) assay was used to measure cell vitality. Flow cytometry was performed to measure the number of cells in the various phases of the cell cycle. PCR and Western blot were applied to determine mRNA and protein expression, respectively.ResultsNobiletin inhibited proliferation of TCA‐8113 and CAL‐27 cells via inducing cell cycle arrest at the G1 phase. In addition, the levels of phosphorylated‐PKA and phosphorylated‐CREB were reduced in nobiletin‐treated TCA‐8113 and CAL‐27 cells. Importantly, our results showed that nobiletin treatment resulted in impaired mitochondrial function and altered glucose consumption, and pyruvate and lactate production. Lastly, nobiletin was found to inhibit the generation of xenografts in vivo. Interestingly, administration of 50 μmol/L Sp‐cAMP, a potent PKA activator, rescued all phenotypes caused by nobiletin.ConclusionsNobiletin inhibits OSCC cell proliferation in a mitochondria‐dependent manner, indicating that it may have a promising role in cancer treatment and attenuation of drug resistance.
Rheological effects on peristaltic transport of Bingham fluid through an elastic tube with variable fluid properties and porous walls
Authors: Choudhari Rajashekhar , Gudekote Manjunatha , Vaidya Hanumesh , Prasad K. V. , Khan Sami U. 
Published: May 2020

AbstractThe peristaltic pumping of non‐Newtonian material configured by a tube is quite interesting phenomenon to examine the behavior of physiological fluids. The present paper investigates the role of variable viscosity and thermal conductivity on the peristaltic mechanism of Bingham fluid in an elastic tube with porous and convective boundary conditions. The long wavelength and small Reynolds number approximation is used to obtain the analytical solutions for velocity, plug flow velocity, streamlines, flow rate, and temperature. The theoretical determination of flux is calculated using the equilibrium condition, and an application to flow through an artery is highlighted by using the tension relation in an elastic tube. It is observed that the rate of flow within the elastic tube declined with variation of variable viscosity. An enhanced temperature distribution near the tube axis has been observed with increment of variable viscosity. An increasing influence of the porous parameter in the bolus size can also be seen from the streamlines plotted.