bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multinuclear Yeast Magnusiomyces (Dipodascus, Endomyces) magnusii is a Promising Isobutanol Producer
Authors: Kurylenko Olena O. , Ruchala Justyna , Dmytruk Kostyantyn V. , Abbas Charles A. , Sibirny Andriy A. 
Published: January 2020

AbstractHigher alcohol isobutanol is a promising liquid fuel. During alcoholic fermentation, Saccharomyces cerevisiae produces only trace amounts of isobutanol. Screening the collection of nonconventional yeasts show that Magnusiomyces magnusii accumulates 440 mg of isobutanol per L in rich YPD medium. Here, the transformation protocol for M. magnusii is adapted based on the use of the dominant markers conferring resistance to nourseothricin or zeocin; the strong constitutive promoter TEF1 is cloned and a reporter system based on LAC4 gene from Kluyveromyces lactis coding for β‐galactosidase is constructed. In order to increase isobutanol production in M. magnusii, the heterologous gene ILV2 from S. cerevisiae is expressed in M. magnusii under control of the TEF1 promoter. The best stabilized transformants produce 620 mg of isobutanol per L in YPD medium and 760 mg L−1 in the medium with 2‐oxoisovalerate. This suggests that M. magnusii is a promising organism for further development of a robust isobutanol producer.
Clearance of porcine circovirus and porcine parvovirus from porcine‐derived pepsin by low pH inactivation and cation exchange chromatography
Authors: Yang Bin , Wang Hua , Kaleas Kimberly , Butler Michelle , Franklin Jayme , Bill Amber , Baylis Sally A. , Chen Qi , Blümel Johannes 
Published: January 2020

AbstractThe contamination of oral rotavirus vaccines by porcine circovirus (PCV) raised questions about potential PCV contamination of other biological products when porcine trypsin or pepsin is used in production process. Several methods can be potentially implemented as a safety barrier when animal derived trypsin or pepsin is used. Removal of PCV is difficult by the commonly used viral filters with the pore size cutoff of approximately 20 nm because of the smaller size of PCV particles that are around 17 nm. It was speculated that operating the chromatography step at a pH higher than pepsin's low pI, but lower than pIs, of most viruses would allow the pepsin to flow through the resin and be recovered from the flow through pool whilst the viruses would be retained on the resin. In this study, we investigated low pH inactivation of viruses including PCV Type 1 (PCV1) and PCV1 removal by cation exchange chromatography (CEX) in the presence of pepsin. Both parvovirus and PCV1 could be effectively inactivated by low pH and PCV1 could be removed by POROS 50HS CEX. The POROS 50HS method presented in this article is helpful for designing other CEX methods for the same purpose and not much difference would be expected for similar product intermediates and same process parameters. While the effectiveness needs to be confirmed for specific applications, the results demonstrate that both low pH (pH 1.7) and CEX methods were successful in eliminating PCV1 and thus either can be considered as an effective virus barrier.
Application of flipped classroom based on the Rain Classroom in the teaching of computer‐aided landscape design
Authors: Da‐Hong Li , Hong‐Yan Li , Wei Li , Guo Jun‐Jie , En‐Zhong Li 
Published: January 2020

AbstractSince the age of the Internet was coming, the smart teaching tool Rain Classroom provides new research ideas and directions for education reform. In this paper, the researchers analyzed the characteristics of Rain Classroom, studied the problems in flipped classroom teaching, designed a new flipped classroom teaching mode based on Rain Classroom, and practiced the new mode in a course on computer‐aided landscape design. Significant academic differences were shown according to questionnaire surveys of students who experienced Rain Classroom learning compared with a control group learning through traditional lecture‐based learning methods. Results suggest that a comparable group of graduate students who participated in the flipped class based on Rain Classroom scored significantly higher (p = .041 < .05) on the “computer‐aided landscape design” by an average of >3 percentage points than that of the control group. According to survey data, students learned more from the Rain Class than from a traditional lecture format, and the class also promoted teamwork skills. Our results show learning in the Rain Classroom can improve the students' learning interest, stimulate students' learning initiative, and promote better learning.
Two‐point‐NGS analysis of cancer genes in cell‐free DNA of metastatic cancer patients
Authors: Palmieri Maria , Baldassarri Margherita , Fava Francesca , Fabbiani Alessandra , Gelli Elisa , Tita Rossella , Torre Pamela , Petrioli Roberto , Hadijstilianou Theodora , Galimberti Daniela , Cinotti Elisa , Bengala Carmelo , Mandalà Marco , Piu Pietro , Miano Salvatora Tindara , Martellucci Ignazio , Vannini Agnese , Pinto Anna Maria , Mencarelli Maria Antonietta , Marsili Stefania , Renieri Alessandra , Frullanti Elisa 
Published: January 2020

AbstractBackgroundAlthough the efficacy of molecularly target agents in vitro, their use in routine setting is limited mainly to the use of anti‐HER2 and antiEGFR agents in vivo. Moreover, core biopsy of a single cancer site may not be representative of the whole expanding clones and cancer molecular profile at relapse may differ with respect to the primary tumor.MethodsWe assessed the status of a large panel of cancer driver genes by cell‐free DNA (cfDNA) analysis in a cohort of 68 patients with 13 different solid tumors at disease progression. Whenever possible, a second cfDNA analysis was performed after a mean of 2.5 months, in order to confirm the identified clone(s) and to check the correlation with clinical evolution.ResultsThe approach was able to identify clones plausibly involved in the disease progression mechanism in about 65% of cases. A mean of 1.4 mutated genes (range 1‐3) for each tumor was found. Point mutations in TP53, PIK3CA, and KRAS and copy number variations in FGFR3 were the gene alterations more commonly observed, with a rate of 48%, 20%, 16%, and 20%, respectively. Two‐points‐Next‐Generation Sequencing (NGS) analysis demonstrated statistically significant correlation between allele frequency variation and clinical outcome (P = .026).ConclusionsIrrespective of the primary tumor mutational burden, few mutated genes are present at disease progression. Clinical outcome is consistent with variation of allele frequency of specific clones indicating that cfDNA two‐point‐NGS analysis of cancer driver genes could be an efficacy tool for precision oncology.
Proteomic changes in skeletal muscle of aged rats in response to resistance training
Authors: de Sousa Neto Ivo Vieira , Carvalho Marcia Mendes , Marqueti Rita de Cassia , Almeida Jeeser Alves , Oliveira Kléber de S. , Barin Fabrício R. , Petriz Bernardo , de Araújo Heloisa Sobreiro Selistre , Franco Octávio Luiz , Durigan João Luiz Quaglioti 
Published: January 2020

Sarcopenia is a multifactorial process defined by loss of strength and skeletal muscle mass, which leads to a reduction in muscle cross‐sectional area (CSA). Although resistance training (RT) has been indicated as a tool to counteract sarcopenia, the protein profile associated with skeletal muscle adaptations remains to be determined. We investigated the effects of 12 weeks of RT on the skeletal muscle proteome profile and CSA of young and older rats. Twenty‐four animals were divided into four groups: young sedentary or trained and older sedentary or trained (six animals per group). A 12‐week RT protocol was performed, which consisted of climbing a vertical ladder. The proteins from the gastrocnemius were analysed by LC‐ESI‐MS/MS. One‐hundred and thirty‐one proteins were identified, of which 28 were assessed between the groups. Ageing induced an increase in proteins associated with the glycolytic pathway, transport and stress response, which represent crucial mechanisms for muscle adaptation. RT upregulated metabolic enzymes, anti‐oxidant activity and transport proteins, besides increasing hypertrophy, regardless of age, suggesting a beneficial adaptation to mitigate age‐related sarcopenia. RT reduced muscle atrophy through the regulation of stress response and by increasing proteins related to energy production and transport, which in turn might protect tissue damage arising from exercise and ageing.Significance of the studyProtein abundance levels related to the metabolic process and stress response were increased in the aged muscle. RT proved to be an important intervention capable of inducing significant effects on muscle proteome regardless of ageing, due to upregulation of glycolytic enzymes, and anti‐oxidant and transport proteins. This effect could lead to a beneficial adaptation in muscle structure, cellular function and overall homeostasis maintenance. This study contributes to better understanding of the basic biology of ageing and clarifies more profoundly the molecular networks behind physiological adaptations promoted by exercise training. Therefore, the results open new perspectives and insights for studies based on transcriptomics, metabolomics and functional assays.
A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins
Authors: Ban Željka , Griesbeck Stefanie , Tomić Sanja , Nitsch Jörn , Marder Todd B. , Piantanida Ivo 
Published: January 2020

AbstractInvited for the cover of this issue are the groups of Todd B. Marder at the Julius‐Maximilians‐Universität Würzburg and Ivo Piantanida at the Ruder Boškovic Institute. The image depicts the molecular structure of a bis‐triarylborane‐based chromophore that is simultaneously detecting ds‐DNA and proteins. Read the full text of the article at 10.1002/chem.201903936.
Ring Enlargement of Three‐Membered Heterocycles by Treatment with In Situ Formed Tricyanomethane
Authors: Banert Klaus , Chityala Madhu , Korb Marcus 
Published: January 2020

AbstractAlthough the chemistry of elusive tricyanomethane (cyanoform) has been studied during a period of more than 150 years, this compound has very rarely been utilized in the synthesis or modification of heterocycles. Three‐membered heterocycles, such as epoxides, thiirane, aziridines, or 2H‐azirines, are now treated with tricyanomethane, which is generated in situ by heating azidomethylidene‐malonodinitrile in tetrahydrofuran at 45 °C or by adding sulfuric acid to potassium tricyanomethanide. This leads to ring expansion with formation of 2‐(dicyanomethylidene)oxazolidine derivatives or creation of the corresponding thiazolidine, imidazolidine, or imidazoline compounds and opens up a new access to these push–pull‐substituted olefinic products. The regio‐ and stereochemistry of the ring‐enlargement processes are discussed, and the proposed reaction mechanisms were confirmed by using 15N‐labeled substrates. It turns out that different mechanisms are operating; however, tricyanomethanide is always acting as a nitrogen‐centered nucleophile, which is quite unusual if compared to other reactions of this species.
Hitting the Jackpot – development of gas chromatography–mass spectrometry (GC–MS) and other rapid screening methods for the analysis of 18 fentanyl‐derived synthetic opioids
Authors: Gilbert Nicolas , Antonides Lysbeth H. , Schofield Christopher J. , Costello Andrew , Kilkelly Brenda , Cain Alan R. , Dalziel Paula R.V. , Horner Karen , Mewis Ryan E. , Sutcliffe Oliver B. 
Published: January 2020

AbstractIn recent years, the occurrence of synthetic opioid fentanyl and its derivatives has grown significantly in forensic casework. This study presents the synthesis and analysis of 18 fentalogs, selected based on information received from local law enforcement. This study provides colorimetric tests, thin‐layer chromatography (TLC) which can potentially be utilized for presumptive screening of the target compounds, as bulk powders or as trace‐level adulterants. The fully validated confirmatory GC–MS method (employing SIM mode) allows the identification of the 18 derivatives, five commonly encountered controlled substances and four adulterants, within 20 minutes. The cross‐validated method described herein provides a sensitive screening and quantitation method for the illicit (and potentially harmful) components at trace levels (LOD = 0.007–0.822 μg/mL and LOQ = 0.023–2.742 μg/mL respectively). Spectral data [1H‐NMR, 13C‐NMR, 19F‐NMR, FT‐IR, and HRMS] and assignments for the synthesized reference materials are also provided in the Supplementary Information for laboratories engaged in the routine analysis of fentanyl and its derivatives.
Electrochemical Tracing of Butein Using Carbon Nanoparticles Interfaced Electrode Processed from Biowaste
Authors: Kanagavalli Pandiyaraj , Radhakrishnan Sivaprakasam , Pandey Gaurav , Ravichandiran Velayutham , Perumal Pazhani Gururaja , Veerapandian Murugan , Hegde Gurumurthy 
Published: January 2020

AbstractNanoparticles of carbon derivatized from pyrolysis of biowaste oil palm leaves were processed as electrochemical transducer material at the interface of glassy carbon electrode. This modified electrode exhibits convincing electron‐transfer property for voltammetric and chronoamperometric quantification of clinically important phytochemical, butein, without the use of external redox mediator and enzyme. A reversible two‐electron transfer redox property observed from butein is distinct at the electrode interface and the current density is found to be superior in phosphate buffered saline electrolyte at pH 7.0. Carbon nanoparticles interfaced electrode system displayed a good stability and sensitivity for butein with a detection limit of 7.6 μM and a dynamic detection concentration ranging from 10 to 100 μM. This bio‐waste translated carbon nanoparticle represent a promising electrode material for various flavonoids detection useful for biological studies.
Mucosal dysbiosis in patients with gastrointestinal follicular lymphoma
Authors: Zeze Keizo , Hirano Atsushi , Torisu Takehiro , Esaki Motohiro , Shibata Hiroki , Moriyama Tomohiko , Umeno Junji , Fujioka Shin , Okamoto Yasuharu , Fuyuno Yuta , Matsuno Yuichi , Kitazono Takanari 
Published: January 2020

AbstractBecause the pathogenesis of gastrointestinal follicular lymphoma (GI‐FL) remains unclear, no standardized treatment strategy has been established. Of the gastrointestinal lymphomas, gastric mucosa‐associated lymphoid tissue lymphomas are strongly associated with Helicobacter pylori; hence, the microbiota may be involved in GI‐FL pathogenesis. However, the association between GI‐FL and the microbiota remains uninvestigated. Therefore, we compared the mucosal microbiotas of GI‐FL patients with those of controls to identify microbiota changes in GI‐FL patients. Mucosal biopsy samples were obtained from the second portion of the duodenum from 20 GI‐FL patients with duodenal lesions and 20 controls. Subsequent 16S rRNA gene sequencing was performed on these samples. QIIME pipeline and LEfSe software were used to analyze the microbiota. The GI‐FL patients had significantly lower alpha diversity (P = .049) than did the controls, with significant differences in the microbial composition (P = .023) evaluated by the beta diversity metrics between the two groups. Comparing the taxonomic compositions indicated that the genera Sporomusa, Rothia, and Prevotella and the family Gemellaceae were significantly less abundant in the GI‐FL patients than in the controls. GI‐FL patients presented altered duodenal mucosal microbial compositions, suggesting that the microbiota might be involved in the GI‐FL pathogenesis.
Downregulation of uPAR promotes urokinase translocation into the nucleus and epithelial to mesenchymal transition in neuroblastoma
Authors: Semina Ekaterina V. , Rubina Kseniya A. , Shmakova Anna A. , Rysenkova Karina D. , Klimovich Polina S. , Aleksanrushkina Natalya A. , Sysoeva Veronika Y. , Karagyaur Maxim N. , Tkachuk Vsevolod A. 
Published: January 2020

AbstractThe urokinase system is involved in a variety of physiological processes, such as fibrinolysis, matrix remodeling, wound healing, and regeneration. Upon binding to its cognate receptor urokinase‐type plasminogen activator receptor (uPAR), urokinase‐type plasminogen activator (uPA) catalyzes the conversion of plasminogen to plasmin and the activation of matrix metalloproteases. Apart from this, uPA–uPAR interaction can lead to the activation of transcription factors, mitogen‐activated protein kinase signaling pathways and RTK cascades. Elevated expression of uPA and uPAR is markedly associated with cancer progression and metastasis and correlates with a poor prognosis in clinics. Targeting the urokinase system has proved to be effective in experimental models in vitro and in vivo, however, in clinics the inhibition of the uPA/uPAR system has fallen short of expectations, suggesting that the question of the functional relevance of uPA/uPAR system is far from being moot. Recently, using CRISPR/Cas9 technology, we have shown that uPAR knockout decreases the proliferation of neuroblastoma Neuro2a cells in vitro. In the present study we demonstrate that uPAR expression is essential for maintaining the epithelial phenotype in Neuro2a cells and that uPAR silencing promotes epithelial‐mesenchymal transition (EMT) and increased cell migration. Accordingly, uPAR knockout results in the downregulation of epithelial markers (E‐cadherin, occludin, and claudin‐5) and in the increase of mesenchymal markers (N‐cadherin, α‐smooth muscle actin, and interleukin‐6). In search of the molecular mechanism underlying these changes, we identified uPA as a key component. Two key insights emerged as a result of this work: in the absence of uPAR, uPA is translocated into the nucleus where it is presumably involved in the activation of transcription factors (nuclear factor κB and Snail) resulting in EMT. In uPAR‐expressing cells, uPAR functions as a uPA “trap” that binds uPA on the cell surface and promotes controlled uPA internalization and degradation in lysosomes.
Impairment of motor but not anxiety‐like behavior caused by the increase of dopamine during development is sustained in zebrafish larvae at later stages
Authors: de Souza Lima Ana Carolina Monteiro , de Alvarenga Kevin Augusto Farias , Codo Beatriz Campos , Sacramento Erika Kelmer , Rosa Daniela Valadão Freitas , Souza Renan Pedra , Romano‐Silva Marco Aurélio , Souza Bruno Rezende 
Published: January 2020

AbstractMany neuropsychiatric disorders are associated with both dopaminergic (DAergic) and developmental hypotheses. Since DAergic receptors are expressed in the developing brain, it is possible that alterations in dopamine (DA) signaling may impair brain development and consequent behavior. In our previous study, using a zebrafish model, we showed that an increase of DA during the 3 to 5 days postfertilization (dpf) developmental window (an important window for GABAergic neuronal differentiation) affects the motor behavior of 5 dpf larvae. In this study, we set out to determine whether these behavioral alterations were sustained in larvae at older stages (7 and 14 dpf). To test this hypothesis, we chronically treated zebrafish larvae from 3 to 5 dpf with DA. After washing the drug, we recorded and analyzed the first 5 and 30 min of the motor behavior of 5, 7, and 14 dpf subjects. We analyzed mobile episodes, distance traveled, time mobile, distance traveled per mobile episode, time in movement per mobile episode, and distance traveled per time mobile. We showed, once again, that an increase of DA during the 3 to 5 dpf developmental window reduces the number of movement episodes initiated by 5 dpf larvae. We also detected a decrease of other motor behavior parameters in 5 dpf DA‐treated larvae. We observed that these alterations are sustained in the 7 dpf larvae. However, we did not see these general locomotor alterations in the 14 dpf larvae. Moreover, we detected a decrease of distance traveled and an increase of time of locomotion per episode in the first 5 min of behavioral analyses in 14 dpf DA‐treated larvae. To test if the alterations in the first 5 min were due to anxiety‐like behavior, we used a light/dark preference paradigm. We recorded 5dpf, 7dpf, and 14dpf larvae for 5 min and analyzed time of freezing, preference for light or dark, number of entries to the dark, percentage of time in the light. We observed that 5dpf larvae treated with DA showed more freezing, less passages to the dark, and more time spent in the light as compared to their control counterparts. But 7dpf and 14dpf larvae did not show these alterations. Taken overall, therefore, our results suggest that DA does play a role in the development of zebrafish motor behavior, and, furthermore, that some behaviors are more sensitive than others to the effects of DAergic imbalances during development.
Design, synthesis, molecular docking, and biological evaluation of novel selenium containing lumefantrine analogues
Authors: Puthran Divyaraj , Poojary Boja , Nayak Soukhyarani Gopal , Purushotham Nikil , Rasheed Mohammed Shafeeulla , Hegde Hemant 
Published: January 2020

AbstractA new series of 1‐(9‐benzylidene‐2,7‐dichloro‐9H‐fluoren‐4‐yl)‐2‐(methylselanyl)ethanol was synthesized by a simple Knoevenagel condensation of 1‐(2,7‐dichloro‐9H‐fluoren‐4‐yl)‐2‐(methylselanyl)ethanol with different substituted aromatic aldehydes in basic media. These synthesized compounds were confirmed on the basis of their elemental analyses, infrared (IR), 1H NMR, 13C NMR, and mass spectral data and screened for the antibacterial and antifungal activity. The preliminary antibacterial and antifungal screening revealed that the compounds 8c (dichloro), 8d (fluoro), 8e (chloro), 8i (methoxy), and 8l (methyl) displayed moderate to good activity. The antibacterial results of these compounds were further supported by in silico molecular docking studies, for the inhibition of Escherichia coli MurB enzyme (PDB code: 2MBR), wherein they showed higher binding energy and good affinity towards the active pocket of the enzyme compared with that of the standard drug Ciprofloxacin. Thus, the plausible mechanism of their antibacterial activity was owed to their inhibitory action of the bacterial MurB enzyme.
Evaluation of Fibrosis in Intestinal Failure–Associated Liver Disease in the Sustain Registry
Authors: Wang Jennifer , Wamuo Obinnaya , Micic Dejan 
Published: January 2020

AbstractBackgroundIntestinal failure–associated liver disease (IFALD) is one of the leading complications in type III intestinal failure (IF). Early recognition of liver‐fibrosis development in IFALD is crucial to the development of strategies aimed at reducing the risk of complications secondary to IFALD. Our aim was to identify patients with advanced fibrosis using a noninvasive index and to study the risk factors for fibrosis development in the Sustain registry.MethodsUsing the Sustain registry, patients requiring >3 months of parenteral nutrition (PN) support were identified. The presence or absence of advanced fibrosis was identified using the Fibrosis‐4 (FIB‐4) index. Risk factors for the presence of a high FIB‐4 score were identified using univariable logistic regression.ResultsTwo hundred seventy‐one adult patients were included. Sixty‐three patients (23.2%) were at risk for advanced fibrosis based on the FIB4‐index. Risk factors for advanced fibrosis included short‐bowel syndrome (odds ratios [ORs]: 1.84; 95% confidence interval [CI], 1.03–3.28), receipt of PN for >1 year (OR: 2.6; 95% CI, 1.46–4.64), receipt of PN for >5 years (OR: 3.05; 95% CI, 1.67–5.59), and days of lipid emulsion use (OR: 1.11; 95% CI, 1–1.24). Small‐intestine–remnant length was inversely associated with advanced fibrosis (OR: 0.97, 95% CI, 0.95–0.99).ConclusionAdvanced fibrosis, as guided by FIB‐4 index, is associated with known risk factors for IFALD. Therefore, the FIB‐4 index is potentially a useful noninvasive tool for identification of individuals at risk for fibrosis in IFALD. Further studies utilizing a gold‐standard fibrosis assessment will be required to validate these results.