bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of Colistin in Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study
Authors: Matar Kamal M. , Al-Refai Batool 
Published: May 2020

AbstractColistin is a polymixin antibiotic (polymixin E) that is produced by Bacillus colistinus bacteria. The aim of the present study was to develop and validate a method to quantify colistin levels in plasma using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique and then apply it in experimental animals (rats) to investigate the pharmacokinetic profile of colistin in this species. Polymyxin B was used as an internal standard (IS) and the quantitation was carried out using ESI + interface and employing multiple reaction monitoring (MRM) mode. A mobile phase consisting of acetonitrile:water:formic acid (30:70:0.1%; v/v/v) was employed and Zorbax eclipse plus C18 (1.8 µm, 2.1 mm i.d. x 50 mm) was the optimal column for this method and utilized at a flow rate of 0.2 mL/min. The full scan mass spectra of precursor/product ions of colistin A were at m/z 585.5 > 100.8, for colistin B at m/z 578.8 > 101 and for the IS at m/z 602.8 > 101. The lower limit of quantification (LLOQ) was 0.5 µg/mL. The method demonstrated acceptable intra-run and inter-run precision and accuracy for both colistin A and colistin B. Colistin was stable when assessed for long-term stability, freeze-thaw stability and autosampler stability. However, it was not stable when stored at room temperature. The matrix effect evaluation showed minimal or no effect. Incurred sample reanalysis findings were within acceptable ranges (<20% of the nominal concentration). The pharmacokinetic parameters of colistin were investigated in rats using the present method. The developed method for colistin demonstrates that it is rapid, sensitive, specific, accurate, precise, and reliable.
Popliteal Artery Branching Variations: A Study on Multidetector CT Angiography
Authors: Oner Serkan , Oner Zulal 
Published: May 2020

AbstractDetermining the branching pattern of the popliteal artery (PA) is an important step in planning some radiological and surgical procedures. The aim of this study was to investigate the course and morphology of the terminal branches of the popliteal artery using multidetector computed tomography (MDCT) angiography, and also to determine possible role gender in branching pattern. Three-hundred forty lower extremity MDCT angiography images for 170 patients (118 M, 52 F), who were between 20–80 years old, were examined. Popliteal artery branching types were grouped as percentage incidences. TPT diameters and lengths in Type IA extremities were compared based on gender and right or left side. Anterior tibial artery (ATA), posterior tibial artery (PTA) and peroneal artery dominance rates were calculated. 5000 times measurement data was mixed so that the cascade mean filter values were calculated for the right and left TPT length each time. It was observed that Type IA was the most common branching pattern (89.4%). The variational pattern incidence was 10.6% and the most common category was Type III (4.1%). The most common pattern was Type IB (3.2%). Variational pattern was 2 times more prevalent in females when compared to the males. The mean TPT diameter was 4.5 mm (2.7–7.3 mm) and there was no difference based on gender and the right-left side. The most common dominant artery for the right and left legs was PTA in both genders. The cut-off values calculated for the right and left TPT independent of gender were 31.30 ± 2.40 and 28.36 ± 2.58, respectively. Three new subtypes were identified as short (S ≤ 2 cm), standard (N = 2–4 cm) and long (L ≥ 4 cm) in Type IA, since it is in a wide variational range although it is a typical PA branching pattern.
Co-chaperones DNAJA1 and DNAJB6 are critical for regulation of polyglutamine aggregation
Authors: Rodríguez-González Claudio , Lin Shiying , Arkan Sertan , Hansen Christian 
Published: May 2020

AbstractHuntington’s disease (HD) is caused by CAG repeat expansion in the huntingtin gene. The expanded polyglutamine (polyQ) repeat of the encoded protein leads to protein misfolding and aggregation, resulting in increased neuronal cell death. DNAJ co-chaperones play a crucial role in transferring misfolded/unfolded proteins to HSP70 chaperones, which play an essential role for protein folding. Here, we investigated the effect of knock out (KO) of three individual DNAJ genes in HEK293 cells expressing polyglutamine74exon1 huntingtin (polyQ74htt). Flourescence microscopy analysis revealed that KO of DNAJB6 resulted in a 5-fold increase in polyQ74htt aggregation and that DNAJA1 KO resulted in a 4-fold decrease of polyQ74htt aggregation. KO of DNAJB1 did not change the propensity of polyQ74htt to aggregate in cells. These findings where confirmed both by fluorescence microscopy analysis and filter trap assay (FTA). DNAJB6 KO cells displayed an increased rate of cell death as assessed by trypan blue exclusion and propidium iodide (PI) uptake assays. These results demonstrate that the DNAJ proteins DNAJA1 and DNAJB6 can modulate polyQ aggregation in opposite manners, and thus that fine-tuning the cellular levels of DNAJ proteins is critical for suppression of polyQ aggregation and cell survival.
Acoustic field induced nonlinear magneto-optical rotation in a diamond mechanical resonator
Authors: Ghaderi Goran Abad Mohsen , Ashrafizadeh Khalifani Fatemeh , Mahmoudi Mohammad 
Published: May 2020

AbstractWe study the nonlinear magneto-optical rotation (MOR) of a linearly polarized microwave probe field passing through many nitrogen-vacancy (NV) centers embedded in a high-Q single-crystal diamond mechanical resonator. On the basis of the strain-mediated coupling mechanism, we establish a three-level closed-loop system in the ground states of the NV center in the presence of a static magnetic field. It is shown that by applying an acoustic field, the birefringence is induced in the system through the cross-Kerr effect, so that the probe field is transmitted with a high intensity and rotated polarization plane by 90 degrees. In addition, we demonstrate that the acoustic field has a major role in enhancing the MOR angle to 90 degrees. Moreover, it is shown that the MOR angle of the polarization plane after passing through the presented system is sensitive to the relative phase of the applied fields. The physical mechanism of the MOR enhancement is explained using the analytical expressions which are in good agreement with the numerical results. The presented scheme can be used as a polarization converter for efficient switching TE/TM modes in optical communication, the depolarization backscattering lidar, polarization spectroscopy and precision measurements.
Cancer genomics predicts disease relapse and therapeutic response to neoadjuvant chemotherapy of hormone sensitive breast cancers
Authors: Zhu Jieqiang , Muskhelishvili Levan , Tong Weida , Borlak Jürgen , Chen Minjun 
Published: May 2020

AbstractSeveral studies provide insight into the landscape of breast cancer genomics with the genomic characterization of tumors offering exceptional opportunities in defining therapies tailored to the patient’s specific need. However, translating genomic data into personalized treatment regimens has been hampered partly due to uncertainties in deviating from guideline based clinical protocols. Here we report a genomic approach to predict favorable outcome to treatment responses thus enabling personalized medicine in the selection of specific treatment regimens. The genomic data were divided into a training set of N = 835 cases and a validation set consisting of 1315 hormone sensitive, 634 triple negative breast cancer (TNBC) and 1365 breast cancer patients with information on neoadjuvant chemotherapy responses. Patients were selected by the following criteria: estrogen receptor (ER) status, lymph node invasion, recurrence free survival. The k-means classification algorithm delineated clusters with low- and high- expression of genes related to recurrence of disease; a multivariate Cox’s proportional hazard model defined recurrence risk for disease. Classifier genes were validated by Immunohistochemistry (IHC) using tissue microarray sections containing both normal and cancerous tissues and by evaluating findings deposited in the human protein atlas repository. Based on the leave-on-out cross validation procedure of 4 independent data sets we identified 51-genes associated with disease relapse and selected 10, i.e. TOP2A, AURKA, CKS2, CCNB2, CDK1 SLC19A1, E2F8, E2F1, PRC1, KIF11 for in depth validation. Expression of the mechanistically linked disease regulated genes significantly correlated with recurrence free survival among ER-positive and triple negative breast cancer patients and was independent of age, tumor size, histological grade and node status. Importantly, the classifier genes predicted pathological complete responses to neoadjuvant chemotherapy (P < 0.001) with high expression of these genes being associated with an improved therapeutic response toward two different anthracycline-taxane regimens; thus, highlighting the prospective for precision medicine. Our study demonstrates the potential of classifier genes to predict risk for disease relapse and treatment response to chemotherapies. The classifier genes enable rational selection of patients who benefit best from a given chemotherapy thus providing the best possible care. The findings encourage independent clinical validation.
Genome-wide identification, transcriptome analysis and alternative splicing events of Hsf family genes in maize
Authors: Zhang Huaning , Li Guoliang , Fu Cai , Duan Shuonan , Hu Dong , Guo Xiulin 
Published: May 2020

AbstractHeat shock transcription factor (Hsf) plays a transcriptional regulatory role in plants during heat stress and other abiotic stresses. 31 non-redundant ZmHsf genes from maize were identified and clustered in the reference genome sequenced by Single Molecule Real Time (SMRT). The amino acid length, chromosome location, and presence of functional domains and motifs of all ZmHsfs sequences were analyzed and determined. Phylogenetics and collinearity analyses reveal gene duplication events in Hsf family and collinearity blocks shared by maize, rice and sorghum. The results of RNA-Seq analysis of anthesis and post-anthesis periods in maize show different expression patterns of ZmHsf family members. Specially, ZmHsf26 of A2 subclass and ZmHsf23 of A6 subclass were distinctly up-regulated after heat shock (HS) at post-anthesis stage. Nanopore transcriptome sequencing of maize seedlings showed that alternative splicing (AS) events occur in ZmHsf04 and ZmHsf17 which belong to subclass A2 after heat shock. Through sequence alignment, semi-quantitative and quantitative RT-PCR, we found that intron retention events occur in response to heat shock, and newly splice isoforms, ZmHsf04-II and ZmHsf17-II, were transcribed. Both new isoforms contain several premature termination codons in their introns which may lead to early termination of translation. The ZmHsf04 expression was highly increased than that of ZmHsf17, and the up-regulation of ZmHsf04-I transcription level were significantly higher than that of ZmHsf04-II after HS.
Substrate influences human removal of freshwater turtle nests in the eastern Brazilian Amazon
Authors: Michalski Fernanda , Norris Darren , Quintana Itxaso , Valerio Andressa , Gibbs James P. 
Published: May 2020

AbstractSubstrate type determines nesting success and fitness in turtles and is a critical consideration for nesting area protection and restoration. Here, we evaluated the effect of substrate on nest removal by humans in the eastern Brazilian Amazon. We analyzed substrate composition and fate of 216 P. unifilis nests along 88 km of rivers. River segment and substrate type were the most important predictors of nest removal by humans. We found up to 36% lower removal of nests in fine sand and experimental results support the hypothesis that wind more often obscures tracks of nesting females in substrates with more (>66%) fine sand. Our findings are useful for informing the restoration of artificial nesting areas across the Amazon, as nesting area substrates should be selected not only to maintain hatchling sex ratios, but also to minimize nest removal by humans.
Triterpenoid acids isolated from Schinus terebinthifolia fruits reduce Staphylococcus aureus virulence and abate dermonecrosis
Authors: Tang Huaqiao , Porras Gina , Brown Morgan M. , Chassagne Francois , Lyles James T. , Bacsa John , Horswill Alexander R. , Quave Cassandra L. 
Published: May 2020

AbstractStaphylococcus aureus relies on quorum sensing to exert virulence to establish and maintain infection. Prior research demonstrated the potent quorum sensing inhibition effects of “430D-F5”, a refined extract derived from the fruits of Schinus terebinthifolia, a medicinal plant used for the traditional treatment of skin and soft tissue infections. We report the isolation and identification of three compounds from 430D-F5 that reduce virulence and abate dermonecrosis: 3-oxo-olean-12-en-28-oic acid (1), 3-oxotirucalla-7,24Z-dien-26-oic acid (2) and 3α-hydroxytirucalla-7,24 Z-dien-27-oic acid (3). Each compound inhibits all S. aureus accessory gene regulator (agr) alleles (IC50 2–70 μM). Dose-dependent responses were also observed in agr-regulated reporters for leucocidin A (lukA, IC50 0.4-25 μM) and glycerol ester hydrolase or lipase (gehB, IC50 1.5–25 μM). Surprisingly, dose-dependent activity against the nuclease reporter (nuc), which is under the control of the sae two-component system, was also observed (IC50 0.4–12.5 μM). Compounds 1-3 exhibited little to no effect on the agr-independent mgrA P2 reporter (a constitutive promoter from the mgrA two-component system) and the esxA reporter (under control of mgrA). Compounds 1-3 inhibited δ-toxin production in vitro and reduced dermonecrosis in a murine in vivo model. This is the first report of triterpenoid acids with potent anti-virulence effects against S. aureus.
Mineral reaction kinetics constrain the length scale of rock matrix diffusion
Authors: Wogelius R. A. , Milodowski A. E. , Field L. P. , Metcalfe R. , Lowe T. , van Veelen A. , Carpenter G. , Norris S. , Yardley B. 
Published: May 2020

AbstractMass transport by aqueous fluids is a dynamic process in shallow crustal systems, redistributing nutrients as well as contaminants. Rock matrix diffusion into fractures (void space) within crystalline rock has been postulated to play an important role in the transient storage of solutes. The reacted volume of host rock involved, however, will be controlled by fluid-rock reactions. Here we present the results of a study which focusses on defining the length scale over which rock matrix diffusion operates within crystalline rock over timescales that are relevant to safety assessment of radioactive and other long-lived wastes. Through detailed chemical and structural analysis of natural specimens sampled at depth from an active system (Toki Granite, Japan), we show that, contrary to commonly proposed models, the length scale of rock matrix diffusion may be extremely small, on the order of centimetres, even over timescales of millions of years. This implies that in many cases the importance of rock matrix diffusion will be minimal. Additional analyses of a contrasting crystalline rock system (Carnmenellis Granite, UK) corroborate these results.
DNA-based identification of predators of the corallivorous Crown-of-Thorns Starfish (Acanthaster cf. solaris) from fish faeces and gut contents
Authors: Kroon Frederieke J. , Lefèvre Carine D. , Doyle Jason R. , Patel Frances , Milton Grant , Severati Andrea , Kenway Matt , Johansson Charlotte L. , Schnebert Simon , Thomas-Hall Peter , Bonin Mary C. , Cameron Darren S. , Westcott David A. 
Published: May 2020

AbstractThe corallivorous Crown-of-Thorns Starfish (CoTS, Acanthaster spp.) has been linked with the widespread loss of scleractinian coral cover on Indo-Pacific reefs during periodic population outbreaks. Here, we re-examine CoTS consumption by coral reef fish species by using new DNA technologies to detect Pacific Crown-of-Thorns Starfish (Acanthaster cf. solaris) in fish faecal and gut content samples. CoTS DNA was detected in samples from 18 different coral reef fish species collected on reefs at various stages of CoTS outbreaks in the Great Barrier Reef Marine Park, nine of which had not been previously reported to feed on CoTS. A comprehensive set of negative and positive control samples confirmed that our collection, processing and analysis procedures were robust, although food web transfer of CoTS DNA cannot be ruled out for some fish species. Our results, combined with the (i) presence of CoTS spines in some samples, (ii) reported predation on CoTS gametes, larvae and settled individuals, and (iii) known diet information for fish species examined, strongly indicate that direct fish predation on CoTS may well be more common than is currently appreciated. We provide recommendations for specific management approaches to enhance predation on CoTS by coral reef fishes, and to support the mitigation of CoTS outbreaks and reverse declines in hard coral cover.
New chlamydosporol derivatives from the endophytic fungus Pleosporales sp. Sigrf05 and their cytotoxic and antimicrobial activities
Authors: Lai Daowan , Mao Ziling , Zhou Zhiyao , Zhao Siji , Xue Mengyao , Dai Jungui , Zhou Ligang , Li Dianpeng 
Published: May 2020

AbstractFive new chlamydosporol derivatives, named pleospyrones A-E (1–5), together with one known congener (6), were isolated from the culture of the endophytic fungus Pleosporales sp. Sigrf05, obtained from the medicinal plant Siraitia grosvenorii. The structures of the new compounds were elucidated mainly by analysis of the HRESIMS, and (1D, 2D) NMR data, while ECD and optical rotation calculations were used to assign the absolute configurations. The plausible biosynthetic pathway of these compounds were proposed. The isolated compounds were evaluated for their cytotoxicity, antifungal and antibacterial activities. Compounds 1, and 4–6 were cytotoxic against the tested cancer cells with IC50 values of 1.26~47.5 μM. Compounds 1–3 showed moderate antifungal activities against Magnaporthe oryzae, while compound 5 displayed weak antibacterial activity.
Drug repurposing of pyrimidine analogs as potent antiviral compounds against human enterovirus A71 infection with potential clinical applications
Authors: Sun Jialei , Yogarajah Thinesshwary , Lee Regina Ching Hua , Kaur Parveen , Inoue Masafumi , Tan Yong Wah , Chu Justin Jang Hann 
Published: May 2020

AbstractEnterovirus A71 (EV-A71) is one of the aetiological agents for the hand, foot and mouth disease (HFMD) in young children and a potential cause of neurological complications in afflicted patients. Since its discovery in 1969, there remains no approved antiviral for EV-A71 and other HFMD-causing enteroviruses. We set out to address the lack of therapeutics against EV-A71 by screening an FDA-approved drug library and found an enrichment of hits including pyrimidine antimetabolite, gemcitabine which showed 90.2% of inhibition on EV-A71 infection. Gemcitabine and other nucleoside analogs, LY2334737 and sofosbuvir inhibition of EV-A71 infection were disclosed using molecular and proteomic quantification, and in vitro and in vivo efficacy evaluation. Gemcitabine displayed a significant reduction of infectious EV-A71 titres by 2.5 logs PFU/mL and was shown to target the early stage of EV-A71 viral RNA and viral protein synthesis process especially via inhibition of the RNA dependent RNA polymerase. In addition, the drug combination study of gemcitabine’s synergistic effects with interferon-β at 1:1 and 1:2 ratio enhanced inhibition against EV-A71 replication. Since gemcitabine is known to metabolize rapidly in vivo, other nucleoside analogs, LY2334737 and sofosbuvir conferred protection in mice against lethal EV-A71 challenge by potentially reducing the death rate, viral titers as well on virus-induced pathology in the limb muscle tissue of mice. Additionally, we found that gemcitabine is competent to inhibit other positive-sense RNA viruses of the Flaviviridae and Togaviridae family. Overall, these drugs provide new insights into targeting viral factors as a broad-spectrum antiviral strategy with potential therapeutic value for future development and are worthy of potential clinical application.
Evidence of language-related left hypofrontality in Major Depression: An EEG Beta band study
Authors: Spironelli Chiara , Maffei Antonio , Romeo Zaira , Piazzon Giulia , Padovan Giordano , Magnolfi Gianna , Pasini Ilenia , Gomez Homen Francesca , Concari Graziano , Angrilli Alessandro 
Published: May 2020

AbstractMajor depression (MDD) has been associated with an altered EEG frontal asymmetry measured in resting state; nevertheless, this association has showed a weak consistency across studies. In the present study, which starts from an evolutionistic view of psychiatric disorders, we investigated frontal asymmetry in MDD, using language as a probe to test the integrity of large inter- and intra-hemispheric networks and processes. Thirty MDD patients (22 women) and 32 matched controls (HC) were recruited for an EEG recording in resting state and during two linguistic tasks, phonological and semantic. Normalized alpha and beta EEG spectral bands were measured across all three conditions in the two groups. EEG alpha amplitude showed no hemispheric asymmetry, regardless of group, both at rest and during linguistic tasks. During resting state, analysis of EEG beta revealed a lack of hemispheric asymmetry in both groups, but during linguistic tasks, HC exhibited the typical greater left frontal beta activation, whereas MDD patients showed a lack of frontal asymmetry and a significantly lower activation of left frontal sites. In depressed patients, positive affect was negatively correlated with depression levels and positively correlated with left frontal EEG beta amplitude. Language represents the human process that requires the largest level of integration between and within the hemispheres; thus, language asymmetry was a valid probe to test the left frontal alteration encompassing highly impairing psychiatric disorders, such as schizophrenia and MDD. Indeed, these severe diseases are marked by delusions, ruminations, thought disorders, and hallucinations, all of which have a clear linguistic or metalinguistic basis.