bluuebunny/crossref_metadata_2025_split huggingface dataset:
ΔFlucs: Brighter Photinus pyralis firefly luciferases identified by surveying consecutive single amino acid deletion mutations in a thermostable variant
Authors: Halliwell Lisa M. , Jathoul Amit P. , Bate Jack P. , Worthy Harley L. , Anderson James C. , Jones D. Dafydd , Murray James A.H. 
Published: September 2017

AbstractThe bright bioluminescence catalyzed by Photinus pyralis firefly luciferase (Fluc) enables a vast array of life science research such as bio imaging in live animals and sensitive in vitro diagnostics. The effectiveness of such applications is improved using engineered enzymes that to date have been constructed using amino acid substitutions. We describe ΔFlucs: consecutive single amino acid deletion mutants within six loop structures of the bright and thermostable ×11 Fluc. Deletion mutations are a promising avenue to explore new sequence and functional space and isolate novel mutant phenotypes. However, this method is often overlooked and to date there have been no surveys of the effects of consecutive single amino acid deletions in Fluc. We constructed a large semi‐rational ΔFluc library and isolated significantly brighter enzymes after finding ×11 Fluc activity was largely tolerant to deletions. Targeting an “omega‐loop” motif (T352‐G360) significantly enhanced activity, altered kinetics, reduced Km for D‐luciferin, altered emission colors, and altered substrate specificity for redshifted analog DL‐infraluciferin. Experimental and in silico analyses suggested remodeling of the Ω‐loop impacts on active site hydrophobicity to increase light yields. This work demonstrates the further potential of deletion mutations, which can generate useful Fluc mutants and broaden the palette of the biomedical and biotechnological bioluminescence enzyme toolbox.
Helical Threads: Enantiomerically Pure Carbo[6]Helicene Oligomers
Authors: Schaack Cédric , Sidler Eric , Trapp Nils , Diederich François 
Published: September 2017

AbstractWe report the synthesis of enantiomerically pure carbo[6]helicene oligomers with buta‐1,3‐diyne‐1,4‐diyl bridges between the helicene nuclei. The synthesis of monomeric (±)‐2,15‐bis[(triisopropylsilyl)ethynyl]carbo[6]helicene was achieved in 25 % yield over six steps. Pure (+)‐(P)‐ and (−)‐(M)‐enantiomers were obtained by HPLC on a chiral stationary phase. The dimeric (+)‐(P)2‐ and (−)‐(M)2‐configured and the tetrameric (+)‐(P)4‐ and (−)‐(M)4‐configured oligomers were obtained by sequential oxidative acetylenic coupling. The ECD spectra of the tetrameric oligomers displayed large Cotton effect intensities of Δϵ=−851 m−1 cm−1 at λ=370 nm ((M)4‐enantiomer). We transformed the buta‐1,3‐diyne‐1,4‐diyl bridge in the dimeric (P)2 and (M)2 oligomer by heteroaromatization into a thiene‐2,5‐diyl linker. Although the resulting chromophore showed reduced ECD intensities, it exhibited a remarkably strong fluorescence emission at 450–500 nm, with an absolute quantum yield of 25 %.
Organoruthenium Complexes with C^N Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action
Authors: Novohradsky Vojtech , Yellol Jyoti , Stuchlikova Olga , Santana María Dolores , Kostrhunova Hana , Yellol Gorakh , Kasparkova Jana , Bautista Delia , Ruiz José , Brabec Viktor 
Published: September 2017

AbstractOur study demonstrates that four novel kinetically inert C,N‐cyclometalated RuII complexes of the type [Ru(C^N)(N^N)2][PF6] containing a handle for functionalization on the C^N ligand are very potent cytotoxic agents against several different human cancer cell lines and are up to 400‐fold more potent than clinically used cisplatin. In addition, the investigated ruthenium complexes are less cytotoxic in noncancerous cells, and exhibit higher selectivity for cancer cells than conventional platinum anticancer drugs. The high potency of the investigated ruthenium compounds can be attributed to several factors, including enhanced internalization and their capability to change mitochondrial transmembrane potential in cells. The new ruthenium complexes also interfere with protein synthesis with a markedly higher potency than conventional inhibitors of DNA translation. Notably, the latter mechanism has not been hitherto described for other cytotoxic Ru compounds and cisplatin.
Isoform specificity of progesterone receptor antibodies
Authors: Fabris Victoria , Abascal María F , Giulianelli Sebastián , May María , Sequeira Gonzalo R , Jacobsen Britta , Lombès Marc , Han Julie , Tran Luan , Molinolo Alfredo , Lanari Claudia 
Published: September 2017

AbstractProgesterone receptors (PR) are prognostic and predictive biomarkers in hormone‐dependent cancers. Two main PR isoforms have been described, PRB and PRA, that differ only in that PRB has 164 extra N‐terminal amino acids. It has been reported that several antibodies empirically exclusively recognize PRA in formalin‐fixed paraffin‐embedded (FFPE) tissues. To confirm these findings, we used human breast cancer xenograft models, T47D‐YA and ‐YB cells expressing PRA or PRB, respectively, MDA‐MB‐231 cells modified to synthesize PRB, and MDA‐MB‐231/iPRAB cells which can bi‐inducibly express either PRA or PRB. Cells were injected into immunocompromised mice to generate tumours exclusively expressing PRA or PRB. PR isoform expression was verified using immunoblots. FFPE samples from the same tumours were studied by immunohistochemistry using H‐190, clone 636, clone 16, and Ab‐6 anti‐PR antibodies, the latter exclusively recognizing PRB. Except for Ab‐6, all antibodies displayed a similar staining pattern. Our results indicate that clones 16, 636, and the H‐190 antibody recognize both PR isoforms. They point to the need for more stringency in evaluating the true specificity of purported PRA‐specific antibodies as the PRA/PRB ratio may have prognostic and predictive value in breast cancer.
Inverted formins: A subfamily of atypical formins
Authors: Hegsted Anna , Yingling Curtis V. , Pruyne David 
Published: September 2017

AbstractFormins are a family of regulators of actin and microtubule dynamics that are present in almost all eukaryotes. These proteins are involved in many cellular processes, including cytokinesis, stress fiber formation, and cell polarization. Here we review one subfamily of formins, the inverted formins. Inverted formins as a group break several formin stereotypes, having atypical biochemical properties and domain organization, and they have been linked to kidney disease and neuropathy in humans. In this review, we will explore recent research on members of the inverted formin sub‐family in mammals, zebrafish, fruit flies, and worms.
The morphological characterization of orientation‐biased displaced large‐field ganglion cells in the central part of goldfish retina
Authors: Hoshi Hideo , Sato Fumi 
Published: September 2017

AbstractThe vertebrate retina has about 30 subtypes of ganglion cells. Each ganglion cell receives synaptic inputs from specific types of bipolar and amacrine cells ramifying at the same depth of the inner plexiform layer (IPL), each of which is thought to process a specific aspect of visual information. Here, we identified one type of displaced ganglion cell in the goldfish retina which had a large and elongated dendritic field. As a population, all of these ganglion cells were oriented in the horizontal axis and perpendicular to the dorsal–ventral axis of the goldfish eye in the central part of retina. This ganglion cell has previously been classified as Type 1.2. However, the circuit elements which synapse with this ganglion cell are not yet characterized. We found that this displaced ganglion cell was directly tracer‐coupled only with homologous ganglion cells at sites containing Cx35/36 puncta. We further illustrated that the processes of dopaminergic neurons often terminated next to intersections between processes of ganglion cells, close to where dopamine D1 receptors were localized. Finally, we showed that Mb1 ON bipolar cells had ribbon synapses in the axonal processes passing through the IPL and made ectopic synapses with this displaced ganglion cell that stratified into stratum 1 of the IPL. These results suggest that the displaced ganglion cell may synapse with both Mb1 cells using ectopic ribbon synapses and OFF cone bipolar cells with regular ribbon synapses in the IPL to function in both scotopic and photopic light conditions.
A comparative study of the class imbalance problem in Twitter spam detection
Authors: Li Chaoliang , Liu Shigang 
Published: September 2017

SummaryRecently, online social network (OSN) such as Twitter has become an important and popular source for real‐time information and news dissemination, and Twitter is inevitably a prime target of spammers. It has been showed that the security threats caused by Twitter spam can reach far beyond the social media platform itself. To mitigate the damage caused by Twitter spam, machine learning classification algorithms have been employed by researchers and communities to detect the Twitter spam. However, most of these studies have overlooked the class imbalance problem in Twitter spam detection. In this paper, we have studied the class imbalance problem in Twitter spam detection. Firstly, we have conducted a comparative study regarding some popular methods in handling the class imbalance problem in order to identify the most effective approach for addressing the class imbalance problem. Then, we have conducted another comparative study from Twitter spam detection based on several classic techniques. Experimental results demonstrate that a fuzy‐based ensemble learning can significantly improve the classification performance on imbalance ground truth Twitter data.
Vibration Ball Milling for the Synthesis of 5′‐Thioadenosine 5′‐Pyrophosphate (P′→5′) Adenosine (dASppA)
Authors: Eguaogie Olga , Vyle Joseph S. 
Published: September 2017

AbstractUsing vibration ball milling, 5′‐chloro‐5′‐deoxyadenosine (CldA) reacts cleanly with 4‐methoxybenzyl mercaptan (MobSH), under basic conditions, to the corresponding thioether (MobSdA), which is isolated following precipitation and trituration. Under acidic conditions, in a one‐pot, two‐step process, MobSdA is transformed into 5′‐deoxy‐5′‐(5‐nitropyridyl‐2‐disulfanyl)‐adenosine (NPySSdA). Michaelis‐Arbuzov (M‐A) reaction of NPySSdA with tris(trimethylsilyl) phosphite proceeds to completion within 30 min as determined by 31P NMR, and the persilylated M‐A product thus formed can be stored in solution under anhydrous conditions at room temperature for several days (in contrast, the anionic phosphorothiolate monoester is labile to hydrolysis). Following evaporation, mechanochemical mixing of the crude M‐A product with the nucleotide donor adenosine 5′‐monophosphomorpholidate under acidic activation in the presence of additional water gives rapid hydrolytic desilylation and phosphate coupling, so that essentially complete reaction is observed after 90 min and dASppA isolated following C‐18 reversed phase HPLC and desalting (>99% pure as determined by monitoring at 260 nm). © 2017 by John Wiley & Sons, Inc.
Solid‐Phase Synthesis of RNA Analogs Containing Phosphorodithioate Linkages
Authors: Yang Xianbin 
Published: September 2017

AbstractThe oligoribonucleotide phosphorodithioate (PS2‐RNA) modification uses two sulfur atoms to replace two non‐bridging oxygen atoms at an internucleotide phosphorodiester backbone linkage. Like a natural phosphodiester RNA backbone linkage, a PS2‐modified backbone linkage is achiral at phosphorus. PS2‐RNAs are highly stable to nucleases and several in vitro assays have demonstrated their biological activity. For example, PS2‐RNAs silenced mRNA in vitro and bound to protein targets in the form of PS2‐aptamers (thioaptamers). Thus, the interest in and promise of PS2‐RNAs has drawn attention to synthesizing, isolating, and characterizing these compounds. RNA‐thiophosphoramidite monomers are commercially available from AM Biotechnologies and this unit describes an effective methodology for solid‐phase synthesis, deprotection, and purification of RNAs having PS2 internucleotide linkages. © 2017 by John Wiley & Sons, Inc.
Is 2‐Hydroxypropyl‐β‐cyclodextrin a Suitable Carrier for Central Administration of Δ9‐Tetrahydrocannabinol? Preclinical Evidence
Authors: Agabio R. , Sanna F. , Lobina C. , Monduzzi M. , Nairi V. , Cugia F. , Mameli S. , Pisanu G. M. , Gessa G. L. , Melis M. R. 
Published: September 2017

ABSTRACT

Preclinical Research

Δ9‐Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinociceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of a suitable solvent precludes its IT administration in humans. 2‐Hydroxypropyl‐β‐cyclodextrin (HPβCD) increases the water solubility of hydrophobic drugs and is approved for IT administration in humans. To investigate whether HPβCD might be a suitable carrier for ICV administration of THC in rats, two formulations containing THC complexed with HPβCD (30 and 135 μg of THC per animal) and vehicle were administered to Wistar rats. The antinociceptive effect (using the tail flick test), locomotor activity, and body temperature were evaluated. ICV injection of 135 μg of THC/HPβCD complex increased tail flick latency, reduced locomotor activity, and had a dual effect on body temperature. The 30 μg THC/HPβCD formulation only produced a hyperthermic effect. All animals appeared healthy, with no difference between the groups. These results were similar to those obtained in other preclinical studies in which THC was administered centrally using solvents that are unsuitable for IT administration in humans because of their toxicity. Our findings suggest that HPβCD may be a useful carrier for IT administration of THC in humans. Drug Dev Res 78 : 411‐419, 2017. © 2017 Wiley Periodicals, Inc.
In vitroandin vivodegradation of microfiber bioresorbable coronary scaffold
Authors: Huang Chi‐Hung , Lee Sheng‐Yang , Horng Sonida , Guy Louis‐Georges , Yu Ting‐Bin 
Published: September 2017

AbstractThe degradation of Mirage Bioresorbable Microfiber Scaffold was evaluatedin vitroandin vivo. The degradation in polymer molecular weight (MW), strut morphology, and integrity was accessed using gel permeation chromatography (GPC), X‐ray micro‐computed tomography (micro‐CT) evaluation. To simulate the physiological degradationin vitro, scaffolds were deployed in silicone mock vessels connected to a peristaltic pumping system, which pumps 37°C phosphate‐buffered saline (PBS, pH 7.4) at a constant rate. At various time points (30D, 60D, 90D, 180D, 270D,and360D), the MW of microfibers decreased to 57.3, 49.8, 36.9, 13.9, 6.4, and 5.1% against the baseline. Thein vivodegradation study was performed by implanting scaffolds in internal thoracic arteries (ITAs) of mini‐swine. At the scheduled sacrifice time points (30D, 90D, 180D, 270D, 360D, and 540D), the implanted ITAs were excised for GPC analysis; the MW of the implanted scaffolds dropped to 58.5, 34.7, 24.8, 16.1, 12.9, and 7.1, respectively. Mass loss of scaffolds reached 72.4% at 540D of implantation. Two stages of hydrolysis were observed inin vitroand invivodegradation kinetics, and the statistical analysis suggested a positive correlation betweenin vivoandin vitrodegradation. After 6 months of incubation in animals, significant strut degradation was seen in the micro‐CT evaluation in all sections as strut fragments and separations. The micro‐CT results further confirmed that every sample at 720D had X‐ray transmission similar to surrounding tissue, thereby indicating full degradation within 2 years. © 2017 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1842–1850, 2018.
Thiopurine metabolite level and toxicity in Indians with inflammatory bowel disease
Authors: Parkar Suruchi P , Dherai Alpa J , Desai Devendra C , Ashavaid Tester F 
Published: September 2017

Background and AimA lower dose requirement and higher toxicity of thiopurine is reported in Asian patients with inflammatory bowel disease (IBD) as compared with Caucasian patients. These reports are based on thiopurine methyltransferase measurement studies rather than metabolite estimation.We studied the utility of thiopurine metabolite estimation in Indian patients with IBD and compared dose and toxicity with Asian and Caucasian patients.MethodsIn this prospective study, 6‐thioguanine nucleotide (6‐TGN) and 6‐methylmercaptopurine levels were determined by HPLC in 76 IBD patients treated with thiopurines. The levels were correlated with dose, disease activity, and toxicity. The dose‐related metabolite levels and toxicity were compared with Caucasian and Asian patients reported in literature.ResultsOf the 76 patients (32 women, mean age: 35.9 [SD: 14.54] years, 36 Crohn's disease and 40 ulcerative colitis), 1 non‐compliant patient had undetectable level of metabolites. Of the 75 patients, 21(28%) had therapeutic level of 6‐TGN, 37(49%) had subtherapeutic level and 17(23%) had supratherapeutic level. The 6‐methylmercaptopurine levels ranged up to 4971 pmol/8 × 108 red blood cells. Six (8%) patients showed toxicity. Thiopurine dose was optimized in 20 (26.31%) patients. Dose‐based metabolite levels were comparable to Asian and Caucasian patients. The toxicity (8%) observed in our patients was less than that reported (12–39%).ConclusionHalf of the patients in this study had low and a quarter had high 6‐TGN levels. One‐fourth of the patients needed dose modification. The dose‐based metabolite levels were comparable and the toxicity was less than that reported in Asian and Caucasian patients.
Ultrastructure of spermatozoa of spider crabs, family Mithracidae (Crustacea, Decapoda, Brachyura): Integrative analyses based on morphological and molecular data
Authors: Assugeni Camila de O. , Magalhães Tatiana , Bolaños Juan A. , Tudge Christopher C. , Mantelatto Fernando L. , Zara Fernando J. 
Published: September 2017

AbstractRecent studies based on morphological and molecular data provide a new perspective concerning taxonomic aspects of the brachyuran family Mithracidae. These studies proposed a series of nominal changes and indicated that the family is actually represented by a different number and representatives of genera than previously thought. Here, we provide a comparative description of the ultrastructure of spermatozoa and spermatophores of some species of Mithracidae in a phylogenetic context. The ultrastructure of the spermatozoa and spermatophore was observed by scanning and transmission electron microscopy. The most informative morphological characters analysed were thickness of the operculum, shape of the perforatorial chamber and shape and thickness of the inner acrosomal zone. As a framework, we used a topology based on a phylogenetic analysis using mitochondrial data obtained here and from previous studies. Our results indicate that closely related species share a series of morphological characteristics of the spermatozoa. A thick operculum, for example, is a feature observed in species of the generaAmphithrax,Teleophrys, andOmalacanthain contrast to the slender operculum observed inMithraculusandMithrax.AmphithraxandTeleophryshave a rhomboid perforatorial chamber, whileMithraculus,Mithrax, andOmalacanthashow a wider, deltoid morphology. Furthermore, our results are in agreement with recently proposed taxonomic changes including the separation of the generaMithrax(previouslyDamithrax),Amphithrax(previouslyMithrax) andMithraculus, and the synonymy ofMithrax caribbaeuswithMithrax hispidus. Overall, the spermiotaxonomy of these species of Mithracidae represent a novel set of data that corroborates the most recent taxonomic revision of the family and can be used in future taxonomic and phylogenetic studies within this family.
Emotional intelligence and individual differences in affective processes underlying task‐contingent conscientiousness
Authors: Minbashian Amirali , Beckmann Nadin , Wood Robert E. 
Published: September 2017

SummaryOrganisational researchers have recently begun to focus on the more dynamic aspects of personality in the workplace. The present study examines individual differences in the affective processes that underlie one such dynamic construct, task‐contingent conscientiousness. Using experience sampling data collected over 3 weeks from 201 managers, we show (a) that individuals differ substantially from each other in the paths that connect task demand, positive and negative affect, and conscientious behaviour; (b) that these individual differences cohere to define person types or classes that represent meaningful differences in the extent to which task‐contingent conscientiousness is mediated affectively; and (c) that emotional intelligence increases the likelihood of membership in classes that are characterised by affectively mediated effects. Theoretical implications of the findings are discussed with reference to the cognitive‐affective personality system model, research on the consequences of affect in the workplace, and the literature on emotional intelligence. Practical applications are suggested for managers who wish to use personality assessment for developmental purposes, especially in relation to facilitating behavioural change.
Big Five Personality and Creativity: The Moderating Effect of Motivational Goal Orientation
Authors: Kaspi‐Baruch Oshrit 
Published: September 2017

AbstractThis study examined the association between the big five personality dimensions and creativity through the moderation of motivational goal orientation. One hundred and ninety students engaged in full‐time employment completed questionnaires, which were used to assess the variables of interest. Regression moderation analyses supported some of the expected hypotheses. The associations between the big five dimensions and creativity were moderated by learning motivational goal orientation. Individuals high in extroversion, emotional stability, and low in conscientiousness, are most creative when they are oriented toward learning. In addition, openness fully predicted creativity, without the moderation of goal orientation. The results are discussed in terms of the interactional nature of personality and goal orientation theory.