bluuebunny/crossref_metadata_2025 huggingface dataset:
Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis
Authors: Shide Kotaro , Kameda Takuro , Kamiunten Ayako , Oji Asami , Ozono Yoshinori , Sekine Masaaki , Honda Arata , Kitanaka Akira , Akizuki Keiichi , Tahira Yuki , Nakamura Kenichi , Hidaka Tomonori , Kubuki Yoko , Abe Hiroo , Miike Tadashi , Iwakiri Hisayoshi , Tahara Yoshihiro , Sueta Mitsue , Hasuike Satoru , Yamamoto Shojiro , Nagata Kenji , Ikawa Masahito , Shimoda Kazuya
Published: March 2019

Calreticulin (CALR) exon 9 frameshift mutations, commonly detected in essential thrombocythemia (ET) and primary myelofibrosis patients, activate signal transducer and activator of transcription (STAT) proteins in the presence of Myeloproliferative Leukemia Virus (MPL) and induce ET in vivo. Loss of the KDEL motif, an endoplasmic reticulum retention signal, and generation of many positively charged amino acids (AAs) in the mutated C-terminus are thought to be important for disease induction. To test this hypothesis, we generated mice harboring a Calr frameshift mutation using the CRISPR/Cas9 system. Deletion of 19-base pairs in exon 9 (c.1099-1117del), designated the del19 mutation, induced loss of the KDEL motif and generated many positively charged AAs, similar to human mutants. Calr del19 mice exhibited mild thrombocytosis, slightly increased megakaryocytes, and mild splenomegaly. In vitro experiments revealed that the murine CALR del19 mutant had a weaker ability to combine with murine MPL than the human CALR del52 mutant. Consequently, STAT5 activation was also very weak downstream of the murine mutant and murine MPL, and may be the reason for the mild disease severity. In summary, loss of the KDEL motif and positively charged AAs in the C-terminus of CALR is insufficient for MPL binding and ET development.
Lysine methylation of transcription factors in cancer
Authors: Han Dong , Huang Mengxi , Wang Ting , Li Zhiping , Chen Yanyan , Liu Chao , Lei Zengjie , Chu Xiaoyuan
Published: March 2019

Protein lysine methylation is a critical and dynamic post-translational modification that can regulate protein stability and function. This post-translational modification is regulated by lysine methyltransferases and lysine demethylases. Recent studies using mass-spectrometric techniques have revealed that in addition to histones, a great number of transcription factors are also methylated, often at multiple sites and to different degrees (mono-, di-, trimethyl lysine). The biomedical significance of transcription factor methylation in human diseases, including cancer, has been explored recently. Some studies have demonstrated that interfering with transcription factor lysine methylation both in vitro and in vivo can inhibit cancer cell proliferation, thereby reversing tumor progression. The inhibitors targeting lysine methyltransferases and lysine demethylases have been under development for the past two decades, and may be used as potential anticancer agents in the clinic. In this review, we focus on the current findings of transcription factor lysine methylation, and the effects on both transcriptional activity and target gene expression. We outlined the biological significance of transcription factor lysine methylation on tumor progression and highlighted its clinical value in cancer therapy.
PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice
Authors: Weber Julia , de la Rosa Jorge , Grove Carolyn S. , Schick Markus , Rad Lena , Baranov Olga , Strong Alexander , Pfaus Anja , Friedrich Mathias J. , Engleitner Thomas , Lersch Robert , Öllinger Rupert , Grau Michael , Menendez Irene Gonzalez , Martella Manuela , Kohlhofer Ursula , Banerjee Ruby , Turchaninova Maria A. , Scherger Anna , Hoffman Gary J. , Hess Julia , Kuhn Laura B. , Ammon Tim , Kim Johnny , Schneider Günter , Unger Kristian , Zimber-Strobl Ursula , Heikenwälder Mathias , Schmidt-Supprian Marc , Yang Fengtang , Saur Dieter , Liu Pentao , Steiger Katja , Chudakov Dmitriy M. , Lenz Georg , Quintanilla-Martinez Leticia , Keller Ulrich , Vassiliou George S. , Cadiñanos Juan , Bradley Allan , Rad Roland
Published: March 2019

B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe PiggyBac transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based in vivo platform for BCL functional genomics, and validate discovered genes, such as Rfx7, a transcription factor, and Phip, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology.
Structure mapping of dengue and Zika viruses reveals functional long-range interactions
Authors: Huber Roland G. , Lim Xin Ni , Ng Wy Ching , Sim Adelene Y. L. , Poh Hui Xian , Shen Yang , Lim Su Ying , Sundstrom Karin B. , Sun Xuyang , Aw Jong Ghut , Too Horng Khit , Boey Peng Hee , Wilm Andreas , Chawla Tanu , Choy Milly M. , Jiang Lu , de Sessions Paola Florez , Loh Xian Jun , Alonso Sylvie , Hibberd Martin , Nagarajan Niranjan , Ooi Eng Eong , Bond Peter J. , Sessions October M. , Wan Yue
Published: March 2019

Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure and interaction mapping on four DENV and ZIKV strains inside virions and in infected cells. Comparative analysis of SHAPE reactivities across serotypes nominates potentially functional regions that are highly structured, conserved, and contain low synonymous mutation rates. Interaction mapping by SPLASH identifies many pair-wise interactions, 40% of which form alternative structures, suggesting extensive structural heterogeneity. Analysis of shared interactions between serotypes reveals a conserved macro-organization whereby interactions can be preserved at physical locations beyond sequence identities. We further observe that longer-range interactions are preferentially disrupted inside cells, and show the importance of new interactions in virus fitness. These findings deepen our understanding of Flavivirus genome organization and serve as a resource for designing therapeutics in targeting RNA viruses.
Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function
Authors: Calzada Elizabeth , Avery Erica , Sam Pingdewinde N. , Modak Arnab , Wang Chunyan , McCaffery J. Michael , Han Xianlin , Alder Nathan N. , Claypool Steven M.
Published: March 2019

Of the four separate PE biosynthetic pathways in eukaryotes, one occurs in the mitochondrial inner membrane (IM) and is executed by phosphatidylserine decarboxylase (Psd1). Deletion of Psd1 is lethal in mice and compromises mitochondrial function. We hypothesize that this reflects inefficient import of non-mitochondrial PE into the IM. Here, we test this by re-wiring PE metabolism in yeast by re-directing Psd1 to the outer mitochondrial membrane or the endomembrane system and show that PE can cross the IMS in both directions. Nonetheless, PE synthesis in the IM is critical for cytochrome bc1 complex (III) function and mutations predicted to disrupt a conserved PE-binding site in the complex III subunit, Qcr7, impair complex III activity similar to PSD1 deletion. Collectively, these data challenge the current dogma of PE trafficking and demonstrate that PE made in the IM by Psd1 support the intrinsic functionality of complex III.
Water-mediated deracemization of a bisporphyrin helicate assisted by diastereoselective encapsulation of chiral guests
Authors: Ousaka Naoki , Yamamoto Shinya , Iida Hiroki , Iwata Takuya , Ito Shingo , Hijikata Yuh , Irle Stephan , Yashima Eiji
Published: March 2019

Deracemization is a powerful method by which a racemic mixture can be transformed into an excess of one enantiomer with the aid of chiral auxiliaries, but has been applied only to small chiral molecular systems. Here we report a deracemization of a racemic double-stranded spiroborate helicate containing a bisporphyrin unit upon encapsulation of chiral aromatic guests between the bisporphyrin. The chiral guest-included helicate is kinetically stable, existing as a mixture of right- and left-handed double helices, which eventually undergo an inversion of the helicity triggered by water resulting from the water-mediated reversible diastereoselective B-O bond cleavage/reformation of the spiroborate groups, thus producing an optically-active helicate with a high enantioselectivity. Quantum chemical calculations suggest that the stereospecific CH-π interactions between the porphyrin hydrogen atoms of the helicate and an aromatic pendant group of the chiral guest play a key role in the enhancement of the helical handedness of the helicate.
Tunable microsecond dynamics of an allosteric switch regulate the activity of a AAA+ disaggregation machine
Authors: Mazal Hisham , Iljina Marija , Barak Yoav , Elad Nadav , Rosenzweig Rina , Goloubinoff Pierre , Riven Inbal , Haran Gilad
Published: March 2019

Large protein machines are tightly regulated through allosteric communication channels. Here we demonstrate the involvement of ultrafast conformational dynamics in allosteric regulation of ClpB, a hexameric AAA+ machine that rescues aggregated proteins. Each subunit of ClpB contains a unique coiled-coil structure, the middle domain (M domain), proposed as a control element that binds the co-chaperone DnaK. Using single-molecule FRET spectroscopy, we probe the M domain during the chaperone cycle and find it to jump on the microsecond time scale between two states, whose structures are determined. The M-domain jumps are much faster than the overall activity of ClpB, making it an effectively continuous, tunable switch. Indeed, a series of allosteric interactions are found to modulate the dynamics, including binding of nucleotides, DnaK and protein substrates. This mode of dynamic control enables fast cellular adaptation and may be a general mechanism for the regulation of cellular machineries.
Intrinsic functional architecture of the non-human primate spinal cord derived from fMRI and electrophysiology
Authors: Wu Tung-Lin , Yang Pai-Feng , Wang Feng , Shi Zhaoyue , Mishra Arabinda , Wu Ruiqi , Chen Li Min , Gore John C.
Published: March 2019

Resting-state functional MRI (rsfMRI) has recently revealed correlated signals in the spinal cord horns of monkeys and humans. However, the interpretation of these rsfMRI correlations as indicators of functional connectivity in the spinal cord remains unclear. Here, we recorded stimulus-evoked and spontaneous spiking activity and local field potentials (LFPs) from monkey spinal cord in order to validate fMRI measures. We found that both BOLD and electrophysiological signals elicited by tactile stimulation co-localized to the ipsilateral dorsal horn. Temporal profiles of stimulus-evoked BOLD signals covaried with LFP and multiunit spiking in a similar way to those observed in the brain. Functional connectivity of dorsal horns exhibited a U-shaped profile along the dorsal-intermediate-ventral axis. Overall, these results suggest that there is an intrinsic functional architecture within the gray matter of a single spinal segment, and that rsfMRI signals at high field directly reflect this underlying spontaneous neuronal activity.
Temperature-controlled repeatable scrambling and induced-sorting of building blocks between cubic assemblies
Authors: Zhan Yi-Yang , Kojima Tatsuo , Ishii Kentaro , Takahashi Satoshi , Haketa Yohei , Maeda Hiromitsu , Uchiyama Susumu , Hiraoka Shuichi
Published: March 2019

Separation of a homogeneous mixture of different components to reach an ordered out-of-equilibrium state in solution has attracted continuous attention. While this can be achieved using external chemical fuels or photo energy, an alternative energy source is heat. Here we realize a temperature-controlled cycle of transitions between ordered and disordered states based on a mixture of two kinds of building blocks that self-assemble into cubic structures (nanocubes). An almost statistical mixture of nanocubes (disordered state) is thermodynamically most stable at lower temperature (25 °C), while homoleptic assemblies composed of single components are preferentially produced at higher temperature (100 °C) followed by rapid cooling. The scrambling of the building blocks between the nanocubes takes place through the exchange of free building blocks dissociated from the nanocubes. Based on this mechanism, it is possible to accelerate, retard, and perfectly block the scrambling by the guest molecules encapsulated in the nanocubes.
Reduced expression of pyruvate kinase in kidney proximal tubule cells is a potential mechanism of pravastatin altered glucose metabolism
Authors: Lee Yong Pyo , Cho Yuri , Kim Eun Jee , Lee Hyojung , Choi Hoon Young , Wang Hye Jin , Kang Eun Seok , Kim Yu Seun , Kim Myoung Soo , Kim Beom Seok
Published: March 2019

Recent studies have reported that statins are associated with increased incidence of diabetes. Although several mechanisms have been proposed, the role of the kidney’s glucose metabolism upon statin treatment is still unclear. Thus, we investigated the role of pravastatin in gluconeogenesis and glycolysis. HK-2 and HepG2 cells were treated with pravastatin and cultured under either high- or normal-cholesterol conditions. In HK-2 cells treated with pravastatin under both high- and normal-cholesterol conditions, the protein expression of only pyruvate kinase isozymes L/R (PKLR) decreased in a dose-dependent manner, while the protein expression of other glucose metabolism related enzymes remained unchanged. Within the in vivo experiment, male C57BL/6 mice were fed either pravastatin-treated normal-fat diets for 2 or 4 weeks or pravastatin-treated high-fat diets for 16 weeks. Protein expression of PKLR in the kidneys from mice that consumed pravastatin-treated high-fat diets decreased significantly compared to the controls. Upon the treatments of pravastatin, only the PKLR expression decreased in lean mice. Furthermore, PKLR activity decreased significantly in the kidney after pravastatin treatments. However, there was no change in enzyme activity in the liver, suggesting that pravastatin decreased PKLR activity only in the kidney. This change may be associated with the hyperglycemic effect of statins.
The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors
Authors: Tormo Eduardo , Ballester Sandra , Adam-Artigues Anna , Burgués Octavio , Alonso Elisa , Bermejo Begoña , Menéndez Silvia , Zazo Sandra , Madoz-Gúrpide Juan , Rovira Ana , Albanell Joan , Rojo Federico , Lluch Ana , Eroles Pilar
Published: March 2019

The mechanisms of chemotherapy resistance in triple negative breast cancer remain unclear, and so, new molecules which might mediate this resistance could optimize treatment response. Here we analyzed the involvement of the miRNA-449 family in the response to doxorubicin. The cell viability, cell-cycle phases, and the expression of in silico target genes and proteins of sensitive/resistant triple negative breast cancer cell lines were evaluated in response to doxorubicin treatment and after gain/loss of miRNAs-449 function achieved by transient transfection. Triple negative breast cancer patients were selected for ex vivo experiments and to evaluate gene and miRNAs expression changes after treatment, as well as survival analysis by Kaplan-Meier. Doxorubicin treatment upregulated miRNAs-449 and DNA-damage responder factors E2F1 and E2F3 in triple negative breast cancer sensitive breast cancer cells, while expression remained unaltered in resistant ones. In vitro overexpression of miRNAs-449 sensitized cells to the treatment and significantly reduced the resistance to doxorubicin. These changes showed also a strong effect on cell cycle regulation. Finally, elevated levels of miRNA-449a associated significantly with better survival in chemotherapy-treated triple negative breast cancer patients. These results reveal for the first time the involvement of the miRNA-449 family in doxorubicin resistance and their predictive and prognostic value in triple negative breast cancer patients.
Radiation Tolerance of Nanopore Sequencing Technology for Life Detection on Mars and Europa
Authors: Sutton Mark A. , Burton Aaron S. , Zaikova Elena , Sutton Ryan E. , Brinckerhoff William B. , Bevilacqua Julie G. , Weng Margaret M. , Mumma Michael J. , Johnson Sarah Stewart
Published: March 2019

The search for life beyond Earth is a key motivator in space exploration. Informational polymers, like DNA and RNA, are key biosignatures for life as we know it. The MinION is a miniature DNA sequencer based on versatile nanopore technology that could be implemented on future planetary missions. A critical unanswered question is whether the MinION and its protein-based nanopores can withstand increased radiation exposure outside Earth’s shielding magnetic field. We evaluated the effects of ionizing radiation on the MinION platform – including flow cells, reagents, and hardware – and discovered limited performance loss when exposed to ionizing doses comparable to a mission to Mars. Targets with harsher radiation environments, like Europa, would require improved radiation resistance via additional shielding or design refinements.
Association of rs10830962 polymorphism with gestational diabetes mellitus risk in a Chinese population
Authors: Xie Kaipeng , Chen Ting , Zhang Yue , Wen Juan , Cui Xianwei , You Lianghui , Zhu Lijun , Xu Bo , Ji Chenbo , Guo Xirong
Published: March 2019

To date, only three polymorphisms (rs10830962, rs7754840 and rs1470579) are included in the genome-wide association study Catalog (www.ebi.ac.uk/gwas). However, the available evidence is limited in pregnant Chinese women. We aimed to explore the associations of three polymorphisms (rs10830962, rs7754840 and rs1470579) with GDM risk in a Chinese population. We conducted a case-control study (964 GDM cases and 1,021 controls) to evaluate the associations of these polymorphisms with GDM risk. A logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs). After adjustment for age, prepregnancy BMI, parity, abnormal pregnancy history and family history of diabetes, the minor allele of rs10830962 (C > G) demonstrated a significant association with an increased risk of GDM (OR = 1.16, 95% CI = 1.02–1.31, P = 0.029 in the additive model). However, no significant association was observed between the other two polymorphisms and GDM. Subsequent functional annotation shows that rs10830962 is located in the regulatory elements of pancreatic islets, alters the binding affinity of motifs and regulates SNORA8 expression. Our findings demonstrate that rs10830962 is associated with an increased risk of GDM in the Chinese population. Further functional characterization is warranted to uncover the mechanism of the genotype-phenotype association.
Nest usurpation: a specialised hunting strategy used to overcome dangerous spider prey
Authors: Michálek Ondřej , Lubin Yael , Pekár Stano
Published: March 2019

Hunting other predators is dangerous, as the tables can turn and the hunter may become the hunted. Specialized araneophagic (spider eating) predators have evolved intriguing hunting strategies that allow them to invade spiders’ webs by adopting a stealthy approach or using aggressive mimicry. Here, we present a newly discovered, specialized hunting strategy of the araneophagic spider Poecilochroa senilis (Araneae: Gnaphosidae), which forces its way into the silk retreat of the potential spider prey and immobilizes it by swathing gluey silk onto its forelegs and mouthparts. Poecilochroa senilis has been reported from the nests of a several, often large, spider species in the Negev desert (Israel), suggesting specialization on spiders as prey. Nevertheless, in laboratory experiments, we found that P. senilis has a wider trophic niche, and fed readily on several small insect species. The specialized nest-invading attack was used more frequently with large spiders, and even small juvenile P. senilis were able to attack and subdue larger spiders. Our observations show that specific hunting tactics, like nest usurpation, allow specialized predators to overcome defences of dangerous prey.
Multiple ionization state of Arq+ ions during collisions near the Bohr velocity
Authors: Zhou Xianming , Cheng Rui , Zhao Yongtao , Wang Yuyu , Lei Yu , Chen Yanhong , Ma Xinwen , Xiao Guoqing
Published: March 2019

In order to clarify the mechanism and the influence of the initial charge state and target atomic parameters for the formation of L-shell multiple ionization state of Arq+ ions produced by the collisions near the Bohr velocity, the k-shell x-ray emission of Ar is measured for 1.2 MeV Arq+(q=4, 6, 8, 9, 11, 12) ions impacting on V target and 3 MeV Ar11+ ions interacting with selected targets (Z2 = 23, 26, 27, 28, 29, 30). It is found that the measured Ar Kα and Kβ x-ray energies shift to the high energy side, and the relative intensity ratios of Kβ/Kα are enlarged than the atomic data, owing to the presence of out-shell multiple vacancies. The multiple ionization is almost independence of the projectile charge state, but is diminished with increasing target atomic number.
Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans
Authors: Chang Anne-Marie , Duffy Jeanne F. , Buxton Orfeu M. , Lane Jacqueline M. , Aeschbach Daniel , Anderson Clare , Bjonnes Andrew C. , Cain Sean W. , Cohen Daniel A. , Frayling Timothy M. , Gooley Joshua J. , Jones Samuel E. , Klerman Elizabeth B. , Lockley Steven W. , Munch Mirjam , Rajaratnam Shantha M. W. , Rueger Melanie , Rutter Martin K. , Santhi Nayantara , Scheuermaier Karine , Van Reen Eliza , Weedon Michael N. , Czeisler Charles A. , Scheer Frank A. J. L. , Saxena Richa
Published: March 2019

The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the ‘gold standard’ for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.
BRD7 deficiency leads to the development of obesity and hyperglycemia
Authors: Lee Junsik M. , Kim Yoo , Salazar Hernández Mario Andrés , Han Youngah , Liu Renyan , Park Sang Won
Published: March 2019

Obesity is a debilitating disease that has become a global epidemic. Although progress is being made, the underlying molecular mechanism by which obesity develops still remains elusive. Recently, we reported that the expression levels of bromodomain-containing protein 7 (BRD7) are significantly reduced in the liver of obese mice. However, it is not clear whether decreased levels of hepatic BRD7 are directly associated with the development of obesity and disturbance in glucose homeostasis. Here, using heterozygous BRD7 knockout and liver-specific BRD7 knockout mouse models, we report that reduced BRD7 levels lead to increased weight gain with little effect on glucose metabolism. On the other hand, upregulating BRD7 in the liver starting at an early age protects mice from gaining excessive weight and developing glucose intolerance and insulin resistance when challenged with a high-fat diet.
The putative C-type lectin Schlaff ensures epidermal barrier compactness in Drosophila
Authors: Zuber Renata , Shaik Khaleelulla Saheb , Meyer Frauke , Ho Hsin-Nin , Speidel Anna , Gehring Nicole , Bartoszewski Slawomir , Schwarz Heinz , Moussian Bernard
Published: March 2019

The stability of extracellular matrices is in general ensured by cross-linking of its components. Previously, we had shown that the integrity of the layered Drosophila cuticle relies on the presence of a covalent cuticular dityrosine network. Production and composition of this structure remained unstudied. In this work, we present our analyses of the schlaff (slf) gene coding for a putative C-type lectin that is needed for the adhesion between the horizontal cuticle layers. The Slf protein mainly localizes between the two layers called epicuticle and procuticle that separate from each other when the function of Slf is reduced or eliminated paralleling the phenotype of a cuticle with reduced extracellular dityrosine. Localisation of the dityrosinylated protein Resilin to the epicuticle-procuticle interface suggests that the dityrosine network mediates the adhesion of the epicuticle to the procuticle. Ultimately, compromised Slf function is associated with massive water loss. In summary, we propose that Slf is implied in the stabilisation of a dityrosine layer especially between the epicuticle and the procuticle that in turn constitutes an outward barrier against uncontrolled water flow.
Interference in speaking while hearing and vice versa
Authors: Fargier Raphaël , Laganaro Marina
Published: March 2019

Even when speakers are not actively doing another task, they can be interfered in their speech planning by concurrent auditory stimuli. In this study, we used picture naming with passive hearing, or active listening, combined to high-density electroencephalographic (EEG) recordings to investigate the locus and origin of interference on speech production. Participants named pictures while ignoring (or paying attention to) auditory syllables presented at different intervals (+150 ms, +300 ms or +450 ms). Interference of passive hearing was observed at all positive stimulus onset asynchronies (SOA) including when distractors appeared 450 ms after picture onset. Analyses of ERPs and microstates revealed modulations appearing in a time-window close to verbal response onset likely relating to post-lexical planning processes. A shift of latency of the N1 auditory component for syllables displayed 450 ms after picture onset relative to hearing in isolation was also observed. Data from picture naming with active listening to auditory syllables also pointed to post-lexical interference. The present study suggests that, beyond the lexical stage, post-lexical processes can be interfered and that the reciprocal interference between utterance planning and hearing relies on attentional demand and possibly competing neural substrates.
Novel combination of feed enzymes to improve the degradation of Chlorella vulgaris recalcitrant cell wall
Authors: Coelho Diogo , Lopes Paula A. , Cardoso Vânia , Ponte Patrícia , Brás Joana , Madeira Marta S. , Alfaia Cristina M. , Bandarra Narcisa M. , Gerken Henri G. , Fontes Carlos M. G. A. , Prates José A. M.
Published: March 2019

In this study, a rational combination of 200 pre-selected Carbohydrate-Active enzymes (CAZymes) and sulfatases were tested, individually or combined, according to their ability to degrade Chlorella vulgaris cell wall to access its valuable nutritional compounds. The disruption of microalgae cell walls by a four-enzyme mixture (Mix) in comparison with the control, enabled to release up to 1.21 g/L of reducing sugars (p < 0.001), led to an eight-fold increase in oligosaccharides release (p < 0.001), and reduced the fluorescence intensity by 47% after staining with Calcofluor White (p < 0.001). The Mix treatment was successful in releasing proteins (p < 0.001), some MUFA (p < 0.05), and the beneficial 18:3n-3 fatty acid (p < 0.05). Even if no variation was detected for chlorophylls (p > 0.05), total carotenoids were increased in the supernatant (p < 0.05) from the Mix treatment, relative to the control. Taken together, these results indicate that this four-enzyme Mix displays an effective capacity to degrade C. vulgaris cell wall. Thus, these enzymes may constitute a good approach to improve the bioavailability of C. vulgaris nutrients for monogastric diets, in particular, and to facilitate the cost-effective use of microalgae by the feed industry, in general.
UV plasmonic properties of colloidal liquid-metal eutectic gallium-indium alloy nanoparticles
Authors: Reineck Philipp , Lin Yiliang , Gibson Brant C. , Dickey Michael D. , Greentree Andrew D. , Maksymov Ivan S.
Published: March 2019

Nanoparticles made of non-noble metals such as gallium have recently attracted significant attention due to promising applications in UV plasmonics. To date, experiments have mostly focused on solid and liquid pure gallium particles immobilized on solid substrates. However, for many applications, colloidal liquid-metal nanoparticle solutions are vital. Here, we experimentally demonstrate strong UV plasmonic resonances of eutectic gallium-indium (EGaIn) liquid-metal alloy nanoparticles suspended in ethanol. We rationalise experimental results through a theoretical model based on Mie theory. Our results contribute to the understanding of UV plasmon resonances in colloidal liquid-metal EGaIn nanoparticle suspensions. They will also enable further research into emerging applications of UV plasmonics in biomedical imaging, sensing, stretchable electronics, photoacoustics, and electrochemistry.
Behaviourally specialized foragers are less efficient and live shorter lives than generalists in wasp colonies
Authors: Santoro Davide , Hartley Stephen , Lester Philip J.
Published: March 2019

A widely held assumption in ecology is that specialists are more efficient than generalists. However, empirical evidence for this fundamental assumption is surprisingly scarce and often contradictory. Theoretically, the evolution of alternative life history strategies is underpinned by a trade-off between activity levels and survival. We investigated the consequences of specialization in a foraging context, by comparing the performance and longevity of closely related individuals in a social insect, the common wasp (Vespula vulgaris). Using radio-frequency identification technology, we monitored the lifetime foraging activity of individual wasps from three colonies kept under natural foraging conditions. Returning foragers were video-recorded as they passed the nest entrance so that their foraging load could be assessed. There were substantial differences in foraging activity and survival within and between colonies. At the colony level, foraging specialization was weak. Yet, workers within each nest demonstrated a remarkable range of foraging specialization levels (defined as the degree of overlap between individual and colony-level task allocation) and efficiencies (defined by the number of successful trips and trip duration). We found that specialist foragers were less efficient than generalist siblings within the same colony. Behavioural specialists accomplished fewer successful trips per foraging day, and their trips were typically relatively longer. Specialized foragers also showed reduced life expectancy. The mortality risk was higher for individuals spending relatively more time in the field, yet we found no link between the level of specialization and relative field exposure. Our extensive dataset of unprecedented detail provides strong empirical evidence that behavioural specialization is not associated with a better lifetime performance, on the contrary, the opposite appears true for the common wasp. We also show that the survival of genetically similar individuals can be linked to life-long differences in behaviour according to classical life-history theory predictions.
pH-induced morphological changes of proteinaceous viral shells
Authors: Roshal D. , Konevtsova O. , Lošdorfer Božič A. , Podgornik R. , Rochal S.
Published: March 2019

Changes in environmental pH can induce morphological changes in empty proteinaceous shells of bacteriophages in vitro that are very similar to changes occurring in viral capsids in vivo after encapsidation of DNA. These changes in capsid shape and size cannot be explained with a simple elastic model alone. We propose a new theoretical framework that combines the elasticity of thin icosahedral shells with the pH dependence of capsid charge distribution. Minimization of the sum of elastic and electrostatic free energies leads to equilibrium shapes of viral shells that depend on a single elastic parameter and the detailed configuration of the imbedded protein charges. Based on the in vitro shell reconstructions of bacteriophage HK97 we elucidate the details of how the reversible transition between Prohead II and Expansion Intermediate II states of the HK97 procapsid is induced by pH changes, as well as some other features of the bacteriophage maturation.
Assessment of functional and structural changes of soil fungal and oomycete communities in holm oak declined dehesas through metabarcoding analysis
Authors: Ruiz Gómez Francisco J. , Navarro-Cerrillo Rafael M. , Pérez-de-Luque Alejandro , Oβwald Wolfgang , Vannini Andrea , Morales-Rodríguez Carmen
Published: March 2019

Forest decline is nowadays a major challenge for ecosystem sustainability. Dehesas, which consists of savannah-like mediterranean ecosystems, are threatened by the holm oak decline in the south-west of Iberian Peninsula. Phytophthora cinnamomi is considered the main agent of holm oak root rot, but little is known about the relationship between diversity of soilborne microbial community and the decline syndrome of holm oak. It would be hypothesized that the changes in the structure and functionality of the soil microbiome might influence tree health status through changes in richness and diversity of beneficial organisms such as mycorrhizal species, or fungal plant pathogens such as Fusarium spp. or Alternaria spp. Total DNA of soil samples from declined oak dehesas was extracted and analyzed through metabarcoding techniques, to evaluate the specific composition and diversity of the fungal and oomycete communities and their relationship with the disease symptoms. The fungal community included a wide range of pathogens and abundance of ectomycorrhizal key taxa related with low defoliation degree. Phytophthora cinnamomi and Pythium spiculum did not appear among the most abundant oomycetes, nor were they related directly to defoliation levels. Moreover, a particular taxon belonging to the genus Trichoderma was strongly correlated with the scarcity of pathogenic Phytophthora spp. The diversity and composition of fungal and oomycete communities were related to the severity of the decline symptoms. The metabarcoding study of microbiome represents a powerful tool to develop biocontrol strategies for the management of the holm oak root rot.
Increased Aortic Arch Calcification and Cardiomegaly is Associated with Rapid Renal Progression and Increased Cardiovascular Mortality in Chronic Kidney Disease
Authors: Chen Szu-Chia , Teh Melvin , Huang Jiun-Chi , Wu Pei-Yu , Chen Chiu-Yueh , Tsai Yi-Chun , Chiu Yi-Wen , Chang Jer-Ming , Chen Hung-Chun
Published: March 2019

Vascular calcification and cardiomegaly are highly prevalent in chronic kidney disease (CKD) patients. However, the association of the combination of aortic arch calcification (AoAC) and cardio-thoracic ratio (CTR) with clinical outcomes in patients with CKD is not well investigated. This study investigated whether the combination of AoAC and CTR is associated with poor clinical outcomes in CKD stages 3–5 patients. We enrolled 568 CKD patients, and AoAC and CTR were determined by chest radiography at enrollment. Rapid renal progression was defined as estimated glomerular filtration rate (eGFR) decline over 3 ml/min/1.73 m2 per year. Both AoAC score and CTR were significantly associated with rapid renal progression. High CTR was correlated with increased risk for cardiovascular mortality. We stratified the patients into four groups according to the median AoAC score of 4 and CTR of 50%. Those with AoAC ≥ 4 and CTR ≥ 50% (vs. AoAC score < 4 and CTR < 50%) were associated with eGFR decline over 3 ml/min/1.73 m2/year and cardiovascular mortality. AoAC and CTR were independently associated with eGFR slope. In conclusion, the combination of increased AoAC and cardiomegaly was associated with rapid renal progression and increased cardiovascular mortality in patients with CKD stage 3–5 patients. We suggest that evaluating AoAC and CTR on chest plain radiography may be a simple and inexpensive method for detecting CKD patients at high risk for adverse clinical outcomes.
HDAC1 and HDAC2 independently regulate common and specific intrinsic responses in murine enteroids
Authors: Gonneaud Alexis , Turgeon Naomie , Jones Christine , Couture Cassandra , Lévesque Dominique , Boisvert François-Michel , Boudreau François , Asselin Claude
Published: March 2019

Both HDAC1 and HDAC2 are class I deacetylases acting as erasers of lysine-acetyl marks on histones and non-histone proteins. Several histone deacetylase inhibitors, either endogenous to the cell, such as the ketogenic β-hydroxybutyrate metabolite, or exogenous, such as butyrate, a microbial-derived metabolite, regulate HDAC activity. Different combinations of intestinal epithelial cell (IEC)-specific Hdac1 and/or Hdac2 deletion differentially alter mucosal homeostasis in mice. Thus, HDAC1 and HDAC2 could act as sensors and transmitters of environmental signals to the mucosa. In this study, enteroid culture models deleted for Hdac1 or Hdac2 were established to determine IEC-specific function as assessed by global transcriptomic and proteomic approaches. Results show that Hdac1 or Hdac2 deficiency altered differentiation of Paneth and goblet secretory cells, which sustain physical and chemical protection barriers, and increased intermediate secretory cell precursor numbers. Furthermore, IEC Hdac1- and Hdac2-dependent common and specific biological processes were identified, including oxidation-reduction, inflammatory responses, and lipid-related metabolic processes, as well as canonical pathways and upstream regulators related to environment-dependent signaling through steroid receptor pathways, among others. These findings uncover unrecognized regulatory similarities and differences between Hdac1 and Hdac2 in IEC, and demonstrate how HDAC1 and HDAC2 may complement each other to regulate the intrinsic IEC phenotype.
Glandular differentiation in pT1 urothelial carcinoma of bladder predicts poor prognosis
Authors: Zhao Guobin , Wang Chao , Tang Yuhong , Liu Xin , Liu Zihao , Li Gang , Mei Yanhui
Published: March 2019

To evaluate the effect of glandular differentiation (GD) on tumor recurrence and progression of pT1 bladder urothelial carcinoma (UC). We performed a retrospective analysis of 82 bladder urothelial carcinoma with glandular differentiation (UCGD) patients which was pathologically diagnosed as pT1, 166 patients of pT1 UC of bladder without histologic variants served as controls. Patients of UCGD were more likely to have higher recurrence (P = 0.002) rate and higher progression rate (P < 0.001). Moreover, UCGD and a poor 5 -year overall survival (OS) (P = 0.02) while there was no difference in cancer-specific survival (CSS) (P = 0.062) between two groups. According to univariate analysis, largest tumor size (HR 1.502, CI 1.158–1.861, P = 0.029), UCGD (HR 1.787, CI 1.298–2.552, P = 0.001), lymphovascular invasion (LVI) (HR 1.226, CI 1.013–1.945, P = 0.039). UCGD (HR 1.367, CI 1.115–1.853, P = 0.038) and LVI (HR 1.416, CI 1.120–2.254, P = 0.013) were prognostic factors associated with disease recurrence and progression, respectively. Additionally, Additionally, UCGD significantly influence disease recurrence (HR 1.871, CI 1.338–2.589, P < 0.001) and progression (HR 1.462, CI 1.138–2.393, p = 0.007). Similarly, LVI significantly influence disease recurrence (HR 1.356, CI 1.053–2.174, P = 0.042) and progression (HR 1.348, CI 1.052–1.944, p = 0.022) in multivariate analysis. UCGD is significantly associated with higher recurrence and progression rate in patients with newly diagnosed pT1. Recurrent cases should be performed radical cystectomy (RC) earlier.
Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis
Authors: Brčić Luka , Barić Ana , Gračan Sanda , Torlak Vesela , Brekalo Marko , Škrabić Veselin , Zemunik Tatijana , Barbalić Maja , Punda Ante , Boraska Perica Vesna
Published: March 2019

Thyroid antibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) are key markers of Hashimoto’s thyroiditis (HT), the most common autoimmune thyroid disorder. Genetic determinants of thyroid antibodies are still poorly known, especially as they were not studied in patients with thyroid diseases. We performed the first genome-wide association analysis of thyroid antibodies in 430 HT patients that may be considered as population extremes for thyroid antibodies distribution. We detected two suggestively associated genetic variants with TgAb, rs6972286 close to ANKRD7 and LSM8 (P = 2.34 × 10−7) and rs756763 inside CA10 (P = 6.05 × 10−7), and one with TPOAb, rs12507813 positioned between TRIM61 and TRIM60 (P = 4.95 × 10−7). Bivariate analysis resulted with three suggestively associated genetic variants that predispose to both antibodies: rs13190616 inside RP11-138J23.1 (P = 2.01 × 10−6), rs561030786 close to DUBR (P = 7.33 × 10−6) and rs12713034 inside FSHR (P = 7.66 × 10−6). All identified genomic regions have a substantial literature record of involvement with female-related traits, immune-mediated diseases and personality traits that are all characterized by increased thyroid antibody levels. Our findings demonstrate the existence of genetic overlap between thyroid autoimmunity in HT and different non-thyroid diseases characterized by the presence of thyroid antibodies. We also suggest that genetic variants that regulate antibody levels may differ between HT patients and individuals with normal thyroid function.
Protein kinase CK2-dependent aerobic glycolysis-induced lactate dehydrogenase A enhances the migration and invasion of cancer cells
Authors: Im Dae-Kyun , Cheong Heesun , Lee Jong Suk , Oh Min-Kyu , Yang Kyung Mi
Published: March 2019

We investigated the intracellular metabolic fluxes of protein kinase CK2-activating (Cα OE) cells and role of lactate dehydrogenase A (LDHA) as a contributor of tumorigenesis after reprogrammed glucose metabolism. Facilitated aerobic glycolysis was confirmed via isotope tracer analysis, in which 13C6-Glc or 13C5-Gln was added to the media, following which metabolites converted from Cα OE cells were identified. We found a greater decrease in cell survival, colony-forming ability, migration, and Cα OE cell invasion under glucose (Glc)-depletion conditions than under glutamine (Gln)-depletion conditions. Cancer cell migration and invasion increased due to LDHA elevation of the altered metabolic axis driven by activated CK2. FX11 treatment and LDHA knockdown suppressed migration and invasion through ROS generation, but this was partially reversed by the antioxidant N-acetylcysteine (NAC). Moreover, LDHA inhibition decreased tumor growth in a mouse xenograft model transplanted with Cα OE cells. Finally, we concluded that LDHA is an excellent metabolic target for tumor therapy, based on CK2α derived aerobic glycolysis.
Fermi level tuning of Ag-doped Bi2Se3 topological insulator
Authors: Uesugi Eri , Uchiyama Takaki , Goto Hidenori , Ota Hiromi , Ueno Teppei , Fujiwara Hirokazu , Terashima Kensei , Yokoya Takayoshi , Matsui Fumihiko , Akimitsu Jun , Kobayashi Kaya , Kubozono Yoshihiro
Published: March 2019

The temperature dependence of the resistivity (ρ) of Ag-doped Bi2Se3 (AgxBi2−xSe3) shows insulating behavior above 35 K, but below 35 K, ρ suddenly decreases with decreasing temperature, in contrast to the metallic behavior for non-doped Bi2Se3 at 1.5–300 K. This significant change in transport properties from metallic behavior clearly shows that the Ag doping of Bi2Se3 can effectively tune the Fermi level downward. The Hall effect measurement shows that carrier is still electron in AgxBi2−xSe3 and the electron density changes with temperature to reasonably explain the transport properties. Furthermore, the positive gating of AgxBi2−xSe3 provides metallic behavior that is similar to that of non-doped Bi2Se3, indicating a successful upward tuning of the Fermi level.
Perovskite-based catalysts for the control of nitrogen oxide emissions from diesel engines
Authors: Jabłońska Magdalena , Palkovits Regina
Published: March 2019

Nitrogen oxides removal over a wide range of perovskite-based catalysts together with their property-activity relationships.
Specific capture of glycosylated graphene oxide by an asialoglycoprotein receptor: a strategic approach for liver-targeting
Authors: Diaz-Galvez Kevin R. , Teran-Saavedra Nayelli G. , Burgara-Estrella Alexel J. , Fernandez-Quiroz Daniel , Silva-Campa Erika , Acosta-Elias Monica , Sarabia-Sainz Hector M. , Pedroza-Montero Martín R. , Sarabia-Sainz Jose A.
Published: March 2019

In this work, we report the evaluation of lactosylated graphene oxide (GO-AL) as a potential drug carrier targeted at an asialoglycoprotein receptor (ASGPR) from hepatic cancer cells.
Carboxylic acid stimulated silver shell isomerism in a triple core–shell Ag84 nanocluster
Authors: Wang Zhi , Sun Hao-Tian , Kurmoo Mohamedally , Liu Qing-Yun , Zhuang Gui-Lin , Zhao Quan-Qin , Wang Xing-Po , Tung Chen-Ho , Sun Di
Published: March 2019

A unique triple core–shell Ag84 nanocluster displaying isomerism, which is controlled by different carboxylic acids and a one-way transformation (SD/Ag84a and SD/Ag84b).
Metal- and radical-free aerobic oxidation of heteroaromatic methanes: an efficient synthesis of heteroaromatic aldehydes
Authors: Ye Rongzi , Cao Yuanjie , Xi Xiaoxiang , Liu Long , Chen Tieqiao
Published: March 2019

A metal-free and radical-free synthesis of heteroaromatic aldehydes was developed through aerobic oxidation of methyl groups in an I2/DMSO/O2 catalytic system.
Low-cost VO2(M1) thin films synthesized by ultrasonic nebulized spray pyrolysis of an aqueous combustion mixture for IR photodetection
Authors: Tadeo Inyalot Jude , Mukhokosi Emma P. , Krupanidhi Saluru B. , Umarji Arun M.
Published: March 2019

We report detailed structural, electrical transport and IR photoresponse properties of large area VO2(M1) thin films deposited by a simple cost-effective two-step technique.
Synthesis of a novel resorcin[4]arene–glucose conjugate and its catalysis of the CuAAC reaction for the synthesis of 1,4-disubstituted 1,2,3-triazoles in water
Authors: Husain Ali A. , Bisht Kirpal S.
Published: March 2019

The Cu(i)-catalyzed azide–alkyne cycloaddition (CuAAC) in aqueous media using resorcin[4]arene glycoconjugate (RG) is reported.