bluuebunny/crossref_metadata_2025 huggingface dataset:
Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface
Authors: Tang Maggie K. S. , Yue Patrick Y. K. , Ip Philip P. , Huang Rui-Lan , Lai Hung-Cheng , Cheung Annie N. Y. , Tse Ka Yu , Ngan Hextan Y. S. , Wong Alice S. T.
Published: June 2018

The limitations of current anti-angiogenic therapies necessitate other targets with complimentary mechanisms. Here, we show for the first time that soluble E-cadherin (sE-cad) (an 80-kDa soluble form), which is highly expressed in the malignant ascites of ovarian cancer patients, is a potent inducer of angiogenesis. In addition to ectodomain shedding, we provide further evidence that sE-cad is abundantly released in the form of exosomes. Mechanistically, sE-cad-positive exosomes heterodimerize with VE-cadherin on endothelial cells and transduce a novel sequential activation of β-catenin and NFκB signaling. In vivo and clinical data prove the relevance of sE-cad-positive exosomes for malignant ascites formation and widespread peritoneal dissemination. These data advance our understanding of the molecular regulation of angiogenesis in ovarian cancer and support the therapeutic potential of targeting sE-cad. The exosomal release of sE-cad, which represents a common route for externalization in ovarian cancer, could potentially be biomarkers for diagnosis and prognosis.
Diversity and evolution of the emerging Pandoraviridae family
Authors: Legendre Matthieu , Fabre Elisabeth , Poirot Olivier , Jeudy Sandra , Lartigue Audrey , Alempic Jean-Marie , Beucher Laure , Philippe Nadège , Bertaux Lionel , Christo-Foroux Eugène , Labadie Karine , Couté Yohann , Abergel Chantal , Claverie Jean-Michel
Published: June 2018

With DNA genomes reaching 2.5 Mb packed in particles of bacterium-like shape and dimension, the first two Acanthamoeba-infecting pandoraviruses remained up to now the most complex viruses since their discovery in 2013. Our isolation of three new strains from distant locations and environments is now used to perform the first comparative genomics analysis of the emerging worldwide-distributed Pandoraviridae family. Thorough annotation of the genomes combining transcriptomic, proteomic, and bioinformatic analyses reveals many non-coding transcripts and significantly reduces the former set of predicted protein-coding genes. Here we show that the pandoraviruses exhibit an open pan-genome, the enormous size of which is not adequately explained by gene duplications or horizontal transfers. As most of the strain-specific genes have no extant homolog and exhibit statistical features comparable to intergenic regions, we suggest that de novo gene creation could contribute to the evolution of the giant pandoravirus genomes.
Nanoscale membranes that chemically isolate and electronically wire up the abiotic/biotic interface
Authors: Cornejo Jose A. , Sheng Hua , Edri Eran , M. Ajo-Franklin Caroline , Frei Heinz
Published: June 2018

By electrochemically coupling microbial and abiotic catalysts, bioelectrochemical systems such as microbial electrolysis cells and microbial electrosynthesis systems synthesize energy-rich chemicals from energy-poor precursors with unmatched efficiency. However, to circumvent chemical incompatibilities between the microbial cells and inorganic materials that result in toxicity, corrosion, fouling, and efficiency-degrading cross-reactions between oxidation and reduction environments, bioelectrochemical systems physically separate the microbial and inorganic catalysts by macroscopic distances, thus introducing ohmic losses, rendering these systems impractical at scale. Here we electrochemically couple an inorganic catalyst, a SnO2 anode, with a microbial catalyst, Shewanella oneidensis, via a 2-nm-thick silica membrane containing -CN and -NO2 functionalized p-oligo(phenylene vinylene) molecular wires. This membrane enables electron flow at 0.51 μA cm−2 from microbial catalysts to the inorganic anode, while blocking small molecule transport. Thus the modular architecture avoids chemical incompatibilities without ohmic losses and introduces an immense design space for scale up of bioelectrochemical systems.
Interplay of the two ancient metabolites auxin and MEcPP regulates adaptive growth
Authors: Jiang Jishan , Rodriguez-Furlan Cecilia , Wang Jin-Zheng , de Souza Amancio , Ke Haiyan , Pasternak Taras , Lasok Hanna , Ditengou Franck A. , Palme Klaus , Dehesh Katayoon
Published: June 2018

The ancient morphoregulatory hormone auxin dynamically realigns dedicated cellular processes that shape plant growth under prevailing environmental conditions. However, the nature of the stress-responsive signal altering auxin homeostasis remains elusive. Here we establish that the evolutionarily conserved plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) controls adaptive growth by dual transcriptional and post-translational regulatory inputs that modulate auxin levels and distribution patterns in response to stress. We demonstrate that in vivo accumulation or exogenous application of MEcPP alters the expression of two auxin reporters, DR5:GFP and DII-VENUS, and reduces the abundance of the auxin-efflux carrier PIN-FORMED1 (PIN1) at the plasma membrane. However, pharmacological intervention with clathrin-mediated endocytosis blocks the PIN1 reduction. This study provides insight into the interplay between these two indispensable signaling metabolites by establishing the mode of MEcPP action in altering auxin homeostasis, and as such, positioning plastidial function as the primary driver of adaptive growth.
Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment
Authors: Scheggia Diego , Mastrogiacomo Rosa , Mereu Maddalena , Sannino Sara , Straub Richard E. , Armando Marco , Managò Francesca , Guadagna Simone , Piras Fabrizio , Zhang Fengyu , Kleinman Joel E. , Hyde Thomas M. , Kaalund Sanne S. , Pontillo Maria , Orso Genny , Caltagirone Carlo , Borrelli Emiliana , De Luca Maria A. , Vicari Stefano , Weinberger Daniel R. , Spalletta Gianfranco , Papaleo Francesco
Published: June 2018

Antipsychotics are the most widely used medications for the treatment of schizophrenia spectrum disorders. While such drugs generally ameliorate positive symptoms, clinical responses are highly variable in terms of negative symptoms and cognitive impairments. However, predictors of individual responses have been elusive. Here, we report a pharmacogenetic interaction related to a core cognitive dysfunction in patients with schizophrenia. We show that genetic variations reducing dysbindin-1 expression can identify individuals whose executive functions respond better to antipsychotic drugs, both in humans and in mice. Multilevel ex vivo and in vivo analyses in postmortem human brains and genetically modified mice demonstrate that such interaction between antipsychotics and dysbindin-1 is mediated by an imbalance between the short and long isoforms of dopamine D2 receptors, leading to enhanced presynaptic D2 function within the prefrontal cortex. These findings reveal one of the pharmacodynamic mechanisms underlying individual cognitive response to treatment in patients with schizophrenia, suggesting a potential approach for improving the use of antipsychotic drugs.
Cellular stress alters 3′UTR landscape through alternative polyadenylation and isoform-specific degradation
Authors: Zheng Dinghai , Wang Ruijia , Ding Qingbao , Wang Tianying , Xie Bingning , Wei Lu , Zhong Zhaohua , Tian Bin
Published: June 2018

Most eukaryotic genes express alternative polyadenylation (APA) isoforms with different 3′UTR lengths, production of which is influenced by cellular conditions. Here, we show that arsenic stress elicits global shortening of 3′UTRs through preferential usage of proximal polyadenylation sites during stress and enhanced degradation of long 3′UTR isoforms during recovery. We demonstrate that RNA-binding protein TIA1 preferentially interacts with alternative 3′UTR sequences through U-rich motifs, correlating with stress granule association and mRNA decay of long 3′UTR isoforms. By contrast, genes with shortened 3′UTRs due to stress-induced APA can evade mRNA clearance and maintain transcript abundance post stress. Furthermore, we show that stress causes distinct 3′UTR size changes in proliferating and differentiated cells, highlighting its context-specific impacts on the 3′UTR landscape. Together, our data reveal a global, 3′UTR-based mRNA stability control in stressed cells and indicate that APA can function as an adaptive mechanism to preserve mRNAs in response to stress.
An anionic phthalocyanine decreases NRAS expression by breaking down its RNA G-quadruplex
Authors: Kawauchi Keiko , Sugimoto Wataru , Yasui Takatoshi , Murata Kohei , Itoh Katsuhiko , Takagi Kazuki , Tsuruoka Takaaki , Akamatsu Kensuke , Tateishi-Karimata Hisae , Sugimoto Naoki , Miyoshi Daisuke
Published: June 2018

Aberrant activation of RAS signalling pathways contributes to aggressive phenotypes of cancer cells. The RAS-targeted therapies for cancer, therefore, have been recognised to be effective; however, current developments on targeting RAS have not advanced due to structural features of the RAS protein. Here, we show that expression of NRAS, a major isoform of RAS, can be controlled by photo-irradiation with an anionic phthalocyanine, ZnAPC, targeting NRAS mRNA. In vitro experiments reveal that ZnAPC binds to a G-quadruplex–forming oligonucleotide derived from the 5′-untranslated region of NRAS mRNA even in the presence of excess double-stranded RNA, which is abundant in cells, resulting in selective cleavage of the target RNA’s G-quadruplex upon photo-irradiation. In line with these results, upon photo-irradiation, ZnAPC decreases NRAS mRNA and NRAS expression and thus viability of cancer cells. These results indicate that ZnAPC may be a prominent photosensitiser for a molecularly targeted photodynamic therapy for cancer.
Mapping biological process relationships and disease perturbations within a pathway network
Authors: Stoney Ruth , Robertson David L , Nenadic Goran , Schwartz Jean-Marc
Published: June 2018

Molecular interaction networks are routinely used to map the organization of cellular function. Edges represent interactions between genes, proteins, or metabolites. However, in living cells, molecular interactions are dynamic, necessitating context-dependent models. Contextual information can be integrated into molecular interaction networks through the inclusion of additional molecular data, but there are concerns about completeness and relevance of this data. We developed an approach for representing the organization of human cellular processes using pathways as the nodes in a network. Pathways represent spatial and temporal sets of context-dependent interactions, generating a high-level network when linked together, which incorporates contextual information without the need for molecular interaction data. Analysis of the pathway network revealed linked communities representing functional relationships, comparable to those found in molecular networks, including metabolism, signaling, immunity, and the cell cycle. We mapped a range of diseases onto this network and find that pathways associated with diseases tend to be functionally connected, highlighting the perturbed functions that result in disease phenotypes. We demonstrated that disease pathways cluster within the network. We then examined the distribution of cancer pathways and showed that cancer pathways tend to localize within the signaling, DNA processes and immune modules, although some cancer-associated nodes are found in other network regions. Altogether, we generated a high-confidence functional network, which avoids some of the shortcomings faced by conventional molecular models. Our representation provides an intuitive functional interpretation of cellular organization, which relies only on high-quality pathway and Gene Ontology data. The network is available athttps://data.mendeley.com/datasets/3pbwkxjxg9/1.
Expression of Cry2Aa, a Bacillus thuringiensis insecticidal protein in transgenic pigeon pea confers resistance to gram pod borer, Helicoverpa armigera
Authors: Singh Shweta , Kumar Nikhil Ram , Maniraj R. , Lakshmikanth R. , Rao K. Y. S. , Muralimohan N. , Arulprakash T. , Karthik K. , Shashibhushan N. B. , Vinutha T. , Pattanayak Debasis , Dash Prasanta K. , Kumar P. Ananda , Sreevathsa Rohini
Published: June 2018

Pigeon pea is an important legume infested by a plethora of insect pests amongst which gram pod borer Helicoverpa armigera is very prominent. Imparting resistance to this insect herbivore is of global importance in attaining food security. Expression of insecticidal crystal proteins (ICP) in diverse crops has led to increased resistance to several pests. We report in this paper, expression of Cry2Aa in transgenic pigeon pea and its effectiveness towards H. armigera by employing Agrobacterium-mediated in planta transformation approach. Approximately 0.8% of T1 generation plants were identified as putative transformants based on screening in the presence of 70 ppm kanamycin as the selection agent. Promising events were further recognized in advanced generations based on integration, expression and bioefficacy of the transgenes. Seven T3 lines (11.8% of the selected T1 events) were categorized as superior as these events demonstrated 80–100% mortality of the challenged larvae and improved ability to prevent damage caused by the larvae. The selected transgenic plants accumulated Cry2Aa in the range of 25–80 µg/g FW. The transgenic events developed in the study can be used in pigeon pea improvement programmes for pod borer resistance.
Author Correction: First Evidence of Coherent Bands of Strong Turbulent Layers Associated with High-Wavenumber Internal-Wave Shear in the Upstream Kuroshio
Authors: Nagai Takeyoshi , Hasegawa Daisuke , Tanaka Takahiro , Nakamura Hirohiko , Tsutsumi Eisuke , Inoue Ryuichiro , Yamashiro Toru
Published: June 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
A novel role of C-terminus in introducing a functionally flexible structure critical for the biological activity of botulinum neurotoxin
Authors: Feltrup Thomas M. , Patel Kruti , Kumar Raj , Cai Shuowei , Singh Bal Ram
Published: June 2018

Botulinum neurotoxin (BoNT) is responsible for botulism, a clinical condition resulting in flaccid muscle paralysis and potentially death. The light chain is responsible for its intracellular toxicity through its endopeptidase activity. Available crystal structures of BoNT/A light chains (LCA) are based on various truncated versions (tLCA) of the full-length LCA (fLCA) and do not necessarily reflect the true structure of LCA in solution. The understanding of the mechanism of action, longevity of intoxication, and an improved development of endopeptidase inhibitors are dependent on first having a better insight into the structure of LCA in solution. Using an array of biophysical techniques, we report that the fLCA structure is significantly more flexible than tLCA in solution, which may be responsible for its dramatically higher enzymatic activity. This seems to be achieved by a much stronger, more rapid binding to substrate (SNAP-25) of the fLCA compared to tLCA. These results suggest that the C-terminus of LCA plays a critical role in introducing a flexible structure, which is essential for its biological function. This is the first report of such a massive structural role of the C-terminus of a protein being critical for maintaining a functional state.
Diverse antimalarials from whole-cell phenotypic screens disrupt malaria parasite ion and volume homeostasis
Authors: Dennis Adelaide S. M. , Rosling James E. O. , Lehane Adele M. , Kirk Kiaran
Published: June 2018

Four hundred structurally diverse drug-like compounds comprising the Medicines for Malaria Venture’s ‘Pathogen Box’ were screened for their effect on a range of physiological parameters in asexual blood-stage malaria (Plasmodium falciparum) parasites. Eleven of these compounds were found to perturb parasite Na+, pH and volume in a manner consistent with inhibition of the putative Na+ efflux P-type ATPase PfATP4. All eleven compounds fell within the subset of 125 compounds included in the Pathogen Box on the basis of their having been identified as potent inhibitors of the growth of asexual blood-stage P. falciparum parasites. All eleven compounds inhibited the Na+-dependent ATPase activity of parasite membranes and showed reduced efficacy against parasites carrying mutations in PfATP4. This study increases the number of chemically diverse structures known to show a ‘PfATP4-associated’ phenotype, and adds to emerging evidence that a high proportion (7–9%) of the structurally diverse antimalarial compounds identified in whole cell phenotypic screens share the same mechanism of action, exerting their antimalarial effect via an interaction with PfATP4.
Impaired hippocampal representation of place in the Fmr1-knockout mouse model of fragile X syndrome
Authors: Arbab Tara , Pennartz Cyriel M. A. , Battaglia Francesco P.
Published: June 2018

Fragile X syndrome (FXS) is an X-chromosome linked intellectual disability and the most common known inherited single gene cause of autism spectrum disorder (ASD). Building upon demonstrated deficits in neuronal plasticity and spatial memory in FXS, we investigated how spatial information processing is affected in vivo in an FXS mouse model (Fmr1-KO). Healthy hippocampal neurons (so-called place cells) exhibit place-related activity during spatial exploration, and their firing fields tend to remain stable over time. In contrast, we find impaired stability and reduced specificity of Fmr1-KO spatial representations. This is a potential biomarker for the cognitive dysfunction observed in FXS, informative on the ability to integrate sensory information into an abstract representation and successfully retain this conceptual memory. Our results provide key insight into the biological mechanisms underlying cognitive disabilities in FXS and ASD, paving the way for a targeted approach to remedy these.
Author Correction: The Methylation Capacity of Arsenic and Insulin Resistance are Associated with Psychological Characteristics in Children and Adolescents
Authors: Lin Ying-Chin , Su Chien-Tien , Shiue Horng-Sheng , Chen Wei-Jen , Chen Yi-Hua , Choy Cheuk-Sing , Chiou Hung-Yi , Han Bor-Cheng , Hsueh Yu-Mei
Published: June 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
AKT signalling selectively regulates PINK1 mitophagy in SHSY5Y cells and human iPSC-derived neurons
Authors: Soutar Marc P. M. , Kempthorne Liam , Miyakawa Shuichi , Annuario Emily , Melandri Daniela , Harley Jasmine , O’Sullivan Gregory A. , Wray Selina , Hancock David C. , Cookson Mark R. , Downward Julian , Carlton Mark , Plun-Favreau Hélène
Published: June 2018

The discovery of mutations within genes associated with autosomal recessive Parkinson’s disease allowed for the identification of PINK1/Parkin regulated mitophagy as an important pathway for the removal of damaged mitochondria. While recent studies suggest that AKT-dependent signalling regulates Parkin recruitment to depolarised mitochondria, little is known as to whether this can also regulate PINK1 mitochondrial accumulation and downstream mitophagy. Here, we demonstrate that inhibition of AKT signalling decreases endogenous PINK1 accumulation in response to mitochondria depolarisation, subsequent Parkin recruitment, phosphorylation of ubiquitin, and ultimately mitophagy. Conversely, we show that upon stimulation of AKT signalling via insulin, the mitophagy pathway is increased in SHSY5Y cells. These data suggest that AKT signalling is an upstream regulator of PINK1 accumulation on damaged mitochondria. Importantly, we show that the AKT pathway also regulates endogenous PINK1-dependent mitophagy in human iPSC-derived neurons.
Author Correction: Laminarinase from Flavobacterium sp. reveals the structural basis of thermostability and substrate specificity
Authors: Qin Hui-Min , Miyakawa Takuya , Inoue Akira , Nakamura Akira , Nishiyama Ryuji , Ojima Takao , Tanokura Masaru
Published: June 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
Unsupervised Hebbian learning experimentally realized with analogue memristive crossbar arrays
Authors: Hansen Mirko , Zahari Finn , Kohlstedt Hermann , Ziegler Martin
Published: June 2018

Conventional transistor electronics are reaching their limits in terms of scalability, power dissipation, and the underlying Boolean system architecture. To overcome this obstacle neuromorphic analogue systems are recently highly investigated. Particularly, the use of memristive devices in VLSI analogue concepts provides a promising pathway to realize novel bio-inspired computing architectures, which are able to unravel the foreseen difficulties of traditional electronics. Currently, a variety of materials and device structures are being studied along with novel computing schemes to make use of the attractive features of memristive devices for neuromorphic computing. However, a number of obstacles still have to be overcome to cast memristive devices into hardware systems. Most important is a physical implementation of memristive devices, which can cope with the high complexity of neural networks. This includes the integration of analogue and electroforming-free memristive devices into crossbar structures with no additional electronic components, such as selector devices. Here, an unsupervised, bio-motivated Hebbian based learning platform for visual pattern recognition is presented. The heart of the system is a crossbar array (16 × 16) which consists of selector-free and forming-free (non-filamentary) memristive devices, which exhibit analogue I-V characteristics.
Vertical Alignment of Liquid Crystals Over a Functionalized Flexible Substrate
Authors: Sivaranjini B. , Mangaiyarkarasi R. , Ganesh V. , Umadevi S.
Published: June 2018

A simple and effective approach for vertical alignment of liquid crystals (LCs) over a functionalized transparent flexible substrate is described. Surface characterization of this commercially available plastic substrate through X-ray photoelectron spectroscopy (XPS) and attenuated total reflection infrared spectroscopy (ATR-IR) indicated that cellulose acetate is main component of the transparent substrate. This substrate was chemically functionalized with a suitable LC compound. A trimethoxysilane terminated new rod-shaped mesogen is synthesized and covalently attached to the pre-treated film through silane condensation reaction. LC functionalization of the polymer film is confirmed through contact angle (CA), atomic force microscopy (AFM), XPS and ATR-IR spectroscopy studies. Versatility of the LC modified flexible substrates for the alignment of bulk LC sample at substrate-LC interface was assessed for nematic (N) and smectic A (SmA) phases. Remarkably, LC functionalized cellulose acetate films were found to be highly efficient in assisting a perfect homeotropic alignment of LCs (for both, a room temperature N and a high temperature SmA phase) over the entire area of the LC sample under observation indicating their superior aligning ability in comparison to their unmodified and octadecyltrimethoxysilane (OTS) modified counterparts. The demonstrated method of surface modification of flexible polymer film is easy, surface modified substrates are stable for several months, retained their aligning ability intact and more importantly they are reusable with maximum delivery.
Author Correction: Carboxythiazole is a key microbial nutrient currency and critical component of thiamin biosynthesis
Authors: Paerl Ryan W. , Bertrand Erin M. , Rowland Elden , Schatt Phillippe , Mehiri Mohamed , Niehaus Thomas D. , Hanson Andrew D. , Riemann Lasse , Bouget Francois-Yves
Published: June 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Effects of sampling effort on biodiversity patterns estimated from environmental DNA metabarcoding surveys
Authors: Grey Erin K. , Bernatchez Louis , Cassey Phillip , Deiner Kristy , Deveney Marty , Howland Kimberly L. , Lacoursière-Roussel Anaïs , Leong Sandric Chee Yew , Li Yiyuan , Olds Brett , Pfrender Michael E. , Prowse Thomas A. A. , Renshaw Mark A. , Lodge David M.
Published: June 2018

Environmental DNA (eDNA) metabarcoding can greatly enhance our understanding of global biodiversity and our ability to detect rare or cryptic species. However, sampling effort must be considered when interpreting results from these surveys. We explored how sampling effort influenced biodiversity patterns and nonindigenous species (NIS) detection in an eDNA metabarcoding survey of four commercial ports. Overall, we captured sequences from 18 metazoan phyla with minimal differences in taxonomic coverage between 18 S and COI primer sets. While community dissimilarity patterns were consistent across primers and sampling effort, richness patterns were not, suggesting that richness estimates are extremely sensitive to primer choice and sampling effort. The survey detected 64 potential NIS, with COI identifying more known NIS from port checklists but 18 S identifying more operational taxonomic units shared between three or more ports that represent un-recorded potential NIS. Overall, we conclude that eDNA metabarcoding surveys can reveal global similarity patterns among ports across a broad array of taxa and can also detect potential NIS in these key habitats. However, richness estimates and species assignments require caution. Based on results of this study, we make several recommendations for port eDNA sampling design and suggest several areas for future research.
β-apo-10′-carotenoids support normal embryonic development during vitamin A deficiency
Authors: Spiegler Elizabeth , Kim Youn-Kyung , Hoyos Beatrice , Narayanasamy Sureshbabu , Jiang Hongfeng , Savio Nicole , Curley Robert W. , Harrison Earl H. , Hammerling Ulrich , Quadro Loredana
Published: June 2018

Vitamin A deficiency is still a public health concern affecting millions of pregnant women and children. Retinoic acid, the active form of vitamin A, is critical for proper mammalian embryonic development. Embryos can generate retinoic acid from maternal circulating β-carotene upon oxidation of retinaldehyde produced via the symmetric cleavage enzyme β-carotene 15,15′-oxygenase (BCO1). Another cleavage enzyme, β-carotene 9′,10′-oxygenase (BCO2), asymmetrically cleaves β-carotene in adult tissues to prevent its mitochondrial toxicity, generating β-apo-10′-carotenal, which can be converted to retinoids (vitamin A and its metabolites) by BCO1. However, the role of BCO2 during mammalian embryogenesis is unknown. We found that mice lacking BCO2 on a vitamin A deficiency-susceptible genetic background (Rbp4−/−) generated severely malformed vitamin A-deficient embryos. Maternal β-carotene supplementation impaired fertility and did not restore normal embryonic development in the Bco2−/−Rbp4−/− mice, despite the expression of BCO1. These data demonstrate that BCO2 prevents β-carotene toxicity during embryogenesis under severe vitamin A deficiency. In contrast, β-apo-10′-carotenal dose-dependently restored normal embryonic development in Bco2−/−Rbp4−/− but not Bco1−/−Bco2−/−Rbp4−/− mice, suggesting that β-apo-10′-carotenal facilitates embryogenesis as a substrate for BCO1-catalyzed retinoid formation. These findings provide a proof of principle for the important role of BCO2 in embryonic development and invite consideration of β-apo-10′-carotenal as a nutritional supplement to sustain normal embryonic development in vitamin A-deprived pregnant women.
Elevated plasma abscisic acid is associated with asymptomatic falciparum malaria and with IgG-/caspase-1-dependent immunity in Plasmodium yoelii-infected mice
Authors: Glennon Elizabeth K. K. , Megawati Dewi , Torrevillas Brandi K. , Ssewanyana Isaac , Huang Liusheng , Aweeka Fran , Greenhouse Bryan , Adams L. Garry , Luckhart Shirley
Published: June 2018

Abscisic acid (ABA) is an ancient stress hormone and is detectable in a wide variety of organisms where it regulates innate immunity and inflammation. Previously, we showed that oral supplementation with ABA decreased parasitemia in a mouse model of malaria, decreased liver and spleen pathology and reduced parasite transmission to mosquitoes. Here, we report that higher circulating ABA levels were associated with a reduced risk of symptomatic malaria in a cohort ofPlasmodium falciparum-infected Ugandan children. To understand possible mechanisms of ABA protection in malaria, we returned to our mouse model to show that ABA effects onPlasmodium yoelii17XNL infection were accompanied by minimal effects on complete blood count and blood chemistry analytes, suggesting a benefit to host health. In addition, orally delivered ABA induced patterns of gene expression in mouse liver and spleen that suggested enhancement of host anti-parasite defenses. To test these inferences, we utilized passive immunization and knockout mice to demonstrate that ABA supplementation increases circulating levels of protective, parasite-specific IgG and requires caspase-1 to reduce parasitemia. Collectively, ABA induces host responses that ameliorate infection and disease in an animal model and suggest that further studies of ABA in the context of human malaria are warranted.
Identification of sources and bioaccumulation pathways of MeHg in subantarctic penguins: a stable isotopic investigation
Authors: Renedo Marina , Amouroux David , Pedrero Zoyne , Bustamante Paco , Cherel Yves
Published: June 2018

Seabirds are widely used as bioindicators of mercury (Hg) contamination in marine ecosystems and the investigation of their foraging strategies is of key importance to better understand methylmercury (MeHg) exposure pathways and environmental sources within the different ecosystems. Here we report stable isotopic composition for both Hg mass-dependent (e.g. δ202Hg) and mass-independent (e.g. Δ199Hg) fractionation (proxies of Hg sources and transformations), carbon (δ13C, proxy of foraging habitat) and nitrogen (δ15N, proxy of trophic position) in blood of four species of sympatric penguins breeding at the subantarctic Crozet Islands (Southern Indian Ocean). Penguins have species-specific foraging strategies, from coastal to oceanic waters and from benthic to pelagic dives, and feed on different prey. A progressive increase to heavier Hg isotopic composition (δ202Hg and Δ199Hg, respectively) was observed from benthic (1.45 ± 0.12 and 1.41 ± 0.06‰) to epipelagic (1.93 ± 0.18 and 1.77 ± 0.13‰) penguins, indicating a benthic-pelagic gradient of MeHg sources close to Crozet Islands. The relative variations of MeHg concentration, δ202Hg and Δ199Hg with pelagic penguins feeding in Polar Front circumpolar waters (1.66 ± 0.11 and 1.54 ± 0.06‰) support that different MeHg sources occur at large scales in Southern Ocean deep waters.
Comparative chloroplast genomics and phylogenetics of nine Lindera species (Lauraceae)
Authors: Zhao Mei-Li , Song Yu , Ni Jun , Yao Xin , Tan Yun-Hong , Xu Zeng-Fu
Published: June 2018

Lindera, a core genus of the Lauraceae family, has important economic uses in eastern Asia and North America. However, its historical diversification has not been clarified. In this study, we report nine newly sequenced Lindera plastomes. The plastomes of these nine Lindera species range from 152,211 (L. nacusua) to 152,968 bp (L. metcalfiana) in length, similar to that of another Lauraceae species, Litsea glutinosa (152,618 bp). The length variation of these plastomes derived from the length variation in the loci ycf1, ycf2, ψycf1, and ndhF-ψycf1. Comparing our sequences with other available plastomes in the Lauraceae indicated that eight hypervariable loci, ihbA-trnG, ndhA, ndhF-rpl32, petA-psbJ, psbK-psbI, rps16, trnS-trnG, and ycf1, could serve as DNA barcodes for species delineation, and that the inverted repeats (IRs) showed contraction/expansion. Further phylogenetic analyses were performed using 32 complete plastomes of Lauraceae and seven barcodes from 14 additional species of Lindera and related species in the core Lauraceae. The results showed that these Lindera species grouped into two or four sub-clades, and that two Litsea species and Laurus nobilis were located in the same sub-clade as five Lindera species. These data support a close relationship between the genera Laurus, Lindera, and Litsea, and suggest that Lindera is polyphyletic.
Development of bicistronic expression system for the enhanced and reliable production of recombinant proteins in Leuconostoc citreum
Authors: Jang Seung Hoon , Cha Ji Won , Han Nam Soo , Jeong Ki Jun
Published: June 2018

The lactic acid bacteria (LAB) Leuconostoc citreum are non-sporulating hetero-fermentative bacteria that play an important role in the fermented food industry. In this study, for the enhanced and reliable production of recombinant proteins in L. citreum, we developed a bicistronic design (BCD) expression system which includes a short leader peptide (1st cistron) followed by target genes (2nd cistron) under the control of a single promoter. Using superfolder green fluorescent protein (sfGFP) as a reporter, the functionality of BCD in L. citreum was verified. Further, to improve the expression in BCD, we tried to engineer a Shine-Dalgarno sequence (SD2) for the 2nd cistron and a promoter by FACS screening of random libraries, and both strong SD2 (eSD2) and promoter (P710V4) were successfully isolated. The usefulness of the engineered BCD with P710V4 and eSD2 was further validated using three model proteins—glutathione-s-transferase, human growth hormone, and α-amylase. All examined proteins were successfully produced with levels highly increased compared with those in the original BCD as well as the monocistronic design (MCD) expression system.
3D biodegradable scaffolds of polycaprolactone with silicate-containing hydroxyapatite microparticles for bone tissue engineering: high-resolution tomography and in vitro study
Authors: Shkarina Svetlana , Shkarin Roman , Weinhardt Venera , Melnik Elizaveta , Vacun Gabriele , Kluger Petra J. , Loza Kateryna , Epple Matthias , Ivlev Sergei I. , Baumbach Tilo , Surmeneva Maria A. , Surmenev Roman A.
Published: June 2018

To date, special interest has been paid to composite scaffolds based on polymers enriched with hydroxyapatite (HA). However, the role of HA containing different trace elements such as silicate in the structure of a polymer scaffold has not yet been fully explored. Here, we report the potential use of silicate-containing hydroxyapatite (SiHA) microparticles and microparticle aggregates in the predominant range from 2.23 to 12.40 µm in combination with polycaprolactone (PCL) as a hybrid scaffold with randomly oriented and well-aligned microfibers for regeneration of bone tissue. Chemical and mechanical properties of the developed 3D scaffolds were investigated with XRD, FTIR, EDX and tensile testing. Furthermore, the internal structure and surface morphology of the scaffolds were analyzed using synchrotron X-ray µCT and SEM. Upon culturing human mesenchymal stem cells (hMSC) on PCL-SiHA scaffolds, we found that both SiHA inclusion and microfiber orientation affected cell adhesion. The best hMSCs viability was revealed at 10 day for the PCL-SiHA scaffolds with well-aligned structure (~82%). It is expected that novel hybrid scaffolds of PCL will improve tissue ingrowth in vivo due to hydrophilic SiHA microparticles in combination with randomly oriented and well-aligned PCL microfibers, which mimic the structure of extracellular matrix of bone tissue.
Pervasive influence of idiosyncratic associative biases during facial emotion recognition
Authors: El Zein Marwa , Wyart Valentin , Grèzes Julie
Published: June 2018

Facial morphology has been shown to influence perceptual judgments of emotion in a way that is shared across human observers. Here we demonstrate that these shared associations between facial morphology and emotion coexist with strong variations unique to each human observer. Interestingly, a large part of these idiosyncratic associations does not vary on short time scales, emerging from stable inter-individual differences in the way facial morphological features influence emotion recognition. Computational modelling of decision-making and neural recordings of electrical brain activity revealed that both shared and idiosyncratic face-emotion associations operate through a common biasing mechanism rather than an increased sensitivity to face-associated emotions. Together, these findings emphasize the underestimated influence of idiosyncrasies on core social judgments and identify their neuro-computational signatures.
Milk cholesterol concentration in mice is not affected by high cholesterol diet- or genetically-induced hypercholesterolaemia
Authors: Dimova Lidiya G. , Lohuis Mirjam A. M. , Bloks Vincent W. , Tietge Uwe J. F. , Verkade Henkjan J.
Published: June 2018

Breast milk cholesterol content may imply to affect short- and long-term cholesterol homeostasis in the offspring. However, mechanisms of regulating milk cholesterol concentration are only partly understood. We used different mouse models to assess the impact of high cholesterol diet (HC)- or genetically-induced hypercholesterolaemia on milk cholesterol content. At day 14 postpartum we determined milk, plasma and tissue lipids in wild type (WT), LDL receptor knockout (Ldlr−/−), and ATP-binding cassette transporter G8 knockout (Abcg8−/−) mice fed either low- or 0.5% HC diet. In chow-fed mice, plasma cholesterol was higher in Ldlr−/− dams compared to WT. HC-feeding increased plasma cholesterol in all three models compared to chow diet. Despite the up to 5-fold change in plasma cholesterol concentration, the genetic and dietary conditions did not affect milk cholesterol levels. To detect possible compensatory changes, we quantified de novo cholesterol synthesis in mammary gland and liver, which was strongly reduced in the various hypercholesterolaemic conditions. Together, these data suggest that milk cholesterol concentration in mice is not affected by conditions of maternal hypercholesterolaemia and is maintained at stable levels via ABCG8- and LDLR-independent mechanisms. The robustness of milk cholesterol levels might indicate an important physiological function of cholesterol supply to the offspring.
Structural insights into the stimulation of S. pombe Dnmt2 catalytic efficiency by the tRNA nucleoside queuosine
Authors: Johannsson Sven , Neumann Piotr , Wulf Alexander , Welp Luisa M. , Gerber Hans-Dieter , Krull Matthias , Diederichsen Ulf , Urlaub Henning , Ficner Ralf
Published: June 2018

Dnmt2 methylates cytosine at position 38 of tRNAAsp in a variety of eukaryotic organisms. A correlation between the presence of the hypermodified nucleoside queuosine (Q) at position 34 of tRNAAsp and the Dnmt2 dependent C38 methylation was recently found in vivo for S. pombe and D. discoideum. We demonstrate a direct effect of the Q-modification on the methyltransferase catalytic efficiency in vitro, as Vmax/K0.5 of purified S. pombe Dnmt2 shows an increase for in vitro transcribed tRNAAsp containing Q34 to 6.27 ∗ 10–3 s−1 µM−1 compared to 1.51 ∗ 10–3 s−1 µM−1 for the unmodified substrate. Q34tRNAAsp exhibits an only slightly increased affinity for Dnmt2 in comparison to unmodified G34tRNA. In order to get insight into the structural basis for the Q-dependency, the crystal structure of S. pombe Dnmt2 was determined at 1.7 Å resolution. It closely resembles the known structures of human and E. histolytica Dnmt2, and contains the entire active site loop. The interaction with tRNA was analyzed by means of mass-spectrometry using UV cross-linked Dnmt2-tRNA complex. These cross-link data and computational docking of Dnmt2 and tRNAAsp reveal Q34 positioned adjacent to the S-adenosylmethionine occupying the active site, suggesting that the observed increase of Dnmt2 catalytic efficiency by queuine originates from optimal positioning of the substrate molecules and residues relevant for methyl transfer.
MicroRNA-21 in cancer-associated fibroblasts supports lung adenocarcinoma progression
Authors: Kunita Akiko , Morita Shigeki , Irisa Tomoko U. , Goto Akiteru , Niki Toshiro , Takai Daiya , Nakajima Jun , Fukayama Masashi
Published: June 2018

Cancer-associated fibroblasts (CAFs) interact closely with cancer cells, supporting their growth and invasion. To investigate the role of microRNA-21 (miR-21) in lung adenocarcinoma, and especially in its CAF component, in situ hybridisation was applied to samples from 89 invasive lung adenocarcinoma cases. MiR-21 expression was observed in both cancer cells and CAFs. When the patients were stratified by expression, miR-21 levels in CAFs (n = 9), but not in cancer cells (n = 21), were inversely correlated with patient survival; patients with miR-21high CAFs exhibited lower survival than those with miR-21low CAFs. The underlying mechanism was investigated in vitro. Conditioned medium (CM) from A549 lung cancer cells increased miR-21 expression in MRC-5 and IMR-90 lung fibroblasts through the transforming growth factor-β pathway, and induced CAF-like morphology and migratory capacity. MiR-21 up-regulation in lung fibroblasts induced a novel CAF-secreted protein, calumenin, as well as known CAF markers (periostin, α-smooth muscle actin, and podoplanin). Moreover, CM from the lung fibroblasts increased A549 cell proliferation in a calumenin-dependent manner. Thus, miR-21 expression in lung fibroblasts may trigger fibroblast trans-differentiation into CAFs, supporting cancer progression. Therefore, CAF miR-21 represents a pivotal prognostic marker for this scar-forming cancer of the lungs.
Conformational rearrangements of the C1 ring in KaiC measure the timing of assembly with KaiB
Authors: Mukaiyama Atsushi , Furuike Yoshihiko , Abe Jun , Koda Shin-ichi , Yamashita Eiki , Kondo Takao , Akiyama Shuji
Published: June 2018

KaiC, the core oscillator of the cyanobacterial circadian clock, is composed of an N-terminal C1 domain and a C-terminal C2 domain, and assembles into a double-ring hexamer upon ATP binding. Cyclic phosphorylation and dephosphorylation at Ser431 and Thr432 in the C2 domain proceed with a period of approximately 24 h in the presence of other clock proteins, KaiA and KaiB, but recent studies have revealed a crucial role for the C1 ring in determining the cycle period. In this study, we mapped dynamic structural changes of the C1 ring in solution using a combination of site-directed tryptophan mutagenesis and fluorescence spectroscopy. We found that the C1 ring undergoes a structural transition, coupled with ATPase activity and the phosphorylation state, while maintaining its hexameric ring structure. This transition triggered by ATP hydrolysis in the C1 ring in specific phosphorylation states is a necessary event for recruitment of KaiB, limiting the overall rate of slow complex formation. Our results provide structural and kinetic insights into the C1-ring rearrangements governing the slow dynamics of the cyanobacterial circadian clock.
Aerosol mixing state matters for particles deposition in human respiratory system
Authors: Ching Joseph , Kajino Mizuo
Published: June 2018

Aerosol particles emitted from various human activities deteriorate air quality and are suggested to increase public health risk. Numerous studies have emphasized the relationship between the mass and/or number concentration of aerosols (or commonly known as particulate matter (PM)) in the atmosphere and the incidence of respiratory and cardiovascular diseases, while very few have examined the deposition efficiency of inhaled particles in the respiratory tract. We present the first examination of particles deposition based on, detailed simulation of aerosol physico-chemical properties by a recently developed particle-resolved aerosol model and the mixing state dependent hygrosocpic growth and deposition computed at particle-level by deposition model. Furthermore, we elucidate the impact of mixing state on deposition efficiency by using a recently introduced aerosol mixing state index. We find that without considering mixing-state-dependent hygroscopic growth of particles leads to overestimation of deposition efficiency; whereas considering an average mixing state leads to underestimation of 5% to 20% of soot particle deposition efficiency in human alveoli. We conclude that aerosol mixing state, which evolves during the interaction between atmospheric chemistry and meteorology, is important for the comprehensive evaluation of air quality and its implication to public health requires further investigation.
Candida albicans Cdc15 is essential for mitotic exit and cytokinesis
Authors: Bates Steven
Published: June 2018

Candida albicans displays a variety of morphological forms, and the ability to switch forms must be linked with cell cycle control. In budding yeast the Mitotic Exit Network (MEN) acts to drive mitotic exit and signal for cytokinesis and cell separation. However, previous reports on the MEN in C. albicans have raised questions on its role in this organism, with the components analysed to date demonstrating differing levels of importance in the processes of mitotic exit, cytokinesis and cell separation. This work focuses on the role of the Cdc15 kinase in C. albicans and demonstrates that, similar to Saccharomyces cerevisiae, it plays an essential role in signalling for mitotic exit and cytokinesis. Cells depleted of Cdc15 developed into elongated filaments, a common response to cell cycle arrest in C. albicans. These filaments emerged exclusively from large budded cells, contained two nuclear bodies and exhibited a hyper-extended spindle, all characteristic of these cells failing to exit mitosis. Furthermore these filaments displayed a clear cytokinesis defect, and CDC15 over-expression led to aberrant cell separation following hyphal morphogenesis. Together, these results are consistent with Cdc15 playing an essential role in signalling for mitotic exit, cytokinesis and cell separation in C. albicans.
Modelling Peri-Perceptual Brain Processes in a Deep Learning Spiking Neural Network Architecture
Authors: Gholami Doborjeh Zohreh , Kasabov Nikola , Gholami Doborjeh Maryam , Sumich Alexander
Published: June 2018

Familiarity of marketing stimuli may affect consumer behaviour at a peri-perceptual processing level. The current study introduces a method for deep learning of electroencephalogram (EEG) data using a spiking neural network (SNN) approach that reveals the complexity of peri-perceptual processes of familiarity. The method is applied to data from 20 participants viewing familiar and unfamiliar logos. The results support the potential of SNN models as novel tools in the exploration of peri-perceptual mechanisms that respond differentially to familiar and unfamiliar stimuli. Specifically, the activation pattern of the time-locked response identified by the proposed SNN model at approximately 200 milliseconds post-stimulus suggests greater connectivity and more widespread dynamic spatio-temporal patterns for familiar than unfamiliar logos. The proposed SNN approach can be applied to study other peri-perceptual or perceptual brain processes in cognitive and computational neuroscience.