bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBotulinum 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

AbstractFour 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

AbstractFragile 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.
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

AbstractThe 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.
Unsupervised Hebbian learning experimentally realized with analogue memristive crossbar arrays
Authors: Hansen Mirko , Zahari Finn , Kohlstedt Hermann , Ziegler Martin 
Published: June 2018

AbstractConventional 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

AbstractA 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.
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

AbstractEnvironmental 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

AbstractVitamin 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

AbstractAbscisic 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

AbstractSeabirds 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

AbstractLindera, 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

AbstractThe 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

AbstractTo 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

AbstractFacial 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

AbstractBreast 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.