bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipid analysis of Eimeria sporozoites reveals exclusive phospholipids, a phylogenetic mosaic of endogenous synthesis, and a host-independent lifestyle
Authors: Kong Pengfei , Lehmann Maik J. , Helms J. Bernd , Brouwers Jos F. , Gupta Nishith
Published: May 2018

Successful inter-host transmission of most apicomplexan parasites requires the formation of infective sporozoites within the oocysts. Unlike all other infective stages that are strictly intracellular and depend on host resources, the sporozoite stage develops outside the host cells, but little is known about its self-governing metabolism. This study deployed Eimeria falciformis, a parasite infecting the mouse as its natural host, to investigate the process of phospholipid biogenesis in sporozoites. Lipidomic analyses demonstrated the occurrence of prototypical phospholipids along with abundant expression of at least two exclusive lipids, phosphatidylthreonine (PtdThr) and inositol phosphorylceramide with a phytosphingosine backbone, in sporozoites. To produce them de novo, the parasite harbors nearly the entire biogenesis network, which is an evolutionary mosaic of eukaryotic-type and prokaryotic-type enzymes. Notably, many have no phylogenetic counterpart or functional equivalent in the mammalian host. Using Toxoplasma gondii as a gene-tractable surrogate to examine Eimeria enzymes, we show a highly compartmentalized network of lipid synthesis spread primarily in the apicoplast, endoplasmic reticulum, mitochondrion, and Golgi complex. Likewise, trans-genera complementation of a Toxoplasma mutant with the PtdThr synthase from Eimeria reveals a convergent role of PtdThr in fostering the lytic cycle of coccidian parasites. Taken together, our work establishes a model of autonomous membrane biogenesis involving significant inter-organelle cooperation and lipid trafficking in sporozoites. Phylogenetic divergence of certain pathways offers attractive drug targets to block the sporulation and subsequent transmission. Not least, our results vindicate the possession of an entire de novo lipid synthesis network in a representative protist adapted to an obligate intracellular parasitic lifestyle.
The histone demethylase Phf2 acts as a molecular checkpoint to prevent NAFLD progression during obesity
Authors: Bricambert Julien , Alves-Guerra Marie-Clotilde , Esteves Pauline , Prip-Buus Carina , Bertrand-Michel Justine , Guillou Hervé , Chang Christopher J. , Vander Wal Mark N. , Canonne-Hergaux François , Mathurin Philippe , Raverdy Violeta , Pattou François , Girard Jean , Postic Catherine , Dentin Renaud
Published: May 2018

Aberrant histone methylation profile is reported to correlate with the development and progression of NAFLD during obesity. However, the identification of specific epigenetic modifiers involved in this process remains poorly understood. Here, we identify the histone demethylase Plant Homeodomain Finger 2 (Phf2) as a new transcriptional co-activator of the transcription factor Carbohydrate Responsive Element Binding Protein (ChREBP). By specifically erasing H3K9me2 methyl-marks on the promoter of ChREBP-regulated genes, Phf2 facilitates incorporation of metabolic precursors into mono-unsaturated fatty acids, leading to hepatosteatosis development in the absence of inflammation and insulin resistance. Moreover, the Phf2-mediated activation of the transcription factor NF-E2-related factor 2 (Nrf2) further reroutes glucose fluxes toward the pentose phosphate pathway and glutathione biosynthesis, protecting the liver from oxidative stress and fibrogenesis in response to diet-induced obesity. Overall, our findings establish a downstream epigenetic checkpoint, whereby Phf2, through facilitating H3K9me2 demethylation at specific gene promoters, protects liver from the pathogenesis progression of NAFLD.
Inharmonic speech reveals the role of harmonicity in the cocktail party problem
Authors: Popham Sara , Boebinger Dana , Ellis Dan P. W. , Kawahara Hideki , McDermott Josh H.
Published: May 2018

The “cocktail party problem” requires us to discern individual sound sources from mixtures of sources. The brain must use knowledge of natural sound regularities for this purpose. One much-discussed regularity is the tendency for frequencies to be harmonically related (integer multiples of a fundamental frequency). To test the role of harmonicity in real-world sound segregation, we developed speech analysis/synthesis tools to perturb the carrier frequencies of speech, disrupting harmonic frequency relations while maintaining the spectrotemporal envelope that determines phonemic content. We find that violations of harmonicity cause individual frequencies of speech to segregate from each other, impair the intelligibility of concurrent utterances despite leaving intelligibility of single utterances intact, and cause listeners to lose track of target talkers. However, additional segregation deficits result from replacing harmonic frequencies with noise (simulating whispering), suggesting additional grouping cues enabled by voiced speech excitation. Our results demonstrate acoustic grouping cues in real-world sound segregation.
Publisher Correction: Emergence of Different Recombinant Porcine Reproductive and Respiratory Syndrome Viruses, China
Authors: Liu Yanyan , Li Jianda , Yang Jie , Zeng Hao , Guo Lihui , Ren Sufang , Sun Wenbo , Chen Zhi , Cong Xiaoyan , Shi Jianli , Chen Lei , Du Yijun , Li Jun , Wang Jinbao , Wu Jiaqiang , Yu Jiang
Published: May 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.
Asymmetric transfer of CO2 across a broken sea surface
Authors: Leighton Timothy G. , Coles David G. H. , Srokosz Meric , White Paul R. , Woolf David K.
Published: May 2018

Most estimates of the climatically-important transfer of atmospheric gases into, and out of, the ocean assume that the ocean surface is unbroken by breaking waves. However the trapping of bubbles of atmospheric gases in the ocean by breaking waves introduces an asymmetry in this flux. This asymmetry occurs as a bias towards injecting gas into the ocean where it dissolves, and against the evasion/exsolution of previously-dissolved gas coming out of solution from the oceans and eventually reaching the atmosphere. Here we use at-sea measurements and modelling of the bubble clouds beneath the ocean surface to show that the numbers of large bubbles found metres below the sea surface in high winds are sufficient to drive a large and asymmetric flux of carbon dioxide. Our results imply a much larger asymmetry for carbon dioxide than previously proposed. This asymmetry contradicts an assumption inherent in most existing estimates of ocean-atmosphere gas transfer. The geochemical and climate implications include an enhanced invasion of carbon dioxide into the stormy temperate and polar seas.
Exciton Relaxation Cascade in two-dimensional Transition Metal Dichalcogenides
Authors: Brem Samuel , Selig Malte , Berghaeuser Gunnar , Malic Ermin
Published: May 2018

Monolayers of transition metal dichalcogenides (TMDs) are characterized by an extraordinarily strong Coulomb interaction giving rise to tightly bound excitons with binding energies of hundreds of meV. Excitons dominate the optical response as well as the ultrafast dynamics in TMDs. As a result, a microscopic understanding of exciton dynamics is the key for a technological application of these materials. In spite of this immense importance, elementary processes guiding the formation and relaxation of excitons after optical excitation of an electron-hole plasma has remained unexplored to a large extent. Here, we provide a fully quantum mechanical description of momentum- and energy-resolved exciton dynamics in monolayer molybdenum diselenide (MoSe2) including optical excitation, formation of excitons, radiative recombination as well as phonon-induced cascade-like relaxation down to the excitonic ground state. Based on the gained insights, we reveal experimentally measurable features in pump-probe spectra providing evidence for the exciton relaxation cascade.
PCR-Stop analysis as a new tool for qPCR assay validation
Authors: Witte Anna Kristina , Mester Patrick , Fister Susanne , Süß Beate , Wagner Martin , Rossmanith Peter
Published: May 2018

Progressively more qPCR assays have been developed in recent years in numerous fields of application. These assays are routinely validated using calibration curves, but essential validation per se such as Poisson analysis is frequently neglected. However, validation is crucial for determination of resolution and quantitative and qualitative limits. The new test method PCR-Stop analysis presented in this work investigates assay performance during initial qPCR cycles. PCRs with one to five pre-runs are performed while the subsequent main qPCR runs reflect pre-run replication rates. Ideally, DNA doubles according to pre-runs, there is no variation between replicates and qPCR starts immediately at the first cycle with its average efficiency. This study shows two exemplary qPCR assays, both with suitable calibration curves and efficiencies. We demonstrated thereby the benefits of PCR-Stop analysis revealing quantitative and qualitative resolution of both assays, the limits of one of those assays and thus avoiding misinterpretations in qPCR analysis. Furthermore, data displayed that a well performing assay starts indeed with its average efficiency.
Nanopore sequencing of drug-resistance-associated genes in malaria parasites, Plasmodium falciparum
Authors: Runtuwene Lucky R. , Tuda Josef S. B. , Mongan Arthur E. , Makalowski Wojciech , Frith Martin C. , Imwong Mallika , Srisutham Suttipat , Nguyen Thi Lan Anh , Tuan Nghia Nguyen , Eshita Yuki , Maeda Ryuichiro , Yamagishi Junya , Suzuki Yutaka
Published: May 2018

Here, we report the application of a portable sequencer, MinION, for genotyping the malaria parasite Plasmodium falciparum. In the present study, an amplicon mixture of nine representative genes causing resistance to anti-malaria drugs is diagnosed. First, we developed the procedure for four laboratory strains (3D7, Dd2, 7G8, and K1), and then applied the developed procedure to ten clinical samples. We sequenced and re-sequenced the samples using the obsolete flow cell R7.3 and the most recent flow cell R9.4. Although the average base-call accuracy of the MinION sequencer was 74.3%, performing >50 reads at a given position improves the accuracy of the SNP call, yielding a precision and recall rate of 0.92 and 0.8, respectively, with flow cell R7.3. These numbers increased significantly with flow cell R9.4, in which the precision and recall are 1 and 0.97, respectively. Based on the SNP information, the drug resistance status in ten clinical samples was inferred. We also analyzed K13 gene mutations from 54 additional clinical samples as a proof of concept. We found that a novel amino-acid changing variation is dominant in this area. In addition, we performed a small population-based analysis using 3 and 5 cases (K13) and 10 and 5 cases (PfCRT) from Thailand and Vietnam, respectively. We identified distinct genotypes from the respective regions. This approach will change the standard methodology for the sequencing diagnosis of malaria parasites, especially in developing countries.
Author Correction: Transcriptome profiling of mouse colonic eosinophils reveals a key role for eosinophils in the induction of s100a8 and s100a9 in mucosal healing
Authors: Reichman Hadar , Moshkovits Italy , Itan Michal , Pasmanik-Chor Metsada , Vogl Thomas , Roth Johannes , Munitz Ariel
Published: May 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.
A phase I single-blind clinical trial to evaluate the safety of oil palm phenolics (OPP) supplementation in healthy volunteers
Authors: Fairus Syed , Leow Soon-Sen , Mohamed Isa Naina , Tan Yew-Ai , Sundram Kalyana , Sambanthamurthi Ravigadevi
Published: May 2018

Plant phenolics are being increasingly consumed globally with limited scientific and clinical evidence pertaining to safety and efficacy. The oil palm fruit contains a cocktail of phenolics, and palm oil production results in high volumes of aqueous by-products enriched in phenolics and bioactives. Several lines of evidence from in vitro and in vivo animal studies confirmed that the aqueous extract enriched in phenolics and other bioactives collectively known as oil palm phenolics (OPP) is safe and has potent bioactivity. A phase one clinical trial was conducted to evaluate the safety and effects of OPP in healthy volunteers. In this single-blind trial, 25 healthy human volunteers were supplemented with 450 mg gallic acid equivalent (GAE)/day of OPP or control treatments for a 60-day period. Fasting blood and urine samples were collected at days 1, 30 and 60. Medical examination was performed during these trial interventions. All clinical biochemistry profiles observed throughout the control and OPP treatment period were in the normal range with no major adverse effect (AE) or serious adverse effect (SAE) observed. Additionally, OPP supplementation resulted in improvement of total cholesterol and LDL-C levels, compared to the control treatment. The outcomes support our previous observations that OPP is safe and may have a protective role in reducing cholesterol levels.
Molecular Evidence of Genome Editing in a Mouse Model of Immunodeficiency
Authors: Abdul-Razak H. H. , Rocca C. J. , Howe S. J. , Alonso-Ferrero M. E. , Wang J. , Gabriel R. , Bartholomae C. C. , Gan C. H. V. , Garín M. I. , Roberts A. , Blundell M. P. , Prakash V. , Molina-Estevez F. J. , Pantoglou J. , Guenechea G. , Holmes M. C. , Gregory P. D. , Kinnon C. , von Kalle C. , Schmidt M. , Bueren J. A. , Thrasher A. J. , Yáñez-Muñoz R. J.
Published: May 2018

Genome editing is the introduction of directed modifications in the genome, a process boosted to therapeutic levels by designer nucleases. Building on the experience of ex vivo gene therapy for severe combined immunodeficiencies, it is likely that genome editing of haematopoietic stem/progenitor cells (HSPC) for correction of inherited blood diseases will be an early clinical application. We show molecular evidence of gene correction in a mouse model of primary immunodeficiency. In vitro experiments in DNA-dependent protein kinase catalytic subunit severe combined immunodeficiency (Prkdc scid) fibroblasts using designed zinc finger nucleases (ZFN) and a repair template demonstrated molecular and functional correction of the defect. Following transplantation of ex vivo gene-edited Prkdc scid HSPC, some of the recipient animals carried the expected genomic signature of ZFN-driven gene correction. In some primary and secondary transplant recipients we detected double-positive CD4/CD8 T-cells in thymus and single-positive T-cells in blood, but no other evidence of immune reconstitution. However, the leakiness of this model is a confounding factor for the interpretation of the possible T-cell reconstitution. Our results provide support for the feasibility of rescuing inherited blood disease by ex vivo genome editing followed by transplantation, and highlight some of the challenges.
Publisher Correction: Structural Implications of Mutations Conferring Rifampin Resistance in Mycobacterium leprae
Authors: Vedithi Sundeep Chaitanya , Malhotra Sony , Das Madhusmita , Daniel Sheela , Kishore Nanda , George Anuja , Arumugam Shantha , Rajan Lakshmi , Ebenezer Mannam , Ascher David B. , Arnold Eddy , Blundell Tom L.
Published: May 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.
Homoharringtonine induced immune alteration for an Efficient Anti-tumor Response in Mouse Models of Non-small Cell Lung Adenocarcinoma Expressing Kras Mutation
Authors: Weng Tzu-Yang , Wu Hsuan Franziska , Li Chung-Yen , Hung Yu-Hsuan , Chang Yu-Wei , Chen Yi-Ling , Hsu Hui-Ping , Chen Yu-Hung , Wang Chih-Yang , Chang Jang-Yang , Lai Ming-Derg
Published: May 2018

Homoharringtonine (HHT), an inhibitor of protein synthesis, has been used to treat leukemia. Its therapeutic effects on non-small cell lung adenocarcinoma carrying KRAS mutation and their immune system are less understood. The present study examined the therapeutic efficacy and the immune effects of HHT in two murine lung tumor models, xenograft and transgenic, carrying the Kras mutation G12D and G12C respectively. HHT exhibited efficient anticancer activity, significantly suppressing lung tumor growthin vitroandin vivo. The levels of 22 cytokines and chemokines in splenocytes of tumor-bearing mice were examined. Interleukin-12 expression was lower in splenocytes of HHT-treated mice when compared to the controls as demonstrated by a cytokine array and an enzyme-linked immunosorbent assay. The expression levels of CD80, CD86, and CD69 in B220+B cells from splenocytes of HHT-treated mice were higher than that of control mice in two mouse tumor models. Furthermore, antitumor effect of HHT was attenuated with depletion of B cells. Increased numbers of CD80+and CD86+B cells were observed in the mice treated with narciclasine, another translation inhibitor. In conclusion, HHT changed the features of immune cells, and exhibited efficient anti-tumor activity against lung tumor carrying mutant Kras expression.
A comprehensive analysis of e-CAS cell line reveals they are mouse macrophages
Authors: Evans Elizabeth , Paillot Romain , López-Álvarez María Rocío
Published: May 2018

The 3Rs principles (Replacement, Reduction and Refinement) are focused on finding alternatives to the use of animals in research. In this regard, cell lines are popular and useful tools for the replacement of primary cells in in vitro studies. However, around 15–30% of cell lines used in research have been misidentified or cross-contaminated generating concerns about the results obtained from experiments that use them. Here we described how old aliquots of an equine macrophage cell line (e-CAS) stored at the Animal Health Trust did not contain equine cells but macrophages of murine origin (m-CAS).
A new genetic mechanism of natural gas accumulation
Authors: Yang Chengyu , Ni Zhiyong , Wang Tieguan , Chen Zhonghong , Hong Haitao , Wen Long , Luo Bing , Wang Wenzhi
Published: May 2018

Natural gas of organic origin is primarily biogenic or thermogenic; however, the formation of natural gas is occasionally attributed to hydrothermal activity. The Precambrian dolomite reservoir of the Anyue gas field is divided into three stages. Dolomite-quartz veins were precipitated after two earlier stages of dolomite deposition. Fluid inclusions in the dolomite and quartz are divided into pure methane (P-type), methane-bearing (M-type), aqueous (W-type), and solid bitumen-bearing (S-type) inclusions. The W-type inclusions within the quartz and buried dolomite homogenized between 107 °C and 223 °C. Furthermore, the trapping temperatures and pressures of the fluid (249 °C to 319 °C and 1619 bar to 2300 bar, respectively) are obtained from the intersections of the isochores of the P-type and the coeval W-type inclusions in the quartz. However, the burial history of the reservoir indicates that the maximum burial temperature did not exceed 230 °C. Thus, the generation of the natural gas was not caused solely by the burial of the dolomite reservoir. The results are also supported by the presence of paragenetic pyrobitumen and MVT lead-zinc ore. A coupled system of occasional invasion by hydrothermal fluids and burial of the reservoir may represent a new genetic model for natural gas accumulation in this gas field.
Influence of Household Water Filters on Bacteria Growth and Trace Metals in Tap Water of Doha, Qatar
Authors: Nriagu Jerome , Xi Chuanwu , Siddique Azhar , Vincent Annette , Shomar Basem
Published: May 2018

Deteriorating water quality from aging infrastructure, growing threat of pollution from industrialization and urbanization, and increasing awareness about waterborne diseases are among the factors driving the surge in worldwide use of point-of-entry (POE) and point-of-use (POU) filters. Any adverse influence of such consumer point-of-use systems on quality of water at the tap remains poorly understood, however. We determined the chemical and microbiological changes in municipal water from the point of entry into the household plumbing system until it leaves from the tap in houses equipped with filters. We show that POE/POU devices can induce significant deterioration of the quality of tap water by functioning as traps and reservoirs for sludge, scale, rust, algae or slime deposits which promote microbial growth and biofilm formation in the household water distribution system. With changes in water pressure and physical or chemical disturbance of the plumbing system, the microorganisms and contaminants may be flushed into the tap water. Such changes in quality of household water carry a potential health risk which calls for some introspection in widespread deployment of POE/POU filters in water distribution systems.
The bioeroding sponge Cliona orientalis will not tolerate future projected ocean warming
Authors: Ramsby Blake D. , Hoogenboom Mia O. , Smith Hillary A. , Whalan Steve , Webster Nicole S.
Published: May 2018

Coral reefs face many stressors associated with global climate change, including increasing sea surface temperature and ocean acidification. Excavating sponges, such as Cliona spp., are expected to break down reef substrata more quickly as seawater becomes more acidic. However, increased bioerosion requires that Cliona spp. maintain physiological performance and health under continuing ocean warming. In this study, we exposed C. orientalis to temperature increments increasing from 23 to 32 °C. At 32 °C, or 3 °C above the maximum monthly mean (MMM) temperature, sponges bleached and the photosynthetic capacity of Symbiodinium was compromised, consistent with sympatric corals. Cliona orientalis demonstrated little capacity to recover from thermal stress, remaining bleached with reduced Symbiodinium density and energy reserves after one month at reduced temperature. In comparison, C. orientalis was not observed to bleach during the 2017 coral bleaching event on the Great Barrier Reef, when temperatures did not reach the 32 °C threshold. While C. orientalis can withstand current temperature extremes (<3 °C above MMM) under laboratory and natural conditions, this species would not survive ocean temperatures projected for 2100 without acclimatisation or adaptation (≥3 °C above MMM). Hence, as ocean temperatures increase above local thermal thresholds, C. orientalis will have a negligible impact on reef erosion.
Investigation of dose-rate effects and cell-cycle distribution under protracted exposure to ionizing radiation for various dose-rates
Authors: Matsuya Yusuke , McMahon Stephen J. , Tsutsumi Kaori , Sasaki Kohei , Okuyama Go , Yoshii Yuji , Mori Ryosuke , Oikawa Joma , Prise Kevin M. , Date Hiroyuki
Published: May 2018

During exposure to ionizing radiation, sub-lethal damage repair (SLDR) competes with DNA damage induction in cultured cells. By virtue of SLDR, cell survival increases with decrease of dose-rate, so-called dose-rate effects (DREs). Here, we focused on a wide dose-rate range and investigated the change of cell-cycle distribution during X-ray protracted exposure and dose-response curves via hybrid analysis with a combination of in vitro experiments and mathematical modelling. In the course of flow-cytometric cell-cycle analysis and clonogenic assays, we found the following responses in CHO-K1 cells: (1) The fraction of cells in S phase gradually increases during 6 h exposure at 3.0 Gy/h, which leads to radio-resistance. (2) Slight cell accumulation in S and G2/M phases is observed after exposure at 6.0 Gy/h for more than 10 hours. This suggests that an increase of SLDR rate for cells in S phase during irradiation may be a reproducible factor to describe changes in the dose-response curve at dose-rates of 3.0 and 6.0 Gy/h. By re-evaluating cell survival for various dose-rates of 0.186–60.0 Gy/h considering experimental-based DNA content and SLDR, it is suggested that the change of S phase fraction during irradiation modulates the dose-response curve and is possibly responsible for some inverse DREs.
Association of a rare variant of the TNFSF13B gene with susceptibility to Rheumatoid Arthritis and Systemic Lupus Erythematosus
Authors: González-Serna David , Ortiz-Fernández Lourdes , Vargas Sofía , García Antonio , Raya Enrique , Fernández-Gutierrez Benjamín , López-Longo Francisco Javier , Balsa Alejandro , González-Álvaro Isidoro , Narvaez Javier , Gómez-Vaquero Carmen , Sabio José Mario , García-Portales Rosa , González-Escribano María Francisca , Tolosa Carles , Carreira Patricia , Kiemeney Lambertus , Coenen Marieke J. H. , Witte Torsten , Schneider Matthias , González-Gay Miguel Ángel , Martín Javier
Published: May 2018

A rare variant (BAFF-var) of the tumor necrosis factor superfamily 13b (TNFSF13B) gene has been recently associated with multiple sclerosis (MS) and systemic lupus erythematosus (SLE). The aim of this study was to investigate the association between TNFSF13B BAFF-var and susceptibility to rheumatoid arthritis (RA) and replicate that association in SLE. 6,218 RA patients, 2,575 SLE patients and 4,403 healthy controls from three different countries were included in the study. TNFSF13B BAFF-var was genotyped using TaqMan allelic discrimination assay. PLINK software was used for statistical analyses. TNFSF13B BAFF-var was significantly associated with RA (p = 0.015, OR = 1.21, 95% CI = 1.03–1.41) in the Spanish cohort. A trend of association was observed in the Dutch (p = 0.115) and German (p = 0.228) RA cohorts. A meta-analysis of the three RA cohorts included in this study revealed a statistically significant association (p = 0.002, OR = 1.24, 95% CI = 1.10–1.38). In addition, TNFSF13B BAFF-var was significantly associated with SLE in the Spanish (p = 0.001, OR = 1.41, 95% CI = 1.14–1.74) and the German cohorts (p = 0.030, OR = 1.86, 95% CI = 1.05–3.28), with a statistically significant p-value obtained in the meta-analysis (p = 0.0002, OR = 1.46, 95% CI = 1.09–2.32). The results obtained confirm the known association of TNFSF13B BAFF-var with SLE and, for the first time, demonstrate that this variant contributes to susceptibility to RA.
Sub-threshold signal encoding in coupled FitzHugh-Nagumo neurons
Authors: Masoliver Maria , Masoller Cristina
Published: May 2018

Despite intensive research, the mechanisms underlying the neural code remain poorly understood. Recent work has focused on the response of a single neuron to a weak, sub-threshold periodic signal. By simulating the stochastic FitzHugh-Nagumo (FHN) model and then using a symbolic method to analyze the firing activity, preferred and infrequent spike patterns (defined by the relative timing of the spikes) were detected, whose probabilities encode information about the signal. As not individual neurons but neuronal populations are responsible for sensory coding and information transfer, a relevant question is how a second neuron, which does not perceive the signal, affects the detection and the encoding of the signal, done by the first neuron. Through simulations of two stochastic FHN neurons we show that the encoding of a sub-threshold signal in symbolic spike patterns is a plausible mechanism. The neuron that perceives the signal fires a spike train that, despite having an almost random temporal structure, has preferred and infrequent patterns which carry information about the signal. Our findings could be relevant for sensory systems composed by two noisy neurons, when only one detects a weak external input.
The evolution of genomic and epigenomic features in two Pleurotus fungi
Authors: Zhang Zhibin , Wen Jiawei , Li Juzuo , Ma Xintong , Yu Yanan , Tan Xiao , Wang Qi , Liu Bao , Li Xiaomeng , Li Yu , Gong Lei
Published: May 2018

Pleurotus tuoliensis (Bailinggu, designated Pt) and P. eryngii var. eryngii (Xingbaogu, designated Pe) are highly valued edible mushrooms. We report de novo assemblies of high-quality genomes for both mushrooms based on PacBio RS II sequencing and annotation of all identified genes. A comparative genomics analysis between Pt and Pe with P. ostreatus as an outgroup taxon revealed extensive genomic divergence between the two mushroom genomes primarily due to the rapid gain of taxon-specific genes and disruption of synteny in either taxon. The re-appraised phylogenetic relationship between Pt and Pe at the genome-wide level validates earlier proposals to designate Pt as an independent species. Variation of the identified wood-decay-related gene content can largely explain the variable adaptation and host specificity of the two mushrooms. On the basis of the two assembled genome sequences, methylomes and the regulatory roles of DNA methylation in gene expression were characterized and compared. The genome, methylome and transcriptome data of these two important mushrooms will provide valuable information for advancing our understanding of the evolution of Pleurotus and related genera and for facilitating genome- and epigenome-based strategies for mushroom breeding.
Resolving the smell of wood - identification of odour-active compounds in Scots pine (Pinus sylvestris L.)
Authors: Schreiner Linda , Bauer Patrick , Buettner Andrea
Published: May 2018

Being one of the most common trees in forests, Pinus sylvestris L. is a frequently used raw material for wood products. Its specific odour is, however, mostly unresolved to date. Accordingly, we investigated Scots pine wood samples grown in Germany for their main odorant composition. We employed dedicated odorant analysis techniques such as gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA) and successfully detected 44 odour-active compounds; of these, 39 substances were successfully identified by gas chromatography-mass spectrometry/olfactometry (GC-MS/O) and two-dimensional gas chromatography-mass spectrometry/olfactometry (2D-GC-MS/O). Among the main odorants found were (E,E)-nona-2,4-dienal, vanillin, phenylacetic acid, 3-phenylpropanoic acid, δ-octalactone and α-pinene, all of them having been detected with high flavour dilution factors during GC-O analyses. The majority of the identified odorants were fatty acid degradation products, plus some terpenoic substances and odorous substances resulting from the degradation of lignin. Although some of the detected substances have previously been reported as constituents of wood, 11 substances are reported here for the first time as odour-active compounds in wood, amongst them heptanoic acid, γ-octalactone, δ-nonalactone and (E,Z,Z)-trideca-2,4,7-trienal.
Exploration of an urban lake management model to simulate chlorine interference based on the ecological relationships among aquatic species
Authors: Yan Zhiqiang , Wang Yafei , Wu Di , Xia Beicheng
Published: May 2018

In eutrophic lakes, algae are known to be sensitive to chlorine, but the impact of chlorine on the wider ecosystem has not been investigated. To quantitatively investigate the effects of chlorine on the urban lake ecosystem and analyze the changes in the aquatic ecosystem structure, a dynamic response model of aquatic species to chlorine was constructed based on the biomass density dynamics of aquatic species of submerged macrophytes, phytoplankton, zooplankton, periphyton, and benthos. The parameters were calibrated using data from the literature and two simulative experiments. The model was then validated using field data from an urban lake with a surface area of approximately 8000 m2 located in the downtown area of Guangzhou, South China. The correlation coefficient (R), root mean square error-observations standard deviation ratio (RSR) and index of agreement (IOA) were used to evaluate the accuracy and reliability of the model and the results were consistent with the observations (0.446 R < 0.985, RSR < 0.7, IOA > 0.6). Comparisons between the simulated and observed trends confirmed the feasibility of using this model to investigate the dynamics of aquatic species under chlorine interference. The model can help managers apply a modest amount of chlorine to control eutrophication and provides scientific support for the management of urban lakes.
Metastatic Brain Tumors Disrupt the Blood-Brain Barrier and Alter Lipid Metabolism by Inhibiting Expression of the Endothelial Cell Fatty Acid Transporter Mfsd2a
Authors: Tiwary Shweta , Morales John E. , Kwiatkowski Sam C. , Lang Frederick F. , Rao Ganesh , McCarty Joseph H.
Published: May 2018

Disruption of the blood-brain barrier (BBB) by cancer cells is linked to metastatic tumor initiation and progression; however, the pathways that drive these events remain poorly understood. Here, we have developed novel patient-derived xenograft (PDX) models of brain metastases that recapitulate pathological growth features found in original patient samples, thus allowing for analysis of BBB disruption by tumor cells. We report that the BBB is selectively disrupted in brain metastases, in part, via inhibition of the endothelial cell-expressed docosahexaenoic acid (DHA) transporter, major facilitator superfamily domain 2a (Mfsd2a). Loss of Mfsd2a expression in the tumor endothelium results in enhanced BBB leakage, but reduced DHA transport and altered lipid metabolism within metastases. Mfsd2a expression in normal cerebral endothelial cells is cooperatively regulated by TGFβ and bFGF signaling pathways, and these pathways are pathologically diminished in the brain metastasis endothelium. These results not only reveal a fundamental pathway underlying BBB disruption by metastatic cancer cells, but also suggest that restoring DHA metabolism in the brain tumor microenvironment may be a novel therapeutic strategy to block metastatic cell growth and survival.
Persistence of Long-lived Memory B Cells specific to Duffy Binding Protein in individuals exposed to Plasmodium vivax
Authors: Changrob Siriruk , McHenry Amy M. , Nyunt Myat Htut , Sattabongkot Jetsumon , Han Eun-Taek , Adams John H. , Chootong Patchanee
Published: May 2018

The major challenge in designing a protective Duffy binding protein region II (DBPII)-based vaccine against blood-stage vivax malaria is the high number of polymorphisms in critical residues targeted by binding-inhibitory antibodies. Here, longevity of antibody and memory B cell response (MBCs) to DBL-TH variants, DBL-TH2, -TH4, -TH5, -TH6 and -TH9 were analyzed in P. vivax-exposed individuals living in a low malaria transmission area of southern Thailand. Antibody to DBL-TH variants were significantly detected during P. vivax infection and it was persisted for up to 9 months post-infection. However, DBL-TH-specific MBC responses were stably maintained longer than antibody response, at least 3 years post-infection in the absence of re-infection. Phenotyping of B cell subsets showed the expansion of activated and atypical MBCs during acute and recovery phase of infection. While the persistence of DBL-TH-specific MBCs was found in individuals who had activated and atypical MBC expansion, anti-DBL-TH antibody responses was rapidly declined in plasma. The data suggested that these two MBCs were triggered by P. vivax infection, its expansion and stability may have impact on antibody responses. Our results provided evidence for ability of DBPII variant antigens in induction of long-lasting MBCs among individuals who were living in low malaria endemicity.
Publisher Correction: Identification of oral cancer related candidate genes by integrating protein-protein interactions, gene ontology, pathway analysis and immunohistochemistry
Authors: Kumar Ravindra , Samal Sabindra K. , Routray Samapika , Dash Rupesh , Dixit Anshuman
Published: May 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.
An α-1,6-and α-1,3-linked glucan produced by Leuconostoc citreum ABK-1 alternansucrase with nanoparticle and film-forming properties
Authors: Wangpaiboon Karan , Padungros Panuwat , Nakapong Santhana , Charoenwongpaiboon Thanapon , Rejzek Martin , Field Robert A. , Pichyangkura Rath
Published: May 2018

Alternansucrase catalyses the sequential transfer of glucose residues from sucrose onto another sucrose molecule to form a long chain polymer, known as “alternan”. The alternansucrase-encoding gene from Leuconostoc citreum ABK-1 (Lcalt) was successfully cloned and expressed in Escherichia coli. Lcalt encoded LcALT of 2,057 amino acid residues; the enzyme possessed an optimum temperature and pH of 40 °C and 5.0, respectively, and its’ activity was stimulated up to 2.4-fold by the presence of Mn2+. Kinetic studies of LcALT showed a high transglycosylation activity, with Km 32.2 ± 3.2 mM and kcat 290 ± 12 s−1. Alternan generated by LcALT (Lc-alternan) harbours partially alternating α-1,6 and α- 1,3 glycosidic linkages confirmed by NMR spectroscopy, methylation analysis, and partial hydrolysis of Lc-alternan products. In contrast to previously reported alternans, Lc-alternan can undergo self-assembly, forming nanoparticles with an average size of 90 nm in solution. At concentrations above 15% (w/v), Lc-alternan nanoparticles disassemble and form a high viscosity solution, while this polymer forms a transparent film once dried.
Broad distribution spectrum from Gaussian to power law appears in stochastic variations in RNA-seq data
Authors: Awazu Akinori , Tanabe Takahiro , Kamitani Mari , Tezuka Ayumi , Nagano Atsushi J.
Published: May 2018

Gene expression levels exhibit stochastic variations among genetically identical organisms under the same environmental conditions. In many recent transcriptome analyses based on RNA sequencing (RNA-seq), variations in gene expression levels among replicates were assumed to follow a negative binomial distribution, although the physiological basis of this assumption remains unclear. In this study, RNA-seq data were obtained from Arabidopsis thaliana under eight conditions (21–27 replicates), and the characteristics of gene-dependent empirical probability density function (ePDF) profiles of gene expression levels were analyzed. For A. thaliana and Saccharomyces cerevisiae, various types of ePDF of gene expression levels were obtained that were classified as Gaussian, power law-like containing a long tail, or intermediate. These ePDF profiles were well fitted with a Gauss-power mixing distribution function derived from a simple model of a stochastic transcriptional network containing a feedback loop. The fitting function suggested that gene expression levels with long-tailed ePDFs would be strongly influenced by feedback regulation. Furthermore, the features of gene expression levels are correlated with their functions, with the levels of essential genes tending to follow a Gaussian-like ePDF while those of genes encoding nucleic acid-binding proteins and transcription factors exhibit long-tailed ePDF.
FHC, an NS4B-interacting Protein, Enhances Classical Swine Fever Virus Propagation and Acts Positively in Viral Anti-apoptosis
Authors: Qian Gui , Lv Huifang , Lin Jihui , Li Xiaomeng , Lv Qizhuang , Wang Tao , Zhang Jing , Dong Wang , Guo Kangkang , Zhang Yanming
Published: May 2018

Classical swine fever virus (CSFV), the etiological agent of classical swine fever, causes enormous economic loss to the pig industry. Ferritin heavy chain (FHC) is a notable anti-apoptotic protein, and existing evidence suggests that CSFV cannot induce apoptosis of host cells, however, the role of FHC in CSFV replication remains unclear. In the present study, we found that recombinant lentivirus-mediated knockdown or overexpression of FHC inhibited or enhanced CSFV replication, respectively, indicating a positive role for FHC in CSFV proliferation. Furthermore, interaction between the CSFV NS4B protein and FHC was confirmed by glutathione S-transferase (GST) pull-down, co-immunoprecipitation (co-IP) and confocal imaging assays. In addition, both CSFV replication and NS4B expression upregulated expression of FHC, which counteracts apoptosis by modulating cellular reactive oxygen species (ROS). These results suggest that FHC, an NS4B-interacting protein, enhances CSFV replication and has a positive role in viral anti-apoptosis by regulating ROS accumulation. This work may provide a new perspective for understanding the mechanism of CSFV pathogenesis.
Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICETn43716385
Authors: Ding Yichen , Teo Jeanette W. P. , Drautz-Moses Daniela I. , Schuster Stephan C. , Givskov Michael , Yang Liang
Published: May 2018

Pseudomonas aeruginosa can cause life-threatening infections in immunocompromised patients. The first-line agents to treat P. aeruginosa infections are carbapenems. However, the emergence of carbapenem-resistant P. aeruginosa strains greatly compromised the effectiveness of carbapenem treatment, which makes the surveillance on their spreading and transmission important. Here we characterized the full-length genomes of two carbapenem-resistant P. aeruginosa clinical isolates that are capable of producing New Delhi metallo-β-lactamase-1 (NDM-1). We show that blaNDM-1 is carried by a novel integrative and conjugative element (ICE) ICETn43716385, which also carries the macrolide resistance gene msr(E) and the florfenicol resistance gene floR. By exogenously expressing msr(E) in P. aeruginosa laboratory strains, we show that Msr(E) can abolish azithromycin-mediated quorum sensing inhibition in vitro and anti-Pseudomonas effect in vivo. We conclude that ICEs are important in transmitting carbapenem resistance, and that anti-virulence treatment of P. aeruginosa infections using sub-inhibitory concentrations of macrolides can be challenged by horizontal gene transfer.
Correction: Corrigendum: Global effects of local food-production crises: a virtual water perspective
Authors: Tamea Stefania , Laio Francesco , Ridolfi Luca
Published: May 2018

Scientific Reports 6: Article number: 18803; published online: 25 January 2016; updated: 22 May 2018 The Acknowledgements section in this Article is incomplete. “The authors acknowledge funding from the Italian Ministry of Education, University and Research (MIUR) through the project “The global virtual-water network: social, economic, and environmental implications” (FIRB - RBFR12BA3Y).
Correction: Corrigendum: HIV-1 Env associates with HLA-C free-chains at the cell membrane modulating viral infectivity
Authors: Serena Michela , Parolini Francesca , Biswas Priscilla , Sironi Francesca , Blanco Miranda Almudena , Zoratti Elisa , Scupoli Maria Teresa , Ziglio Serena , Valenzuela-Fernandez Agustin , Gibellini Davide , Romanelli Maria Grazia , Siccardi Antonio , Malnati Mauro , Beretta Alberto , Zipeto Donato
Published: May 2018

Scientific Reports 7: Article number: 40037; published online: 04 January 2017; updated: 22 May 2018 The original version of this Article contained an error in Figure 7A, where the immunoblot of flotillin from HeLa was a duplicate of the immunoblot of flotillin from HeLa-LAI. This error has been corrected in the HTML and PDF versions of the Article and the figure has been appropriately delineated.
Role of the supracellular actomyosin cable during epithelial wound healing
Authors: Yang Yanjun , Levine Herbert
Published: May 2018

We demonstrate how the supracellular actomyosin cable contributes to the epithelial wound healing and its interplay with other mechanisms.
An improved k-nearest neighbour method to diagnose breast cancer
Authors: Li Qingbo , Li Wenjie , Zhang Jialin , Xu Zhi
Published: May 2018

An algorithm of entropy weighted local-hyperplane k-nearest-neighbor is proposed for the identification of Raman spectra and is effective for cancer diagnosis.
Electrochemiluminescence biosensing based on different modes of switching signals
Authors: Zhuo Ying , Wang Hai-Jun , Lei Yan-Mei , Zhang Pu , Liu Jia-Li , Chai Ya-Qin , Yuan Ruo
Published: May 2018

Electrochemiluminescence (ECL) has attracted much attention in various fields of analysis owing to low background signals, high sensitivity, and excellent controllability.
Platforms for rapid cancer characterization by ambient mass spectrometry: advancements, challenges and opportunities for improvement towards intrasurgical use
Authors: Woolman Michael , Zarrine-Afsar Arash
Published: May 2018

Ambient Mass Spectrometry (MS) analysis is widely used to characterize biological and non-biological samples.
Examples of unwanted variation when characterising dissolved organic matter using direct injection electrospray mass spectrometry and chemometrics
Authors: Nielsen N. J. , Christensen P. , Stedmon C. , Christensen J. H.
Published: May 2018

We describe a methodology for comparing and contrasting a large number of dissolved organic matter samples based on their electrospray ionization mass spectral characteristics and emphasize the importance of quality control samples to monitor unwanted variation.
Synergistic breast tumor cell killing achieved by intracellular co-delivery of doxorubicin and disulfiramviacore–shell–corona nanoparticles
Authors: Tao Xiaoguang , Gou Jingxin , Zhang Qianying , Tan Xinyi , Ren Tianyang , Yao Qing , Tian Bin , Kou Longfa , Zhang Ling , Tang Xing
Published: May 2018

Core–shell–corona nanoparticles for co-delivery of hydrophilic doxorubicin and hydrophobic disulfiram.
Self-assembled, bivalent aptamers on graphene oxide as an efficient anticoagulant
Authors: Lai Pei-Xin , Mao Ju-Yi , Unnikrishnan Binesh , Chu Han-Wei , Wu Chien-Wei , Chang Huan-Tsung , Huang Chih-Ching
Published: May 2018

Self-assembly of a bivalent thrombin-binding aptamer on graphene oxide that is easy to prepare, cost-effective, and highly biocompatible and showsin vivoanticoagulant activity.
Noninvasive rapid bacteria-killing and acceleration of wound healing through photothermal/photodynamic/copper ion synergistic action of a hybrid hydrogel
Authors: Li Mu , Liu Xiangmei , Tan Lei , Cui Zhenduo , Yang Xianjin , Li Zhaoyang , Zheng Yufeng , Yeung Kelvin Wai Kwok , Chu Paul K. , Wu Shuilin
Published: May 2018

Bacterial infection often delays healing of wounded tissues and so it is essential to improve the antibacterial efficiency in situ.
Network-like arrangement of mixed-valence uranium oxide nanoparticles after glutathione-induced reduction of uranium(vi)
Authors: Kretzschmar Jerome , Haubitz Toni , Hübner René , Weiss Stephan , Husar Richard , Brendler Vinzenz , Stumpf Thorsten
Published: May 2018

2–5 nm UO2+x nanocrystals yielded under near-neutral conditions arrange as 20–40 nm chain-like building blocks, and finally form network-like aggregates.
Bis-reaction-trigger as a strategy to improve the selectivity of fluorescent probes
Authors: Li Dan , Cheng Juan , Wang Cheng-Kun , Ying Huazhou , Hu Yongzhou , Han Feng , Li Xin
Published: May 2018

Equipping a fluorophore with two ONOO−-specific reaction triggers yielded a probe able to report various degrees of nitrosative stress in live cells.
The environmental-sensitivity of a fluorescent ZTRS–Cd(ii) complex was applied to discriminate different types of surfactants and determine their CMC values
Authors: Deng Fei , Long Shuangshuang , Qiao Qinglong , Xu Zhaochao
Published: May 2018

One probe to distinguish four types of surfactants based on Cd(ii) binding modes between imidic acid and amide tautomeric forms.
Low dimensional solids based on Mo6cluster cyanides and Mn2+, Mn3+or Cd2+metal ions: crystal chemistry, magnetic and optical properties
Authors: Daigre Gilles , Lemoine Pierric , Pham Thi Diep , Demange Valérie , Gautier Régis , Naumov Nikolay G. , Ledneva Alexandra , Amela-Cortes Maria , Dumait Noée , Audebrand Nathalie , Cordier Stéphane
Published: May 2018

Five new cluster compounds based on [Mo6Bri8(CN)a6]2−and [Mo6Bri6Qi2(CN)a6]n−(Q = S, Se,n= 3, 4) cluster units have been synthesized and characterized.
Comment on “Insight into the reversible structural crystalline-state transformation from MIL-53(Al) to MIL-68(Al)” by A. Perea-Cachero, E. Romero, C. Téllez and J. Coronas, CrystEngComm, 2018, 20, 402
Authors: Kriesten Martin , Hoffmann Kilian , Hartmann Martin
Published: May 2018

The inadvertently published phase transformation from MIL-53 to MIL-68 is merely a deformation of the MIL-53 structure upon DMF adsorption.