bluuebunny/crossref_metadata_2025 huggingface dataset:
Toll-like receptor 4 modulates the cochlear immune response to acoustic injury
Authors: Vethanayagam R R , Yang W , Dong Y , Hu B H
Published: June 2016

Acoustic overstimulation traumatizes the cochlea, resulting in auditory dysfunction. As a consequence of acoustic injury, the immune system in the cochlea is activated, leading to the production of inflammatory mediators and the infiltration of immune cells. However, the molecular mechanisms responsible for initiating these immune responses remain unclear. Here, we investigate the functional role of Toll-like receptor 4 (Tlr4), a cellular receptor that activates the innate immune system, in the regulation of cochlear responses to acoustic overstimulation. Using a Tlr4 knockout mouse model, we examined how Tlr4 deficiency affects sensory cell pathogenesis, auditory dysfunction and cochlear immune activity. We demonstrate that Tlr4 knockout does not affect sensory cell viability under physiological conditions, but reduces the level of sensory cell damage and cochlear dysfunction after acoustic injury. Together, these findings suggest that Tlr4 promotes sensory cell degeneration and cochlear dysfunction after acoustic injury. Acoustic injury provokes a site-dependent inflammatory response in both the organ of Corti and the tissues of the lateral wall and basilar membrane. Tlr4 deficiency affects these inflammatory responses in a site-dependent manner. In the organ of Corti, loss of Tlr4 function suppresses the production of interleukin 6 (Il6), a pro-inflammatory molecule, after acoustic injury. By contrast, the production of inflammatory mediators, including Il6, persists in the lateral wall and basilar membrane. In addition to immune molecules, Tlr4 knockout inhibits the expression of major histocompatibility complex class II, an antigen-presenting molecule, in macrophages, suggesting that Tlr4 participates in the antigen-presenting function of macrophages after acoustic trauma. Together, these results suggest that Tlr4 regulates multiple aspects of the immune response in the cochlea and contributes to cochlear pathogenesis after acoustic injury.
The dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2)
Authors: Jeong Yujin , Kim Ji-Nu , Kim Min Woo , Bucca Giselda , Cho Suhyung , Yoon Yeo Joon , Kim Byung-Gee , Roe Jung-Hye , Kim Sun Chang , Smith Colin P. , Cho Byung-Kwan
Published: June 2016

Individual Streptomyces species have the genetic potential to produce a diverse array of natural products of commercial, medical and veterinary interest. However, these products are often not detectable under laboratory culture conditions. To harness their full biosynthetic potential, it is important to develop a detailed understanding of the regulatory networks that orchestrate their metabolism. Here we integrate nucleotide resolution genome-scale measurements of the transcriptome and translatome of Streptomyces coelicolor, the model antibiotic-producing actinomycete. Our systematic study determines 3,570 transcription start sites and identifies 230 small RNAs and a considerable proportion (∼21%) of leaderless mRNAs; this enables deduction of genome-wide promoter architecture. Ribosome profiling reveals that the translation efficiency of secondary metabolic genes is negatively correlated with transcription and that several key antibiotic regulatory genes are translationally induced at transition growth phase. These findings might facilitate the design of new approaches to antibiotic discovery and development.
LRP6 acts as a scaffold protein in cardiac gap junction assembly
Authors: Li Jun , Li Changming , Liang Dandan , Lv Fei , Yuan Tianyou , The Erlinda , Ma Xiue , Wu Yahan , Zhen Lixiao , Xie Duanyang , Wang Shiyi , Liu Yuan , Huang Jian , Shi Jingyi , Liu Yi , Shi Dan , Xu Liang , Lin Li , Peng Luying , Cui Jianmin , Zhu Weidong , Chen Yi-Han
Published: June 2016

Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor in the canonical Wnt/β-catenin signalling. Here, we report the scaffold function of LRP6 in gap junction formation of cardiomyocytes. Cardiac LRP6 is spatially restricted to intercalated discs and binds to gap junction protein connexin 43 (Cx43). A deficiency in LRP6 disrupts Cx43 gap junction formation and thereby impairs the cell-to-cell coupling, which is independent of Wnt/β-catenin signalling. The defect in Cx43 gap junction resulting from LRP6 reduction is attributable to the defective traffic of de novo Cx43 proteins from the endoplasmic reticulum to the Golgi apparatus, leading to the lysosomal degradation of Cx43 proteins. Accordingly, the hearts of conditional cardiac-specific Lrp6-knockout mice consistently exhibit overt reduction of Cx43 gap junction plaques without any abnormality in Wnt signalling and are predisposed to lethal arrhythmias. These findings uncover a distinct role of LRP6 as a platform for intracellular protein trafficking.
Improving GENCODE reference gene annotation using a high-stringency proteogenomics workflow
Authors: Wright James C. , Mudge Jonathan , Weisser Hendrik , Barzine Mitra P. , Gonzalez Jose M. , Brazma Alvis , Choudhary Jyoti S. , Harrow Jennifer
Published: June 2016

Complete annotation of the human genome is indispensable for medical research. The GENCODE consortium strives to provide this, augmenting computational and experimental evidence with manual annotation. The rapidly developing field of proteogenomics provides evidence for the translation of genes into proteins and can be used to discover and refine gene models. However, for both the proteomics and annotation groups, there is a lack of guidelines for integrating this data. Here we report a stringent workflow for the interpretation of proteogenomic data that could be used by the annotation community to interpret novel proteogenomic evidence. Based on reprocessing of three large-scale publicly available human data sets, we show that a conservative approach, using stringent filtering is required to generate valid identifications. Evidence has been found supporting 16 novel protein-coding genes being added to GENCODE. Despite this many peptide identifications in pseudogenes cannot be annotated due to the absence of orthogonal supporting evidence.
Demonstration of a positron beam-driven hollow channel plasma wakefield accelerator
Authors: Gessner Spencer , Adli Erik , Allen James M. , An Weiming , Clarke Christine I. , Clayton Chris E. , Corde Sebastien , Delahaye J. P. , Frederico Joel , Green Selina Z. , Hast Carsten , Hogan Mark J. , Joshi Chan , Lindstrøm Carl A. , Lipkowitz Nate , Litos Michael , Lu Wei , Marsh Kenneth A. , Mori Warren B. , O’Shea Brendan , Vafaei-Najafabadi Navid , Walz Dieter , Yakimenko Vitaly , Yocky Gerald
Published: June 2016

Plasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that may disrupt the beam quality. Hollow plasma channels have been proposed as a technique for generating accelerating fields without transverse forces. Here we demonstrate a method for creating an extended hollow plasma channel and measure the wakefields created by an ultrarelativistic positron beam as it propagates through the channel. The plasma channel is created by directing a high-intensity laser pulse with a spatially modulated profile into lithium vapour, which results in an annular region of ionization. A peak decelerating field of 230 MeV m−1 is inferred from changes in the beam energy spectrum, in good agreement with theory and particle-in-cell simulations.
Wafer-scale fabrication and growth dynamics of suspended graphene nanoribbon arrays
Authors: Suzuki Hiroo , Kaneko Toshiro , Shibuta Yasushi , Ohno Munekazu , Maekawa Yuki , Kato Toshiaki
Published: June 2016

Adding a mechanical degree of freedom to the electrical and optical properties of atomically thin materials can provide an excellent platform to investigate various optoelectrical physics and devices with mechanical motion interaction. The large scale fabrication of such atomically thin materials with suspended structures remains a challenge. Here we demonstrate the wafer-scale bottom–up synthesis of suspended graphene nanoribbon arrays (over 1,000,000 graphene nanoribbons in 2 × 2 cm2 substrate) with a very high yield (over 98%). Polarized Raman measurements reveal graphene nanoribbons in the array can have relatively uniform-edge structures with near zigzag orientation dominant. A promising growth model of suspended graphene nanoribbons is also established through a comprehensive study that combined experiments, molecular dynamics simulations and theoretical calculations with a phase-diagram analysis. We believe that our results can contribute to pushing the study of graphene nanoribbons into a new stage related to the optoelectrical physics and industrial applications.
Creation of a library of induced pluripotent stem cells from Parkinsonian patients
Authors: Holmqvist Staffan , Lehtonen Šárka , Chumarina Margarita , Puttonen Katja A , Azevedo Carla , Lebedeva Olga , Ruponen Marika , Oksanen Minna , Djelloul Mehdi , Collin Anna , Goldwurm Stefano , Meyer Morten , Lagarkova Maria , Kiselev Sergei , Koistinaho Jari , Roybon Laurent
Published: June 2016

Induced pluripotent stem cells (iPSCs) are becoming an important source of pre-clinical models for research focusing on neurodegeneration. They offer the possibility for better understanding of common and divergent pathogenic mechanisms of brain diseases. Moreover, iPSCs provide a unique opportunity to develop personalized therapeutic strategies, as well as explore early pathogenic mechanisms, since they rely on the use of patients’ own cells that are otherwise accessible only post-mortem, when neuronal death-related cellular pathways and processes are advanced and adaptive. Neurodegenerative diseases are in majority of unknown cause, but mutations in specific genes can lead to familial forms of these diseases. For example, mutations in the superoxide dismutase 1 gene lead to the motor neuron disease amyotrophic lateral sclerosis (ALS), while mutations in the SNCA gene encoding for alpha-synuclein protein lead to familial Parkinson’s disease (PD). The generations of libraries of familial human ALS iPSC lines have been described, and the iPSCs rapidly became useful models for studying cell autonomous and non-cell autonomous mechanisms of the disease. Here we report the generation of a comprehensive library of iPSC lines of familial PD and an associated synucleinopathy, multiple system atrophy (MSA). In addition, we provide examples of relevant neural cell types these iPSC can be differentiated into, and which could be used to further explore early disease mechanisms. These human cellular models will be a valuable resource for identifying common and divergent mechanisms leading to neurodegeneration in PD and MSA.
Predictive value of the composition of the vaginal microbiota in bacterial vaginosis, a dynamic study to identify recurrence-related flora
Authors: Xiao Bingbing , Niu Xiaoxi , Han Na , Wang Ben , Du Pengcheng , Na Risu , Chen Chen , Liao Qinping
Published: June 2016

Bacterial vaginosis (BV) is a highly prevalent disease in women and increases the risk of pelvic inflammatory disease. It has been given wide attention because of the high recurrence rate. Traditional diagnostic methods based on microscope providing limited information on the vaginal microbiota increase the difficulty in tracing the development of the disease in bacteria resistance condition. In this study, we used deep-sequencing technology to observe dynamic variation of the vaginal microbiota at three major time points during treatment, at D0 (before treatment), D7 (stop using the antibiotics) and D30 (the 30-day follow-up visit). Sixty-five patients with BV were enrolled (48 were cured and 17 were not cured) and their bacterial composition of the vaginal microbiota was compared. Interestingly, we identified 9 patients might be recurrence. We also introduced a new measurement point of D7, although its microbiota were significantly inhabited by antibiotic and hard to be observed by traditional method. The vaginal microbiota in deep-sequencing-view present a strong correlation to the final outcome. Thus, coupled with detailed individual bioinformatics analysis and deep-sequencing technology, we may illustrate a more accurate map of vaginal microbial to BV patients, which provide a new opportunity to reduce the rate of recurrence of BV.
Correction: Corrigendum: Stiffness in vortex—like structures due to chirality-domains within a coupled helical rare-earth superlattice
Authors: Paul Amitesh
Published: June 2016

Scientific Reports 6: Article number: 19315; Published online: 13 January 2016; Updated: 02 June 2016 To better reflect the contributions to this study, the author wishes to make the following changes. In the Acknowledgements section, “We are thankful to J. Voigt for the sample preparation and MPMS measurements.
Magnetic Trapping of Bacteria at Low Magnetic Fields
Authors: Wang Z. M. , Wu R. G. , Wang Z. P. , Ramanujan R. V.
Published: June 2016

A suspension of non-magnetic entities in a ferrofluid is referred to as an inverse ferrofluid. Current research to trap non-magnetic entities in an inverse ferrofluid focuses on using large permanent magnets to generate high magnetic field gradients, which seriously limits Lab-on-a-Chip applications. On the other hand, in this work, trapping of non-magnetic entities, e.g., bacteria in a uniform external magnetic field was studied with a novel chip design. An inverse ferrofluid flows in a channel and a non-magnetic island is placed in the middle of this channel. The magnetic field was distorted by this island due to the magnetic susceptibility difference between this island and the surrounding ferrofluid, resulting in magnetic forces applied on the non-magnetic entities. Both the ferromagnetic particles and the non-magnetic entities, e.g., bacteria were attracted towards the island, and subsequently accumulate in different regions. The alignment of the ferrimagnetic particles and optical transparency of the ferrofluid was greatly enhanced by the bacteria at low applied magnetic fields. This work is applicable to lab-on-a-chip based detection and trapping of non-magnetic entities bacteria and cells.
Cotesia vestalis teratocytes express a diversity of genes and exhibit novel immune functions in parasitism
Authors: Gao Fei , Gu Qi-juan , Pan Jing , Wang Ze-hua , Yin Chuan-lin , Li Fei , Song Qi-sheng , Strand Michael R. , Chen Xue-xin , Shi Min
Published: June 2016

Some endoparasitoid wasps lay eggs that produce cells called teratocytes. In this study, we sequenced and analyzed the transcriptome of teratocytes from the solitary endoparasitoid Cotesia vestalis (Braconidae), which parasitizes larval stage Plutella xylostella (Plutellidae). Results identified many teratocyte transcripts with potential functions in affecting host immune defenses, growth or metabolism. Characterization of teratocyte-secreted venom-like protein 8 (TSVP-8) indicated it inhibits melanization of host hemolymph in vitro, while two predicted anti-microbial peptides (CvT-def 1 and 3) inhibited the growth of bacteria. Results also showed the parasitized hosts lacking teratocytes experienced higher mortality after immune challenge by pathogens than hosts with teratocytes. Taken together, these findings indicate that C. vestalis teratocytes secrete products that alter host immune functions while also producing anti-microbial peptides with functions that help protect the host from infection by other organisms.
Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress
Authors: Prasad Kasavajhala V. S. K. , Abdel-Hameed Amira A. E. , Xing Denghui , Reddy Anireddy S. N.
Published: June 2016

Abiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response.
Correction: Corrigendum: Universal lineshapes at the crossover between weak and strong critical coupling in Fano-resonant coupled oscillators
Authors: Zanotto Simone , Tredicucci Alessandro
Published: June 2016

Scientific Reports 6: Article number: 24592; Published online: 19 April 2016; Updated: 02 June 2016 The Acknowledgements section in this Article is incomplete. “The authors gratefully acknowledge Raffaele Colombelli for precious suggestions and insights on the application of coupled-mode models to strongly-coupled systems”.
Immuno-targeting the multifunctional CD38 using nanobody
Authors: Li Ting , Qi Shali , Unger Mandy , Hou Yun Nan , Deng Qi Wen , Liu Jun , Lam Connie M. C. , Wang Xian Wang , Xin Du , Zhang Peng , Koch-Nolte Friedrich , Hao Quan , Zhang Hongmin , Lee Hon Cheung , Zhao Yong Juan
Published: June 2016

CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be a good target for immunotherapy of the disease. CD38 is also a signaling enzyme responsible for the metabolism of two novel calcium messenger molecules. To be able to target this multifunctional protein, we generated a series of nanobodies against CD38 with high affinities. Crystal structures of the complexes of CD38 with the nanobodies were solved, identifying three separate epitopes on the carboxyl domain. Chromobodies, engineered by tagging the nanobody with fluorescence proteins, provide fast, simple and versatile tools for quantifying CD38 expression. Results confirmed that CD38 was highly expressed in malignant MM cells compared with normal white blood cells. The immunotoxin constructed by splicing the nanobody with a bacterial toxin, PE38 shows highly selective cytotoxicity against patient-derived MM cells as well as the cell lines, with half maximal effective concentration reaching as low as 10−11 molar. The effectiveness of the immunotoxin can be further increased by stimulating CD38 expression using retinoid acid. These results set the stage for the development of clinical therapeutics as well as diagnostic screening for myeloma.
Tomato 26S Proteasome subunit RPT4a regulates ToLCNDV transcription and activates hypersensitive response in tomato
Authors: Sahu Pranav Pankaj , Sharma Namisha , Puranik Swati , Chakraborty Supriya , Prasad Manoj
Published: June 2016

Involvement of 26S proteasomal subunits in plant pathogen-interactions, and the roles of each subunit in independently modulating the activity of many intra- and inter-cellular regulators controlling physiological and defense responses of a plant were well reported. In this regard, we aimed to functionally characterize a Solanum lycopersicum 26S proteasomal subunit RPT4a (SlRPT4) gene, which was differentially expressed after Tomato leaf curl New Delhi virus (ToLCNDV) infection in tolerant cultivar H-88-78-1. Molecular analysis revealed that SlRPT4 protein has an active ATPase activity. SlRPT4 could specifically bind to the stem-loop structure of intergenic region (IR), present in both DNA-A and DNA-B molecule of the bipartite viral genome. Lack of secondary structure in replication-associated gene fragment prevented formation of DNA-protein complex suggesting that binding of SlRPT4 with DNA is secondary structure specific. Interestingly, binding of SlRPT4 to IR inhibited the function of RNA Pol-II and subsequently reduced the bi-directional transcription of ToLCNDV genome. Virus-induced gene silencing of SlRPT4 gene incited conversion of tolerant attributes of cultivar H-88-78-1 into susceptibility. Furthermore, transient overexpression of SlRPT4 resulted in activation of programmed cell death and antioxidant enzymes system. Overall, present study highlights non-proteolytic function of SlRPT4 and their participation in defense pathway against virus infection in tomato.
Robust Statistical Detection of Power-Law Cross-Correlation
Authors: Blythe Duncan A. J. , Nikulin Vadim V. , Müller Klaus-Robert
Published: June 2016

We show that widely used approaches in statistical physics incorrectly indicate the existence of power-law cross-correlations between financial stock market fluctuations measured over several years and the neuronal activity of the human brain lasting for only a few minutes. While such cross-correlations are nonsensical, no current methodology allows them to be reliably discarded, leaving researchers at greater risk when the spurious nature of cross-correlations is not clear from the unrelated origin of the time series and rather requires careful statistical estimation. Here we propose a theory and method (PLCC-test) which allows us to rigorously and robustly test for power-law cross-correlations, correctly detecting genuine and discarding spurious cross-correlations, thus establishing meaningful relationships between processes in complex physical systems. Our method reveals for the first time the presence of power-law cross-correlations between amplitudes of the alpha and beta frequency ranges of the human electroencephalogram.
The response of an egg parasitoid to substrate-borne semiochemicals is affected by previous experience
Authors: Peri Ezio , Salerno Gianandrea , Slimani Takoua , Frati Francesca , Conti Eric , Colazza Stefano , Cusumano Antonino
Published: June 2016

Animals can adjust their behaviour according to previous experience gained during foraging. In parasitoids, experience plays a key role in host location, a hierarchical process in which air-borne and substrate-borne semiochemicals are used to find hosts. In nature, chemical traces deposited by herbivore hosts when walking on the plant are adsorbed by leaf surfaces and perceived as substrate-borne semiochemicals by parasitoids. Chemical traces left on cabbage leaves by adults of the harlequin bug (Murgantia histrionica) induce an innate arrestment response in the egg parasitoid Trissolcus brochymenae characterized by an intense searching behaviour on host-contaminated areas. Here we investigated whether the T. brochymenae response to host walking traces left on leaf surfaces is affected by previous experience in the context of parasitoid foraging behaviour. We found that: 1) an unrewarded experience (successive encounters with host-contaminated areas without successful oviposition) decreased the intensity of the parasitoid response; 2) a rewarded experience (successful oviposition) acted as a reinforcing stimulus; 3) the elapsed time between two consecutive unrewarded events affected the parasitoid response in a host-gender specific manner. The ecological role of these results to the host location process of egg parasitoids is discussed.
Quantifying intrinsic and extrinsic control of single-cell fates in cancer and stem/progenitor cell pedigrees with competing risks analysis
Authors: Cornwell J. A. , Hallett R. M. , der Mauer S. Auf , Motazedian A. , Schroeder T. , Draper J. S. , Harvey R. P. , Nordon R. E.
Published: June 2016

The molecular control of cell fate and behaviour is a central theme in biology. Inherent heterogeneity within cell populations requires that control of cell fate is studied at the single-cell level. Time-lapse imaging and single-cell tracking are powerful technologies for acquiring cell lifetime data, allowing quantification of how cell-intrinsic and extrinsic factors control single-cell fates over time. However, cell lifetime data contain complex features. Competing cell fates, censoring, and the possible inter-dependence of competing fates, currently present challenges to modelling cell lifetime data. Thus far such features are largely ignored, resulting in loss of data and introducing a source of bias. Here we show that competing risks and concordance statistics, previously applied to clinical data and the study of genetic influences on life events in twins, respectively, can be used to quantify intrinsic and extrinsic control of single-cell fates. Using these statistics we demonstrate that 1) breast cancer cell fate after chemotherapy is dependent on p53 genotype; 2) granulocyte macrophage progenitors and their differentiated progeny have concordant fates; and 3) cytokines promote self-renewal of cardiac mesenchymal stem cells by symmetric divisions. Therefore, competing risks and concordance statistics provide a robust and unbiased approach for evaluating hypotheses at the single-cell level.
TLR9-ERK-mTOR signaling is critical for autophagic cell death induced by CpG oligodeoxynucleotide 107 combined with irradiation in glioma cells
Authors: Li Xiaoli , Cen Yanyan , Cai Yongqing , Liu Tao , Liu Huan , Cao Guanqun , Liu Dan , Li Bin , Peng Wei , Zou Jintao , Pang Xueli , Zheng Jiang , Zhou Hong
Published: June 2016

Synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) function as potential radiosensitizers for glioma treatment, although the underlying mechanism is unclear. It was observed that CpG ODN107, when combined with irradiation, did not induce apoptosis. Herein, the effect of CpG ODN107 + irradiation on autophagy and the related signaling pathways was investigated.In vitro, CpG ODN107 + irradiation induced autophagosome formation, increased the ratio of LC3 II/LC3 I, beclin 1 and decreased p62 expression in U87 cells. Meanwhile, CpG ODN107 also increased LC3 II/LC3 I expression in U251 and CHG-5 cells.In vivo, CpG ODN107 combined with local radiotherapy induced autophagosome formation in orthotopic transplantation tumor. Investigation of the molecular mechanisms demonstrated that CpG ODN107 + irradiation increased the levels of TLR9 and p-ERK and decreased the level of p-mTOR in glioma cells. Further, TLR9-specific siRNA could affect the expressions of p-ERK and autophagy-related proteins in glioma cells. Taken together, CpG ODN107 combined with irradiation could induce autophagic cell death and this effect was closely related to the TLR9-ERK-mTOR signaling pathway in glioma cells, providing new insights into the investigation mechanism of CpG ODN.
The co-chaperone Cdc37 regulates the rabies virus phosphoprotein stability by targeting to Hsp90AA1 machinery
Authors: Xu Yunbin , Liu Fei , Liu Juan , Wang Dandan , Yan Yan , Ji Senlin , Zan Jie , Zhou Jiyong
Published: June 2016

Cdc37, as a kinase-specific co-chaperone of the chaperone Hsp90AA1 (Hsp90), actively aids with the maturation, stabilization and activation of the cellular or viral kinase/kinase-like targets. Phosphoprotein (P) of rabies virus (RABV) is a multifunctional, non-kinase protein involved in interferon antagonism, viral transcription and replication. Here, we demonstrated that the RABV non-kinase P is chaperoned by Cdc37 and Hsp90 during infection. We found that Cdc37 and Hsp90 affect the RABV life cycle directly. Activity inhibition and knockdown of Cdc37 and Hsp90 increased the instability of the viral P protein. Overexpression of Cdc37 and Hsp90 maintained P’s stability but did not increase the yield of infectious RABV virions. We further demonstrated that the non-enzymatic polymerase cofactor P protein of all the genotypes of lyssaviruses is a target of the Cdc37/Hsp90 complex. Cdc37, phosphorylated or unphosphorylated on Ser13, aids the P protein to load onto the Hsp90 machinery, with or without Cdc37 binding to Hsp90. However, the interaction between Cdc37 and Hsp90 appears to have additional allosteric regulation of the conformational switch of Hsp90. Our study highlighted a novel mechanism in which Cdc37/Hsp90 chaperones a non-kinase target, which has significant implications for designing therapeutic targets against Rabies.
Eyes wide shut: Transcranial alternating current stimulation drives alpha rhythm in a state dependent manner
Authors: Ruhnau Philipp , Neuling Toralf , Fuscá Marco , Herrmann Christoph S. , Demarchi Gianpaolo , Weisz Nathan
Published: June 2016

Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. The present study aims to investigate the phase relationship between the external tACS signal and concurrent brain activity. Subjects were stimulated with tACS at individual alpha frequency during eyes open and eyes closed resting states. Electrodes were placed at Cz and Oz, which should affect parieto-occipital areas most strongly. Source space magnetoencephalography (MEG) data were used to estimate phase coherence between tACS and brain activity. Phase coherence was significantly increased in areas in the occipital pole in eyes open resting state only. The lag between tACS and brain responses showed considerable inter-individual variability. In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices. Interestingly, this effect is state dependent and is clearly observed with eyes open but only to a lesser extent with eyes closed.
Attractiveness of volatiles from different body parts to the malaria mosquito Anopheles coluzzii is affected by deodorant compounds
Authors: Verhulst Niels O. , Weldegergis Berhane T. , Menger David , Takken Willem
Published: June 2016

Mosquitoes display biting preferences among different sites of the human body. In addition to height or convection currents, body odour may play a role in the selection of these biting sites. Previous studies have shown that skin emanations are important host-finding cues for mosquitoes. In this study, skin emanations were collected from armpits, hands and feet; the volatile profiles were analysed and tested for their attractiveness to the malaria mosquito Anopheles coluzzii. Skin emanations collected from armpits were less attractive to An. coluzzii compared to hands or/and feet. The difference may have been caused by deodorant residues, which were found in the armpit samples and not in those of hands and feet. In a subsequent experiment, volunteers were asked to avoid using skincare products for five days and thereafter, no differences in attractiveness of the body parts to mosquitoes were found. The detected deodorant compound isopropyl tetradecanoate inhibited mosquito landings in a repellent bioassay. It is concluded that the volatiles emanated from different body parts induced comparable levels of attraction in mosquitoes and that skincare products may reduce a person’s attractiveness to mosquitoes.
The CebE/MsiK Transporter is a Doorway to the Cello-oligosaccharide-mediated Induction of Streptomyces scabies Pathogenicity
Authors: Jourdan Samuel , Francis Isolde Maria , Kim Min Jung , Salazar Joren Jeico C. , Planckaert Sören , Frère Jean-Marie , Matagne André , Kerff Frédéric , Devreese Bart , Loria Rosemary , Rigali Sébastien
Published: June 2016

Streptomyces scabiesis an economically important plant pathogen well-known for damaging root and tuber crops by causing scab lesions. Thaxtomin A is the main causative agent responsible for the pathogenicity ofS. scabiesand cello-oligosaccharides are environmental triggers that induce the production of this phytotoxin. How cello-oligosaccharides are sensed or transported in order to induce the virulent behavior ofS. scabies? Here we report that the cellobiose and cellotriose binding protein CebE and MsiK, the ATPase providing energy for carbohydrates transport, are the protagonists of the cello-oligosaccharide mediated induction of thaxtomin production inS. scabies. Our work provides the first example where the transport and not the sensing of major constituents of the plant host is the central mechanism associated with virulence of the pathogen. Our results allow to draw a complete pathway from signal transport to phytotoxin production where each step of the cascade is controlled by CebR, the cellulose utilization regulator. We propose the high affinity of CebE to cellotriose as possible adaptation ofS. scabiesto colonize expanding plant tissue. Our work further highlights how genes associated with primary metabolism in nonpathogenicStreptomycesspecies have been recruited as basic elements of virulence in plant pathogenic species.
Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody
Authors: Sugata Kenji , Yasunaga Jun-ichirou , Miura Michi , Akari Hirofumi , Utsunomiya Atae , Nosaka Kisato , Watanabe Yuko , Suzushima Hitoshi , Koh Ki-Ryang , Nakagawa Masanori , Kohara Michinori , Matsuoka Masao
Published: June 2016

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia and inflammatory diseases. Because anti-HTLV-1 immune responses are critical for suppressing infected cells, enhancing cellular immunity is beneficial for the treatment of HTLV-1-associated diseases. Using simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaques, we analyzed the immune responses to viral antigens and the dynamics of virus-infected cells. The chemokine receptor CCR4 is expressed on STLV-1 infected cells and administration of humanized monoclonal antibody to CCR4, mogamulizumab, dramatically decreased the number of STLV-1-infected cells in vivo. Concurrently, mogamulizumab treatment enhanced STLV-1 specific CD4+ and CD8+ T cell responses by simultaneously targeting CCR4+ effector regulatory T (Treg) cells and infected cells. Mogamulizumab promoted the phagocytosis of CCR4+ infected cells by macrophages, which likely enhanced antigen presentation. Vaccination with recombinant vaccinia virus (rVV) expressing viral antigens suppressed the proviral load and the number of Tax-expressing cells. Enhanced T-cell responses were also observed in some ATL patients who were treated with mogamulizumab. This study shows that mogamulizumab works not only by killing CCR4+ infected cells directly, but also by enhancing T cell responses by increasing the phagocytosis of infected cells by antigen-presenting cells and suppressing CCR4+ effector Treg cells.
Handedness is related to neural mechanisms underlying hemispheric lateralization of face processing
Authors: Frässle Stefan , Krach Sören , Paulus Frieder Michel , Jansen Andreas
Published: June 2016

While the right-hemispheric lateralization of the face perception network is well established, recent evidence suggests that handedness affects the cerebral lateralization of face processing at the hierarchical level of the fusiform face area (FFA). However, the neural mechanisms underlying differential hemispheric lateralization of face perception in right- and left-handers are largely unknown. Using dynamic causal modeling (DCM) for fMRI, we aimed to unravel the putative processes that mediate handedness-related differences by investigating the effective connectivity in the bilateral core face perception network. Our results reveal an enhanced recruitment of the left FFA in left-handers compared to right-handers, as evidenced by more pronounced face-specific modulatory influences on both intra- and interhemispheric connections. As structural and physiological correlates of handedness-related differences in face processing, right- and left-handers varied with regard to their gray matter volume in the left fusiform gyrus and their pupil responses to face stimuli. Overall, these results describe how handedness is related to the lateralization of the core face perception network and point to different neural mechanisms underlying face processing in right- and left-handers. In a wider context, this demonstrates the entanglement of structurally and functionally remote brain networks, suggesting a broader underlying process regulating brain lateralization.
Correction: Corrigendum: Intrinsic challenges in ancient microbiome reconstruction using 16S rRNA gene amplification
Authors: Ziesemer Kirsten A. , Mann Allison E. , Sankaranarayanan Krithivasan , Schroeder Hannes , Ozga Andrew T. , Brandt Bernd W. , Zaura Egija , Waters-Rist Andrea , Hoogland Menno , Salazar-García Domingo C. , Aldenderfer Mark , Speller Camilla , Hendy Jessica , Weston Darlene A. , MacDonald Sandy J. , Thomas Gavin H. , Collins Matthew J. , Lewis Cecil M. , Hofman Corinne , Warinner Christina
Published: June 2016

Scientific Reports 5: Article number: 16498; Published online: 13 November 2015; Updated: 02 June 2016 The Acknowledgements section in this Article is incomplete. “This work was supported by the European Research Council (FP7 ERC-Synergy Nexus1492 project grant number 319209) and the US National Institutes of Health (R01 GM089886), the BBVA Foundation (I Ayudas a Investigadores, Innovadores y Creadores), the Generalitat Valenciana (VALi+d APOSTD/2014/123 and GV/2015/060), the European Union (EUROTAST FP7 PEOPLE-2010 MC ITN, Braudel-IFER-FMSH; FP7/2007-2013 - MSCA-COFUND, n°245743), and the Centre for Chronic Diseases and Disorders (C2D2) Research Priming Fund grant to CFS.
Crystallographic Lattice Boltzmann Method
Authors: Namburi Manjusha , Krithivasan Siddharth , Ansumali Santosh
Published: June 2016

Current approaches to Direct Numerical Simulation (DNS) are computationally quite expensive for most realistic scientific and engineering applications of Fluid Dynamics such as automobiles or atmospheric flows. The Lattice Boltzmann Method (LBM), with its simplified kinetic descriptions, has emerged as an important tool for simulating hydrodynamics. In a heterogeneous computing environment, it is often preferred due to its flexibility and better parallel scaling. However, direct simulation of realistic applications, without the use of turbulence models, remains a distant dream even with highly efficient methods such as LBM. In LBM, a fictitious lattice with suitable isotropy in the velocity space is considered to recover Navier-Stokes hydrodynamics in macroscopic limit. The same lattice is mapped onto a cartesian grid for spatial discretization of the kinetic equation. In this paper, we present an inverted argument of the LBM, by making spatial discretization as the central theme. We argue that the optimal spatial discretization for LBM is a Body Centered Cubic (BCC) arrangement of grid points. We illustrate an order-of-magnitude gain in efficiency for LBM and thus a significant progress towards feasibility of DNS for realistic flows.
Flt1/VEGFR1 heterozygosity causes transient embryonic edema
Authors: Otowa Yasunori , Moriwaki Kazumasa , Sano Keigo , Shirakabe Masanori , Yonemura Shigenobu , Shibuya Masabumi , Rossant Janet , Suda Toshio , Kakeji Yoshihiro , Hirashima Masanori
Published: June 2016

Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that Flt1 heterozygous (Flt1+/−) mouse embryos grow up to adult without life-threatening abnormalities but exhibit a transient embryonic edema around the nuchal and back regions, which is reminiscent of increased nuchal translucency in human fetuses. Vascular permeability is enhanced and an intricate infolding of the plasma membrane and huge vesicle-like structures are seen in Flt1+/− capillary endothelial cells. Flk1 tyrosine phosphorylation is elevated in Flt1+/− embryos, but Flk1 heterozygosity does not suppress embryonic edema caused by Flt1 heterozygosity. When Flt1 mutants are crossed with Aspp1−/− mice which exhibit a transient embryonic edema with delayed formation and dysfunction of lymphatic vessels, only 5.7% of Flt1+/−; Aspp1−/− mice survive, compared to expected ratio (25%). Our results demonstrate that Flt1 heterozygosity causes a transient embryonic edema and can be a risk factor for embryonic lethality in combination with other mutations causing non-lethal vascular phenotype.
In vivo Magnetic Resonance Microscopy and Hypothermic Anaesthesia of a Disease Model in Medaka
Authors: Ueno Tomohiro , Suzuki Hirokazu , Hiraishi Masahiro , Amano Hideaki , Fukuyama Hidenao , Sugimoto Naozo
Published: June 2016

In medical and pharmacological research, various human disease models in small fish, such as medaka (Oryzias latipes), have been created. To investigate these disease models noninvasively, magnetic resonance imaging (MRI) is suitable because these small fish are no longer transparent as adults. However, their small body size requires a high spatial resolution and a water pool should be avoided to maximize the strength of MRI. We developedin vivomagnetic resonance microscopy (MR microscopy) without a water pool by combining hypothermic anaesthesia and a 14.1 T MR microscope. Usingin vivoMR microscopy, we noninvasively evaluated the hepatic steatosis level of a non-alcoholic fatty liver disease model in medaka and followed the individual disease progression. The steatosis level was quantified by the MRI-estimated proton density fat-fraction (MRI-PDFF), which estimates the triglyceride fat concentration in liver tissue and is recognized as an imaging biomarker. The MRI-PDFF results agreed with a histological analysis. Moreover, we optimized the hypothermic anaesthesia procedure to obtain a recovery proportion of 1 in the experiment involving MR microscopy. Recovered medaka could not be distinguished from naïve medaka after the experiment. Therefore, thein vivoMR microscopy will expand the possibilities of a human disease model in fish.
Quench field sensitivity of two-particle correlation in a Hubbard model
Authors: Zhang X. Z. , Lin S. , Song Z.
Published: June 2016

Short-range interaction can give rise to particle pairing with a short-range correlation, which may be destroyed in the presence of an external field. We study the transition between correlated and uncorrelated particle states in the framework of one- dimensional Hubbard model driven by a field. We show that the long time-scale transfer rate from an initial correlated state to final uncorrelated particle states is sensitive to the quench field strength and exhibits a periodic behavior. This process involves an irreversible energy transfer from the field to particles, leading to a quantum electrothermal effect.
EphrinB2 regulates the emergence of a hemogenic endothelium from the aorta
Authors: Chen Inn-Inn , Caprioli Arianna , Ohnuki Hidetaka , Kwak Hyeongil , Porcher Catherine , Tosato Giovanna
Published: June 2016

Adult-type intraembryonic hematopoiesis arises from specialized endothelial cells of the dorsal aorta (DA). Despite the critical importance of this specialized endothelium for establishment of hematopoietic stem cells and adult hematopoietic lineages, the mechanisms regulating its emergence are incompletely understood. We show that EphrinB2, a principal regulator of endothelial cell function, controls the development of endothelium producing adult-type hematopoiesis. The absence of EphrinB2 impairs DA-derived hematopoiesis. Transmembrane EphrinB2 and its EphB4 receptor interact in the emerging DA, which transiently harbors EphrinB2+ and EphB4+ endothelial cells, thereby providing an opportunity for bi-directional cell-to-cell signaling to control the emergence of the hemogenic endothelium. Embryonic Stem (ES) cell-derived EphrinB2+ cells are enriched with hemogenic endothelial precursors. EphrinB2 silencing impairs ES generation of hematopoietic cells but not generation of endothelial cells. The identification of EphrinB2 as an essential regulator of adult hematopoiesis provides important insight in the regulation of early hematopoietic commitment.
Changes in soil organic carbon in croplands subjected to fertilizer management: a global meta-analysis
Authors: Han Pengfei , Zhang Wen , Wang Guocheng , Sun Wenjuan , Huang Yao
Published: June 2016

Cropland soil organic carbon (SOC) is undergoing substantial alterations due to both environmental and anthropogenic changes. Although numerous case studies have been conducted, there remains a lack of quantification of the consequences of such environmental and anthropogenic changes on the SOC sequestration across global agricultural systems. Here, we conducted a global meta-analysis of SOC changes under different fertilizer managements, namely unbalanced application of chemical fertilizers (UCF), balanced application of chemical fertilizers (CF), chemical fertilizers with straw application (CFS), and chemical fertilizers with manure application (CFM). We show that topsoil organic carbon (C) increased by 0.9 (0.7–1.0, 95% confidence interval (CI)) g kg−1 (10.0%, relative change, hereafter the same), 1.7 (1.2–2.3) g kg−1 (15.4%), 2.0 (1.9–2.2) g kg−1 (19.5%) and 3.5 (3.2–3.8) g kg−1 (36.2%) under UCF, CF, CFS and CFM, respectively. The C sequestration durations were estimated as 28–73 years under CFS and 26–117 years under CFM but with high variability across climatic regions. At least 2.0 Mg ha−1 yr−1 C input is needed to maintain the SOC in ~85% cases. We highlight a great C sequestration potential of applying CF, and adopting CFS and CFM is highly important for either improving or maintaining current SOC stocks across all agro–ecosystems.
Radio frequency spectral characterization and model parameters extraction of high Q optical resonators
Authors: Abdallah Zeina , Boucher Yann G. , Fernandez Arnaud , Balac Stéphane , Llopis Olivier
Published: June 2016

A microwave domain characterization approach is proposed to determine the properties of high quality factor optical resonators. This approach features a very high precision in frequency and aims to acquire a full knowledge of the complex transfer function (amplitude and phase) characterizing an optical resonator using a microwave vector network analyzer. It is able to discriminate between the different coupling regimes, from the under-coupling to the selective amplification, and it is used together with a model from which the main resonator parameters are extracted, i.e. coupling factor, intrinsic losses, phase slope, intrinsic and external quality factor.