bluuebunny/crossref_metadata_2025 huggingface dataset:
Biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents
Authors: Ma Junying , Huang Hongbo , Xie Yunchang , Liu Zhiyong , Zhao Jin , Zhang Chunyan , Jia Yanxi , Zhang Yun , Zhang Hua , Zhang Tianyu , Ju Jianhua
Published: August 2017

Tuberculosis remains one of the world’s deadliest communicable diseases, novel anti-tuberculosis agents are urgently needed due to severe drug resistance and the co-epidemic of tuberculosis/human immunodeficiency virus. Here, we show the isolation of six anti-mycobacterial ilamycin congeners (1–6) bearing rare L-3-nitro-tyrosine and L-2-amino-4-hexenoic acid structural units from the deep sea-derived Streptomyces atratus SCSIO ZH16. The biosynthesis of the rare L-3-nitrotyrosine and L-2-amino-4-hexenoic acid units as well as three pre-tailoring and two post-tailoring steps are probed in the ilamycin biosynthetic machinery through a series of gene inactivation, precursor chemical complementation, isotope-labeled precursor feeding experiments, as well as structural elucidation of three intermediates (6–8) from the respective mutants. Most impressively, ilamycins E1/E2, which are produced in high titers by a genetically engineered mutant strain, show very potent anti-tuberculosis activity with an minimum inhibitory concentration value ≈9.8 nM to Mycobacterium tuberculosis H37Rv constituting extremely potent and exciting anti-tuberculosis drug leads.
High-quality monolayer superconductor NbSe2 grown by chemical vapour deposition
Authors: Wang Hong , Huang Xiangwei , Lin Junhao , Cui Jian , Chen Yu , Zhu Chao , Liu Fucai , Zeng Qingsheng , Zhou Jiadong , Yu Peng , Wang Xuewen , He Haiyong , Tsang Siu Hon , Gao Weibo , Suenaga Kazu , Ma Fengcai , Yang Changli , Lu Li , Yu Ting , Teo Edwin Hang Tong , Liu Guangtong , Liu Zheng
Published: August 2017

The discovery of monolayer superconductors bears consequences for both fundamental physics and device applications. Currently, the growth of superconducting monolayers can only occur under ultrahigh vacuum and on specific lattice-matched or dangling bond-free substrates, to minimize environment- and substrate-induced disorders/defects. Such severe growth requirements limit the exploration of novel two-dimensional superconductivity and related nanodevices. Here we demonstrate the experimental realization of superconductivity in a chemical vapour deposition grown monolayer material—NbSe2. Atomic-resolution scanning transmission electron microscope imaging reveals the atomic structure of the intrinsic point defects and grain boundaries in monolayer NbSe2, and confirms the low defect concentration in our high-quality film, which is the key to two-dimensional superconductivity. By using monolayer chemical vapour deposited graphene as a protective capping layer, thickness-dependent superconducting properties are observed in as-grown NbSe2 with a transition temperature increasing from 1.0 K in monolayer to 4.56 K in 10-layer.
Correlated electronic states at domain walls of a Mott-charge-density-wave insulator 1T-TaS2
Authors: Cho Doohee , Gye Gyeongcheol , Lee Jinwon , Lee Sung-Hoon , Wang Lihai , Cheong Sang-Wook , Yeom Han Woong
Published: August 2017

Domain walls in interacting electronic systems can have distinct localized states, which often govern physical properties and may lead to unprecedented functionalities and novel devices. However, electronic states within domain walls themselves have not been clearly identified and understood for strongly correlated electron systems. Here, we resolve the electronic states localized on domain walls in a Mott-charge-density-wave insulator 1T-TaS2 using scanning tunneling spectroscopy. We establish that the domain wall state decomposes into two nonconducting states located at the center of domain walls and edges of domains. Theoretical calculations reveal their atomistic origin as the local reconstruction of domain walls under the strong influence of electron correlation. Our results introduce a concept for the domain wall electronic property, the walls own internal degrees of freedom, which is potentially related to the controllability of domain wall electronic properties.
Chaperones rescue the energetic landscape of mutant CFTR at single molecule and in cell
Authors: Bagdany Miklos , Veit Guido , Fukuda Ryosuke , Avramescu Radu G. , Okiyoneda Tsukasa , Baaklini Imad , Singh Jay , Sovak Guy , Xu Haijin , Apaja Pirjo M. , Sattin Sara , Beitel Lenore K. , Roldan Ariel , Colombo Giorgio , Balch William , Young Jason C. , Lukacs Gergely L.
Published: August 2017

Molecular chaperones are pivotal in folding and degradation of the cellular proteome but their impact on the conformational dynamics of near-native membrane proteins with disease relevance remains unknown. Here we report the effect of chaperone activity on the functional conformation of the temperature-sensitive mutant cystic fibrosis channel (∆F508-CFTR) at the plasma membrane and after reconstitution into phospholipid bilayer. Thermally induced unfolding at 37 °C and concomitant functional inactivation of ∆F508-CFTR are partially suppressed by constitutive activity of Hsc70 and Hsp90 chaperone/co-chaperone at the plasma membrane and post-endoplasmic reticulum compartments in vivo, and at single-molecule level in vitro, indicated by kinetic and thermodynamic remodeling of the mutant gating energetics toward its wild-type counterpart. Thus, molecular chaperones can contribute to functional maintenance of ∆F508-CFTR by reshaping the conformational energetics of its final fold, a mechanism with implication in the regulation of metastable ABC transporters and other plasma membrane proteins activity in health and diseases.
The onset of widespread marine red beds and the evolution of ferruginous oceans
Authors: Song Haijun , Jiang Ganqing , Poulton Simon W. , Wignall Paul B. , Tong Jinnan , Song Huyue , An Zhihui , Chu Daoliang , Tian Li , She Zhenbing , Wang Chengshan
Published: August 2017

Banded iron formations were a prevalent feature of marine sedimentation ~3.8–1.8 billion years ago and they provide key evidence for ferruginous oceans. The disappearance of banded iron formations at ~1.8 billion years ago was traditionally taken as evidence for the demise of ferruginous oceans, but recent geochemical studies show that ferruginous conditions persisted throughout the later Precambrian, and were even a feature of Phanerozoic ocean anoxic events. Here, to reconcile these observations, we track the evolution of oceanic Fe-concentrations by considering the temporal record of banded iron formations and marine red beds. We find that marine red beds are a prominent feature of the sedimentary record since the middle Ediacaran (~580 million years ago). Geochemical analyses and thermodynamic modelling reveal that marine red beds formed when deep-ocean Fe-concentrations were > 4 nM. By contrast, banded iron formations formed when Fe-concentrations were much higher (> 50 μM). Thus, the first widespread development of marine red beds constrains the timing of deep-ocean oxygenation.
Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis
Authors: Liu Yongmei , Reynolds Lindsay M. , Ding Jingzhong , Hou Li , Lohman Kurt , Young Tracey , Cui Wei , Huang Zhiqing , Grenier Carole , Wan Ma , Stunnenberg Hendrik G. , Siscovick David , Hou Lifang , Psaty Bruce M. , Rich Stephen S. , Rotter Jerome I. , Kaufman Joel D. , Burke Gregory L. , Murphy Susan , Jacobs David R. , Post Wendy , Hoeschele Ina , Bell Douglas A. , Herrington David , Parks John S. , Tracy Russell P. , McCall Charles E. , Stein James H.
Published: August 2017

Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator,ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development.ARID5BCpG (cg25953130) methylation is inversely associated with bothARID5Bexpression and atherosclerosis, consistent with this CpG residing in anARID5Benhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions thatARID5Bexpression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes,ARID5Bknockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest thatARID5Bexpression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.
MHC matching improves engraftment of iPSC-derived neurons in non-human primates
Authors: Morizane Asuka , Kikuchi Tetsuhiro , Hayashi Takuya , Mizuma Hiroshi , Takara Sayuki , Doi Hisashi , Mawatari Aya , Glasser Matthew F. , Shiina Takashi , Ishigaki Hirohito , Itoh Yasushi , Okita Keisuke , Yamasaki Emi , Doi Daisuke , Onoe Hirotaka , Ogasawara Kazumasa , Yamanaka Shinya , Takahashi Jun
Published: August 2017

The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting.
Designing artificial 2D crystals with site and size controlled quantum dots
Authors: Xie Xuejun , Kang Jiahao , Cao Wei , Chu Jae Hwan , Gong Yongji , Ajayan Pulickel M. , Banerjee Kaustav
Published: August 2017

Ordered arrays of quantum dots in two-dimensional (2D) materials would make promising optical materials, but their assembly could prove challenging. Here we demonstrate a scalable, site and size controlled fabrication of quantum dots in monolayer molybdenum disulfide (MoS2), and quantum dot arrays with nanometer-scale spatial density by focused electron beam irradiation induced local 2H to 1T phase change in MoS2. By designing the quantum dots in a 2D superlattice, we show that new energy bands form where the new band gap can be controlled by the size and pitch of the quantum dots in the superlattice. The band gap can be tuned from 1.81 eV to 1.42 eV without loss of its photoluminescence performance, which provides new directions for fabricating lasers with designed wavelengths. Our work constitutes a photoresist-free, top-down method to create large-area quantum dot arrays with nanometer-scale spatial density that allow the quantum dots to interfere with each other and create artificial crystals. This technique opens up new pathways for fabricating light emitting devices with 2D materials at desired wavelengths. This demonstration can also enable the assembly of large scale quantum information systems and open up new avenues for the design of artificial 2D materials.
Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication
Authors: Wang Ying , Lee Sangwon , Ha Ya , Lam Wing , Chen Shao-Ru , Dutschman Ginger E. , Gullen Elizabeth A. , Grill Susan P. , Cheng Yao , Fürstner Alois , Francis Samson , Baker David C. , Yang Xiaoming , Lee Kuo-Hsiung , Cheng Yung-Chi
Published: August 2017

Tylophorine analogs have been shown to exhibit diverse activities against cancer, inflammation, arthritis, and lupus in vivo. In this study, we demonstrated that two tylophorine analogs, DCB-3503 and rac-cryptopleurine, exhibit potent inhibitory activity against hepatitis C virus (HCV) replication in genotype 1b Con 1 isolate. The inhibition of HCV replication is at least partially mediated through cellular heat shock cognate protein 70 (Hsc70). Hsc70 associates with the HCV replication complex by primarily binding to the poly U/UC motifs in HCV RNA. The interaction of DCB-3503 and rac-cryptopleurine with Hsc70 promotes the ATP hydrolysis activity of Hsc70 in the presence of the 3′ poly U/UC motif of HCV RNA. Regulating the ATPase activity of Hsc70 may be one of the mechanisms by which tylophorine analogs inhibit HCV replication. This study demonstrates the novel anti-HCV activity of tylophorine analogs. Our results also highlight the importance of Hsc70 in HCV replication.
Analysis of the first Taraxacum kok-saghyz transcriptome reveals potential rubber yield related SNPs
Authors: Luo Zinan , Iaffaldano Brian J. , Zhuang Xiaofeng , Fresnedo-Ramírez Jonathan , Cornish Katrina
Published: August 2017

Taraxacum kok-saghyz (TK) is a potential alternative crop for natural rubber (NR) production, due to its high molecular weight rubber, short breeding cycle, and diverse environmental adaptation. However, improvements in rubber yield and agronomically relevant traits are still required before it can become a commercially-viable crop. An RNA-Seq based transcriptome was developed from a pool of roots from genotypes with high and low rubber yield. A total of 55,532 transcripts with lengths over 200 bp were de novo assembled. As many as 472 transcripts were significantly homologous to 49 out of 50 known plant putative rubber biosynthesis related genes. 158 transcripts were significantly differentially expressed between high rubber and low rubber genotypes. 21,036 SNPs were different in high and low rubber TK genotypes. Among these, 50 SNPs were found within 39 transcripts highly homologous to 49 publically-searched rubber biosynthesis related genes. 117 SNPs were located within 36 of the differentially expressed gene sequences. This comprehensive TK transcriptomic reference, and large set of SNPs including putative exonic markers associated with rubber related gene homologues and differentially expressed genes, provides a solid foundation for further genetic dissection of rubber related traits, comparative genomics and marker-assisted selection for the breeding of TK.
A Meta-analysis of Voxel-based Brain Morphometry Studies in Obstructive Sleep Apnea
Authors: Shi Yan , Chen Lizhou , Chen Taolin , Li Lei , Dai Jing , Lui Su , Huang Xiaoqi , Sweeney John A. , Gong Qiyong
Published: August 2017

Gray matter (GM) anomalies may represent a critical pathology underlying obstructive sleep apnea (OSA). However, the evidence regarding their clinical relevance is inconsistent. We conducted a meta-analysis of voxel-based morphometry (VBM) studies of patients with OSA to identify their brain abnormalities. A systematic search was conducted based on PRISMA guidelines, and a meta-analysis was performed using the anisotropic effect-size-based algorithms (ASE-SDM) to quantitatively estimate regional GM changes in patients with OSA. Fifteen studies with 16 datasets comprising 353 untreated patients with OSA and 444 healthy controls were included. Our results revealed GM reductions in the bilateral anterior cingulate/paracingulate gyri (ACG/ApCG), left cerebellum (lobules IV/V and VIII), bilateral superior frontal gyrus (SFG, medial rostral part), right middle temporal gyrus (MTG), and right premotor cortex. Moreover, GM reductions in the bilateral ACG/ApCG were positively associated with body mass index (BMI) and age among patients with OSA, and GM reductions in the SFG (medial rostral part) were negatively associated with Epworth sleepiness scale (ESS) scores and sex (male). These abnormalities may represent structural brain underpinnings of neurocognitive abnormalities and respiratory-related abnormalities in OSA. ﻿In particular, this study adds to Psychoradiology, which is a promising subspecialty of clinical radiology mainly for psychiatric disorders.
Phylogeny and expression pattern analysis of TCP transcription factors in cassava seedlings exposed to cold and/or drought stress
Authors: Lei Ning , Yu Xiang , Li Shuxia , Zeng Changying , Zou Liangping , Liao Wenbin , Peng Ming
Published: August 2017

The TCP transcription factors usually act as integrators of multiple growth regulatory and environmental stimuli. However, little is known about this gene family in the important tropical crop cassava (Manihot esculenta). In this study, 36 TCP genes were identified and renamed based on cassava whole-genome sequence and their sequence similarity with Arabidopsis TCPs. Typical TCP domains were detected in these proteins by multiple sequence alignment analysis. Evolutionary analysis indicated that MeTCPs could be divided into 8 subgroups, which was further supported by gene structure and conserved motif analyses. qRT-PCR analysis revealed tissue-specific and hormone-responsive expression patterns of MeTCP genes. Moreover, with global expression and promoter analysis, we found that MeTCPs showed similar or distinct expression patterns under cold and/or drought stress, suggesting that they might participate in distinct signaling pathways. Our study provides the first comprehensive analysis of TCP gene family in the cassava genome. The data will be useful for uncovering the potential functions of MeTCP genes, and their possible roles in mediating hormone and abiotic stress responses in cassava.
Customized binary and multi-level HfO2−x-based memristors tuned by oxidation conditions
Authors: He Weifan , Sun Huajun , Zhou Yaxiong , Lu Ke , Xue Kanhao , Miao Xiangshui
Published: August 2017

The memristor is a promising candidate for the next generation non-volatile memory, especially based on HfO2−x, given its compatibility with advanced CMOS technologies. Although various resistive transitions were reported independently, customized binary and multi-level memristors in unified HfO2−x material have not been studied. Here we report Pt/HfO2−x/Ti memristors with double memristive modes, forming-free and low operation voltage, which were tuned by oxidation conditions of HfO2−x films. As O/Hf ratios of HfO2−x films increase, the forming voltages, SET voltages, and Roff/Ron windows increase regularly while their resistive transitions undergo from gradually to sharply in I/V sweep. Two memristors with typical resistive transitions were studied to customize binary and multi-level memristive modes, respectively. For binary mode, high-speed switching with 103 pulses (10 ns) and retention test at 85 °C (>104 s) were achieved. For multi-level mode, the 12-levels stable resistance states were confirmed by ongoing multi-window switching (ranging from 10 ns to 1 μs and completing 10 cycles of each pulse). Our customized binary and multi-level HfO2−x-based memristors show high-speed switching, multi-level storage and excellent stability, which can be separately applied to logic computing and neuromorphic computing, further suitable for in-memory computing chip when deposition atmosphere may be fine-tuned.
A Valuable Biochar from Poplar Catkins with High Adsorption Capacity for Both Organic Pollutants and Inorganic Heavy Metal Ions
Authors: Liu Xia , Sun Ju , Duan Shengxia , Wang Yanan , Hayat Tasawar , Alsaedi Ahmed , Wang Chengming , Li Jiaxing
Published: August 2017

In this paper, biochar derived from poplar catkins was used as an economical and renewable adsorbent for adsorption organic and inorganic pollutants such as, dyes, organic compounds, and heavy metal ions from wastewater. Mesoporous activated carbonized poplar catkins (ACPCs) were produced from char as a by-product by carbonized poplar catkins (CPCs). With their high surface area, ACPCs exhibited the maximum adsorption capacities of 71.85 and 110.17 mg/g for the removal of inorganic U(VI) and Co(II). Compared other biochars adsorbents, ACPCs can also adsorb organic pollutants with the maximum adsorption capacities of 534, 154, 350, 148 and 384 mg/g for methylene blue (MB), methyl orange (MO), Congo red (CR), chloramphenicol (CAP) and naphthalene. The adsorption of organic pollutants was fitted with pseudo-first order, pseudo-second order, and intra-particle diffusion kinetic models figure out the kinetic parameters and adsorption mechanisms. Langmuir adsorption isotherm was found to be suitable for Co(II) and U(VI) adsorption and thermodynamic studies indicated adsorption processes to be endothermic and spontaneous. The adsorption process includes both outer-sphere surface complexes and hydrogen-bonding interactions. The results showed that biochar derived from poplar catkins was a potential material to remove pollutants in wastewater.
Improved vessel painting with carbocyanine dye-liposome solution for visualisation of vasculature
Authors: Konno Alu , Matsumoto Naoya , Okazaki Shigetoshi
Published: August 2017

Vessel painting is one of the most accessible and cost-effective techniques for visualising vasculature by fluorescence microscopy. In this method, the hydrophobic carbocyanine dye DiIC18 labels the plasma membrane via insertion of its alkyl chains into the lipid bilayer. A major disadvantage of this procedure is that it does not stain veins and some microvessels in mouse brain. Furthermore, DiIC18 molecules can aggregate during perfusion, thereby occluding arteries and reducing the success rate and reproducibility of the experiment. To overcome these problems, we developed an improved vessel painting procedure that employs neutral liposomes (NLs) and DiIC12. NLs prevented DiI aggregation under physiological conditions whereas DiIC12 showed enhanced dye incorporation into liposomes and consequently increased staining intensity. Using this method, we successfully labelled all major blood vessel types in the mouse brain, including both veins and microvessels. Thus, liposome-mediated vessel painting is a simple and efficient method for visualising vasculature.
Identifying Defects with Guided Algorithms in Bragg Coherent Diffractive Imaging
Authors: Ulvestad A. , Nashed Y. , Beutier G. , Verdier M. , Hruszkewycz S. O. , Dupraz M.
Published: August 2017

Crystallographic defects such as dislocations can significantly alter material properties and functionality. However, imaging these imperfections during operation remains challenging due to the short length scales involved and the reactive environments of interest. Bragg coherent diffractive imaging (BCDI) has emerged as a powerful tool capable of identifying dislocations, twin domains, and other defects in 3D detail with nanometer spatial resolution within nanocrystals and grains in reactive environments. However, BCDI relies on phase retrieval algorithms that can fail to accurately reconstruct the defect network. Here, we use numerical simulations to explore different guided phase retrieval algorithms for imaging defective crystals using BCDI. We explore different defect types, defect densities, Bragg peaks, and guided algorithm fitness metrics as a function of signal-to-noise ratio. Based on these results, we offer a general prescription for phasing of defective crystals with no a priori knowledge.
Spin-relaxation time in materials with broken inversion symmetry and large spin-orbit coupling
Authors: Szolnoki Lénárd , Kiss Annamária , Dóra Balázs , Simon Ferenc
Published: August 2017

We study the spin-relaxation time in materials where a large spin-orbit coupling (SOC) is present which breaks the spatial inversion symmetry. Such a spin-orbit coupling is realized in zincblende structures and heterostructures with a transversal electric field and the spin relaxation is usually described by the so-called D’yakonov-Perel’ (DP) mechanism. We combine a Monte Carlo method and diagrammatic calculation based approaches in our study; the former tracks the time evolution of electron spins in a quasiparticle dynamics simulation in the presence of the built-in spin-orbit magnetic fields and the latter builds on the spin-diffusion propagator by Burkov and Balents. Remarkably, we find a parameter free quantitative agreement between the two approaches and it also returns the conventional result of the DP mechanism in the appropriate limit. We discuss the full phase space of spin relaxation as a function of SOC strength, its distribution, and the magnitude of the momentum relaxation rate. This allows us to identify two novel spin-relaxation regimes; where spin relaxation is strongly non-exponential and the spin relaxation equals the momentum relaxation. A compelling analogy between the spin-relaxation theory and the NMR motional narrowing is highlighted.
Microbial Communities Associated with Primary and Metastatic Head and Neck Squamous Cell Carcinoma – A High Fusobacterial and Low Streptococcal Signature
Authors: Shin Jae M. , Luo Ting , Kamarajan Pachiyappan , Fenno J. Christopher , Rickard Alexander H. , Kapila Yvonne L.
Published: August 2017

Given the potential relationship between head and neck squamous cell carcinoma (HNSCC) and microbial dysbiosis, we profiled the microbiome within healthy normal and tumorous (primary and metastatic) human tissues from the oral cavity, larynx-pharynx, and lymph nodes using 16S rRNA sequencing. Alpha and beta diversity analyses revealed that normal tissues had the greatest richness in community diversity, while the metastatic populations were most closely related to one another. Compared to the normal, the microbiota associated with tumors supported altered abundances in the phyla Fusobacteria, Firmicutes, Actinobacteria and Proteobacteria. Most notably, the relative abundance of Fusobacterium increased whereas Streptococcus decreased in both primary and metastatic samples. Principal coordinate analysis indicated a separation and clustering of samples by tissue status. However, random forest analysis revealed that the microbial profiles alone were a poor predictor for primary and metastatic HNSCC samples. Here, we report that the microbial communities residing in the tumorous tissues are compositionally distinct compared to the normal adjacent tissues. However, likely due to the smaller sample size and sample-to-sample heterogeneity, our prediction models were not able to distinguish by sample types. This work provides a foundation for future studies aimed at understanding the role of the dysbiotic tissue microbiome in HNSCC.
Frequency sensitivity in mammalian hearing from a fundamental nonlinear physics model of the inner ear
Authors: Kanders Karlis , Lorimer Tom , Gomez Florian , Stoop Ruedi
Published: August 2017

A dominant view holds that the outer and middle ear are the determining factors for the frequency dependence of mammalian hearing sensitivity, but this view has been challenged. In the ensuing debate, there has been a missing element regarding in what sense and to what degree the biophysics of the inner ear might contribute to this frequency dependence. Here, we show that a simple model of the inner ear based on fundamental physical principles, reproduces, alone, the experimentally observed frequency dependence of the hearing threshold. This provides direct cochlea modeling support of the possibility that the inner ear could have a substantial role in determining the frequency dependence of mammalian hearing.
Durable superhydrophobic surfaces made by intensely connecting a bipolar top layer to the substrate with a middle connecting layer
Authors: Zhi Jinghui , Zhang Li-Zhi
Published: August 2017

This study reported a simple fabrication method for a durable superhydrophobic surface. The superhydrophobic top layer of the durable superhydrophobic surface was connected intensely to the substrate through a middle connecting layer. Glycidoxypropyltrimethoxysilane (KH-560) after hydrolysis was used to obtain a hydrophilic middle connecting layer. It could be adhered to the hydrophilic substrate by covalent bonds. Ring-open reaction with octadecylamine let the KH-560 middle layer form a net-like structure. The net-like sturcture would then encompass and station the silica particles that were used to form the coarse micro structures, intensely to increase the durability. The top hydrophobic layer with nano-structures was formed on the KH-560 middle layer. It was obtained by a bipolar nano-silica solution modified by hexamethyldisilazane (HMDS). This layer was connected to the middle layer intensely by the polar Si hydroxy groups, while the non-polar methyl groups on the surface, accompanied by the micro and nano structures, made the surface rather hydrophobic. The covalently interfacial interactions between the substrate and the middle layer, and between the middle layer and the top layer, strengthened the durability of the superhydrophobic surface. The abrasion test results showed that the superhydrophobic surface could bear 180 abrasion cycles on 1200 CW sandpaper under 2 kPa applied pressure.
Intranasally administered in situ gelling nanocomposite system of dimenhydrinate: preparation, characterization and pharmacodynamic applicability in chemotherapy induced emesis model
Authors: Barakat Sara S. , Nasr Maha , Ahmed Rania F. , Badawy Sabry S. , Mansour Samar
Published: August 2017

The aim of the current manuscript was to test the applicability of a nanocomposite system of penetration enhancer vesicles (PEVs) within polymeric in situ forming gel network composed of poloxamer and hyaluronic acid for the intranasal delivery of the antiemetic dimenhydrinate (DMH). PEVs were prepared using phospholipids and labrasol/transcutol/PEG 400 as penetration enhancers, and characterized for entrapment efficiency (EE%), particle size, zeta potential and morphology. The nanocomposite in situ forming gel system was characterized for its sol-gel temperature, viscosity and mucoadhesiveness, and was pharmacodynamically tested on a cisplatin induced emesis model in rats in terms of food, water, kaolin intake and stomach weight content. The selected PEVs formula displayed EE% of 83% for DMH, particle size of 121 nm and a surface charge of 0.83 mV. The selected nanocomposite in situ gelling formula showed a viscosity of 2.13 Pa.S, mucoadhesive force of 0.62 N and DMH controlled release over 6 hours. The pharmacodynamic study showed the superiority of the nanocomposite in situ gelling formula; being administered at a lower dose than the oral marketed formula. The described nanocomposite system proved to be successful for the intranasal delivery of DMH, thus presenting a promising delivery modality for similar antiemetics.
Location of the Central Retinal Vessel Trunk in the Laminar and Prelaminar Tissue of Healthy and Glaucomatous Eyes
Authors: Wang Bo , Lucy Katie A. , Schuman Joel S. , Ishikawa Hiroshi , Bilonick Richard A. , Sigal Ian A. , Kagemann Larry , Lu Chen , Fujimoto James G. , Wollstein Gadi
Published: August 2017

Glaucoma is a leading cause of blindness that leads to characteristic changes in the optic nerve head (ONH) region, such as nasalization of vessels. It is unknown whether the spatial location of this vessel shift inside the ONH occurs within the lamina cribrosa (LC) or the prelaminar tissue. The purpose of this study was to compare the location of the central retinal vessel trunk (CRVT) in the LC and prelaminar tissue in living healthy and glaucomatous eyes. We acquired 3-dimensional ONH scans from 119 eyes (40 healthy, 29 glaucoma suspect, and 50 glaucoma) using optical coherence tomography (OCT). The CRVT location was manually delineated in separate projection images of the LC and prelamina. We found that the CRVT in glaucoma suspect and glaucomatous eyes was located significantly more nasally compared to healthy eyes at the level of the prelamina. There was no detectable difference found in the location of the CRVT at the level of the LC between diagnostic groups. While the nasal location of the CRVT in the prelamina has been associated with glaucomatous axonal death, our results suggest that the CRVT in the LC is anchored in the tissue with minimal variation in glaucomatous eyes.
Alcohols react with MCM-41 at room temperature and chemically modify mesoporous silica
Authors: Björklund Sebastian , Kocherbitov Vitaly
Published: August 2017

Mesoporous silica has received much attention due to its well-defined structural order, high surface area, and tunable pore diameter. To successfully employ mesoporous silica for nanotechnology applications it is important to consider how it is influenced by solvent molecules due to the fact that most preparation procedures involve treatment in various solvents. In the present work we contribute to this important topic with new results on how MCM-41 is affected by a simple treatment in alcohol at room temperature. The effects of alcohol treatment are characterized by TGA, FTIR, and sorption calorimetry. The results are clear and show that treatment of MCM-41 in methanol, ethanol, propanol, butanol, pentanol, or octanol at room temperature introduces alkoxy groups that are covalently bound to the silica surface. It is shown that alcohol treated MCM-41 becomes more hydrophobic and that this effect is sequentially more prominent going from methanol to octanol. Chemical formation of alkoxy groups onto MCM-41 occurs both for calcined and hydroxylated MCM-41 and the alkoxy groups are hydrolytically unstable and can be replaced by silanol groups after exposure to water. The results are highly relevant for mesoporous silica applications that involve contact or treatment in protic solvents, which is very common.
The Genetic Origin of Short Tail in Endangered Korean Dog, DongGyeongi
Authors: Yoo DongAhn , Kim Kwondo , Kim Hyaekang , Cho Seoae , Kim Jin Nam , Lim Dajeong , Choi Seog-Gyu , Choi Bong-Hwan , Kim Heebal
Published: August 2017

The tail of many animal species is responsible for various physiological functions. The functional importance of tail may have brought tail-loss to attention in many evolutionary and developmental studies. To provide a better explanation for the loss of tail, the current study aims to identify the evolutionary history and putative causal variants for the short tail in DongGyeongi (DG), an endangered dog breed, which is also the only dog in Korea that possesses a short tail. Whole genome sequencing was conducted on 22 samples of DG, followed by an investigation of population stratification with 10 other dog breeds. The genotypes, selective sweep and demography of DG were also investigated. As a result, we discovered the unique genetic structure of DG and suggested two possible ways in which the short tail phenotype developed. Moreover, this study suggested that selective sweep genes, ANKRD11 and ACVR2B may contribute to the reduction in tail length, and non-synonymous variant in the coding sequence of T gene and the CpG island variant of SFRP2 gene are the candidate causal variants for the tail-loss.
Bacterial community diversity on in-shell walnut surfaces from six representative provinces in China
Authors: Zhang Lihui , Wang Shaojin
Published: August 2017

Walnuts (Juglans regia) have been associated with foodborne illness outbreaks in recent years. Thus, the purpose of this study was to investigate the distribution of bacteria on in-shell walnut surfaces from six representative provinces in China. The bacterial populations on walnut surfaces were investigated by high-throughput sequencing based on the bacterial 16 S rRNA hypervariable region V4. Twenty-eight samples were collected from fourteen regions in six provinces and harvested in different periods (the fresh in 2016 and the old in 2015). Proteobacteria was the most dominant phylum in all samples except for XJ1. In XJ1, and the most abundant phylum was Cyanobacteria, which also accounted for a large proportion of the abundance in YN1, YN11, XJ2 and SC11. In addition, Firmicutes and Actinobacteria were also the abundant phyla in the given samples. Some genera belonging to the opportunistic pathogens were detected, such as Pseudomonas, Acinetobacter, Burkholderia and Bacillus. The results revealed that the composition and abundance of bacterial consortiums on walnut surfaces varied among the geographical sites where they were harvested. Moreover, the storage time of samples also had impact on the abundance of bacteria. This study may provide a better understanding of the bacterial communities’ diversity on in-shell walnut surfaces.
Pseudo-acetylation of multiple sites on human Tau proteins alters Tau phosphorylation and microtubule binding, and ameliorates amyloid beta toxicity
Authors: Gorsky Marianna Karina , Burnouf Sylvie , Sofola-Adesakin Oyinkan , Dols Jacqueline , Augustin Hrvoje , Weigelt Carina Marianne , Grönke Sebastian , Partridge Linda
Published: August 2017

Tau is a microtubule-associated protein that is highly soluble and natively unfolded. Its dysfunction is involved in the pathogenesis of several neurodegenerative disorders including Alzheimer’s disease (AD), where it aggregates within neurons. Deciphering the physiological and pathogenic roles of human Tau (hTau) is crucial to further understand the mechanisms leading to its dysfunction in vivo. We have used a knock-out/knock-in strategy in Drosophila to generate a strain with hTau inserted into the endogenous fly tau locus and expressed under the control of the endogenous fly tau promoter, thus avoiding potential toxicity due to genetic over-expression. hTau knock-in (KI) proteins were expressed at normal, endogenous levels, bound to fly microtubules and were post-translationally modified, hence displaying physiological properties. We used this new model to investigate the effects of acetylation on hTau toxicity in vivo. The simultaneous pseudo-acetylation of hTau at lysines 163, 280, 281 and 369 drastically decreased hTau phosphorylation and significantly reduced its binding to microtubules in vivo. These molecular alterations were associated with ameliorated amyloid beta toxicity. Our results indicate acetylation of hTau on multiple sites regulates its biology and ameliorates amyloid beta toxicity in vivo.
Expression of IL-33 in ocular surface epithelium induces atopic keratoconjunctivitis with activation of group 2 innate lymphoid cells in mice
Authors: Imai Yasutomo , Hosotani Yuka , Ishikawa Hiroto , Yasuda Koubun , Nagai Makoto , Jitsukawa Orie , Gomi Fumi , Nakanishi Kenji , Yoshimoto Tomohiro , Nakamura Takahiro , Yamanishi Kiyofumi
Published: August 2017

In a transgenic mouse line hK14mIL33tg, with the expression of interleukin-33 (IL-33) driven by a keratin 14 promoter, keratoconjunctivitis developed spontaneously between 18 and 22 weeks of age under specific-pathogen-free conditions. These mice showed blepharitis and corneal impairments, and the histology revealed epithelial thickening in the conjunctiva and the cornea with infiltration of eosinophils, mast cells and basophils. IL-5, IL-13 and CCL11 were abundant in lacrimal fluid in the mice, and the gene expressions of IL-4, IL-5, IL-13, IL-33, Prg2 and Mmcp8 were significantly increased in the cornea. Furthermore, group 2 innate lymphoid cells (ILC2) producing IL-5 and IL-13 were markedly increased in the cornea. These phenotypes closely resemble human atopic keratoconjunctivitis (AKC). The characteristic ocular phenotype in these mice strongly suggests that IL-33 is crucial for the development of AKC. The mouse line may be useful as a novel model for research and development of therapeutic strategies for AKC.
(S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats
Authors: li Wan , Liu Huihui , Jiang Hanjie , Wang Chen , Guo Yongfei , Sun Yi , Zhao Xin , Xiong Xin , Zhang Xianhua , Zhang Ke , Nie Zongxiu , Pu Xiaoping
Published: August 2017

Chronic cerebral hypoperfusion is a pathological state that is associated with the cognitive impairments in vascular dementia. Oxiracetam is a nootropic drug that is commonly used to treat cognitive deficits of cerebrovascular origins. However, oxiracetam is currently used as a racemic mixture whose effective ingredient has not been identified to date. In this study, we first identified that (S)-oxiracetam, but not (R)-oxiracetam, was the effective ingredient that alleviated the impairments of spatial learning and memory by ameliorating neuron damage and white matter lesions, increasing the cerebral blood flow, and inhibiting astrocyte activation in chronic cerebral hypoperfused rats. Furthermore, using MALDI-MSI and LC-MS/MS, we demonstrated that (S)-oxiracetam regulated ATP metabolism, glutamine-glutamate and anti-oxidants in the cortex region of hypoperfused rats. Altogether, our results strongly suggest that (S)-oxiracetam alone could be a nootropic drug for the treatment of cognitive impairments caused by cerebral hypoperfusion.
CDC42 expression is altered by dioxin exposure and mediated by multilevel regulations via AhR in human neuroblastoma cells
Authors: Xu Tuan , Xie Heidi Q. , Li Yunping , Xia Yingjie , Chen Yangsheng , Xu Li , Wang Lingyun , Zhao Bin
Published: August 2017

Emerging evidence has shown that dioxin causes dysregulation of microRNAs (miRs) in a variety of tissues or cells. However, little is known about dioxin effects on neuronal miRs expression. In the present study, 277 differentially expressed miRs were identified by miRs microarray analysis in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, at 10−10 M) treated SK-N-SH neuroblastoma cells. Among them, 53 miRs exhibited changes of more than 0.4-fold. Consistent with the microarray data, we verified the induction effect of TCDD on hsa-miR-608 expression, which is a primate-specific miR associated with brain functions. Bioinformatics analysis showed involvement of hsa-miR-608 in cytoskeleton organization, in which one of the hsa-miR-608 target genes, Cell Division Cycle 42 (CDC42), might play a role. We also confirmed induction of CDC42 expression by TCDD in SK-N-SH cells. TCDD induced the expression of CDC42 mRNA in hsa-miR-608 inhibitor transfected cells more obviously than in control cells, suggesting involvement of both transcriptional and post-transcriptional mechanisms in the TCDD-induced CDC42 regulation. Furthermore, CH223191, an antagonist of the aryl hydrocarbon receptor (AhR), counteracted TCDD-induced hsa-miR-608 and CDC42 expression. These results indicated that AhR not only mediates transcriptional induction of CDC42, but also hsa-miR-608-induced post-transcriptional regulation of CDC42 in dioxin treated neuroblastoma cells.
Functional analysis of a novel, thyroglobulin-embedded microRNA gene deregulated in papillary thyroid carcinoma
Authors: Kolanowska Monika , Wójcicka Anna , Kubiak Anna , Świerniak Michał , Kotlarek Marta , Maciąg Monika , Gaj Paweł , Koperski Łukasz , Górnicka Barbara , Jażdżewski Krystian
Published: August 2017

MicroRNAs, non-coding regulators of gene expression, are known culprits of thyroid cancer. Using next-generation sequencing, we identified a novel microRNA gene, encoded within an important thyroid regulator – thyroglobulin, and analyzed its functionality in the thyroid gland. In vitro and in silico analyses proved that the novel miR-TG is processed from the precursor, and co-expressed with thyroglobulin. Both genes are specific for thyroid tissue and downregulated in papillary thyroid carcinoma by 44% (p = 0.04) and 48% (p = 0.001), respectively. Putative target genes for miR-TG were identified using in silico tools, which pinpointed MAP4K4, an oncogene upregulated in thyroid cancer. Analysis of transcriptome by RNA-seq revealed that overexpression of miR-TG in PTC-derived cell line led to downregulation of several genes, including MAP4K4 (fold change 0,82; p = 0.036). The finding was confirmed by SQ-PCR (fold change 071; p = 0.004). Direct interaction between miR-TG and MAP4K4 was confirmed in the luciferase assay (p = 0.0006). Functional studies showed increase proliferation in K1 cell line transfected with miR-TG. We propose that in normal thyroid miR-TG plays a fine-tuning effect on the maintenance of MAPK pathway, inhibiting the expression of miR’s target MAP4K4. This regulation is disturbed in cancer due to downregulation of the novel, thyroglobulin-embedded microRNA, characterized in this study.
Dual roles of Aβ in proliferative processes in an amyloidogenic model of Alzheimer’s disease
Authors: Baglietto-Vargas David , Sánchez-Mejias Elisabeth , Navarro Victoria , Jimenez Sebastián , Trujillo-Estrada Laura , Gómez-Arboledas Angela , Sánchez-Mico Maria , Sánchez-Varo Raquel , Vizuete Marisa , Dávila José Carlos , García-Verdugo José Manuel , Vitorica Javier , Gutierrez Antonia
Published: August 2017

Alzheimer’s disease is a major neurodegenerative disorder that leads to severe cognitive deficits in the elderly population. Over the past two decades, multiple studies have focused on elucidating the causative factors underlying memory defects in Alzheimer’s patients. In this regard, new evidence linking Alzheimer’s disease-related pathology and neuronal stem cells suggests that hippocampal neurogenesis impairment is an important factor underlying these cognitive deficits. However, because of conflicting results, the impact of Aβ pathology on neurogenesis/gliogenesis remains unclear. Here, we investigated the effect of Aβ on neuronal and glial proliferation by using an APP/PS1 transgenic model and in vitro assays. Specifically, we showed that neurogenesis is affected early in the APP/PS1 hippocampus, as evidenced by a significant decrease in the proliferative activity due to a reduced number of both radial glia-like neural stem cells (type-1 cells) and intermediate progenitor cells (type-2 cells). Moreover, we demonstrated that soluble Aβ from APP/PS1 mice impairs neuronal cell proliferation using neurosphere cultures. On the other hand, we showed that oligomeric Aβ stimulates microglial proliferation, whereas no effect was observed on astrocytes. These findings indicate that Aβ has a differential effect on hippocampal proliferative cells by inhibiting neuronal proliferation and triggering the formation of microglial cells.
RETRACTED ARTICLE: Sorcin Predicts Poor Prognosis and Promotes Metastasis by Facilitating Epithelial-mesenchymal Transition in Hepatocellular Carcinoma
Authors: Lei Xiong , Liang Yahang , Chen Jian , Xiao Shuai , Lei Jian , Li Jianfeng , Duanmu Jinzhong , Jiang Qunguang , Liu Dongning , Tang Cheng , Li Taiyuan
Published: August 2017

Metastasis-associated recurrence is the main cause for the poor prognosis of hepatocellular carcinoma (HCC). However, the detailed molecular mechanisms underlying HCC metastasis remain elusive. Though some data indicated the oncogenic role of Sorcin in tumors, the prognostic value and biological role of Sorcin in HCC is still unknown. In this study, it demonstrated that Sorcin expression levels were significantly upregulated in HCC tumor tissues compared with matched adjacent nontumorous liver tissues and normal liver tissues, and such expression level correlated with HCC metastasis. High Sorcin expression was significantly correlated with aggressive clinicopathological characteristics such as multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P < 0.05). HCC patients with high Sorcin expression had both shorter survival and higher recurrence than those with low Sorcin expression (all P < 0.05). Sorcin expression was an independent and significant risk factor for survival and recurrence of HCC patients. Results of functional experiments showed that Sorcin could promote HCC cell proliferation, migration, and invasion in vitro, and facilitate HCC growth and metastasis in vivo. Mechanistically, Sorcin exerted its role by activating extracellular signal-regulated kinase (ERK) pathway and promoted metastasis by facilitating epithelial-mesenchymal transition (EMT) in HCC.