bluuebunny/crossref_metadata_2025 huggingface dataset:
A distinct holoenzyme organization for two-subunit pyruvate carboxylase
Authors: Choi Philip H. , Jo Jeanyoung , Lin Yu-Cheng , Lin Min-Han , Chou Chi-Yuan , Dietrich Lars E. P. , Tong Liang
Published: October 2016

Pyruvate carboxylase (PC) has important roles in metabolism and is crucial for virulence for some pathogenic bacteria. PC contains biotin carboxylase (BC), carboxyltransferase (CT) and biotin carboxyl carrier protein (BCCP) components. It is a single-chain enzyme in eukaryotes and most bacteria, and functions as a 500 kD homo-tetramer. In contrast, PC is a two-subunit enzyme in a collection of Gram-negative bacteria, with the α subunit containing the BC and the β subunit the CT and BCCP domains, and it is believed that the holoenzyme has α4β4 stoichiometry. We report here the crystal structures of a two-subunit PC from Methylobacillus flagellatus. Surprisingly, our structures reveal an α2β4 stoichiometry, and the overall architecture of the holoenzyme is strikingly different from that of the homo-tetrameric PCs. Biochemical and mutagenesis studies confirm the stoichiometry and other structural observations. Our functional studies in Pseudomonas aeruginosa show that its two-subunit PC is important for colony morphogenesis.
ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation
Authors: Seo Ji Hae , Park Ji-Hyeon , Lee Eun Ji , Vo Tam Thuy Lu , Choi Hoon , Kim Jun Yong , Jang Jae Kyung , Wee Hee-Jun , Lee Hye Shin , Jang Se Hwan , Park Zee Yong , Jeong Jaeho , Lee Kong-Joo , Seok Seung-Hyeon , Park Jin Young , Lee Bong Jin , Lee Mi-Ni , Oh Goo Taeg , Kim Kyu-Won
Published: October 2016

Heat shock protein (Hsp)70 is a molecular chaperone that maintains protein homoeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. However, the mechanisms by which Hsp70 balances these opposing functions under stress conditions remain unknown. Here, we demonstrate that Hsp70 preferentially facilitates protein refolding after stress, gradually switching to protein degradation via a mechanism dependent on ARD1-mediated Hsp70 acetylation. During the early stress response, Hsp70 is immediately acetylated by ARD1 at K77, and the acetylated Hsp70 binds to the co-chaperone Hop to allow protein refolding. Thereafter, Hsp70 is deacetylated and binds to the ubiquitin ligase protein CHIP to complete protein degradation during later stages. This switch is required for the maintenance of protein homoeostasis and ultimately rescues cells from stress-induced cell death in vitro and in vivo. Therefore, ARD1-mediated Hsp70 acetylation is a regulatory mechanism that temporally balances protein refolding/degradation in response to stress.
Spontaneous assembly of chemically encoded two-dimensional coacervate droplet arrays by acoustic wave patterning
Authors: Tian Liangfei , Martin Nicolas , Bassindale Philip G. , Patil Avinash J. , Li Mei , Barnes Adrian , Drinkwater Bruce W. , Mann Stephen
Published: October 2016

The spontaneous assembly of chemically encoded, molecularly crowded, water-rich micro-droplets into periodic defect-free two-dimensional arrays is achieved in aqueous media by a combination of an acoustic standing wave pressure field and in situ complex coacervation. Acoustically mediated coalescence of primary droplets generates single-droplet per node micro-arrays that exhibit variable surface-attachment properties, spontaneously uptake dyes, enzymes and particles, and display spatial and time-dependent fluorescence outputs when exposed to a reactant diffusion gradient. In addition, coacervate droplet arrays exhibiting dynamical behaviour and exchange of matter are prepared by inhibiting coalescence to produce acoustically trapped lattices of droplet clusters that display fast and reversible changes in shape and spatial configuration in direct response to modulations in the acoustic frequencies and fields. Our results offer a novel route to the design and construction of ‘water-in-water’ micro-droplet arrays with controllable spatial organization, programmable signalling pathways and higher order collective behaviour.
Nano-inspired fluidic interactivity for boiling heat transfer: impact and criteria
Authors: Kim Beom Seok , Choi Geehong , Shin Sangwoo , Gemming Thomas , Cho Hyung Hee
Published: October 2016

The enhancement of boiling heat transfer, the most powerful energy-transferring technology, will lead to milestones in the development of high-efficiency, next-generation energy systems. Perceiving nano-inspired interface functionalities from their rough morphologies, we demonstrate interface-induced liquid refreshing is essential to improve heat transfer by intrinsically avoiding Leidenfrost phenomenon. High liquid accessibility of hemi-wicking and catalytic nucleation, triggered by the morphological and hydrodynamic peculiarities of nano-inspired interfaces, contribute to the critical heat flux (CHF) and the heat transfer coefficient (HTC). Our experiments show CHF is a function of universal hydrodynamic characteristics involving interfacial liquid accessibility and HTC is improved with a higher probability of smaller nuclei with less superheat. Considering the interface-induced and bulk liquid accessibility at boiling, we discuss functionalizing the interactivity between an interface and a counteracting fluid seeking to create a novel interface, a so-called smart interface, for a breakthrough in boiling and its pragmatic application in energy systems.
Illusions of having small or large invisible bodies influence visual perception of object size
Authors: van der Hoort Björn , Ehrsson H. Henrik
Published: October 2016

The size of our body influences the perceived size of the world so that objects appear larger to children than to adults. The mechanisms underlying this effect remain unclear. It has been difficult to dissociate visual rescaling of the external environment based on an individual’s visible body from visual rescaling based on a central multisensory body representation. To differentiate these potential causal mechanisms, we manipulated body representation without a visible body by taking advantage of recent developments in body representation research. Participants experienced the illusion of having a small or large invisible body while object-size perception was tested. Our findings show that the perceived size of test-objects was determined by the size of the invisible body (inverse relation) and by the strength of the invisible body illusion. These findings demonstrate how central body representation directly influences visual size perception, without the need for a visible body, by rescaling the spatial representation of the environment.
Beatquency domain and machine learning improve prediction of cardiovascular death after acute coronary syndrome
Authors: Liu Yun , Scirica Benjamin M. , Stultz Collin M. , Guttag John V.
Published: October 2016

Frequency domain measures of heart rate variability (HRV) are associated with adverse events after a myocardial infarction. However, patterns in the traditional frequency domain (measured in Hz, or cycles per second) may capture different cardiac phenomena at different heart rates. An alternative is to consider frequency with respect to heartbeats, or beatquency. We compared the use of frequency and beatquency domains to predict patient risk after an acute coronary syndrome. We then determined whether machine learning could further improve the predictive performance. We first evaluated the use of pre-defined frequency and beatquency bands in a clinical trial dataset (N = 2302) for the HRV risk measure LF/HF (the ratio of low frequency to high frequency power). Relative to frequency, beatquency improved the ability of LF/HF to predict cardiovascular death within one year (Area Under the Curve, or AUC, of 0.730 vs. 0.704, p < 0.001). Next, we used machine learning to learn frequency and beatquency bands with optimal predictive power, which further improved the AUC for beatquency to 0.753 (p < 0.001), but not for frequency. Results in additional validation datasets (N = 2255 and N = 765) were similar. Our results suggest that beatquency and machine learning provide valuable tools in physiological studies of HRV.
Steady flow and heat transfer analysis of Phan-Thein-Tanner fluid in double-layer optical fiber coating analysis with Slip Conditions
Authors: Khan Zeeshan , Shah Rehan Ali , Islam Saeed , Jan Bilal , Imran Muhammad , Tahir Farisa
Published: October 2016

Modern optical fibers require double-layer coating on the glass fiber to provide protection from signal attenuation and mechanical damage. The most important plastic resins used in wires and optical fibers are plastic polyvinyl chloride (PVC) and low-high density polyethylene (LDPE/HDPE), nylon and Polysulfone. In this paper, double-layer optical fiber coating is performed using melt polymer satisfying PTT fluid model in a pressure type die using wet-on-wet coating process. The assumption of fully developed flow of Phan-Thien-Tanner (PTT) fluid model, two-layer liquid flows of an immiscible fluid is modeled in an annular die, where the fiber is dragged at a higher speed. The equations characterizing the flow and heat transfer phenomena are solved exactly and the effects of emerging parameters (Deborah and slip parameters, characteristic velocity, radii ratio and Brinkman numbers on the axial velocity, flow rate, thickness of coated fiber optics, and temperature distribution) are reported in graphs. It is shown that an increase in the non-Newtonian parameters increase the velocity in the absence or presence of slip parameters which coincides with related work. The comparison is done with experimental work by taking λ → 0 (non-Newtonian parameter).
B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation
Authors: Bjarnadóttir Kristbjörg , Benkhoucha Mahdia , Merkler Doron , Weber Martin S. , Payne Natalie L. , Bernard Claude C. A. , Molnarfi Nicolas , Lalive Patrice H.
Published: October 2016

Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B–TGF-β1−/−) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG). In this model, B–TGF-β1−/− mice showed an earlier onset of neurologic impairment compared to their littermate controls. Exacerbated EAE susceptibility in B–TGF-β1−/− mice was associated with augmented CNS T helper (Th)1/17 responses. Moreover, selective B cell TGF-β1–deficiency increased the frequencies and activation of myeloid dendritic cells, potent professional antigen-presenting cells (APCs), suggesting that B cell-derived TGF-β1 can constrain Th1/17 responses through inhibition of APC activity. Collectively our data suggest that B cells can down-regulate the function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-β1, findings that may be relevant to B cell-targeted therapies.
Loss of Atg16 delays the alcohol-induced sedation response via regulation of Corazonin neuropeptide production in Drosophila
Authors: Varga Kata , Nagy Péter , Arsikin Csordás Katarina , Kovács Attila L. , Hegedűs Krisztina , Juhász Gábor
Published: October 2016

Autophagy defects lead to the buildup of damaged proteins and organelles, reduced survival during starvation and infections, hypersensitivity to stress and toxic substances, and progressive neurodegeneration. Here we show that, surprisingly, Drosophila mutants lacking the core autophagy gene Atg16 are not only defective in autophagy but also exhibit increased resistance to the sedative effects of ethanol, unlike Atg7 or Atg3 null mutant flies. This mutant phenotype is rescued by the re-expression of Atg16 in Corazonin (Crz)-producing neurosecretory cells that are known to promote the sedation response during ethanol exposure, and RNAi knockdown of Atg16 specifically in these cells also delays the onset of ethanol-induced coma. We find that Atg16 and Crz colocalize within these neurosecretory cells, and both Crz protein and mRNA levels are decreased in Atg16 mutant flies. Thus, Atg16 promotes Crz production to ensure a proper organismal sedation response to ethanol.
Biotransformation of ferulic acid to vanillin in the packed bed-stirred fermentors
Authors: Yan Lei , Chen Peng , Zhang Shuang , Li Suyue , Yan Xiaojuan , Wang Ningbo , Liang Ning , Li Hongyu
Published: October 2016

We performed the biotransformation of ferulic acid to vanillin using Bacillus subtilis (B. subtilis) in the stirring packed-bed reactors filled with carbon fiber textiles (CFT). Scanning electron microscope (SEM), HPLC, qRT-PCR and ATP assay indicated that vanillin biotransformation is tightly related to cell growth, cellar activity and the extent of biofilm formation. The biotransformation was affected by hydraulic retention time (HRT), temperature, initial pH, stirring speed and ferulic acid concentration, and the maximum vanillin production was obtained at 20 h, 35 °C, 9.0, 200 rpm, 1.5 g/L, respectively. Repeated batch biotransformation performed under this optimized condition showed that the maximum productivity (0.047 g/L/h) and molar yield (60.43%) achieved in immobilized cell system were 1.84 and 3.61 folds higher than those achieved in free cell system. Therefore, the stirring reactor packed with CFT carrier biofilm formed by B. subtilis represented a valid biocatalytic system for the production of vanillin.
Structural and Functional Characterization of the VQ Protein Family and VQ Protein Variants from Soybean
Authors: Zhou Yuan , Yang Yan , Zhou Xinjian , Chi Yingjun , Fan Baofang , Chen Zhixiang
Published: October 2016

Proteins containing the FxxxVQxhTG or VQ motif interact with WRKY transcription factors. Although VQ proteins have been reported in several plants, knowledge about their structures, functions and evolution is still very limited. Here, we report structural and functional analysis of the VQ protein family from soybean. Like Arabidopsis homologues, soybean VQ proteins bind only Group I and IIc WRKY proteins and a substantial number of their genes are responsive to stress-associated phytohormones. Overexpression of some soybean VQ genes in Arabidopsis had strong effects on plant growth, development, disease resistance and heat tolerance. Phylogenetic analysis, sequence alignment and site-directed mutagenesis revealed that the region immediately upstream of the FxxxVQxhTG motif also affects binding to WRKY proteins. Consistent with a larger WRKY-binding VQ domain, soybean VQ22 protein from cultivated soybean contains a 4-amino acid deletion in the region preceding its VQ motif that completely abolishes its binding to WRKY proteins. By contrast, the 4-amino acid deletion is absent in the VQ22 protein from wild soybean species (Glycine soja). Overexpression of wild soybean VQ22 in cultivated soybean inhibited growth, particularly after cold treatment. Thus, the mutation of soybean VQ22 is associated with advantageous phenotypes and may have been positively selected during evolution.
Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58
Authors: Xu Wan-Xiang , Wang Jian , Tang Hai-Ping , He Ya-Ping , Zhu Qian-Xi , Gupta Satish K. , Gu Shao-Hua , Huang Qiang , Ji Chao-Neng , Liu Ling-Feng , Li Gui-Ling , Xu Cong-Jian , Xie Yi
Published: October 2016

To enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate complete IgG-epitome of the protein. Here, we describe results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were mapped on E6, E7 and L1 proteins using rabbits antisera to the respective recombinant proteins. Using sequence alignment based on BCE minimal motif, the specificity and conservativeness of each mapped BCE were delineated mainly among known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1 that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18 BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like particles, suggesting that these are antibody accessible BCEs. Also, a highly conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR-HPVs, which could be used as the first peptide reference marker for judging HR-HPVs. Altogether, this study provides systemic and exhaustive information on linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope diagnostic reagents/chips for testing viral antibodies and ‘universal’ preventive HPV peptide vaccine based on L1 conserved BCEs.
A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms
Authors: Jones Alan M. , Westwood Isaac M. , Osborne James D. , Matthews Thomas P. , Cheeseman Matthew D. , Rowlands Martin G. , Jeganathan Fiona , Burke Rosemary , Lee Diane , Kadi Nadia , Liu Manjuan , Richards Meirion , McAndrew Craig , Yahya Norhakim , Dobson Sarah E. , Jones Keith , Workman Paul , Collins Ian , van Montfort Rob L. M.
Published: October 2016

The heat shock protein 70s (HSP70s) are molecular chaperones implicated in many cancers and of significant interest as targets for novel cancer therapies. Several HSP70 inhibitors have been reported, but because the majority have poor physicochemical properties and for many the exact mode of action is poorly understood, more detailed mechanistic and structural insight into ligand-binding to HSP70s is urgently needed. Here we describe the first comprehensive fragment-based inhibitor exploration of an HSP70 enzyme, which yielded an amino-quinazoline fragment that was elaborated to a novel ATP binding site ligand with different physicochemical properties to known adenosine-based HSP70 inhibitors. Crystal structures of amino-quinazoline ligands bound to the different conformational states of the HSP70 nucleotide binding domain highlighted the challenges of a fragment-based approach when applied to this particular flexible enzyme class with an ATP-binding site that changes shape and size during its catalytic cycle. In these studies we showed that Ser275 is a key residue in the selective binding of ATP. Additionally, the structural data revealed a potential functional role for the ATP ribose moiety in priming the protein for the formation of the ATP-bound pre-hydrolysis complex by influencing the conformation of one of the phosphate binding loops.
The detection accuracy of cone beam CT for osseous defects of the temporomandibular joint: a systematic review and meta-analysis
Authors: Ma Ruo-han , Yin Shuang , Li Gang
Published: October 2016

The purpose of this review was to evaluate whether cone-beam computed tomography (CBCT) is reliable for the detection of bone changes of the temporomandibular joint (TMJ). Studies collected from the PubMed, Web of Science, Cochrane Library, ScienceDirect, Embase, Wanfang and CNKI databases were searched, and the publishing time was limited from January 1990 to December 2015. Eight studies (23 experimental research groups) were eventually included for further analysis. The pooled sensitivity was 0.67 and the pooled specificity was 0.87, which leads to a relatively large area (0.84) under the Receiver Operating Characteristic (ROC) curve. The related pooled positive likelihood ratio (+LR) and the pooled negative likelihood ratio (−LR) were 5.2 and 0.38, respectively. The subgroup analysis was conducted for four subgroups categorized by voxel size (≤0.2; >0.2, ≤0.3; >0.3, ≤0.4; >0.4, and ≤0.5 (mm)), and the “>0.4, ≤0.5” subgroup had a higher pooled sensitivity and pooled specificity than the other groups. The present study demonstrates that CBCT has a relatively high diagnostic accuracy for TMJ bone changes, although its reliability is limited. Voxel size did not play a role in the accuracy of CBCT.
Association between dietary patterns and metabolic syndrome in Chinese adults: a propensity score-matched case-control study
Authors: Xia Yang , Gu Yeqing , Yu Fei , Zhang Qing , Liu Li , Meng Ge , Wu Hongmei , Du Huanmin , Shi Hongbin , Guo Xiaoyan , Liu Xing , Li Chunlei , Han Peipei , Dong Renwei , Wang Xiuyang , Bao Xue , Su Qian , Fang Liyun , Liu Fangfang , Yang Huijun , Kang Li , Ma Yixuan , Yu Bin , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Guo Qi , Wu Yuntang , Song Kun , Huang Guowei , Wang Guolin , Niu Kaijun
Published: October 2016

Previous studies indicated that dietary patterns were associated with metabolic syndrome (MS), but little is known in Chinese. We design this case-control study to evaluate the associations between dietary patterns and MS in Chinese adults. In this study, 1492 participants with MS were matched with 1492 controls using the 1:1 ratio propensity score matching methods. Dietary intake was assessed using a valid self-administered food frequency questionnaire, and MS was defined in accordance with the criteria of the American Heart Association scientific statement of 2009. Higher scores for the high-protein/cholesterol pattern were associated with higher prevalence of MS. Compared with the participants in the lowest quartile, the odds ratio (OR) for the extreme quartile was 1.36 (95% confidence interval (CI), 1.10–1.68) and the P for trend <0.01 after adjusted for the other two dietary pattern scores. We also found a moderate consumption of the balanced pattern was associated with the lowest prevalence of MS. The ORs across quartiles of the balanced pattern were 1 (reference), 0.83 (95% CI, 0.68–1.02), 0.69 (95% CI, 0.56–0.85), and 0.84 (95% CI, 0.68–1.04) after adjustment. Our study demonstrates that there is a strong association between a diet rich in animal offal, animal blood, meat, and sausage and a higher prevalence of MS.
The Important Role of Halogen Bond in Substrate Selectivity of Enzymatic Catalysis
Authors: Jiang Shuiqin , Zhang Lujia , Cui Dongbin , Yao Zhiqiang , Gao Bei , Lin Jinping , Wei Dongzhi
Published: October 2016

The use of halogen bond is widespread in drug discovery, design, and clinical trials, but is overlooked in drug biosynthesis. Here, the role of halogen bond in the nitrilase-catalyzed synthesis of ortho-, meta-, and para-chlorophenylacetic acid was investigated. Different distributions of halogen bond induced changes of substrate binding conformation and affected substrate selectivity. By engineering the halogen interaction, the substrate selectivity of the enzyme changed, with the implication that halogen bond plays an important role in biosynthesis and should be used as an efficient and reliable tool in enzymatic drug synthesis.
Plant growth promoting rhizobacteria Dietzia natronolimnaea modulates the expression of stress responsive genes providing protection of wheat from salinity stress
Authors: Bharti Nidhi , Pandey Shiv Shanker , Barnawal Deepti , Patel Vikas Kumar , Kalra Alok
Published: October 2016

Plant growth promoting rhizobacteria (PGPR) hold promising future for sustainable agriculture. Here, we demonstrate a carotenoid producing halotolerant PGPR Dietzia natronolimnaea STR1 protecting wheat plants from salt stress by modulating the transcriptional machinery responsible for salinity tolerance in plants. The expression studies confirmed the involvement of ABA-signalling cascade, as TaABARE and TaOPR1 were upregulated in PGPR inoculated plants leading to induction of TaMYB and TaWRKY expression followed by stimulation of expression of a plethora of stress related genes. Enhanced expression of TaST, a salt stress-induced gene, associated with promoting salinity tolerance was observed in PGPR inoculated plants in comparison to uninoculated control plants. Expression of SOS pathway related genes (SOS1 and SOS4) was modulated in PGPR-applied wheat shoots and root systems. Tissue-specific responses of ion transporters TaNHX1, TaHAK, and TaHKT1, were observed in PGPR-inoculated plants. The enhanced gene expression of various antioxidant enzymes such as APX, MnSOD, CAT, POD, GPX and GR and higher proline content in PGPR-inoculated wheat plants contributed to increased tolerance to salinity stress. Overall, these results indicate that halotolerant PGPR-mediated salinity tolerance is a complex phenomenon that involves modulation of ABA-signalling, SOS pathway, ion transporters and antioxidant machinery.
Temperature controls organic carbon sequestration in a subarctic lake
Authors: Rantala Marttiina V. , Luoto Tomi P. , Nevalainen Liisa
Published: October 2016

Widespread ecological reorganizations and increases in organic carbon (OC) in lakes across the Northern Hemisphere have raised concerns about the impact of the ongoing climate warming on aquatic ecosystems and carbon cycling. We employed diverse biogeochemical techniques on a high-resolution sediment record from a subarctic lake in northern Finland (70°N) to examine the direction, magnitude and mechanism of change in aquatic carbon pools prior to and under the anthropogenic warming. Coupled variation in the elemental and isotopic composition of the sediment and a proxy-based summer air temperature reconstruction tracked changes in aquatic production, depicting a decline during a cool climate interval between ~1700–1900 C.E. and a subsequent increase over the 20th century. OC accumulation rates displayed similar coeval variation with temperature, mirroring both changes in aquatic production and terrestrial carbon export. Increase in sediment organic content over the 20th century together with high inferred aquatic UV exposure imply that the 20th century increase in OC accumulation is primarily connected to elevated lake production rather than terrestrial inputs. The changes in the supply of autochthonous energy sources were further reflected higher up the benthic food web, as evidenced by biotic stable isotopic fingerprints.
Attenuation of synaptic toxicity and MARK4/PAR1-mediated Tau phosphorylation by methylene blue for Alzheimer’s disease treatment
Authors: Sun Wenchao , Lee Seongsoo , Huang Xiaoran , Liu Song , Inayathullah Mohammed , Kim Kwang-Min , Tang Hongxiang , Ashford J. Wesson , Rajadas Jayakumar
Published: October 2016

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by genotypic and phenotypic heterogeneity. Critical components of the two AD pathological pathways, Aβ-amyloidosis and Tauopathy, have been considered as therapeutic targets. Among them, much effort is focused on aberrant Tau phosphorylation and targeting Tau-phosphorylating kinases. Methylene blue (MB), a phenothiazine dye that crosses the blood-brain barrier, has been shown to hit multiple molecular targets involved in AD and have beneficial effects in clinical studies. Here we present evidence that microtubule affinity-regulating kinase (MARK4) is a novel target of MB. MB partially rescued the synaptic toxicity in Drosophila larva overexpressing PAR1 (MARK analog). In 293T culture, MB decreased MARK4-mediated Tau phosphorylation in a dose dependent manner. Further studies revealed a two-fold mechanism by MB including down-regulation of MARK4 protein level through ubiquitin-proteasome pathway and inhibition of MARK4 kinase activity in vitro. This study highlights the importance of MARK4 as a viable target for Tauopathy and provides fresh insight into the complex mechanism used by MB to treat AD.
Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness
Authors: Pongkitwitoon Suphannee , Uzer Gunes , Rubin Janet , Judex Stefan
Published: October 2016

Mesenchymal stem cells (MSC) responding to mechanical cues generated by physical activity is critical for skeletal development and remodeling. Here, we utilized low intensity vibrations (LIV) as a physiologically relevant mechanical signal and hypothesized that the confined cytoskeletal configuration imposed by 2D culture will enable human bone marrow MSCs (hBMSC) to respond more robustly when LIV is applied in-plane (horizontal-LIV) rather than out-of-plane (vertical-LIV). All LIV signals enhanced hBMSC proliferation, osteogenic differentiation, and upregulated genes associated with cytoskeletal structure. The cellular response was more pronounced at higher frequencies (100 Hz vs 30 Hz) and when applied in the horizontal plane. Horizontal but not vertical LIV realigned the cell cytoskeleton, culminating in increased cell stiffness. Our results show that applying very small oscillatory motions within the primary cell attachment plane, rather than perpendicular to it, amplifies the cell’s response to LIV, ostensibly facilitating a more effective transfer of intracellular forces. Transcriptional and structural changes in particular with horizontal LIV, together with the strong frequency dependency of the signal, emphasize the importance of intracellular cytoskeletal configuration in sensing and responding to high-frequency mechanical signals at low intensities.
Structural basis for PPAR partial or full activation revealed by a novel ligand binding mode
Authors: Capelli Davide , Cerchia Carmen , Montanari Roberta , Loiodice Fulvio , Tortorella Paolo , Laghezza Antonio , Cervoni Laura , Pochetti Giorgio , Lavecchia Antonio
Published: October 2016

The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of the metabolic homeostasis and therefore represent valuable therapeutic targets for the treatment of metabolic diseases. The development of more balanced drugs interacting with PPARs, devoid of the side-effects showed by the currently marketed PPARγ full agonists, is considered the major challenge for the pharmaceutical companies. Here we present a structure-based virtual screening approach that let us identify a novel PPAR pan-agonist with a very attractive activity profile and its crystal structure in the complex with PPARα and PPARγ, respectively. In PPARα this ligand occupies a new pocket whose filling is allowed by the ligand-induced switching of the F273 side chain from a closed to an open conformation. The comparison between this pocket and the corresponding cavity in PPARγ provides a rationale for the different activation of the ligand towards PPARα and PPARγ, suggesting a novel basis for ligand design.
Two-photon interference of temporally separated photons
Authors: Kim Heonoh , Lee Sang Min , Moon Han Seb
Published: October 2016

We present experimental demonstrations of two-photon interference involving temporally separated photons within two types of interferometers: a Mach-Zehnder interferometer and a polarization-based Michelson interferometer. The two-photon states are probabilistically prepared in a symmetrically superposed state within the two interferometer arms by introducing a large time delay between two input photons; this state is composed of two temporally separated photons, which are in two different or the same spatial modes. We then observe two-photon interference fringes involving both the Hong-Ou-Mandel interference effect and the interference of path-entangled two-photon states simultaneously in a single interferometric setup. The observed two-photon interference fringes provide simultaneous observation of the interferometric properties of the single-photon and two-photon wavepackets. The observations can also facilitate a more comprehensive understanding of the origins of the interference phenomena arising from spatially bunched/anti-bunched two-photon states comprised of two temporally separated photons within the interferometer arms.
Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In Compacted Nucleosome Arrays
Authors: Mishra Laxmi N. , Pepenella Sharon , Rogge Ryan , Hansen Jeffrey C. , Hayes Jeffrey J.
Published: October 2016

The activation of a silent gene locus is thought to involve pioneering transcription factors that initiate changes in the local chromatin structure to increase promoter accessibility and binding of downstream effectors. To better understand the molecular requirements for the first steps of locus activation, we investigated whether acetylation of a single nucleosome is sufficient to alter DNA accessibility within a condensed 25-nucleosome array. We found that acetylation mimics within the histone H4 tail domain increased accessibility of the surrounding linker DNA, with the increased accessibility localized to the immediate vicinity of the modified nucleosome. In contrast, acetylation mimics within the H3 tail had little effect, but were able to synergize with H4 tail acetylation mimics to further increase accessibility. Moreover, replacement of the central nucleosome with a nucleosome free region also resulted in increased local, but not global DNA accessibility. Our results indicate that modification or disruption of only a single target nucleosome results in significant changes in local chromatin architecture and suggest that very localized chromatin modifications imparted by pioneer transcription factors are sufficient to initiate a cascade of events leading to promoter activation.
Critical Role of Transcription Factor PU.1 in the Function of the OX40L/TNFSF4 Promoter in Dendritic Cells
Authors: Yashiro Takuya , Hara Mutsuko , Ogawa Hideoki , Okumura Ko , Nishiyama Chiharu
Published: October 2016

PU.1 is a hematopoietic lineage-specific transcription factor belonging to the Ets family. We investigated the role of PU.1 in the expression of OX40L in dendritic cells (DCs), because the regulatory mechanism of cell type-specific expression of OX40L, which is mainly restricted to antigen-presenting cells, is largely unknown despite the critical involvement in Th2 and Tfh development. PU.1 knockdown decreased the expression of OX40L in mouse DCs. Chromatin immunoprecipitation (ChIP) assays demonstrated that PU.1 constitutively bound to the proximal region of the OX40L promoter. Reporter assays and electrophoretic mobility shift assays revealed that PU.1 transactivated the OX40L promoter through direct binding to the most-proximal Ets motif. We found that this Ets motif is conserved between mouse and human, and that PU.1 bound to the human OX40L promoter in ChIP assay using human monocyte-derived DCs. ChIP assays based on ChIP-seq datasets revealed that PU.1 binds to several sites distant from the transcription start site on the OX40L gene in addition to the most-proximal site in mouse DCs. In the present study, the structure of the OX40L promoter regulated by PU.1 is determined. It is also suggested that PU.1 is involved in mouse OX40L expression via multiple binding sites on the gene.
Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic analysis
Authors: Liu Wenjun , Zhang Jiachao , Wu Chunyan , Cai Shunfeng , Huang Weiqiang , Chen Jing , Xi Xiaoxia , Liang Zebin , Hou Qiangchuan , Zhou Bin , Qin Nan , Zhang Heping
Published: October 2016

The human gut microbiota varies considerably among world populations due to a variety of factors including genetic background, diet, cultural habits and socioeconomic status. Here we characterized 110 healthy Mongolian adults gut microbiota by shotgun metagenomic sequencing and compared the intestinal microbiome among Mongolians, the Hans and European cohorts. The results showed that the taxonomic profile of intestinal microbiome among cohorts revealed the Actinobaceria and Bifidobacterium were the key microbes contributing to the differences among Mongolians, the Hans and Europeans at the phylum level and genus level, respectively. Metagenomic species analysis indicated that Faecalibacterium prausnitzii and Coprococcus comeswere enrich in Mongolian people which might contribute to gut health through anti-inflammatory properties and butyrate production, respectively. On the other hand, the enriched genus Collinsella, biomarker in symptomatic atherosclerosis patients, might be associated with the high morbidity of cardiovascular and cerebrovascular diseases in Mongolian adults. At the functional level, a unique microbial metabolic pathway profile was present in Mongolian’s gut which mainly distributed in amino acid metabolism, carbohydrate metabolism, energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. We can attribute the specific signatures of Mongolian gut microbiome to their unique genotype, dietary habits and living environment.
CXCL13/CXCR5 enhances sodium channel Nav1.8 current density via p38 MAP kinase in primary sensory neurons following inflammatory pain
Authors: Wu Xiao-Bo , Cao De-Li , Zhang Xin , Jiang Bao-Chun , Zhao Lin-Xia , Qian Bin , Gao Yong-Jing
Published: October 2016

CXCL13 is a B lymphocyte chemoattractant and activates CXCR5 receptor in the immune system. Here we investigated whether CXCL13/CXCR5 mediates inflammatory pain in dorsal root ganglia (DRG) and the underlying mechanisms. Peripheral injection of complete Freund’s Adjuvant (CFA) increased the expression of CXCL13 and CXCR5 in DRG neurons. In Cxcr5−/− mice, CFA-induced pain hypersensitivity were attenuated. Whole-cell patch-clamp recording showed that the excitability of dissociated DRG neurons was increased after CFA injection or CXCL13 incubation from wild-type (WT) mice, but not from Cxcr5−/− mice. Additionally, sodium channel Nav1.8 was co-expressed with CXCR5 in dissociated DRG neurons, and the increased neuronal excitability induced by CFA or CXCL13 was reduced by Nav1.8 blocker. Intrathecal injection of Nav1.8 blocker also attenuated intrathecal injection of CXCL13-induced pain hypersensitivity. Furthermore, CXCL13 increased Nav1.8 current density in DRG neurons, which was inhibited by p38 MAP kinase inhibitor. CFA and CXCL13 increased p38 phosphorylation in the DRG of WT mice but not Cxcr5−/− mice. Finally, intrathecal p38 inhibitor alleviated CXCL13-induced pain hypersensitivity. Taken together, these results demonstrated that CXCL13, upregulated by peripheral inflammation, acts on CXCR5 on DRG neurons and activates p38, which increases Nav1.8 current density and further contributes to the maintenance of inflammatory pain.
lncScore: alignment-free identification of long noncoding RNA from assembled novel transcripts
Authors: Zhao Jian , Song Xiaofeng , Wang Kai
Published: October 2016

RNA-Seq based transcriptome assembly has been widely used to identify novel lncRNAs. However, the best-performing transcript reconstruction methods merely identified 21% of full-length protein-coding transcripts from H. sapiens. Those partial-length protein-coding transcripts are more likely to be classified as lncRNAs due to their incomplete CDS, leading to higher false positive rate for lncRNA identification. Furthermore, potential sequencing or assembly error that gain or abolish stop codons also complicates ORF-based prediction of lncRNAs. Therefore, it remains a challenge to identify lncRNAs from the assembled transcripts, particularly the partial-length ones. Here, we present a novel alignment-free tool, lncScore, which uses a logistic regression model with 11 carefully selected features. Compared to other state-of-the-art alignment-free tools (e.g. CPAT, CNCI, and PLEK), lncScore outperforms them on accurately distinguishing lncRNAs from mRNAs, especially partial-length mRNAs in the human and mouse datasets. In addition, lncScore also performed well on transcripts from five other species (Zebrafish, Fly, C. elegans, Rat, and Sheep). To speed up the prediction, multithreading is implemented within lncScore, and it only took 2 minute to classify 64,756 transcripts and 54 seconds to train a new model with 21,000 transcripts with 12 threads, which is much faster than other tools. lncScore is available athttps://github.com/WGLab/lncScore.
Switchable thulium-doped fiber laser from polarization rotation vector to scalar soliton
Authors: Wu Zhichao , Fu Songnian , Jiang Kai , Song Jue , Li Huizi , Tang Ming , Shum Ping , Liu Deming
Published: October 2016

We experimentally demonstrate switchable temporal soliton generation from a thulium-doped fiber laser (TDFL), using carbon nanotubes as the mode-locker. With the help of residual polarization dependent loss of a wavelength division multiplexer, a weak nonlinear polarization rotation (NPR) effect can be achieved within the laser cavity, which may provide joint contribution for passive mode-locking operation. By finely adjusting the polarization to alter the strength of NPR-based saturable absorption, the TDFL either approaches the operation regime of scalar soliton with strong NPR effect, or generates polarization rotation locked vector soliton (PRLVS) with weak NPR effect. The scalar solitons and PRLVSs possess 3-dB optical spectrum bandwidth of 2.2 nm and 2 nm, pulse-width of 1.8 ps and 2 ps, respectively. Moreover, the PRLVSs demonstrate a typical energy exchange between two polarized components on optical spectra and a period-doubling feature in time domain. Such operation principle can also be used in 1550 nm band fiber lasers and other nonlinear systems.
Caging the uncageable: using metal complex release for photochemical control over irreversible inhibition
Authors: Huisman Matthew , White Jessica K. , Lewalski Veronica G. , Podgorski Izabela , Turro Claudia , Kodanko Jeremy J.
Published: October 2016

Light provides control over irreversible inhibition with Ru(ii)-caged epoxysuccinyl compounds and release of a Ru(ii) complex from a protein–inhibitor conjugate.
Theoretical study of the H/D isotope effect on phase transition of hydrogen-bonded organic conductor κ-H3(Cat-EDT-TTF)2
Authors: Yamamoto Kaichi , Kanematsu Yusuke , Nagashima Umpei , Ueda Akira , Mori Hatsumi , Tachikawa Masanori
Published: October 2016

κ-H3(Cat-EDT-TTF)2 (H-TTF) is a hydrogen-bonded π-electron system. Only its isotopologue, D-TTF, shows the phase transition. We obtained a symmetric single-well effective-PEC for H-TTF and low-barrier effective-PEC for D-TTF.
Green synthesis of multimodal ‘OFF–ON’ activatable MRI/optical probes
Authors: Gallo J. , Vasimalai N. , Fernandez-Arguelles M. T. , Bañobre-López M.
Published: October 2016

We report a simple and green protocol for the preparation of redox responsive multimodal MRI/optical contrast agents based on Mn nanosheets and carbon dots.
The crystallisation of copper(ii) phenylphosphonates
Authors: Wilke Manuel , Kabelitz Anke , Gorelik Tatiana E. , Buzanich Ana Guilherme , Reinholz Uwe , Kolb Ute , Rademann Klaus , Emmerling Franziska
Published: October 2016

The crystal structures and syntheses of four different copper(ii) phenylphosphonates, the monophenylphosphonates α-, β-, and γ-Cu(O3PC6H5)·H2O (α-CuPhPmH (1) β-CuPhPmH (2) and γ-CuPhPmH (3)), and the diphosphonate Cu(HO3PC6H5)2·H2O (CuPhP2mH (4)), are presented.
Enhanced photocatalytic performance of BiOBr/NH2-MIL-125(Ti) composite for dye degradation under visible light
Authors: Zhu Shuai-Ru , Liu Peng-Fei , Wu Meng-Ke , Zhao Wen-Na , Li Guo-Chang , Tao Kai , Yi Fei-Yan , Han Lei
Published: October 2016

BiOBr/NH2-MIL-125(Ti) composite photocatalysts have been prepared by incorporating NH2-MIL-125(Ti) with BiOBr and exhibited improved photocatalytic activity under visible light compared to pristine BiOBr and NH2-MIL-125(Ti).
A luminescent cationic metal–organic framework featuring [Cu–pyrazolate]3 units for volatile organic compound sensing
Authors: Kivi Charlie E. , Song Datong
Published: October 2016

A luminescent 3D metal–organic framework for VOC sensing.
In situ TEM observation of the Boudouard reaction: multi-layered graphene formation from CO on cobalt nanoparticles at atmospheric pressure
Authors: Bremmer G. Marien , Zacharaki Eirini , Sjåstad Anja O. , Navarro Violeta , Frenken Joost W. M. , Kooyman Patricia J.
Published: October 2016

Using a MEMS nanoreactor in combination with a specially designed in situ Transmission Electron Microscope (TEM) holder and gas supply system, we imaged the formation of multiple layers of graphene encapsulating a cobalt nanoparticle, at 1 bar CO : N2 (1 : 1) and 500 °C. The cobalt nanoparticle was imaged live in a TEM during the Boudouard reaction. The in situ/operando TEM studies give insight into the behaviour of the catalyst at the nanometer-scale, under industrially relevant conditions. When switching from Fischer–Tropsch syngas conditions (CO : H2 : N2 1 : 2 : 3 at 1 bar) to CO-rich conditions (CO : N2 1 : 1 at 1 bar), we observed the formation of multi-layered graphene on Co nanoparticles at 500 °C. Due to the high temperature, the surface of the Co nanoparticles facilitated the Boudouard reaction, causing CO dissociation and the formation of layers of graphene. After the formation of the first patches of graphene at the surface of the nanoparticle, more and more layers grew over the course of about 40 minutes. In its final state, around 10 layers of carbon capped the nanoparticle. During this process, the carbon shell caused mechanical stress in the nanoparticle, inducing permanent deformation.
Ammonium molybdate phosphate functionalized silicon dioxide impregnated in calcium alginate for highly efficient removal of 137Cs from aquatic bodies
Authors: Saha Sudeshna , Singhal R. K. , Basu H. , Pimple M. V.
Published: October 2016

Development of new hybrid material (SiO2-AMP–Ca-Alg beads) for cesium uptake without disturbing the water quality parameters.
Synthesis and characterization of trinuclear N-heterocyclic carbene–palladium(ii) complexes and their applications in the Suzuki–Miyaura cross-coupling reaction
Authors: Wang Tao , Liu Lantao , Xu Kai , Xie Huanping , Shen Hui , Zhao Wen-Xian
Published: October 2016

Five novel trinuclear N-heterocyclic carbene–palladium(ii) complexes 5a–e were conveniently synthesized in one step. The obtained palladium(ii) complexes were the effective catalyst precursors for the Suzuki–Miyaura coupling.
A new method for improving the ion conductivity of anion exchange membranes by using TiO2 nanoparticles coated with ionic liquid
Authors: Chu Yuhao , Chen Yuenan , Chen Nanjun , Wang Fanghui , Zhu Hong
Published: October 2016

Recently a new method for increasing the ion conductivity of anion exchange membranes (AEM) was developed based on the novel materials ionic liquids (ILs).
Synthesis and characteristics of chloroform-treated silicon carbide-derived carbon layers
Authors: Chun Y. S. , Lee E. S. , Jeong M. G. , Lim D. S.
Published: October 2016

The pores reduced for CDC layers synthesized using (d–f) bubbled chloroform compared to that of (a–c) chlorine gas.
Photonic contacting of gas–liquid phases in a falling film microreactor for continuous-flow photochemical catalysis with visible light
Authors: Rehm Thomas H. , Gros Sylvain , Löb Patrick , Renken Albert
Published: October 2016

A microstructured falling film reactor was applied to the dye-sensitized photochemical conversion of 1,5-dihydroxynaphthalene to juglone for reactor and process evaluation.
Robust superhydrophobic carbon nanofiber network inlay-gated mesh for water-in-oil emulsion separation with high flux
Authors: Lin Xiangde , Heo Jiwoong , Jeong Hyejoong , Choi Moonhyun , Chang Minwook , Hong Jinkee
Published: October 2016

A superhydrophobic carbon nanofiber network inlay-gated mesh with high durability and separation performance was developed for oil–water emulsion separation.
Ultra-long Na2Ti3O7 nanowires@carbon cloth as a binder-free flexible electrode with a large capacity and long lifetime for sodium-ion batteries
Authors: Li Zhihong , Shen Wei , Wang Cong , Xu Qunjie , Liu Haimei , Wang Yonggang , Xia Yongyao
Published: October 2016

A binder-free flexible electrode, ultra-long Na2Ti3O7 nanowires@carbon cloth, with large stable capacity and long lifetime was successfully synthesized by a one-pot hydrothermal method and demonstrates excellent sodium-ion storage performance for flexible energy-storage devices.