bluuebunny/crossref_metadata_2025 huggingface dataset:
Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma
Authors: Bjørklund Sunniva Stordal , Panda Anshuman , Kumar Surendra , Seiler Michael , Robinson Doug , Gheeya Jinesh , Yao Ming , Alnæs Grethe I. Grenaker , Toppmeyer Deborah , Riis Margit , Naume Bjørn , Børresen-Dale Anne-Lise , Kristensen Vessela N. , Ganesan Shridar , Bhanot Gyan
Published: July 2017

Cancer cells can have different patterns of exon usage of individual genes when compared to normal tissue, suggesting that alternative splicing may play a role in shaping the tumor phenotype. The discovery and identification of gene variants has increased dramatically with the introduction of RNA-sequencing technology, which enables whole transcriptome analysis of known, as well as novel isoforms. Here we report alternative splicing and transcriptional events among subtypes of invasive ductal carcinoma in The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Alternative exon usage was widespread, and although common events were shared among three subtypes, ER+ HER2−, ER− HER2−, and HER2+, many events on the exon level were subtype specific. Additional RNA-seq analysis was carried out in an independent cohort of 43 ER+ HER2− and ER− HER2− primary breast tumors, confirming many of the exon events identified in the TCGA cohort. Alternative splicing and transcriptional events detected in five genes, MYO6, EPB41L1, TPD52, IQCG, and ACOX2 were validated by qRT-PCR in a third cohort of 40 ER+ HER2− and ER− HER2− patients, showing that these events were truly subtype specific.
Versatile functional roles of horizontal cells in the retinal circuit
Authors: Chaya Taro , Matsumoto Akihiro , Sugita Yuko , Watanabe Satoshi , Kuwahara Ryusuke , Tachibana Masao , Furukawa Takahisa
Published: July 2017

In the retinal circuit, environmental light signals are converted into electrical signals that can be decoded properly by the brain. At the first synapse of the visual system, information flow from photoreceptors to bipolar cells is modulated by horizontal cells (HCs), however, their functional contribution to retinal output and individual visual function is not fully understood. In the current study, we investigated functional roles for HCs in retinal ganglion cell (RGC) response properties and optokinetic responses by establishing a HC-depleted mouse line. We observed that HC depletion impairs the antagonistic center-surround receptive field formation of RGCs, supporting a previously reported HC function revealed by pharmacological approaches. In addition, we found that HC loss reduces both the ON and OFF response diversities of RGCs, impairs adjustment of the sensitivity to ambient light at the retinal output level, and alters spatial frequency tuning at an individual level. Taken together, our current study suggests multiple functional aspects of HCs crucial for visual processing.
Macroscopic Singlet-Triplet Qubit in Synthetic Spin-One Chain in Semiconductor Nanowires
Authors: Jaworowski Blazej , Rogers Nick , Grabowski Marek , Hawrylak Pawel
Published: July 2017

We show here how to create macroscopic quantum states in a semiconductor device: a chain of InAs quantum dots embedded in an InP nanowire. Filling the nanowire with 4 electrons per dot creates a synthetic spin-one chain, with four-fold degenerate topological ground state protected by a Haldane gap. The four states correspond to two spin-½ quasiparticles localised at the ends of the macroscopic wire. The quasiparticle spins are mapped onto a robust, macroscopic, singlet-triplet qubit. These predictions are supported by a microscopic theory and extensive numerical simulations.
Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting
Authors: Anisenko Andrey N. , Knyazhanskaya Ekaterina S. , Zalevsky Artur O. , Agapkina Julia Yu , Sizov Aleksander I. , Zatsepin Timofey S. , Gottikh Marina B.
Published: July 2017

Human Ku70/Ku80 protein is known to influence HIV-1 replication. One of the possible reasons may be the protection of integrase from proteasomal degradation by Ku70 subunit. We demonstrated that recombinant HIV-1 integrase and Ku70 form a stable complex, while no interaction of Ku70 with integrase from prototype foamy virus was observed. By analyzing protein subdomains we determined two binding sites in the structure of both Ku70 and integrase: the 51–160 a.a. region of integrase interacts with residues 251–438 of Ku70, whereas Ku70 N-terminal domain (1–250 a.a.) contacts an α6-helix in the 200–220 a.a. integrase region. Single substitutions within integrase (E212A or L213A) block the interaction with Ku70 thus indicating that the binding site formed by the 200–220 a.a. integrase region is crucial for complex formation. E212A/L213A substitutions decreased the integrase capacity to bind Ku70 in HEK293T cells. A conjugate of 2′-ОMe-GGUUUUUGUGU oligonucleotide with eosin is shown by molecular modeling to shield integrase residues E212/L213 and is effective in blocking complex formation of Ku70 with integrase what makes the complex between α6-helix and Ku70(1–250) a possible target for drug development.
Fat binding capacity and modulation of the gut microbiota both determine the effect of wheat bran fractions on adiposity
Authors: Suriano Francesco , Bindels Laure B. , Verspreet Joran , Courtin Christophe M. , Verbeke Kristin , Cani Patrice D. , Neyrinck Audrey M. , Delzenne Nathalie M.
Published: July 2017

The aim of this study was to determine the impact of different wheat bran fractions on the gut microbiota and fat binding capacity to explain their differential effects on metabolic and inflammatory disorders induced by a western diet (WD) in mice. Wheat bran derived arabinoxylan oligosaccharides (AXOS), a crude fraction of wheat bran (WB), or the same wheat bran with reduced particle size (WBs) were added to the WD of mice for 8 weeks. AXOS shifted the gut microbiota composition, blunted Clostridium and Turicibacter genera and strongly promoted Bifidobacterium and Butyricicoccus genera, independently of changes in gut antimicrobial peptide expression. AXOS was the most efficient to reduce adiposity. Only WB fraction promoted fat excretion and differed from the other fractions by the capacity to increase the Akkermansia genus and to counteract gut interleukin 1 beta (IL1β) overexpression. Strikingly, WBs promoted steatosis and adipose tissue inflammation, despite its ability -like WB- to increase bacterial diversity. In conclusion, wheat bran fractions differently affect metabolic and inflammatory disorders associated with WD feeding, depending on their particle size, their fat binding capacity and their influence on the gut microbiota. Those results might be useful to take into account in nutritional advices to control obesity.
Information processing in patterned magnetic nanostructures with edge spin waves
Authors: Lara Antonio , Robledo Moreno Javier , Guslienko Konstantin Y. , Aliev Farkhad G.
Published: July 2017

Low dissipation data processing with spins is one of the promising directions for future information and communication technologies. Despite a significant progress, the available magnonic devices are not broadband yet and have restricted capabilities to redirect spin waves. Here we propose a breakthrough approach to spin wave manipulation in patterned magnetic nanostructures with unmatched characteristics, which exploits a spin wave analogue to edge waves propagating along a water-wall boundary. Using theory, micromagnetic simulations and experiment we investigate spin waves propagating along the edges in magnetic structures, under an in-plane DC magnetic field inclined with respect to the edge. The proposed edge spin waves overcome important challenges faced by previous technologies such as the manipulation of the spin wave propagation direction, and they substantially improve the capability of transmitting information at frequencies exceeding 10 GHz. The concept of the edge spin waves allows to design a broad of logic devices such as splitters, interferometers, or edge spin wave transistors with unprecedented characteristics and a potentially strong impact on information technologies.
Dynamics and function of CXCR4 in formation of the granule cell layer during hippocampal development
Authors: Mimura-Yamamoto Yuka , Shinohara Hiroshi , Kashiwagi Taichi , Sato Toru , Shioda Seiji , Seki Tatsunori
Published: July 2017

In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR4 which is expressed by the GCPs and is a receptor of the CXCL12 chemokine secreted by cells surrounding the DG. In the VZ, CXCR4 was expressed on the plasma membrane of the GCPs. During their migration and in the DG, CXCR4 was internalized and accumulated as puncta close to the centrosomes, Golgi apparatus, and lysosomes. Phosphatase analysis suggested that both phosphorylated and dephosphorylated CXCR4 exist on the plasma membrane, whereas CXCR4 in intracellular puncta was mainly dephosphorylated. Intraventricular administration of the CXCR4 antagonist AMD3100 resulted in the disappearance of CXCR4 expression from the intracellular puncta, and its appearance on the plasma membranes. Furthermore, AMD3100 treatment resulted in precocious differentiation, delayed migration, and ectopic GCPs. Taken together, these results suggest that during the development and migration of GCPs, CXCR4 on the plasma membrane is phosphorylated, internalized, sorted to the centrosomes, Golgi apparatus, and lysosomes, and functionally regulates GCP differentiation, migration and positioning.
Controlled modification of biomolecules by ultrashort laser pulses in polar liquids
Authors: Gruzdev Vitaly , Korkin Dmitry , Mooney Brian P. , Havelund Jesper F. , Møller Ian Max , Thelen Jay J.
Published: July 2017

Targeted chemical modification of peptides and proteins by laser pulses in a biologically relevant environment, i.e. aqueous solvent at room temperature, allows for accurate control of biological processes. However, the traditional laser methods of control of chemical reactions are applicable only to a small class of photosensitive biomolecules because of strong and ultrafast perturbations from biomolecule-solvent interactions. Here, we report excitation of harmonics of vibration modes of solvent molecules by femtosecond laser pulses to produce controlled chemical modifications of non-photosensitive peptides and proteins in polar liquids under room conditions. The principal modifications included lysine formylation and methionine sulfoxidation both of which occur with nearly 100% yield under atmospheric conditions. That modification occurred only if the laser irradiance exceeded certain threshold level. The threshold, type, and extent of the modifications were completely controlled by solvent composition, laser wavelength, and peak irradiance of ultrashort laser pulses. This approach is expected to assist in establishing rigorous control over a broad class of biological processes in cells and tissues at the molecular level.
Safe Brain Tumor Resection Does not Depend on Surgery Alone - Role of Hemodynamics
Authors: Bette Stefanie , Wiestler Benedikt , Wiedenmann Felicitas , Kaesmacher Johannes , Bretschneider Martin , Barz Melanie , Huber Thomas , Ryang Yu-Mi , Kochs Eberhard , Zimmer Claus , Meyer Bernhard , Boeckh-Behrens Tobias , Kirschke Jan S. , Gempt Jens
Published: July 2017

Aim of this study was to determine if perioperative hemodynamics have an impact on perioperative infarct volume and patients’ prognosis. 201 cases with surgery for a newly diagnosed or recurrent glioblastoma were retrospectively analyzed. Clinical data and perioperative hemodynamic parameters, blood tests and time of surgery were recorded. Postoperative infarct volume was quantitatively assessed by semiautomatic segmentation. Mean diastolic blood pressure (dBP) during surgery (rho −0.239, 95% CI −0.11 – −0.367, p = 0.017), liquid balance (rho 0.236, 95% CI 0.1–0.373, p = 0.017) and mean arterial pressure (MAP) during surgery (rho −0.206, 95% CI −0.07 – −0.34, p = 0.041) showed significant correlation to infarct volume. A rank regression model including also age and recurrent surgery as possible confounders revealed mean intraoperative dBP, liquid balance and length of surgery as independent factors for infarct volume. Univariate survival analysis showed mean intraoperative dBP and MAP as significant prognostic factors, length of surgery also remained as significant prognostic factor in a multivariate model. Perioperative close anesthesiologic monitoring of blood pressure and liquid balance is of high significance during brain tumor surgery and should be performed to prevent or minimize perioperative infarctions and to prolong survival.
TRIB1 is a positive regulator of hepatocyte nuclear factor 4-alpha
Authors: Soubeyrand Sébastien , Martinuk Amy , McPherson Ruth
Published: July 2017

The TRIB1 locus has been linked to both cardiovascular disease and hepatic steatosis. Recent efforts have revealed TRIB1 to be a major regulator of liver function, largely, but not exclusively, via CEBPA degradation. We recently uncovered a functional interaction between TRIB1 and HNF4A, another key regulator of hepatic function, whose molecular underpinnings remained to be clarified. Here we have extended these findings. In hepatoma models, HNF4A levels were found to depend on TRIB1, independently of its impact on CEBPA. Using a reporter assay model, MTTP reporter activity, which depends on HNF4A, positively correlated with TRIB1 levels. Confocal microscopy demonstrated partial colocalization of TRIB1 and HNF4A. Using overexpressed proteins we demonstrate that TRIB1 and HNF4A can form complexes in vivo. Mapping of the interaction interfaces identified two distinct regions within TRIB1 which associated with the N-terminal region of HNF4A. Lastly, the TRIB1-HNF4A interaction resisted competition with a CEPBA-derived peptide, suggesting different binding modalities. Together these findings establish that TRIB1 is required for HNF4A function. This regulatory axis represents a novel CEBPA-independent aspect of TRIB1 function predicted to play an important role in liver physiology.
A mammalian mirtron miR-1224 promotes tube-formation of human primary endothelial cells by targeting anti-angiogenic factor epsin2
Authors: Sakai Eiko , Miura Yusuke , Suzuki-Kouyama Emi , Oka Kengo , Tachibana Masashi , Kawabata Kenji , Sakurai Fuminori , Mizuguchi Hiroyuki
Published: July 2017

Angiogenesis, new vessel formation from pre-existing vessels, is a highly conserved event through vertebrates. However, the system for tuning angiogenesis by species-intrinsic factors is totally unknown. miR-1224 is a member of mammal-specific mirtrons, which were identified as non-canonical microRNAs. We found that the expression of miR-1224 was upregulated in capillary-like tube-forming human umbilical vein endothelial cells on Matrigel. Enforced expression of miR-1224 stimulated tube formation, whereas repression of endogenous miR-1224 inhibited formation. Enforced expression of miR-1224 enhanced VEGF signaling and repressed NOTCH signaling. The adaptor protein of clathrin-dependent endocytosis, epsin2, which has been shown to be a suppressor of angiogenesis, was a direct target of miR-1224. Knockdown of EPN2 stimulated tube formation, while overexpression of EPN2 repressed miR-1224-mediated stimulation. Our findings indicate that miR-1224 is a mammal specific modulator of angiogenesis.
Neural processing of biological motion in autism: An investigation of brain activity and effective connectivity
Authors: Alaerts Kaat , Swinnen Stephan P. , Wenderoth Nicole
Published: July 2017

The superior temporal sulcus (STS) forms a key region for social information processing and disruptions of its function have been associated with socio-communicative impairments characteristic of autism spectrum disorders (ASD). Task-based fMRI was applied in 15 adults with ASD and 15 matched typical-controls (TC) to explore differences in activity and effective connectivity of STS while discriminating either ‘intact’ versus ‘scrambled’ biological motion point light displays (explicit processing) or responding to a color-change while the ‘intact’ versus ‘scrambled’ nature of the stimulus was irrelevant for the task (implicit processing). STS responded stronger to ‘intact’ than ‘scrambled’ stimuli in both groups, indicating that the basic encoding of ‘biological’ versus ‘non-biological’ motion seems to be intact in ASD. Only in the TC-group however, explicit attention to the biological motion content induced an augmentation of STS-activity, which was not observed in the ASD-group. Overall, these findings suggest an inadequacy to recruit STS upon task demand in ASD, rather than a generalized alteration in STS neural processing. The importance of attention orienting for recruiting relevant neural resources was further underlined by the observation that connectivity between STS and medial prefrontal cortex (mPFC), a key region in attention regulation, effectively modulated STS-recruitment in the ASD-group.
A clinicopathological analysis of 153 acral melanomas and the relevance of mechanical stress
Authors: Sheen Yi-Shuan , Liao Yi-Hua , Lin Ming-Hsien , Chen Jau-Shiuh , Liau Jau-Yu , Tseng Yu-Ju , Lee Chih-Hung , Chang Yih-Leong , Chu Chia-Yu
Published: July 2017

The pathogenesis of melanomas emerging in plantar surfaces remains unclear; however, mechanical stress has been reported to increase the formation of melanomas. In this study, we conducted a multicenter retrospective analysis of 153 acral melanomas diagnosed between 2000 and 2015 in Taiwan. The male-to-female ratio of the patients in question was 1:1.28, and the mean age at diagnosis was 68 years. We examined whether melanomas which developed in different areas of the patients’ soles differed in their associations with various clinicopathological characteristics and survival. Testing by goodness of fit indicated that stress-bearing areas were significantly more conducive to the generation of melanomas than non-stress-bearing areas (P < 0.0001). More specifically, compared to the arch, the rear of the foot and front of the foot were significantly more conducive to the generation of melanomas (P < 0.0001 and P < 0.0001, respectively). The distribution pattern was not associated with differences in age, gender, right/left foot involvement, ulceration, mitosis, lymph node metastasis, tumor thickness, or stage. The overall, distant metastasis-free, and recurrence-free survival rates did not differ significantly between the stress-bearing and non-stress-bearing areas. Furthermore, while acral melanomas tended to develop on stress-bearing areas, the distribution pattern was not associated with the prognostic index or survival.
Loss of type 9 adenylyl cyclase triggers reduced phosphorylation of Hsp20 and diastolic dysfunction
Authors: Li Yong , Baldwin Tanya A. , Wang Yan , Subramaniam Janani , Carbajal Anibal Garza , Brand Cameron S. , Cunha Shane R. , Dessauer Carmen W.
Published: July 2017

Adenylyl cyclase type 9 (AC9) is found tightly associated with the scaffolding protein Yotiao and the IKs ion channel in heart. But apart from potential IKs regulation, physiological roles for AC9 are unknown. We show that loss of AC9 in mice reduces less than 3% of total AC activity in heart but eliminates Yotiao-associated AC activity. AC9−/− mice exhibit no structural abnormalities but show a significant bradycardia, consistent with AC9 expression in sinoatrial node. Global changes in PKA phosphorylation patterns are not altered in AC9−/− heart, however, basal phosphorylation of heat shock protein 20 (Hsp20) is significantly decreased. Hsp20 binds AC9 in a Yotiao-independent manner and deletion of AC9 decreases Hsp20-associated AC activity in heart. In addition, expression of catalytically inactive AC9 in neonatal cardiomyocytes decreases isoproterenol-stimulated Hsp20 phosphorylation, consistent with an AC9-Hsp20 complex. Phosphorylation of Hsp20 occurs largely in ventricles and is vital for the cardioprotective effects of Hsp20. Decreased Hsp20 phosphorylation suggests a potential baseline ventricular defect for AC9−/−. Doppler echocardiography of AC9−/− displays a decrease in the early ventricular filling velocity and ventricular filling ratio (E/A), indicative of grade 1 diastolic dysfunction and emphasizing the importance of local cAMP production in the context of macromolecular complexes.
Fibulin-4 deposition requires EMILIN-1 in the extracellular matrix of osteoblasts
Authors: Schiavinato Alvise , Keene Douglas R. , Imhof Thomas , Doliana Roberto , Sasaki Takako , Sengle Gerhard
Published: July 2017

Tissue microenvironments formed by extracellular matrix networks play an important role in regulating tissue structure and function. Extracellular microfibrillar networks composed of fibrillins and their associated ligands such as LTBPs, fibulins, and EMILINs are of particular interest in this regard since they provide a specialized cellular microenvironment guiding proper morphology and functional behavior of specialized cell types. To understand how cellular microenvironments composed of intricate microfibrillar networks influence cell fate decisions in a contextual manner, more information about the spatiotemporal localization, deposition, and function of their components is required. By employing confocal immunofluorescence and electron microscopy we investigated the localization and extracellular matrix deposition of EMILIN-1 and -2 in tissues of the skeletal system such as cartilage and bone as well as in in vitro cultures of osteoblasts. We found that upon RNAi mediated depletion of EMILIN-1 in primary calvarial osteoblasts and MC3T3-E1 cells only fibulin-4 matrix deposition was lost while other fibulin family members or LTBPs remained unaffected. Immunoprecipitation and ELISA-style binding assays confirmed a direct interaction between EMILIN-1 and fibulin-4. Our data suggest a new function for EMILIN-1 which implies the guidance of linear fibulin-4 matrix deposition and thereby fibulin-4 fiber formation.
Airborne Bacterial Communities in Three East Asian Cities of China, South Korea, and Japan
Authors: Lee Jae Young , Park Eun Ha , Lee Sunghee , Ko GwangPyo , Honda Yasushi , Hashizume Masahiro , Deng Furong , Yi Seung-muk , Kim Ho
Published: July 2017

The global diversity of airborne bacteria has not yet been studied, despite its importance in human health and climate change. Here, we focused on the diversity of airborne bacteria and their correlations with meteorological/environmental conditions in China, South Korea, and Japan. Beijing (China) had more diverse airborne bacteria, followed by Seoul (South Korea) and Nagasaki (Japan), and seasonal variations were observed. Beijing and Seoul had more diverse airborne bacteria during the winter, whereas Nagasaki showed greater diversity during the summer. According to principal component analysis and Bray-Curtis similarity, higher similarity was observed between Beijing and Seoul than between Seoul and Nagasaki during all seasons except summer. Among meteorological/environmental variables, temperature and humidity were highly correlated with the diversity of airborne bacteria on the measurement day, whereas wind speeds and the frequency of northwest winds were highly correlated for 2–3-day moving averages. Thus, proximity and resuspension could enhance bacterial diversity in East Asian cities.
Thermal Diffusivity Mapping of Graphene Based Polymer Nanocomposites
Authors: Gresil Matthieu , Wang Zixin , Poutrel Quentin-Arthur , Soutis Constantinos
Published: July 2017

Nanoparticle dispersion is widely recognised as a challenge in polymer nanocomposites fabrication. The dispersion quality can affect the physical and thermomechanical properties of the material system. Qualitative transmission electronic microscopy, often cumbersome, remains as the ‘gold standard’ for dispersion characterisation. However, quantifying dispersion at macroscopic level remains a difficult task. This paper presents a quantitative dispersion characterisation method using non-contact infrared thermography mapping that measures the thermal diffusivity (α) of the graphene nanocomposite and relates α to a dispersion index. The main advantage of the proposed method is its ability to evaluate dispersion over a large area at reduced effort and cost, in addition to measuring the thermal properties of the system. The actual resolution of this thermal mapping reaches 200 µm per pixel giving an accurate picture of graphene nanoplatelets (GNP) dispersion. The post-dispersion treatment shows an improvement in directional thermal conductivity of the composite of up to 400% increase at 5 wt% of GNP. The Maxwell-Garnet effective medium approximation is proposed to estimate thermal conductivity that compare favourably to measured data. The development of a broadly applicable dispersion quantification method will provide a better understanding of reinforcement mechanisms and effect on performance of large scale composite structures.
Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition
Authors: Ng Wai-Lung , Li Ho-Chuen , Lau Kit-Man , Chan Anthony K. N. , Lau Clara Bik-San , Shing Tony K. M.
Published: July 2017

Carbasugar sodium-glucose cotransporter 2 (SGLT2) inhibitors are highly promising drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the clinical usage of carbasugar SGLT2 inhibitors has been underexplored, due to the lengthy synthetic routes and the lack of structure-activity relationship (SAR) studies of these compounds. Herein, we report a concise and stereodivergent synthetic route towards some novel carbasugar SGLT2 inhibitors, featuring an underexploited, regioselective, and stereospecific palladium-catalyzed allyl-aryl coupling reaction. This synthetic strategy, together with computational modeling, revealed the unexpected SAR of these carbasugar SGLT2 inhibitors, and enabled the discovery of a highly selective and potent SGLT2 inhibitor.
Polymicrobial Infections In Brain Tissue From Alzheimer’s Disease Patients
Authors: Pisa Diana , Alonso Ruth , Fernández-Fernández Ana M. , Rábano Alberto , Carrasco Luis
Published: July 2017

Several studies have advanced the idea that the etiology of Alzheimer’s disease (AD) could be microbial in origin. In the present study, we tested the possibility that polymicrobial infections exist in tissue from the entorhinal cortex/hippocampus region of patients with AD using immunohistochemistry (confocal laser scanning microscopy) and highly sensitive (nested) PCR. We found no evidence for expression of early (ICP0) or late (ICP5) proteins of herpes simplex virus type 1 (HSV-1) in brain sections. A polyclonal antibody against Borrelia detected structures that appeared not related to spirochetes, but rather to fungi. These structures were not found with a monoclonal antibody. Also, Borrelia DNA was undetectable by nested PCR in the ten patients analyzed. By contrast, two independent Chlamydophila antibodies revealed several structures that resembled fungal cells and hyphae, and prokaryotic cells, but most probably were unrelated to Chlamydophila spp. Finally, several structures that could belong to fungi or prokaryotes were detected using peptidoglycan and Clostridium antibodies, and PCR analysis revealed the presence of several bacteria in frozen brain tissue from AD patients. Thus, our results show that polymicrobial infections consisting of fungi and bacteria can be revealed in brain tissue from AD patients.
Genome-wide identification and characterization of circular RNAs by high throughput sequencing in soybean
Authors: Zhao Wei , Cheng Yihui , Zhang Chi , You Qingbo , Shen Xinjie , Guo Wei , Jiao Yongqing
Published: July 2017

Circular RNAs (circRNAs) arise during pre-mRNA splicing, in which the 3′ and 5′ ends are linked to each other by a covalent bond. Soybean is an ancient tetraploid, which underwent two whole genome duplications. Most of soybean genes are paralogous genes with multiple copies. Although many circRNAs have been identified in animals and plants, little is known about soybean circRNAs, especially about circRNAs derived from paralogous genes. Here, we used deep sequencing technology coupled with RNase R enrichment strategy and bioinformatic approach to uncover circRNAs in soybean. A total of 5,372 circRNAs were identified, approximately 80% of which were paralogous circRNAs generated from paralogous genes. Despite high sequence homology, the paralogous genes could produce different paralogous circRNAs with different expression patterns. Two thousand and one hundred thirty four circRNAs were predicted to be 92 miRNAs target mimicry. CircRNAs and circRNA isoforms exhibited tissue-specific expression patterns in soybean. Based on the function of circRNA-host genes, the soybean circRNAs may participate in many biological processes such as developmental process, multi-organism process, and metabolic process. Our study not only provided a basis for research into the function of circRNAs in soybean but also new insights into the plant circRNA kingdom.
The inducible blockage of RNAi reveals a role for polyunsaturated fatty acids in the regulation of dsRNA-endocytic capacity in Bactrocera dorsalis
Authors: Dong Xiaolong , Li Xiaoxue , Li Qiujia , Jia Hongmei , Zhang Hongyu
Published: July 2017

Exogenous double-stranded RNA (dsRNA) can trigger gene silencing through the RNA interference (RNAi) pathway. Our previous research established thatBactrocera dorsaliscan block RNAi after an initial priming of exposure to dsRNA. However, the mechanism underlying this phenomenon is not yet fully understood. Here, we demonstrate that fatty acid biosynthesis and metabolism pathways play important roles in the blockage of RNAi induced by dsRNA priming. The ratio of linoleic acid (LA) to arachidonic acid (AA) was significantly increased in the hemolymph ofB. dorsalisfollowing dsRNA priming, and further, the endocytosis of dsRNA into the midgut cells ofB. dorsaliswas inhibited in these samples. The expression levels of most genes involved in the fatty acid biosynthesis and metabolism pathways were altered following priming with dsRNA. Furthermore, altering the composition of fatty acids via the injection of AA can facilitate the uptake of ingested dsRNA into the midgut cells ofDrosophila melanogasterand successfully induce an RNAi effect, which cannot be achieved via feeding in fruit flies. Our results suggest that polyunsaturated fatty acids are involved in the regulation of the dsRNA-endocytic ability inB. dorsalis.
Transformation of patchouli alcohol to β-patchoulene by gastric juice: β-patchoulene is more effective in preventing ethanol-induced gastric injury
Authors: Liu Yuhong , Liang Jiali , Wu Jiazhen , Chen Hanbin , Zhang Zhenbiao , Yang Hongmei , Chen Liping , Chen Haiming , Su Ziren , Li Yucui
Published: July 2017

Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into β-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.
Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle
Authors: Marcucci Lorenzo , Washio Takumi , Yanagida Toshio
Published: July 2017

Recent experimental evidence in skeletal muscle demonstrated the existence of a thick-filament mechanosensing mechanism, acting as a second regulatory system for muscle contraction, in addition to calcium-mediated thin filament regulation. These two systems cooperate to generate force, but the extent to which their interaction is relevant in physiologically contracting muscle was not yet assessed experimentally. Therefore, we included both regulatory mechanisms in a mathematical model of rat trabecula and whole ventricle. No additional regulatory mechanisms were considered in our model. Our simulations suggested that mechanosensing regulation is not limited to the initial phases of contraction but, instead, is crucial during physiological contraction. An important consequence of this finding is that titin mediated thick filament activation can account for several sarcomere length dependencies observed in contracting muscle. Under the hypothesis that a similar mechanism is acting on cardiac muscle, and within the limits of a finite element left ventricle model, we predict that these two regulatory mechanisms are crucial for the molecular basis of the Frank-Starling law of the heart.
Estimating utility weights and quality-adjusted life year loss for colorectal cancer-related health states in Korea
Authors: Lee Jin Yong , Ock Minsu , Jo Min-Woo , Son Woo-Seung , Lee Hyeon-Jeong , Kim Seon-Ha , Kim Hyun Joo , Lee Jong Lyul
Published: July 2017

We aimed to assess utility weight of health states associated with colorectal cancer (CRC) that reflect the societal preference of the Korean population and to estimate the quality-adjusted life year (QALY) loss with CRC. We recruited 607 individuals from the Korean population; they were surveyed via face-to-face computer-assisted interviews. The participants evaluated each CRC-associated health state using standard gamble. Utility weight for each health state was calculated as the possibility of full health restoration. Moreover, we estimated total QALY loss due to CRC in Korean individuals aged ≥30 years in 2013. To calculate QALY due to morbidity, we yielded utility weights and used epidemiologic data of CRC on severity from the National Cancer Control Institute. QALY loss due to mortality was calculated using mortality of CRC and life expectancy data from the Korean Statistical Information Service. The highest and lowest utility weights were assigned to “adenomatous polyps” and “metastatic colon cancer”, respectively. Total QALY loss due to CRC in Korea was 173,662; these patients were more likely to be men or be included in the 70–74-year age group. These utility weights may be useful for conducting cost-utility studies of cancer screening for CRC and for measuring disease burden with QALY.
Acetylsalicylic acid differentially limits the activation and expression of cell death markers in human platelets exposed to Staphylococcus aureus strains
Authors: Chabert Adrien , Damien Pauline , Verhoeven Paul O. , Grattard Florence , Berthelot Philippe , Zeni Fabrice , Panicot-Dubois Laurence , Robert Stéphane , Dignat-George Françoise , Eyraud Marie-Ange , Pozzetto Bruno , Payrastre Bernard , Cognasse Fabrice , Garraud Olivier , Hamzeh-Cognasse Hind
Published: July 2017

Beyond their hemostatic functions, platelets alter their inflammatory response according to the bacterial stimulus.Staphylococcus aureusis associated with exacerbated inflammation and thrombocytopenia, which is associated with poor prognosis during sepsis. Acetylsalicylic acid and statins prevent platelet aggregation and decrease the mortality rate during sepsis. Therefore, we assessed whether these two molecules could reducein vitroplatelet activation and the inflammatory response toS. aureus. Platelets were exposed to clinical strains ofS. aureusin the presence or absence of acetylsalicylic acid or fluvastatin. Platelet activation, aggregation, and release of soluble sCD62P, sCD40 Ligand, RANTES and GROα were assessed. Platelet cell death was evaluated by analyzing the mitochondrial membrane potential, phosphatidylserine exposure, platelet microparticle release and caspase-3 activation. AllS. aureusstrains induced platelet activation but not aggregation and decreased the platelet count, the expression of cell death markers and the release of RANTES and GROα. Acetylsalicylic acid but not fluvastatin limited platelet activation and inflammatory factor release and restored the platelet count by protecting platelets fromStaphylococcus-induced expression of cell death markers. This study demonstrates that acetylsalicylic acid limitsS. aureus-induced effects on platelets by reducing cell death, revealing new strategies to reduce the platelet contribution to bacteremia-associated inflammation.
Ferroelectric-Paraelectric Transition In A Membrane With Quenched-Induced δ-Phase Of PVDF
Authors: García-Zaldívar O. , Escamilla-Díaz T. , Ramírez-Cardona M. , Hernández-Landaverde M. A. , Ramírez-Bon R. , Yañez-Limón J. M. , Calderón-Piñar F.
Published: July 2017

The stabilization of δ-phase of poly(vinylidene fluoride) PVDF in a 14 µm-thickness ferroelectric membrane is achieved by a simple route based on the use of a dimethylformamide (DMF)/acetone solvent, in which the application of external electric field is not required. X-ray diffraction and calorimetric experiments on heating reveal that, at 154 °C, the original mixture between ferroelectric δ-phase and paraelectric α-phase transits to a system with only this latter phase in the crystalline fraction. A gradual and slight increment of amorphous fraction up to the melting at 161 °C is also observed. The existence of δ-phase is corroborated by the occurrence of a broad maximum around 154 °C in dielectric permittivity measurements, as well as the hysteresis loops observed at room temperature. These results suggest a wide thermal window for a stable δ-phase, between room temperature and 154 °C, a subsequent transition into α-phase and the corresponding melting at 161 °C. The broad dielectric maximum observed around 154 °C in dielectric and calorimetric measurements, can be associated with a diffuse ferroelectric-paraelectric transition.
FTY720 Induces Autophagy-Associated Apoptosis in Human Oral Squamous Carcinoma Cells, in Part, through a Reactive Oxygen Species/Mcl-1-Dependent Mechanism
Authors: Bai Li-Yuan , Chiu Chang-Fang , Chiu Shih-Jiuan , Chu Po-Chen , Weng Jing-Ru
Published: July 2017

In this study, we interrogated the mechanism by which the immunosuppressant FTY720 mediates anticancer effects in oral squamous cell carcinoma (OSCC) cells. FTY720 differentially suppressed the viability of the OSCC cell lines SCC4, SCC25, and SCC2095 with IC50 values of 6.1, 6.3, and 4.5 μM, respectively. This antiproliferative effect was attributable to the ability of FTY720 to induce caspase-dependent apoptosis. Mechanistic evidence suggests that FTY720-induced apoptosis was associated with its ability to inhibit Akt-NF-κB signaling, to facilitate the proteasomal degradation of the antiapoptotic protein Mcl-1, and to increase reactive oxygen species (ROS) generation. Both overexpression of Mcl-1 and inhibition of ROS partially protected cells from FTY720-induced caspase-9 activation, PARP cleavage and cytotoxicity. In addition, FTY720 induced autophagy in OSCC cells, as manifested by LC3B-II conversion, decreased p62 expression, and accumulation of autophagosomes. Inhibition of autophagy by bafilomycin A1 protected cells from FTY720-induced apoptosis. Together, these findings suggest an intricate interplay between autophagy and apoptosis in mediating the tumor-suppressive effect in OSCC cells, which underlies the translational potential of FTY720 in fostering new therapeutic strategies for OSCC.
β-caryophyllene emitted from a transgenic Arabidopsis or chemical dispenser repels Diaphorina citri, vector of Candidatus Liberibacters
Authors: Alquézar Berta , Volpe Haroldo Xavier Linhares , Magnani Rodrigo Facchini , de Miranda Marcelo Pedreira , Santos Mateus Almeida , Wulff Nelson Arno , Bento Jose Mauricio Simões , Parra José Roberto Postali , Bouwmeester Harro , Peña Leandro
Published: July 2017

Production of citrus, the main fruit tree crop worldwide, is severely threatened by Huanglongbing (HLB), for which as yet a cure is not available. Spread of this bacterial disease in America and Asia is intimately connected with dispersal and feeding of the insect vector Diaphorina citri, oligophagous on rutaceous host plants. Effective control of this psyllid is an important component in successful HLB management programs. Volatiles released from the non-host guava have been shown to be repellent to the psyllid and to inhibit its response to citrus odour. By analysing VOC emission from guava we identified one volatile compound, (E)-β-caryophyllene, which at certain doses exerts a repellent effect on D. citri. Non-host plant rejection mediated by (E)-β-caryophyllene is demonstrated here by using Arabidopsis over-expression and knock-out lines. For the first time, results indicate that genetically engineered Arabidopsis plants with modified emission of VOCs can alter the behaviour of D. citri. This study shows that transgenic plants with an inherent ability to release (E)-β-caryophyllene can potentially be used in new protection strategies of citrus trees against HLB.
The aspirin metabolite salicylate inhibits lysine acetyltransferases and MUC1 induced epithelial to mesenchymal transition
Authors: Fernandez Harvey R. , Lindén Sara K.
Published: July 2017

MUC1 is a transmembrane mucin that can promote cancer progression, and its upregulation correlates with a worse prognosis in colon cancer. We examined the effects of overexpression of MUC1 in colon cancer cells, finding that it induced epithelial to mesenchymal transition (EMT), including enhanced migration and invasion, and increased Akt phosphorylation. When the clones were treated with the aspirin metabolite salicylate, Akt phosphorylation was decreased and EMT inhibited. As the salicylate motif is necessary for the activity of the lysine acetyltransferase (KAT) inhibitor anacardic acid, we hypothesized these effects were associated with the inhibition of KAT activity. This was supported by anacardic acid treatment producing the same effect on EMT. In vitro KAT assays confirmed that salicylate directly inhibited PCAF/Kat2b, Tip60/Kat5 and hMOF/Kat8, and this inhibition was likely involved in the reversal of EMT in the metastatic prostate cancer cell line PC-3. Salicylate treatment also inhibited EMT induced by cytokines, illustrating the general effect it had on this process. The inhibition of both EMT and KATs by salicylate presents a little explored activity that could explain some of the anti-cancer effects of aspirin.
A multi-protease, multi-dissociation, bottom-up-to-top-down proteomic view of the Loxosceles intermedia venom
Authors: Trevisan-Silva Dilza , Bednaski Aline V. , Fischer Juliana S.G. , Veiga Silvio S. , Bandeira Nuno , Guthals Adrian , Marchini Fabricio K. , Leprevost Felipe V. , Barbosa Valmir C. , Senff-Ribeiro Andrea , Carvalho Paulo C.
Published: July 2017

Venoms are a rich source for the discovery of molecules with biotechnological applications, but their analysis is challenging even for state-of-the-art proteomics. Here we report on a large-scale proteomic assessment of the venom of Loxosceles intermedia, the so-called brown spider. Venom was extracted from 200 spiders and fractioned into two aliquots relative to a 10 kDa cutoff mass. Each of these was further fractioned and digested with trypsin (4 h), trypsin (18 h), pepsin (18 h), and chymotrypsin (18 h), then analyzed by MudPIT on an LTQ-Orbitrap XL ETD mass spectrometer fragmenting precursors by CID, HCD, and ETD. Aliquots of undigested samples were also analyzed. Our experimental design allowed us to apply spectral networks, thus enabling us to obtain meta-contig assemblies, and consequently de novo sequencing of practically complete proteins, culminating in a deep proteome assessment of the venom. Data are available via ProteomeXchange, with identifier PXD005523.
Formation and stability of an active PdZn nanoparticle catalyst on a hydrotalcite-based support for ethanol dehydrogenation
Authors: De Waele J. , Galvita V. V. , Poelman H. , Detavernier C. , Thybaut J. W.
Published: July 2017

A subsequent hydrogen–air treatment prior to reaction is important for a highly active innovative nanoparticle PdZn catalyst for ethanol dehydrogenation.
Total synthesis of (−)-kainic acid and (+)-allo-kainic acid through SmI2-mediated intramolecular coupling between allyl chloride and an α,β-unsaturated ester
Authors: Suzuki Junya , Miyano Natsumi , Yashiro Shunpei , Umezawa Taiki , Matsuda Fuyuhiko
Published: July 2017

A 3,4-disubsituted pyrrolidine ring was effectively cyclized through SmI2-mediated reductive coupling between allyl chloride and an α,β-unsaturated ester.
Involvement of P-glycoprotein and multidrug and toxin extrusion protein 1 in hepatic and renal berberine efflux in mice
Authors: Wang Guofeng , Jin Jingyi , Zeng Jiakai , Shi Rong , Dai Yan , Wu Jiasheng , Li Yuanyuan , Wang Tianming , Ma Yueming
Published: July 2017

Involvement of P-glycoprotein (P-gp) and multidrug and toxin extrusion protein 1 (MATE1) in the hepatic and renal efflux of berberine was identified using transfected cells, a mouse model, and molecular docking.
Adsorption properties of NO molecules on the hexagonal LaCoO3(0 0 1) surface: a density functional theory study
Authors: Liu Zhijie , Wang Yanxin , Gao Hongwei
Published: July 2017

Six types of adsorption configurations, together with two different adsorption sites for NO adsorption on LaCoO3, were investigatedviadensity functional theory.
The protective effects of Shikonin on lipopolysaccharide/d-galactosamine-induced acute liver injury via inhibiting MAPK and NF-κB and activating Nrf2/HO-1 signaling pathways
Authors: Tian Ye , Li Zheng , Shen Bingyu , Wu Lin , Han Lu , Zhang Qiaoling , Feng Haihua
Published: July 2017

Shikonin (SHK) has various biological and pharmacological activities, including anticancer, antibacterial and anti-inflammation activities.
Perovskite photodetectors prepared by flash evaporation printing
Authors: Wei Haoming , Ma He , Tai Meiqian , Wei Yang , Li Dongqi , Zhao Xingyue , Lin Hong , Fan Shoushan , Jiang Kaili
Published: July 2017

A flash evaporation printing methodology based on CNT films has been employed to fabricate perovskite photodetectors with high quality.
DBP and C70 based inverted tandem solar cells using a simple interconnecting layer
Authors: Wang Zhongqiang , Sano Takeshi , Zhuang Taojun , Sasabe Hisahiro , Kido Junji
Published: July 2017

Inverted tandem structure cells with a simple interconnecting layer based on tetraphenyldibenzoperiflanthene (DBP) and fullerene-70 (C70) were studied in this work.
Uniform coating of TiO2 on high aspect ratio substrates with complex morphology by vertical forced-flow atomic layer deposition
Authors: Liu Kuang-I. , Kei Chi-Chung , Mishra Mrinalini , Chen Po-Hsun , Liu Wei-Szu , Perng Tsong-Pyng
Published: July 2017

A forced-flow ALD system equipped with multiple reactors where the precursors are forced to flow vertically through porous substrate.
Theoretical insights into C–C bond formation through isonitrile insertion into a Cp*Ti complex
Authors: Du Ming-Ran , Zhang Xiang-Biao , Si Sheng-Meng , Yang Feng , Wang Lei
Published: July 2017

Reaction of Cp*(Cl)Ti(2,3-dimethylbutadiene) with isonitriles is studied using DFT, detailed elementary reaction steps and N-substitution effects of isonitrile are examined.
Highly efficient heterogeneous copper-catalyzed decarboxylative cross-coupling of potassium polyfluorobenzoates with aryl halides leading to polyfluorobiaryls
Authors: Lin Yang , Cai Mingzhong , Fang Zhiqiang , Zhao Hong
Published: July 2017

The decarboxylative cross-coupling of potassium polyfluorobenzoates with aryl halides has been achieved using a recyclable MCM-41-immobilized 1,10-phenanthroline copper(i) complex.