bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of gp130 expression in hepatocytes attenuates tumor progression in the DEN model
Authors: Hatting M , Spannbauer M , Peng J , Al Masaoudi M , Sellge G , Nevzorova Y A , Gassler N , Liedtke C , Cubero F J , Trautwein C
Published: March 2015

Chronic liver inflammation is a crucial event in the development and growth of hepatocellular carcinoma (HCC). Compelling evidence has shown that interleukin-6 (IL-6)/gp130-dependent signaling has a fundamental role in liver carcinogenesis. Thus, in the present study we aimed to investigate the role of gp130 in hepatocytes for the initiation and progression of HCC. Hepatocyte-specific gp130 knockout mice (gp130Δhepa) and control animals (gp130f/f) were treated with diethylnitrosamine (DEN). The role of gp130 for acute injury (0–144 h post treatment), tumor initiation (24 weeks) and progression (40 weeks) was analyzed. After acute DEN-induced liver injury we observed a reduction in the inflammatory response in gp130Δhepa animals as reflected by decreased levels of IL-6 and oncostatin M. The loss of gp130 slightly attenuated the initiation of HCC 24 weeks after DEN treatment. In contrast, 40 weeks after DEN treatment, male and female gp130Δhepa mice showed smaller tumors and reduced tumor burden, indicating a role for hepatocyte-specific gp130 expression during HCC progression. Oxidative stress and DNA damage were substantially and similarly increased by DEN in both gp130f/f and gp130Δhepa animals. However, gp130Δhepa livers revealed aberrant STAT5 activation and decreased levels of transforming growth factor-β (TGFβ), pSMAD2/3 and SMAD2, whereas phosphorylation of STAT3 at Tyr705 and Ser727 was absent. Our results indicate that gp130 deletion in hepatocytes reduces progression, but not HCC initiation in the DEN model. Gp130 deletion resulted in STAT3 inhibition but increased STAT5 activation and diminished TGF-dependent signaling. Hence, blocking gp130 in hepatocytes might be an interesting therapeutic target to inhibit the growth of HCC.
RanBP9 at the intersection between cofilin and Aβ pathologies: rescue of neurodegenerative changes by RanBP9 reduction
Authors: Woo J A , Boggess T , Uhlar C , Wang X , Khan H , Cappos G , Joly-Amado A , De Narvaez E , Majid S , Minamide L S , Bamburg J R , Morgan D , Weeber E , Kang D E
Published: March 2015

Molecular pathways underlying the neurotoxicity and production of amyloid β protein (Aβ) represent potentially promising therapeutic targets for Alzheimer’s disease (AD). We recently found that overexpression of the scaffolding protein RanBP9 increases Aβ production in cell lines and in transgenic mice while promoting cofilin activation and mitochondrial dysfunction. Translocation of cofilin to mitochondria and induction of cofilin–actin pathology require the activation/dephosphorylation of cofilin by Slingshot homolog 1 (SSH1) and cysteine oxidation of cofilin. In this study, we found that endogenous RanBP9 positively regulates SSH1 levels and mediates Aβ-induced translocation of cofilin to mitochondria and induction of cofilin–actin pathology in cultured cells, primary neurons, and in vivo. Endogenous level of RanBP9 was also required for Aβ-induced collapse of growth cones in immature neurons (days in vitro 9 (DIV9)) and depletion of synaptic proteins in mature neurons (DIV21). In vivo, amyloid precursor protein (APP)/presenilin-1 (PS1) mice exhibited 3.5-fold increased RanBP9 levels, and RanBP9 reduction protected against cofilin–actin pathology, synaptic damage, gliosis, and Aβ accumulation associated with APP/PS1 mice. Brains slices derived from APP/PS1 mice showed significantly impaired long-term potentiation (LTP), and RanBP9 reduction significantly enhanced paired pulse facilitation and LTP, as well as partially rescued contextual memory deficits associated with APP/PS1 mice. Therefore, these results underscore the critical importance of endogenous RanBP9 not only in Aβ accumulation but also in mediating the neurotoxic actions of Aβ at the level of synaptic plasticity, mitochondria, and cofilin–actin pathology via control of the SSH1-cofilin pathway in vivo.
MiR-216b is involved in pathogenesis and progression of hepatocellular carcinoma through HBx-miR-216b-IGF2BP2 signaling pathway
Authors: Liu F-y , Zhou S-j , Deng Y-l , Zhang Z-y , Zhang E-l , Wu Z-b , Huang Z-y , Chen X-p
Published: March 2015

This study aims to investigate the expression status of miRNA-216b in familial hepatocellular carcinoma (HCC) and the correlation between miRNA-216b expression and pathogenesis, as well as the progression of HCC. The expression profile of miRNAs in plasma of peripheral blood between HCC patients with HCC family history and healthy volunteers without HCC family history was determined by microarray. Using real-time quantitative PCR to detect the expression in paired tissues from 150 patients with HCC, miR-216b was selected as its expression value in HCC patients was significantly lower compared with healthy volunteers. Next, miR-216b expression and the clinicopathological features of HCC were evaluated. The effect of miR-216b expression on tumor cells was investigated by regulating miR-216b expression in SMMC-7721 and HepG2 in vitro and in vivo. Finally, we explored mRNA targets of miR-216b. In 150 HCC, 37 (75%) tumors showed reduced miR-216b expression comparing with their adjacent liver tissues. The decreased expression of miR-216b was significantly correlated with tumor volume (P=0.044), HBV infection (P=0.026), HBV DNA quantitative (P=0.001) and vascular invasion (P=0.032). The 5-year disease-free survival and overall rates after liver resection in low expression and high expression groups of miR-216b are 62% and 54%, 25% and 20%, respectively. MiR-216b overexpression inhibited cell proliferation, migration and invasion, and miR-216b inhibition did the opposite. The expression of hepatitis B virus x protein (HBx) has tight correlation with downregulation of miR-216b. Furthermore, miR-216b downregulated the expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and exerted its tumor-suppressor function through inhibition of protein kinase B and extracellular signal-regulated kinase signaling downstream of IGF2. MiR-216b inhibits cell proliferation, migration and invasion of HCC by regulating IGF2BP2 and it is regulated by HBx.
Spanning the scales of granular materials through microscopic force imaging
Authors: Brodu Nicolas , Dijksman Joshua A. , Behringer Robert P.
Published: March 2015

If you walk on sand, it supports your weight. How do the disordered forces between particles in sand organize, to keep you from sinking? This simple question is surprisingly difficult to answer experimentally: measuring forces in three dimensions, between deeply buried grains, is challenging. Here we describe experiments in which we have succeeded in measuring forces inside a granular packing subject to controlled deformations. We connect the measured micro-scale forces to the macro-scale packing force response with an averaging, mean field calculation. This calculation explains how the combination of packing structure and contact deformations produce the observed nontrivial mechanical response of the packing, revealing a surprising microscopic particle deformation enhancement mechanism.
Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease
Authors: Eslam Mohammed , Hashem Ahmed M. , Leung Reynold , Romero-Gomez Manuel , Berg Thomas , Dore Gregory J. , Chan Henry L.K. , Irving William L. , Sheridan David , Abate Maria L. , Adams Leon A. , Mangia Alessandra , Weltman Martin , Bugianesi Elisabetta , Spengler Ulrich , Shaker Olfat , Fischer Janett , Mollison Lindsay , Cheng Wendy , Powell Elizabeth , Nattermann Jacob , Riordan Stephen , McLeod Duncan , Armstrong Nicola J. , Douglas Mark W. , Liddle Christopher , Booth David R. , George Jacob , Ahlenstiel Golo ,   the International Hepatitis C Genetics Consortium (IHCGC), Ampuero Javier , Bassendine Margaret , Wong Vincent W. S. , Rosso Chiara , White Rose , Mezzabotta Lavinia , Suppiah Vijayaprakash , Michalk Monika , Malik Barbara , Matthews Gail , Applegate Tanya , Grebely Jason , Fragomeli Vincenzo , Jonsson Julie R. , Santaro Rosanna
Published: March 2015

Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis.
Highly specific in vivo gene delivery for p53-mediated apoptosis and genetic photodynamic therapies of tumour
Authors: Tseng S.-Ja , Liao Zi-Xian , Kao Shih-Han , Zeng Yi-Fang , Huang Kuo-Yen , Li Hsin-Jung , Yang Chung-Lin , Deng Yu-Fan , Huang Chi-Feng , Yang Shuenn-Chen , Yang Pan-Chyr , Kempson Ivan M.
Published: March 2015

Anticancer therapies are often compromised by nonspecific effects and challenged by tumour environments’ inherent physicochemical and biological characteristics. Often, therapeutic effect can be increased by addressing multiple parameters simultaneously. Here we report on exploiting extravasation due to inherent vascular leakiness for the delivery of a pH-sensitive polymer carrier. Tumours’ acidic microenvironment instigates a charge reversal that promotes cellular internalization where endosomes destabilize and gene delivery is achieved. We assess our carrier with an aggressive non-small cell lung carcinoma (NSCLC) in vivo model and achieve >30% transfection efficiency via systemic delivery. Rejuvenation of the p53 apoptotic pathway as well as expression of KillerRed protein for sensitization in photodynamic therapy (PDT) is accomplished. A single administration greatly suppresses tumour growth and extends median animal survival from 28 days in control subjects to 68 days. The carrier has capacity for multiple payloads for greater therapeutic response where inter-individual variability can compromise efficacy.
Accelerated exploration of multi-principal element alloys with solid solution phases
Authors: Senkov O.N. , Miller J.D. , Miracle D.B. , Woodward C.
Published: March 2015

Recent multi-principal element, high entropy alloy (HEA) development strategies vastly expand the number of candidate alloy systems, but also pose a new challenge—how to rapidly screen thousands of candidate alloy systems for targeted properties. Here we develop a new approach to rapidly assess structural metals by combining calculated phase diagrams with simple rules based on the phases present, their transformation temperatures and useful microstructures. We evaluate over 130,000 alloy systems, identifying promising compositions for more time-intensive experimental studies. We find the surprising result that solid solution alloys become less likely as the number of alloy elements increases. This contradicts the major premise of HEAs—that increased configurational entropy increases the stability of disordered solid solution phases. As the number of elements increases, the configurational entropy rises slowly while the probability of at least one pair of elements favouring formation of intermetallic compounds increases more rapidly, explaining this apparent contradiction.
Nanospheres of doxorubicin as cross-linkers for a supramolecular hydrogelation
Authors: Xue Qiang , Ren He , Xu Chao , Wang Gang , Ren Chunhua , Hao Jihui , Ding Dan
Published: March 2015

In this study, we synthesized a peptide of Nap-GFFYGRGD, which could self-assemble into supramolecular nanofibers. The peptide itself could only form nanofibers but not hydrogels due to the relative weak inter-fiber interactions. The resulting nanofibers were then utilized as the vehicles for anticancer drug doxorubicin. It was found that the nanofibers of Nap-GFFYGRGD could not encapsulate doxorubicin, whereas the drug formed nanospheres, which were located at the surface of the nanofibers. Due to the electrostatic interactions between the negatively charged nanofibers and the positively charged doxorubicin nanospheres, the doxorubicin nanospheres were able to serve as a cross-linker to increase the inter-fiber interactions, leading to the formation of stable three-dimentional fiber networks and hydrogels. The resulting doxorubicin-peptide hydrogels were capable of releasing the drug in a sustained manner, which also showed comparable cytotoxicity as compared to free doxorubicin against a variety of cancer cell lines including HeLa and MCF-7 cancer cells. Therefore, this successful example using drug as the peptide nanofiber cross-linkers provided a new strategy for fabricating supramolecular hydrogelation for controlled delivery of anticancer drugs.
Structure of human dipeptidyl peptidase 10 (DPPY): a modulator of neuronal Kv4 channels
Authors: Bezerra Gustavo Arruda , Dobrovetsky Elena , Seitova Alma , Fedosyuk Sofiya , Dhe-Paganon Sirano , Gruber Karl
Published: March 2015

The voltage-gated potassium channel family (Kv) constitutes the most diverse class of ion channels in the nervous system. Dipeptidyl peptidase 10 (DPP10) is an inactive peptidase that modulates the electrophysiological properties, cell-surface expression and subcellular localization of voltage-gated potassium channels. As a consequence, DPP10 malfunctioning is associated with neurodegenerative conditions like Alzheimer and fronto-temporal dementia, making this protein an attractive drug target. In this work, we report the crystal structure of DPP10 and compare it to that of DPP6 and DPP4. DPP10 belongs to the S9B serine protease subfamily and contains two domains with two distinct folds: a β-propeller and a classical α/β-hydrolase fold. The catalytic serine, however, is replaced by a glycine, rendering the protein enzymatically inactive. Difference in the entrance channels to the active sites between DPP10 and DPP4 provide an additional rationale for the lack of activity. We also characterize the DPP10 dimer interface focusing on the alternative approach for designing drugs able to target protein-protein interactions.
New Compound Sets Identified from High Throughput Phenotypic Screening Against Three Kinetoplastid Parasites: An Open Resource
Authors: Peña Imanol , Pilar Manzano M. , Cantizani Juan , Kessler Albane , Alonso-Padilla Julio , Bardera Ana I. , Alvarez Emilio , Colmenarejo Gonzalo , Cotillo Ignacio , Roquero Irene , de Dios-Anton Francisco , Barroso Vanessa , Rodriguez Ana , Gray David W. , Navarro Miguel , Kumar Vinod , Sherstnev Alexander , Drewry David H. , Brown James R. , Fiandor Jose M. , Julio Martin J.
Published: March 2015

Using whole-cell phenotypic assays, the GlaxoSmithKline high-throughput screening (HTS) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted and the potential for non-specific cytotoxicity determined. Hit compounds were chemically clustered and triaged for desirable physicochemical properties. The hypothetical biological target space covered by these diversity sets was investigated through bioinformatics methodologies. Consequently, three anti-kinetoplastid chemical boxes of ~200 compounds each were assembled. Functional analyses of these compounds suggest a wide array of potential modes of action against kinetoplastid kinases, proteases and cytochromes as well as potential host–pathogen targets. This is the first published parallel high throughput screening of a pharma compound collection against kinetoplastids. The compound sets are provided as an open resource for future lead discovery programs and to address important research questions.
Photoinduced modulation and relaxation characteristics in LaAlO3/SrTiO3 heterointerface
Authors: Jin K. X. , Lin W. , Luo B. C. , Wu T.
Published: March 2015

We report the modulation and relaxation characteristics in the two-dimensional electron gas system at LaAlO3/SrTiO3 heterointerface induced by the ultraviolet light illumination (365 nm). The suppression of Kondo effect at the interface illuminated by the light originates from the light irradiation-induced decoherence effect of localized states. It is interesting to note that the persistent and transient photoinduced effects are simultaneously observed and the photoinduced maximum change values in resistance are 80.8% and 51.4% at T = 20 K, respectively. Moreover, the photoinduced relaxation processes after the irradiation are systematically analyzed using the double exponential model. These results provide the deeper understanding of the photoinduced effect and the experimental evidence of tunable Kondo effect in oxides-based two-dimensional electron gas systems.
AKT and 14-3-3 Regulate Notch4 Nuclear Localization
Authors: Ramakrishnan Gopalakrishnan , Davaakhuu Gantulga , Chung Wen Cheng , Zhu He , Rana Ajay , Filipovic Aleksandra , Green Andrew R. , Atfi Azeddine , Pannuti Antonio , Miele Lucio , Tzivion Guri
Published: March 2015

Members of the Notch family of transmembrane receptors, Notch1-4 in mammals, are involved in the regulation of cell fate decisions and cell proliferation in various organisms. The Notch4 isoform, which is specific to mammals, was originally identified as a viral oncogene in mice, Int3, able to initiate mammary tumors. In humans, Notch4 expression appears to be associated with breast cancer stem cells and endocrine resistance. Following ligand binding, the Notch4 receptor undergoes cleavage at the membrane and the Notch4-intracellular domain (ICD), translocates to the nucleus and regulates gene transcription. Little is known on the mechanisms regulating Notch4-ICD and its nuclear localization. Here, we describe the identification of four distinct AKT phosphorylation sites in human Notch4-ICD and demonstrate that AKT binds Notch4-ICD and phosphorylates all four sites in vitro and in vivo. The phosphorylation in cells is regulated by growth factors and is sensitive to phosphatidyl inositol-3 kinase (PI3K) inhibitors. This phosphorylation generates binding sites to the 14-3-3 regulatory proteins, which are involved in the regulation of nucleocytoplasmic shuttling of target proteins, restricting phosphorylated Notch4-ICD to the cytoplasm. Our findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling.
Excess of Rare Variants in Genes that are Key Epigenetic Regulators of Spermatogenesis in the Patients with Non-Obstructive Azoospermia
Authors: Li Zesong , Huang Yi , Li Honggang , Hu Jingchu , Liu Xiao , Jiang Tao , Sun Guangqing , Tang Aifa , Sun Xiaojuan , Qian Weiping , Zeng Yong , Xie Jun , Zhao Wei , Xu Yu , He Tingting , Dong Chengliang , Liu Qunlong , Mou Lisha , Lu Jingxiao , Lin Zheguang , Wu Song , Gao Shengjie , Guo Guangwu , Feng Qiang , Li Yingrui , Zhang Xiuqing , Wang Jun , Yang Huanming , Wang Jian , Xiong Chengliang , Cai Zhiming , Gui Yaoting
Published: March 2015

Non-obstructive azoospermia (NOA), a severe form of male infertility, is often suspected to be linked to currently undefined genetic abnormalities. To explore the genetic basis of this condition, we successfully sequenced ~650 infertility-related genes in 757 NOA patients and 709 fertile males. We evaluated the contributions of rare variants to the etiology of NOA by identifying individual genes showing nominal associations and testing the genetic burden of a given biological process as a whole. We found a significant excess of rare, non-silent variants in genes that are key epigenetic regulators of spermatogenesis, such as BRWD1, DNMT1, DNMT3B, RNF17, UBR2, USP1 and USP26, in NOA patients (P = 5.5 × 10−7), corresponding to a carrier frequency of 22.5% of patients and 13.7% of controls (P = 1.4 × 10−5). An accumulation of low-frequency variants was also identified in additional epigenetic genes (BRDT and MTHFR). Our study suggested the potential associations of genetic defects in genes that are epigenetic regulators with spermatogenic failure in human.
Revealing bending and force in a soft body through a plant root inspired approach
Authors: Lucarotti Chiara , Totaro Massimo , Sadeghi Ali , Mazzolai Barbara , Beccai Lucia
Published: March 2015

An emerging challenge in soft robotics research is to reveal mechanical solicitations in a soft body. Nature provides amazing clues to develop unconventional components that are capable of compliant interactions with the environment and living beings, avoiding mechanical and algorithmic complexity of robotic design. We inspire from plant-root mechanoperception and develop a strategy able to reveal bending and applied force in a soft body with only two sensing elements of the same kind and a null computational effort. The stretching processes that lead to opposite tissue deformations on the two sides of the root wall are emulated with two tactile sensing elements, made of soft and stretchable materials, which conform to reversible changes in the shape of the body they are built in and follow its deformations. Comparing the two sensory responses, we can discriminate the concave and the convex side of the bent body. Hence, we propose a new strategy to reveal in a soft body the maximum bending angle (or the maximum deflection) and the externally applied force according to the body's mechanical configuration.
Effect of solute atoms on dislocation motion in Mg: An electronic structure perspective
Authors: Tsuru T. , Chrzan D. C.
Published: March 2015

Solution strengthening is a well-known approach to tailoring the mechanical properties of structural alloys. Ultimately, the properties of the dislocation/solute interaction are rooted in the electronic structure of the alloy. Accordingly, we compute the electronic structure associated with and the energy barriers to dislocation cross-slip. The energy barriers so obtained can be used in the development of multiscale models for dislocation mediated plasticity. The computed electronic structure can be used to identify substitutional solutes likely to interact strongly with the dislocation. Using the example of a-type screw dislocations in Mg, we compute accurately the Peierls barrier to prismatic plane slip and argue that Y, Ca, Ti and Zr should interact strongly with the studied dislocation and thereby decrease the dislocation slip anisotropy in the alloy.
Involvement of the left insula in the ecological validity of the human voice
Authors: Tamura Yuri , Kuriki Shinji , Nakano Tamami
Published: March 2015

A subtle difference between a real human and an artificial object that resembles a human evokes an impression of a large qualitative difference between them. This suggests the existence of a neural mechanism that processes the sense of humanness. To examine the presence of such a mechanism, we compared the behavioral and brain responses of participants who listened to human and artificial singing voices created from vocal fragments of a real human voice. The behavioral experiment showed that the song sung by human voices more often elicited positive feelings and feelings of humanness than the same song sung by artificial voices, although the lyrics, melody and rhythm were identical. Functional magnetic resonance imaging revealed significantly higher activation in the left posterior insula in response to human voices than in response to artificial voices. Insular activation was not merely evoked by differences in acoustic features between the voices. Therefore, these results suggest that the left insula participates in the neural processing of the ecological quality of the human voice.
The effects of delayed auditory feedback revealed by bone conduction microphone in adult zebra finches
Authors: Fukushima Makoto , Margoliash Daniel
Published: March 2015

Vocal control and learning are critically dependent on auditory feedback in songbirds and humans. Continuous delayed auditory feedback (cDAF) robustly disrupts speech fluency in normal humans and has ameliorative effects in some stutterers; however, evaluations of the effects of cDAF on songbirds are rare. We exposed singing young (141–151 days old) adult zebra finch males to high-amplitude cDAF. cDAF exposure was achieved by the recording of bone-conducted sounds using a piezoelectric accelerometer, which resulted in high-quality song recordings that were relatively uncontaminated by airborne sounds. Under this condition of cDAF, birds rapidly (2–6 days) changed their song syllable timing. The one bird for which we were able to maintain the accelerometer recordings over a long period of time recovered slowly over more than a month after cDAF was discontinued. These results demonstrate that cDAF can cause substantial changes in the motor program for syllable timing generation over short intervals of time in adult zebra finches.
Evidences of adaptive traits to rocky substrates undermine paradigm of habitat preference of the Mediterranean seagrass Posidonia oceanica
Authors: Badalamenti Fabio , Alagna Adriana , Fici Silvio
Published: March 2015

Posidonia oceanica meadows are acknowledged as one of the most valuable ecosystems of the Mediterranean Sea. P. oceanica has been historically described as a species typically growing on mobile substrates whose development requires precursor communities. Here we document for the first time the extensive presence of sticky hairs covering P. oceanica seedling roots. Adhesive root hairs allow the seedlings to firmly anchor to rocky substrates with anchorage strength values up to 5.23 N, regardless of the presence of algal cover and to colonise bare rock without the need for precursor assemblages to facilitate settlement. Adhesive root hairs are a morphological trait common on plants living on rocks in high-energy habitats, such as the riverweed Podostemaceae and the seagrass Phyllospadix scouleri. The presence of adhesive root hairs in P. oceanica juveniles suggests a preference of this species for hard substrates. Such an adaptation leads to hypothesize a new microsite driven bottleneck in P. oceanica seedling survival linked to substrate features. The mechanism described can favour plant establishment on rocky substrates, in contrast with traditional paradigms. This feature may have strongly influenced P. oceanica pattern of colonisation through sexual propagules in both the past and present.
Acute ER stress regulates amyloid precursor protein processing through ubiquitin-dependent degradation
Authors: Jung Eun Sun , Hong HyunSeok , Kim Chaeyoung , Mook-Jung Inhee
Published: March 2015

Beta-amyloid (Aβ), a major pathological hallmark of Alzheimer's disease (AD), is derived from amyloid precursor protein (APP) through sequential cleavage by β-secretase and γ-secretase enzymes. APP is an integral membrane protein and plays a key role in the pathogenesis of AD; however, the biological function of APP is still unclear. The present study shows that APP is rapidly degraded by the ubiquitin-proteasome system (UPS) in the CHO cell line in response to endoplasmic reticulum (ER) stress, such as calcium ionophore, A23187, induced calcium influx. Increased levels of intracellular calcium by A23187 induces polyubiquitination of APP, causing its degradation. A23187-induced reduction of APP is prevented by the proteasome inhibitor MG132. Furthermore, an increase in levels of the endoplasmic reticulum-associated degradation (ERAD) marker, E3 ubiquitin ligase HRD1, proteasome activity and decreased levels of the deubiquitinating enzyme USP25 were observed during ER stress. In addition, we found that APP interacts with USP25. These findings suggest that acute ER stress induces degradation of full-length APP via the ubiquitin-proteasome proteolytic pathway.
Precise in-frame integration of exogenous DNA mediated by CRISPR/Cas9 system in zebrafish
Authors: Hisano Yu , Sakuma Tetsushi , Nakade Shota , Ohga Rie , Ota Satoshi , Okamoto Hitoshi , Yamamoto Takashi , Kawahara Atsuo
Published: March 2015

The CRISPR/Cas9 system provides a powerful tool for genome editing in various model organisms, including zebrafish. The establishment of targeted gene-disrupted zebrafish (knockouts) is readily achieved by CRISPR/Cas9-mediated genome modification. Recently, exogenous DNA integration into the zebrafish genome via homology-independent DNA repair was reported, but this integration contained various mutations at the junctions of genomic and integrated DNA. Thus, precise genome modification into targeted genomic loci remains to be achieved. Here, we describe efficient, precise CRISPR/Cas9-mediated integration using a donor vector harbouring short homologous sequences (10–40 bp) flanking the genomic target locus. We succeeded in integrating with high efficiency an exogenous mCherry or eGFP gene into targeted genes (tyrosinase and krtt1c19e) in frame. We found the precise in-frame integration of exogenous DNA without backbone vector sequences when Cas9 cleavage sites were introduced at both sides of the left homology arm, the eGFP sequence and the right homology arm. Furthermore, we confirmed that this precise genome modification was heritable. This simple method enables precise targeted gene knock-in in zebrafish.
The relationship between response inhibition and posttraumatic stress symptom clusters in adolescent earthquake survivors: An event-related potential study
Authors: Wu Jianhui , Yuan Yiran , Cao Chengqi , Zhang Kan , Wang Li , Zhang Liang
Published: March 2015

Posttraumatic stress disorder (PTSD) patients experience impaired response inhibition. Little is known about the relationship between response inhibition abnormalities and distinct PTSD symptom clusters. This study investigated the relationship between response inhibition processing and a five-factor model of posttraumatic stress symptomatology in adolescents. The event-related potentials of 54 unmedicated adolescent earthquake survivors (age 15–18 years) were recorded as they completed a Go/NoGo task. The PTSD Checklist-Specific Stressor Version (PCL-S) was used to assess PTSD symptoms. Regression analyses were conducted to examine the associations between the five symptom-cluster model and response inhibition processing. The results revealed that the avoidance symptom cluster score, but not the numbing or other clusters' scores, was positively associated with NoGo-P3 latency. These results suggest that a specific PTSD symptom cluster—avoidance—has a distinct association with the slowed speed of the late step of response inhibition processing, i.e., decision or success of response inhibition in adolescent earthquake survivors.
Ultrafast hydrogen bond dynamics and partial electron transfer after photoexcitation of diethyl ester of 7-(diethylamino)-coumarin-3-phosphonic acid and its benzoxaphosphorin analog
Authors: Wagner M. S. , Ilieva E. D. , Petkov P. St. , Nikolova R. D. , Kienberger R. , Iglev H.
Published: March 2015

The solvation dynamics after optical excitation of two phosphono-substituted coumarin derivatives dissolved in various solutions are studied by fluorescence up-conversion spectroscopy and quantum chemical simulations.
Ionic liquid-induced all-α to α + β conformational transition in cytochrome c with improved peroxidase activity in aqueous medium
Authors: Bharmoria Pankaj , Trivedi Tushar J. , Pabbathi Ashok , Samanta Anunay , Kumar Arvind
Published: March 2015

Choline dioctylsulfosuccinate [Cho][AOT] (a surface active ionic liquid) has been found to induce all-α to α + β conformational transition in the secondary structure of enzyme cytochromec(Cytc) with an enhanced peroxidase activity in its aqueous vesicular phase at pH 7.0.
Excitation and quenching mechanisms in the near-UV photodissociation of CH3Br and CH3Cl adsorbed on D2O or CH3OH on Cu(110)
Authors: Jensen E. T.
Published: March 2015

Photochemical processes for CH3X (X = Cl, Br, I) adsorbed on top of thin films of D2O or CH3OH on a Cu(110) substrate is studied by time-of-flight mass spectrometry for a range of UV wavelengths (351–193 nm).
Upper or lower critical solution temperature, or both? Studies on cationic copolymers of N-isopropylacrylamide
Authors: Karjalainen Erno , Aseyev Vladimir , Tenhu Heikki
Published: March 2015

The solution properties of statistical copolymers of N-isopropyl acrylamide (NIPAm) and cationic (3-acrylamidopropyl) trimethylammonium chloride (AMPTMA) have been studied.
Mussel inspired preparation of highly dispersible and biocompatible carbon nanotubes
Authors: Wan Qing , Tian Jianwen , Liu Meiying , Zeng Guangjian , Li Zhen , Wang Ke , Zhang Qingsong , Deng Fengjie , Zhang Xiaoyong , Wei Yen
Published: March 2015

A novel method for preparation of water dispersible and biocompatible carbon nanotubesviamussel inspired PEGylation has been developed for the first time.
Rational design, synthesis, and 2D-QSAR study of anti-oncological alkaloids against hepatoma and cervical carcinoma
Authors: Girgis Adel S. , Panda Siva S. , Aziz Marian N. , Steel Peter J. , Dennis Hall C. , Katritzky Alan R.
Published: March 2015

A series of novel substituted dispiro-oxindole were synthesized and screened for anti-cancer properties. The anti-cancer data were validated by QSAR studies.
Naked-eye-based selective detection of pyrophosphate with a Zn2+ complex in aqueous solution and electrospun nanofibers
Authors: Li Zhanxian , Zhang Wenying , Liu Xingjiang , Liu Chunxia , Yu Mingming , Wei Liuhe
Published: March 2015

Based on keto–enol transformation process, a zinc complex as a naked-eye-based chemosensor for pyrophosphate in aqueous solution and electrospun nanofibers has been developed.
The Zishen Yutai pill shows no reproductive toxicity on embryo-fetal development in rats and rabbits
Authors: Zhou Jie , Zhou Li , Chong Liming , Wang Zhonghui , Huang Qiuling , Wu Yubing , Yang Yang , Ma Aicui , Wang Rong , Jiang Juan , Yan Dawei , Sun Zuyue
Published: March 2015

High dose of Zishen Yutai pill (ZYP) showed mild maternal toxicity in rat (24 g kg−1 d−1, 96× clinical dose) and no reproductive toxicity in rabbit (6 g kg−1 d−1, 24× clinical dose). ZYP could be safely used at the clinical dose during pregnancy.
Self-calibrating highly sensitive dynamic capacitance sensor: towards rapid sensing and counting of particles in laminar flow systems
Authors: Guha S. , Schmalz K. , Wenger Ch. , Herzel F.
Published: March 2015

In this report we propose a sensor architecture and a corresponding read-out technique on silicon for detection of dynamic capacitance change that can be applied to rapid particle counting and single particle sensing in a fluidic system.
Determination of Fe, Cr and Cu in used lubricating oils by ET AAS using a microemulsion process for sample preparation
Authors: Leite Clarice C. , Zmozinski Ariane V. , Vale Maria Goreti R. , Silva Márcia M.
Published: March 2015

Samples were prepared as microemulsions investigated through a pseudo-ternary phase diagram. Calibration curves with inorganic standards were used for quantification. The method is accurate, simple, fast, and causes less environmental impact.
Cell response and bioactivity of titania–zirconia–zirconium titanate nanotubes with different nanoscale topographies fabricated in a non-aqueous electrolyte
Authors: Minagar Sepideh , Li Yuncang , Berndt Christopher C. , Wen Cuie
Published: March 2015

Cell adhesion on the TiO2–ZrO2–ZrTiO4 nanotubes fabricated via anodization using a non-aqueous electrolyte was significantly influenced by the nanoscale topographical parameters.
2H → 1T phase transition and hydrogen evolution activity of MoS2, MoSe2, WS2 and WSe2 strongly depends on the MX2 composition
Authors: Ambrosi Adriano , Sofer Zdeněk , Pumera Martin
Published: March 2015

We investigate herein the 2H → 1T phase transition upon chemical exfoliation of the four most widely considered TMD materials: MoS2, MoSe2, WS2 and WSe2.
1,4,8,11,15,18,22,25-Alkylsulfanyl phthalocyanines: effect of macrocycle distortion on spectroscopic and packing properties
Authors: Zorlu Yunus , Kumru Ufuk , İşci Ümit , Divrik Burcin , Jeanneau Erwann , Albrieux Florian , Dede Yavuz , Ahsen Vefa , Dumoulin Fabienne
Published: March 2015

The effect of phthalocyanine macrocycle distortion on its spectroscopic and packing properties is studied, by comparing two phthalocyanines octa-non-peripherally substituted by alkanethiols of different bulkiness (n-hexyl and tert-butyl).
Chirality sensing using Ag+–thiol coordination polymers
Authors: Zhang Qian , Hong Yuan , Chen Na , Tao Dan-Dan , Li Zhao , Jiang Yun-Bao
Published: March 2015

Achiral coordination polymers of a thiol ligand with Ag+ in aqueous solution were shown to be able to sense the chirality of a monosaccharide that binds with the boronic acid group designed to be equipped in the thiol ligand.
Amine-catalyzed tunable reactions of allenoates with dithioesters: formal [4+2] and [2+2] cycloadditions for the synthesis of 2,3-dihydro-1,4-oxathiines and enantioenriched thietanes
Authors: Yang Hai-Bin , Yuan Yu-Chao , Wei Yin , Shi Min
Published: March 2015

The chemoselective [4+2] vs. [2+2] cycloaddition between allenoates and dithioesters has been developed on the basis of switching the nucleophilic amine catalyst, offering a divergent synthesis of sulfur-containing heterocycles.
Structural and electronic properties of organo-halide hybrid perovskites from ab initio molecular dynamics
Authors: Quarti Claudio , Mosconi Edoardo , De Angelis Filippo
Published: March 2015

Ab initio molecular dynamics simulations of MAPbI3 and FAPbI3 perovskites demonstrate their structural flexibility and a cation-induced sub-ps localization of electronic states.
Synthesis of new zeolite structures
Authors: Li Jiyang , Corma Avelino , Yu Jihong
Published: March 2015

The advances in the synthesis of new zeolite structures in the past decade are presented, which are achieved by utilization of the synthetic strategies primarily based on pre-designed SDAs, heteroatom substitution, and topotactic transformations.
Silver nanowire-embedded PDMS with a multiscale structure for a highly sensitive and robust flexible pressure sensor
Authors: Joo Yunsik , Byun Junghwan , Seong Narkhyeon , Ha Jewook , Kim Hyunjong , Kim Sangwoo , Kim Taehoon , Im Hwarim , Kim Donghyun , Hong Yongtaek
Published: March 2015

A highly sensitive and flexible capacitive-type pressure sensor, array and fingertip sensing device are fabricated with a multiscale-structured electrode.
High performance quinacridone-based polymers in film transistors and photovoltaics: effects of vinylene linkage on crystallinity and morphology
Authors: Li Hui , Wang Xuedong , Liu Fangbin , Fu Hongbing
Published: March 2015

Incorporating a vinylene linkage into quinacridone-based polymers induces a short π–π stacking distance and contributes good intercalation of fullerenes to polymers.
Determination of benzoylurea insecticides in environmental water and honey samples using ionic-liquid-mingled air-assisted liquid–liquid microextraction based on solidification of floating organic droplets
Authors: Yang Miyi , Xi Xuefei , Yang Xiaoling , Bai Lizhen , Lu Runhua , Zhou Wenfeng , Zhang Sanbing , Gao Haixiang
Published: March 2015

This method combined the advantages of air-assisted liquid–liquid microextraction and solidified floating organic droplet microextraction with a mixture extractant.
Micro-wheels composed of self-assembled tungsten oxide nanorods for highly sensitive detection of low level toxic chlorine gas
Authors: Van Tong Pham , Hoa Nguyen Duc , Van Duy Nguyen , Van Hieu Nguyen
Published: March 2015

Gas nanosensor based on micro-wheels composed of self-assembled tungsten oxide nanorods exhibited excellent sensing performance to ppb level Cl2.
Synthesis, characterization and biological properties of new hybrid carbosilane–viologen–phosphorus dendrimers
Authors: Moreno Silvia , Szwed Aleksandra , El Brahmi Nabil , Milowska Katarzyna , Kurowska Joanna , Fuentes-Paniagua Elena , Pedziwiatr-Werbicka Elzbieta , Gabryelak Teresa , Katir Nadia , Javier de la Mata F. , Muñoz-Fernández Ma Angeles , Gomez-Ramirez Rafael , Caminade Anne-Marie , Majoral Jean-Pierre , Bryszewska Maria
Published: March 2015

Hybrid carbosilane–viologen–phosphorus dendrimers were prepared, as an example of the synthetic “onion peel” approach, on the search of new physical–chemical and biological properties, respecting traditional dendritic architectures.
Meglumine catalyzed one-pot, three-component combinatorial synthesis of pyrazoles bearing a coumarin unit
Authors: Li Xiao-Tang , Liu Yu-Heng , Liu Xin , Zhang Zhan-Hui
Published: March 2015

Meglumine has been found to be an efficient catalyst for the synthesis of pyrazolylcoumarins by one-pot three-component reaction of salicylaldehyde, 4-hydroxy-6-methyl-2H-pyran-2-one, and hydrazine.
NCN pincer palladium complexes based on 1,3-dipicolyl-3,4,5,6-tetrahydropyrimidin-2-ylidenes: synthesis, characterization and catalytic activities
Authors: Yang Liangru , Zhang Xinchi , Mao Pu , Xiao Yongmei , Bian Huanyu , Yuan Jinwei , Mai Wenpeng , Qu Lingbo
Published: March 2015

NCN pincer six-membered NHC palladium complexes were synthesized, characterized and used in Heck reaction of aryl bromides with olefines.
Adsorption of hexavalent chromium by polyacrylonitrile (PAN)-based activated carbon fibers from aqueous solution
Authors: Jiang Zhengjiang , Liu Yunguo , Zeng Guangming , Xu Weihua , Zheng Bohong , Tan Xiaofei , Wang Shufan
Published: March 2015

Polyacrylonitrile (PAN)-based activated carbon fibers (PAC400 and PAC600) were prepared by heating Zn(NO3)2 pretreated-PAN at 400 °C and 600 °C for the removal of Cr(vi) from aqueous solution.
Facile fabrication of silica–polymer–graphene collaborative nanostructure-based hybrid materials with high conductivity and robust mechanical performance
Authors: Ye Wenqiong , Zhang Ling , Li Chunzhong
Published: March 2015

SiO2@poly(methyl methacrylate)–reduced graphene oxide composites with outstanding thermal stability, robust mechanical performance and excellent conductivity have been prepared by dispersion polymerization and electrostatic assembly.
Experimental and theoretical study of antioxidative properties of some salicylaldehyde and vanillic Schiff bases
Authors: Petrović Zorica D. , Đorović Jelena , Simijonović Dušica , Petrović Vladimir P. , Marković Zoran
Published: March 2015

A set of ten phenolic Schiff bases was evaluated for their antioxidative properties. Two of them, one salicylaldehyde and one vanillic, showed high activity. Parameters obtained by DFT supported the experimental findings.
Novel magnetic antimicrobial nanocomposites for bone tissue engineering applications
Authors: Bhowmick Arundhati , Saha Arijit , Pramanik Nilkamal , Banerjee Subhash , Das Manas , Kundu Patit Paban
Published: March 2015

Here we have developed novel bone-like superparamagnetic nanocomposites for bone tissue engineering. These nanocomposites exhibited high water uptake ability, excellent mechanical properties, good antimicrobial activities and blood compatibility.
Metabolomic study of Chinese medicine Huang Qin decoction as an effective treatment for irinotecan-induced gastrointestinal toxicity
Authors: Wang Jing , Fan Hongyan , Wang Yong , Wang Xu , Zhang Pei , Chen Jiaqing , Tian Yuan , Zhang Wei , Xu Fengguo , Zhang Zunjian
Published: March 2015

Metabolomic study revealed Chinese medicine HQD reducing irinotecan-induced gastrointestinal toxicity by regulating glutamine, tryptophan and lipid metabolisms.
Sub-nanoscale free volume and local elastic modulus of chitosan–carbon nanotube biomimetic nanocomposite scaffold-materials
Authors: Axpe Eneko , Bugnicourt Loic , Merida David , Goiriena-Goikoetxea Maite , Unzueta Iraultza , Sanchez-Eugenia Ruben , Garcia Jose Angel , Plazaola Fernando , Contera Sonia
Published: March 2015

Nanoscale elastic modulus and mass transport properties calculated with free volume theory of biomimetic nanocomposite scaffolds for tissue engineering and 3D cell cultures applications.
Self-organization of an optomagnetic CoFe2O4–ZnS nanocomposite: preparation and characterization
Authors: Amiri Zarandi Ali , Sabbagh Alvani Ali A. , Salimi Reza , Sameie Hassan , Moosakhani Shima , Poelman Dirk , Rosei Federico
Published: March 2015

We report an advanced method for the self-organization of an optomagnetic nanocomposite composed of both fluorescent ZnS quantum dots and CoFe2O4magnetic nanoparticles with acceptable saturation magnetization and satisfactory luminescence characteristics.
Aggregation and supramolecular chirality of 5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrin on an achiral poly(2-(dimethylamino)ethyl methylacrylate)-grafted ethylene-vinyl alcohol membrane
Authors: Zhao Lizhi , Liu Manman , Li Sensen , Li Ang , An Huiqin , Ye Hui , Zhang Yuzhong
Published: March 2015

Supramolecular chirality was achieved by aggregation of an achiral porphyrin on an achiral polymeric porous membrane surface.
Highly luminescent flexible amino-functionalized graphene quantum dots@cellulose nanofiber–clay hybrids for white-light emitting diodes
Authors: Tetsuka H. , Nagoya A. , Asahi R.
Published: March 2015

Bright colorful luminescent flexible amino-functionalized graphene quantum dots (af-GQDs)@cellulose nanofiber (CNF)–clay hybrids are potentially applicable in white LEDs.
Outcomes of Group Audiological Rehabilitation for Unaided Adults With Hearing Impairment and Their Significant Others
Authors: Lucía Habanec O. , Kelly-Campbell Rebecca J.
Published: March 2015

Purpose

The purpose of this study was to evaluate the outcomes of a group audiological rehabilitation (GAR) program designed for working adults who do not use amplification and for their significant others.

Method

A quasirandomized control design was used to measure outcomes of the GAR program. Twenty-four couples participated in weekly GAR group sessions designed to address communication problems encountered in the workplace and at home. Twelve couples were placed on a waiting list as a control group. Assessments were completed at time frames prior to the sessions, post–waiting list, immediately after the sessions, and 12 weeks after. These included direct measures for the adults with hearing impairment, proxy measures from the significant others, and direct measures for the significant others.

Results

Results indicated adults with hearing impairment and their significant others experienced significant improvements following participation in the GAR program. These improvements were maintained in the short term (12 weeks).

Conclusions

Working adults with hearing impairment who do not use amplification can benefit from GAR sessions. Significant others of working adults with hearing impairment experience third-party disability, which can also be alleviated through participation in GAR sessions.