bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIn 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

AbstractThe 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

AbstractUsing 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

AbstractWe 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

AbstractMembers 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

AbstractNon-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

AbstractAn 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

AbstractSolution 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

AbstractA 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

AbstractVocal 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

AbstractPosidonia 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

AbstractBeta-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

AbstractThe 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

AbstractPosttraumatic 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.
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.
Prevalence of Klippel-Feil Syndrome in a Surgical Series of Patients with Cervical Spondylotic Myelopathy: Analysis of the Prospective, Multicenter AOSpine North America Study
Authors: Nouri Aria , Tetreault Lindsay , Zamorano Juan J. , Mohanty Chandan B. , Fehlings Michael G. 
Published: March 2015

Study Design Prospective study. Objective To evaluate the prevalence of Klippel-Feil syndrome (KFS) in a prospective data set of patients undergoing surgical treatment for cervical spondylotic myelopathy (CSM) and to evaluate if magnetic resonance imaging (MRI) features in patients with KFS are more pronounced than those of non-KFS patients with CSM. Methods A retrospective analysis of baseline MRI data from the AOSpine prospective and multicenter CSM-North American study was conducted. All the patients presented with at least one clinical sign of myelopathy and underwent decompression surgery. The MRIs and radiographs were reviewed by three investigators. The clinical and imaging findings were compared with patients without KFS but with CSM. Results Imaging analysis discovered 5 of 131 patients with CSM (∼3.82%) had single-level congenital fusion of the cervical spine. The site of fusion differed for all the patients. One patient underwent posterior surgery and four patients received anterior surgery. Postoperative follow-up was available for four of the five patients with KFS and indicated stable or improved functional status. All five patients demonstrated pathologic changes of adjacent segments and hyperintensity signal changes in the spinal cord on T2-weighted MRI. Multiple MRI features, most notably maximum canal compromise ( p = 0.05) and T2 signal hyperintensity area ( p = 0.05), were worse in patients with CSM and KFS. Conclusions The high prevalence of KFS in our surgical series of patients with CSM may serve as an indication that these patients are prone to increased biomechanical use of segments adjacent to fused vertebra. This supposition is supported by a tendency of patients with KFS to present with more extensive MRI evidence of degeneration than non-KFS patients with CSM.
p63 sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling
Authors: Memmi Elisa Maria , Sanarico Anna Giulia , Giacobbe Arianna , Peschiaroli Angelo , Frezza Valentina , Cicalese Angelo , Pisati Federica , Tosoni Daniela , Zhou Huiqing , Tonon Giovanni , Antonov Alexey , Melino Gerry , Pelicci Pier Giuseppe , Bernassola Francesca 
Published: March 2015

Significance
p63, the sister homolog of p53, is a master regulator of epithelial stem cell (SC) biology. p63 is indeed intimately implicated in the maintenance of the self-renewal capacity of stratified epithelia and their derivatives, including the mammary gland. Although the physiological role of p63 in normal mammary SCs is now acknowledged, proof of its implications in breast cancer SCs remains elusive. Here, we find that mammary cancer stem cells (CSCs) possess increased levels of p63 expression compared with normal progenitors. p63 promotes self-renewal and expansion of mammary CSCs and breast tumor growth in vivo. Additionally, this study provides a link between p63 and the Sonic Hedgehog signaling pathway in the regulation of breast cancer stemness.