bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cargo–carrier interactions significantly contribute to micellar conformation and biodistribution
Authors: Press Adrian T , Ramoji Anuradha , vd Lühe Moritz , Rinkenauer Alexandra C , Hoff Jessica , Butans Marianne , Rössel Carsten , Pietsch Christian , Neugebauer Ute , Schacher Felix H , Bauer Michael 
Published: October 2017

AbstractStrategies to deliver drugs using nanocarriers, which are passively or actively targeted to their alleged site of action might favorably affect benefit–risk profiles of novel therapeutics. Here we tested the hypothesis whether the physico-chemical properties of the cargo as well as the actual conditions during encapsulation interfere during formulation of nanoparticular cargo–carrier systems. On the basis of previous work, a versatile class of nanocarriers is polyether-based ABC triblock terpolymer micelles with diameters below 50 nm. Their tunable chemistry and size allows to systematically vary important parameters. We demonstrate in vivo differences in pharmacokinetics and biodistribution not only dependent on micellar net charge but also on the properties of encapsulated (model) drugs and their localization within the micelles. On the basis of in vitro and in vivo evidence we propose that depending on drug cargo and encapsulation conditions micelles with homogeneous or heterogeneous corona structure are formed, contributing to an altered pharmacokinetic profile as differences in cargo location occur. Thus, these interactions have to be considered when a carrier system is selected to achieve optimal delivery to a given tissue.
Modulation of telomere protection by the PI3K/AKT pathway
Authors: Méndez-Pertuz Marinela , Martínez Paula , Blanco-Aparicio Carmen , Gómez-Casero Elena , Belen García Ana , Martínez-Torrecuadrada Jorge , Palafox Marta , Cortés Javier , Serra Violeta , Pastor Joaquin , Blasco Maria A. 
Published: October 2017

AbstractTelomeres and the insulin/PI3K pathway are considered hallmarks of aging and cancer. Here, we describe a role for PI3K/AKT in the regulation of TRF1, an essential component of the shelterin complex. PI3K and AKT chemical inhibitors reduce TRF1 telomeric foci and lead to increased telomeric DNA damage and fragility. We identify the PI3Kα isoform as responsible for this TRF1 inhibition. TRF1 is phosphorylated at different residues by AKT and these modifications regulate TRF1 protein stability and TRF1 binding to telomeric DNA in vitro and are important for in vivo TRF1 telomere location and cell viability. Patient-derived breast cancer PDX mouse models that effectively respond to a PI3Kα specific inhibitor, BYL719, show decreased TRF1 levels and increased DNA damage. These findings functionally connect two of the major pathways for cancer and aging, telomeres and the PI3K pathway, and pinpoint PI3K and AKT as novel targets for chemical modulation of telomere protection.
Mammalian γ2 AMPK regulates intrinsic heart rate
Authors: Yavari Arash , Bellahcene Mohamed , Bucchi Annalisa , Sirenko Syevda , Pinter Katalin , Herring Neil , Jung Julia J. , Tarasov Kirill V. , Sharpe Emily J. , Wolfien Markus , Czibik Gabor , Steeples Violetta , Ghaffari Sahar , Nguyen Chinh , Stockenhuber Alexander , Clair Joshua R. St. , Rimmbach Christian , Okamoto Yosuke , Yang Dongmei , Wang Mingyi , Ziman Bruce D. , Moen Jack M. , Riordon Daniel R. , Ramirez Christopher , Paina Manuel , Lee Joonho , Zhang Jing , Ahmet Ismayil , Matt Michael G. , Tarasova Yelena S. , Baban Dilair , Sahgal Natasha , Lockstone Helen , Puliyadi Rathi , de Bono Joseph , Siggs Owen M. , Gomes John , Muskett Hannah , Maguire Mahon L. , Beglov Youlia , Kelly Matthew , dos Santos Pedro P. N. , Bright Nicola J. , Woods Angela , Gehmlich Katja , Isackson Henrik , Douglas Gillian , Ferguson David J. P. , Schneider Jürgen E. , Tinker Andrew , Wolkenhauer Olaf , Channon Keith M. , Cornall Richard J. , Sternick Eduardo B. , Paterson David J. , Redwood Charles S. , Carling David , Proenza Catherine , David Robert , Baruscotti Mirko , DiFrancesco Dario , Lakatta Edward G. , Watkins Hugh , Ashrafian Houman 
Published: October 2017

AbstractAMPK is a conserved serine/threonine kinase whose activity maintains cellular energy homeostasis. Eukaryotic AMPK exists as αβγ complexes, whose regulatory γ subunit confers energy sensor function by binding adenine nucleotides. Humans bearing activating mutations in the γ2 subunit exhibit a phenotype including unexplained slowing of heart rate (bradycardia). Here, we show that γ2 AMPK activation downregulates fundamental sinoatrial cell pacemaker mechanisms to lower heart rate, including sarcolemmal hyperpolarization-activated current (If) and ryanodine receptor-derived diastolic local subsarcolemmal Ca2+ release. In contrast, loss of γ2 AMPK induces a reciprocal phenotype of increased heart rate, and prevents the adaptive intrinsic bradycardia of endurance training. Our results reveal that in mammals, for which heart rate is a key determinant of cardiac energy demand, AMPK functions in an organ-specific manner to maintain cardiac energy homeostasis and determines cardiac physiological adaptation to exercise by modulating intrinsic sinoatrial cell behavior.
Tracing the origin and evolution of supergene mimicry in butterflies
Authors: Zhang Wei , Westerman Erica , Nitzany Eyal , Palmer Stephanie , Kronforst Marcus R. 
Published: October 2017

AbstractSupergene mimicry is a striking phenomenon but we know little about the evolution of this trait in any species. Here, by studying genomes of butterflies from a recent radiation in which supergene mimicry has been isolated to the gene doublesex, we show that sexually dimorphic mimicry and female-limited polymorphism are evolutionarily related as a result of ancient balancing selection combined with independent origins of similar morphs in different lineages and secondary loss of polymorphism in other lineages. Evolutionary loss of polymorphism appears to have resulted from an interaction between natural selection and genetic drift. Furthermore, molecular evolution of the supergene is dominated not by adaptive protein evolution or balancing selection, but by extensive hitchhiking of linked variants on the mimetic dsx haplotype that occurred at the origin of mimicry. Our results suggest that chance events have played important and possibly opposing roles throughout the history of this classic example of adaptation.
Advanced glycation end products promote VEGF expression and thus choroidal neovascularization via Cyr61-PI3K/AKT signaling pathway
Authors: Sun Lijuan , Huang Tonglie , Xu Wenqin , Sun Jiaxing , Lv Yang , Wang Yusheng 
Published: October 2017

AbstractChoroidal neovascularisation (CNV) causes severe vision loss among old patients, especially those with diabetes. Previously, Cyr61 has been found to play a critical role in the pathogenesis of both AMD and diabetes. In the present study, we found that increased CNV severity together with higher expression of Cyr61 and VEGF in diabetes mice compared with control mice. Moreover, knockdown of Cyr61 decreased CNV severity. In vitro mechanism study revealed that the advanced glycation end products (AGEs) significantly increased the expression of Cyr61 in retinal pigment epithelial (RPE) cells, mimicking the effects of diabetes. In turn, the increased Cyr61 enhanced VEGF expression through FAK and PI3K/Akt pathways. Chemically blocking the above pathway significantly inhibited CNV formation, providing a new strategy for clinical prevention and treatment of CNV in related diseases.
Akap350 Recruits Eb1 to The Spindle Poles, Ensuring Proper Spindle Orientation and Lumen Formation in 3d Epithelial Cell Cultures
Authors: Almada Evangelina , Tonucci Facundo M. , Hidalgo Florencia , Ferretti Anabela , Ibarra Solange , Pariani Alejandro , Vena Rodrigo , Favre Cristián , Girardini Javier , Kierbel Arlinet , Larocca M. Cecilia 
Published: October 2017

AbstractThe organization of epithelial cells to form hollow organs with a single lumen requires the accurate three-dimensional arrangement of cell divisions. Mitotic spindle orientation is defined by signaling pathways that provide molecular links between specific spots at the cell cortex and astral microtubules, which have not been fully elucidated. AKAP350 is a centrosomal/Golgi scaffold protein, implicated in the regulation of microtubule dynamics. Using 3D epithelial cell cultures, we found that cells with decreased AKAP350 expression (AKAP350KD) formed polarized cysts with abnormal lumen morphology. Analysis of mitotic cells in AKAP350KD cysts indicated defective spindle alignment. We established that AKAP350 interacts with EB1, a microtubule associated protein that regulates spindle orientation, at the spindle poles. Decrease of AKAP350 expression lead to a significant reduction of EB1 levels at spindle poles and astral microtubules. Conversely, overexpression of EB1 rescued the defective spindle orientation induced by deficient AKAP350 expression. The specific delocalization of the AKAP350/EB1complex from the centrosome decreased EB1 levels at astral microtubules and lead to the formation of 3D-organotypic structures which resembled AKAP350KD cysts. We conclude that AKAP350 recruits EB1 to the spindle poles, ensuring EB1 presence at astral microtubules and proper spindle orientation during epithelial morphogenesis.
Molecular phylogenetic analysis of new Entoloma rhodopolium-related species in Japan and its identification method using PCR-RFLP
Authors: Kondo Kazunari , Nakamura Kosuke , Ishigaki Takumi , Sakata Kozue , Obitsu Saemi , Noguchi Akio , Fukuda Nozomi , Nagasawa Eiji , Teshima Reiko , Nishimaki-Mogami Tomoko 
Published: October 2017

AbstractPoisonous Entoloma rhodopolium and other similar species including edible E. sarcopum are morphologically diverse. People mistake poisonous species for edible species. Classification and the detection method of these species need to be defined. The morphological and phylogenetic studies have been reported in northern Europe. In Japan, the genetic study remains unsolved. Thus, phylogenetic analysis of E. rhodopolium was conducted using ITS and RPB2 sequences, and the result was compared with that of European species. Japanese E. rhodopolium was classified into three clades, none of which belonged to the true European E. rhodopolium and other known species. Three species were defined as new species. Entoloma rhodopolium clade-I (named E. lacus) was genetically close to but morphologically separated from E. majaloides. Clade-II (E. subrhodopolium) was classified to the same group as E. sinuatum and E. subsinuatum, but distinct from these species. Clade-III was segregated from known Entoloma species including E. lupinum, and named E. pseudorhodopolium. Based on the classification, a simple identification method PCR-RFLP was developed to discriminate between poisonous species and edible E. sarcopum, which is very similar in morphology. The study can help to clarify the taxonomy of complex E. rhodopolium-related species, and to prevent food poisoning.
Implementation of controlled quantum teleportation with an arbitrator for secure quantum channels via quantum dots inside optical cavities
Authors: Heo Jino , Hong Chang-Ho , Kang Min-Sung , Yang Hyeon , Yang Hyung-Jin , Hong Jong-Phil , Choi Seong-Gon 
Published: October 2017

AbstractWe propose a controlled quantum teleportation scheme to teleport an unknown state based on the interactions between flying photons and quantum dots (QDs) confined within single- and double-sided cavities. In our scheme, users (Alice and Bob) can teleport the unknown state through a secure entanglement channel under the control and distribution of an arbitrator (Trent). For construction of the entanglement channel, Trent utilizes the interactions between two photons and the QD-cavity system, which consists of a charged QD (negatively charged exciton) inside a single-sided cavity. Subsequently, Alice can teleport the unknown state of the electron spin in a QD inside a double-sided cavity to Bob’s electron spin in a QD inside a single-sided cavity assisted by the channel information from Trent. Furthermore, our scheme using QD-cavity systems is feasible with high fidelity, and can be experimentally realized with current technologies.
Diverse coordinate frames on sensorimotor areas in visuomotor transformation
Authors: Fujiwara Yusuke , Lee Jongho , Ishikawa Takahiro , Kakei Shinji , Izawa Jun 
Published: October 2017

AbstractThe visuomotor transformation during a goal-directed movement may involve a coordinate transformation from visual ‘extrinsic’ to muscle-like ‘intrinsic’ coordinate frames, which might be processed via a multilayer network architecture composed of neural basis functions. This theory suggests that the postural change during a goal-directed movement task alters activity patterns of the neurons in the intermediate layer of the visuomotor transformation that recieves both visual and proprioceptive inputs, and thus influence the multi-voxel pattern of the blood oxygenation level dependent signal. Using a recently developed multi-voxel pattern decoding method, we found extrinsic, intrinsic and intermediate coordinate frames along the visuomotor cortical pathways during a visuomotor control task. The presented results support the hypothesis that, in human, the extrinsic coordinate frame was transformed to the muscle-like frame over the dorsal pathway from the posterior parietal cortex and the dorsal premotor cortex to the primary motor cortex.
Introgressive replacement of natives by invading Arion pest slugs
Authors: Zemanova Miriam A. , Knop Eva , Heckel Gerald 
Published: October 2017

AbstractHybridization with invasive species is one of the major threats to the phenotypic and genetic persistence of native organisms worldwide.Arion vulgaris(syn.lusitanicus) is a major agricultural pest slug that successfully invaded many European countries in recent decades, but its impact on closely related native species remains unclear. Here, we hypothesized that the regional decline of nativeA. rufusis connected with the spread of invasiveA. vulgaris, and tested whether this can be linked to hybridization between the two species by analyzing 625Arionsp. along altitudinal transects in three regions in Switzerland. In each region, we observed clear evidence of different degrees of genetic admixture, suggesting recurrent hybridization beyond the first generation. We found spatial differences in admixture patterns that might reflect distinct invasion histories among the regions. Our analyses provide a landscape level perspective for the genetic interactions between invasive and native animals during the invasion. We predict that without specific management action,A. vulgariswill further expand its range, which might lead to local extinction ofA. rufusand other native slugs in the near future. Similar processes are likely occurring in other regions currently invaded byA. vulgaris.
Associated factors of acute primary angle closure glaucoma in a sub-group of Chinese people: comparison between attack eyes and normal controls
Authors: Liu Lifang , Liu Xinyu , Huang Chukai , Wang Geng , Ma Di , Zhang Wanqi , Zheng Ce , Zhang Mingzhi 
Published: October 2017

AbstractAcute primary angle closure glaucoma (APACG) is an ophthalmic emergency that may lead to irreversible blindness. Although efforts were made to control intraocular pressure, disease progression still existed. Anterior segment optical coherence tomography (AS OCT) may provide a new insight into mechanism of APACG. In order to seek out associated factors by AS OCT, We compared anterior segment parameters between 74 APACG and 48 normal eyes. Analysis of variance, principle component analysis and logistic regression were used. APACG group had more women (75.7% vs 47.9%, p = 0.002), smaller anterior chamber (anterior chamber depth, ACD; anterior chamber area, ACA; all p = 0.001), narrower angle (AOD500, AOD750, angle opening distance at 500um and 750um; TISA500, TISA750, trabecular-iris space area at 500um and 750um; ARA500, ARA750, angle recess area at 500um and 750um; all p < 0.001), thinner iris (iris thickness at 750um, IT750; maximum of iris thickness, ITMAX; all p < 0.001), larger iris area (IA, p < 0.001) and lens vault (LV, p = 0.005). Principle component extracted were AOD500, AOD750, TISA500, TISA750, ARA500, ARA750, IA, PD (pupillary diameter), ACD, ACA and IT750. After adjusting for confounding factors, AOD750 (b = 12.40 ± 2.56, p < 0.001), IT750 (b = 10.50 ± 3.45, p = 0.002) and IA (b = −1.56 ± 0.77, p = 0.044) were significantly associated with occurrence of APACG.
Iron deposition in substantia nigra: abnormal iron metabolism, neuroinflammatory mechanism and clinical relevance
Authors: Liu Zhuo , Shen Hui-cong , Lian Teng-hong , Mao Lei , Tang Shou-xian , Sun Li , Huang Xi-yan , Guo Peng , Cao Chen-jie , Yu Shu-yang , Zuo Li-jun , Wang Xiao-Min , Chen Sheng-Di , Chan Piu , Zhang Wei 
Published: October 2017

AbstractParkinson disease (PD) is associated with multiple factors, including iron, which is demonstrated to deposit excessively in PD brains. We detected iron deposition by susceptibility weighted image (SWI) and measured the levels of iron metabolism-related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum of PD patients and control subjects. Clinical symptoms of PD were evaluated by series of rating scales. Relationships among above factors were analyzed. Results showed that corrected phase (CP) value of substantia nigra (SN) was significantly decreased in PD group compared to control group, hence, SN was the main region with excessive iron deposition. In PD group, ferritin was significantly elevated in CSF and reduced in serum compared to control group, and levels of ferritin in CSF and serum were both significantly and positively correlated with CP value of SN, thus, abnormal iron metabolism in central and peripheral systems was associated with iron deposition. CP value of SN in PD group was significantly and negatively correlated with interleukin-1β level in CSF, so interleukin-1β might be a neuroinflammatory factor produced by excessive iron in SN. Iron deposition in SN was significantly correlated with motor symptoms and part of non-motor symptoms of PD.
In vivo measurement of regional corneal tangent modulus
Authors: Hon Ying , Chen Guo-Zhen , Lu Shu-Hao , Lam David CC , Lam Andrew KC 
Published: October 2017

AbstractCurrently available clinical devices are unable to measure corneal biomechanics other than at the central region. Corneal stiffness (S), thickness, and radius of curvature was measured at the central cornea (primary fixation) and 3 mm from the temporal limbus (primary and nasal fixations). The corneal tangent modulus (E) of 25 healthy subjects was calculated from these data. After confirming normality, repeated measures analysis of variance (RMANOVA) revealed significant difference in S (F(2, 48) = 21.36, p < 0.001) at different corneal regions and direction of fixations. E also varied significantly at different corneal regions and direction of fixations (RMANOVA: F(2, 48) = 23.06, p < 0.001). A higher S and a lower E were observed at the temporal region compared with the corneal centre. Nasal fixation further increased S and E values compared with primary fixation. Due to the specific arrangement of corneal collagen fibrils, heterogeneity of corneal biomechanical properties is expected. In future clinical practice, localized corneal biomechanical alternation and measurement might assist corneal disease detection and post-surgery management. In addition, practitioners should be aware of the fixation effect on corneal biomechanical measurement.
Attenuation of temporal correlations of neuronal oscillations in patients with mild spastic diplegia
Authors: Gao Fei , Wu Xiangci , Feng Yi , Jia Huibin 
Published: October 2017

AbstractThe aim of this study was to investigate the temporal correlations of neuronal oscillations in patients with mild spastic diplegia (MSD). Resting-state electroencephalography (EEG) was recorded from 15 male adolescent and young adult patients with MSD and 15 healthy controls. We characterized the temporal correlations of neuronal oscillations, both on long temporal scale (i.e., >1 second) and short-to-intermediate temporal scale (i.e., <≈1 second) using detrended fluctuation analysis (DFA) and an analysis of the life- and waiting-time statistics of oscillation bursts respectively. The DFA exponents at alpha and beta bands, the life-time biomarker of alpha oscillation, and the life- and waiting-time biomarkers of beta oscillation were significantly attenuated in the patients compared with controls. Moreover, altered scalp distributions of some temporal correlation measures were found at alpha and beta bands in these patients. All these findings suggest that MSD is associated with highly volatile neuronal states of alpha and beta oscillations on short-to-intermediate and much longer time scales, which may be related to cognitive dysfunction in patients with MSD.
Enhanced omnidirectional and weatherability of Cu2ZnSnSe4 solar cells with ZnO functional nanorod arrays
Authors: Lai Fang-I , Yang Jui-Fu , Liao Wei-Xiang , Kuo Shou-Yi 
Published: October 2017

AbstractThis paper presents the use of nanorods of different sizes, deposited from a chemical solution, as an antireflection layer in copper–zinc–tin selenide (CZTSe) solar cells. With the aid of the nanorods, the surface reflection of the CZTSe solar cells was reduced from 7.76% to 2.97%, and a cell efficiency of 14% was obtained as a result. Omni-directional anti-reflection was verified by the angle-dependent reflection measurements. The nanorod arrays also provided the CZTSe solar cells with a hydrophobic surface, allowing it to exhibit high resistance against humidity during weatherability tests. This shows that the surface passivation brought by the nanorod layer at the surface could effectively extend the lifetime of the CZTSe solar cells. The rate of efficiency decay of the CZTSe solar cells was reduced by 46.85% from that of the device without a nanorod array at the surface, indicating that this surface layer not only provided effective resistance against reflection at the device surface, but also served as a passivation layer and humidity-resistant surface-protection layer.
Metoprolol prevents chronic obstructive sleep apnea-induced atrial fibrillation by inhibiting structural, sympathetic nervous and metabolic remodeling of the atria
Authors: Sun Li , Yan Sen , Wang Xiaoyu , Zhao Shiqi , Li Hui , Wang Yike , Lu Shuang , Dong Xinwen , Zhao Jing , Yu Shengzhu , Li Minghui , Li Yue 
Published: October 2017

AbstractChronic obstructive sleep apnea (OSA) may promote the development of atrial fibrillation (AF) by inducing atrial electrical and structural remodeling as well as autonomic nerve hyperinnervation. Here, we investigated the roles of metoprolol in regulation of atrial remodeling induced by chronic OSA. A canine model of chronic OSA was established by stopping the ventilator and closing the airway for 4 h/day every other day for 12 weeks, while metoprolol (5 mg·kg-1·day-1) was continuously administered. Using that model, we observed that increases in sympathetic sprouting and atrial structural remodeling were sharply inhibited by metoprolol. Moreover, metoprolol dramatically inhibited the impairment of atrial energy metabolism by activating the Sirt1-AMPK pathway. In vitro, metoprolol significantly activated the Sirt1-AMPK pathway in intermittent hypoxic and isoproterenol-treated HL-1 cells, and the effect was abolished by the coadministration of EX-527, an inhibitor of Sirt1 activation. In summary, metoprolol protects against chronic OSA-induced atrial remodeling. Our results suggest a new and feasible treatment strategy for AF induced by OSA.