bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors
Authors: Echeverry N , Ziltener G , Barbone D , Weder W , Stahel R A , Broaddus V C , Felley-Bosco E 
Published: May 2015

AbstractMalignant pleural mesothelioma (MPM) originates in most of the cases from chronic inflammation of the mesothelium due to exposure to asbestos fibers. Given the limited effect of chemotherapy, a big effort is being made to find new treatment options. The PI3K/mTOR pathway was reported to be upregulated in MPM. We tested the cell growth inhibition properties of two dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 on 19 MPM cell lines. We could identify resistant and sensitive lines; however, there was no correlation to the downregulation of PI3K/mTOR activity markers. As a result of mTOR inhibition, both drugs efficiently induced long-term autophagy but not cell death. Autophagy blockade by chloroquine in combination with the dual PI3K/mTOR inhibitors significantly induced caspase-independent cell death involving RIP1 in the sensitive cell line SPC212. Cell death in the resistant cell line Mero-82 was less pronounced, and it was not induced via RIP1-dependent mechanism, suggesting the involvement of RIP1 downstream effectors. Cell death induction was confirmed in 3D systems. Based on these results, we identify autophagy as one of the main mechanisms of cell death resistance against dual PI3K/mTOR inhibitors in MPM. As PI3K/mTOR inhibitors are under investigation in clinical trials, these results may help interpreting their outcome and suggest ways for intervention.
Myocardial MiR-30 downregulation triggered by doxorubicin drives alterations in β-adrenergic signaling and enhances apoptosis
Authors: Roca-Alonso L , Castellano L , Mills A , Dabrowska A F , Sikkel M B , Pellegrino L , Jacob J , Frampton A E , Krell J , Coombes R C , Harding S E , Lyon A R , Stebbing J 
Published: May 2015

AbstractThe use of anthracyclines such as doxorubicin (DOX) has improved outcome in cancer patients, yet associated risks of cardiomyopathy have limited their clinical application. DOX-associated cardiotoxicity is frequently irreversible and typically progresses to heart failure (HF) but our understanding of molecular mechanisms underlying this and essential for development of cardioprotective strategies remains largely obscure. As microRNAs (miRNAs) have been shown to play potent regulatory roles in both cardiovascular disease and cancer, we investigated miRNA changes in DOX-induced HF and the alteration of cellular processes downstream. Myocardial miRNA profiling was performed after DOX-induced injury, either via acute application to isolated cardiomyocytes or via chronic exposure in vivo, and compared with miRNA profiles from remodeled hearts following myocardial infarction. The miR-30 family was downregulated in all three models. We describe here that miR-30 act regulating the β-adrenergic pathway, where preferential β1- and β2-adrenoceptor (β1AR and β2AR) direct inhibition is combined with Giα-2 targeting for fine-tuning. Importantly, we show that miR-30 also target the pro-apoptotic gene BNIP3L/NIX. In aggregate, we demonstrate that high miR-30 levels are protective against DOX toxicity and correlate this in turn with lower reactive oxygen species generation. In addition, we identify GATA-6 as a mediator of DOX-associated reductions in miR-30 expression. In conclusion, we describe that DOX causes acute and sustained miR-30 downregulation in cardiomyocytes via GATA-6. miR-30 overexpression protects cardiac cells from DOX-induced apoptosis, and its maintenance represents a potential cardioprotective and anti-tumorigenic strategy for anthracyclines.
Mcl-1 is a key regulator of the ovarian reserve
Authors: Omari S , Waters M , Naranian T , Kim K , Perumalsamy A L , Chi M , Greenblatt E , Moley K H , Opferman J T , Jurisicova A 
Published: May 2015

AbstractA majority of ovarian follicles are lost to natural death, but the disruption of factors involved in maintenance of the oocyte pool results in a further untimely follicular depletion known as premature ovarian failure. The anti-apoptotic B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia-1 (MCL-1) has a pro-survival role in various cell types; however, its contribution to oocyte survival is unconfirmed. We present a phenotypic characterization of oocytes deficient in Mcl-1, and establish its role in maintenance of the primordial follicle (PMF) pool, growing oocyte survival and oocyte quality. Mcl-1 depletion resulted in the premature exhaustion of the ovarian reserve, characterized by early PMF loss because of activation of apoptosis. The increasingly diminished surviving cohort of growing oocytes displayed elevated markers of autophagy and mitochondrial dysfunction. Mcl-1-deficient ovulated oocytes demonstrated an increased susceptibility to cellular fragmentation with activation of the apoptotic cascade. Concomitant deletion of the pro-apoptotic Bcl-2 member Bcl-2-associated X protein (Bax) rescued the PMF phenotype and ovulated oocyte death, but did not prevent the mitochondrial dysfunction associated with Mcl-1 deficiency and could not rescue long-term breeding performance. We thus recognize MCL-1 as the essential survival factor required for conservation of the postnatal PMF pool, growing follicle survival and effective oocyte mitochondrial function.
Integrated digital inverters based on two-dimensional anisotropic ReS2 field-effect transistors
Authors: Liu Erfu , Fu Yajun , Wang Yaojia , Feng Yanqing , Liu Huimei , Wan Xiangang , Zhou Wei , Wang Baigeng , Shao Lubin , Ho Ching-Hwa , Huang Ying-Sheng , Cao Zhengyi , Wang Laiguo , Li Aidong , Zeng Junwen , Song Fengqi , Wang Xinran , Shi Yi , Yuan Hongtao , Hwang Harold Y. , Cui Yi , Miao Feng , Xing Dingyu 
Published: May 2015

AbstractSemiconducting two-dimensional transition metal dichalcogenides are emerging as top candidates for post-silicon electronics. While most of them exhibit isotropic behaviour, lowering the lattice symmetry could induce anisotropic properties, which are both scientifically interesting and potentially useful. Here we present atomically thin rhenium disulfide (ReS2) flakes with unique distorted 1T structure, which exhibit in-plane anisotropic properties. We fabricated monolayer and few-layer ReS2 field-effect transistors, which exhibit competitive performance with large current on/off ratios (∼107) and low subthreshold swings (100 mV per decade). The observed anisotropic ratio along two principle axes reaches 3.1, which is the highest among all known two-dimensional semiconducting materials. Furthermore, we successfully demonstrated an integrated digital inverter with good performance by utilizing two ReS2 anisotropic field-effect transistors, suggesting the promising implementation of large-scale two-dimensional logic circuits. Our results underscore the unique properties of two-dimensional semiconducting materials with low crystal symmetry for future electronic applications.
Microwave spectroscopy of the low-filling-factor bilayer electron solid in a wide quantum well
Authors: Hatke A. T. , Liu Y. , Engel L. W. , Shayegan M. , Pfeiffer L. N. , West K. W. , Baldwin K. W. 
Published: May 2015

AbstractAt the low Landau filling factor termination of the fractional quantum Hall effect series, two-dimensional electron systems exhibit an insulating phase that is understood as a form of pinned Wigner solid. Here we use microwave spectroscopy to probe the transition to the insulator for a wide quantum well sample that can support single-layer or bilayer states depending on its overall carrier density. We find that the insulator exhibits a resonance which is characteristic of a bilayer solid. The resonance also reveals a pair of transitions within the solid, which are not accessible to dc transport measurements. As density is biased deeper into the bilayer solid regime, the resonance grows in specific intensity, and the transitions within the insulator disappear. These behaviours are suggestive of a picture of the insulating phase as an emulsion of liquid and solid components.
Surface lattice resonances and magneto-optical response in magnetic nanoparticle arrays
Authors: Kataja M. , Hakala T. K. , Julku A. , Huttunen M. J. , van Dijken S. , Törmä P. 
Published: May 2015

AbstractStructuring metallic and magnetic materials on subwavelength scales allows for extreme confinement and a versatile design of electromagnetic field modes. This may be used, for example, to enhance magneto-optical responses, to control plasmonic systems using a magnetic field, or to tailor magneto-optical properties of individual nanostructures. Here we show that periodic rectangular arrays of magnetic nanoparticles display surface plasmon modes in which the two directions of the lattice are coupled by the magnetic field-controllable spin–orbit coupling in the nanoparticles. When breaking the symmetry of the lattice, we find that the optical response shows Fano-type surface lattice resonances whose frequency is determined by the periodicity orthogonal to the polarization of the incident field. In striking contrast, the magneto-optical Kerr response is controlled by the period in the parallel direction. The spectral separation of the response for longitudinal and orthogonal excitations provides versatile tuning of narrow and intense magneto-optical resonances.
Female rule in lemurs is ancestral and hormonally mediated
Authors: Petty Joseph M. A. , Drea Christine M. 
Published: May 2015

AbstractFemale social dominance (FSD) over males is unusual in mammals, yet characterizes most Malagasy lemurs, which represent almost 30% of all primates. Despite its prevalence in this suborder, both the evolutionary trajectory and proximate mechanism of FSD remain unclear. Potentially associated with FSD is a suite of behavioural, physiological and morphological traits in females that implicates (as a putative mechanism) ‘masculinization’ via androgen exposure; however, relative to conspecific males, female lemurs curiously show little evidence of raised androgen concentrations. By observing mixed‐sex pairs of related Eulemur species, we identified two key study groups ‐‐ one comprised of species expressing FSD and increased female scent marking, the other comprised of species (from a recently evolved clade) showing equal status between the sexes and the more traditional pattern of sexually dimorphic behaviour. Comparing females from these two groups, we show that FSD is associated with more masculine androgen profiles. Based on the widespread prevalence of male‐like features in female lemurs and a current phylogeny, we suggest that relaxation of hormonally mediated FSD emerged only recently and that female masculinization may be the ancestral lemur condition, an idea that could revolutionize our understanding of the ancient socioecology and evolution of primate social systems.
Structure-based discovery of the first non-covalent inhibitors of Leishmania major tryparedoxin peroxidase by high throughput docking
Authors: Brindisi Margherita , Brogi Simone , Relitti Nicola , Vallone Alessandra , Butini Stefania , Gemma Sandra , Novellino Ettore , Colotti Gianni , Angiulli Gabriella , Di Chiaro Francesco , Fiorillo Annarita , Ilari Andrea , Campiani Giuseppe 
Published: May 2015

AbstractLeishmaniasis is a neglected vector-born disease caused by a protozoan of the genus Leishmania and affecting more than 1.300.000 people worldwide. The couple tryparedoxin/tryparedoxin peroxidase is essential for parasite survival in the host since it neutralizes the hydrogen peroxide produced by macrophages during the infection. Herein we report a study aimed at discovering the first class of compounds able to non-covalently inhibit tryparedoxin peroxidase. We have solved the high-resolution structure of Tryparedoxin peroxidase I from Leishmania major (LmTXNPx) in the reduced state and in fully folded conformation. A first series of compounds able to inhibit LmTXNPx was identified by means of the high throughput docking technique. The inhibitory activity of these compounds was validated by a Horseradish peroxidase-based enzymatic assay and their affinity for LmTXNPx calculated by surface plasmon resonance experiments. On the basis of these results, the analysis of the enzyme-inhibitor docked models allowed us to rationally design and synthesize a series of N,N-disubstituted 3-aminomethyl quinolones. These compounds showed an inhibitory potency against LmTXNPx in the micromolar range. Among them, compound 12 represents the first non-covalent LmTXNPx inhibitor reported to date and could pave the way to the discovery of a new class of drugs against leishmaniasis.
Single-cell evaluation of red blood cell bio-mechanical and nano-structural alterations upon chemically induced oxidative stress
Authors: Sinha Ameya , Chu Trang T. T. , Dao Ming , Chandramohanadas Rajesh 
Published: May 2015

AbstractErythroid cells, specifically red blood cells (RBCs), are constantly exposed to highly reactive radicals during cellular gaseous exchange. Such exposure often exceeds the cells' innate anti-oxidant defense systems, leading to progressive damage and eventual senescence. One of the contributing factors to this process are alterations to hemoglobin conformation and globin binding to red cell cytoskeleton. However, in addition to the aforementioned changes, it is possible that oxidative damage induces critical changes to the erythrocyte cytoskeleton and corresponding bio-mechanical and nano-structural properties of the red cell membrane. To quantitatively characterize how oxidative damage accounts for such changes, we employed single-cell manipulation techniques such as micropipette aspiration and atomic force microscopy (AFM) on RBCs. These investigations demonstrated visible morphological changes upon chemically induced oxidative damage (using hydrogen peroxide, diamide, primaquine bisphosphate and cumene hydroperoxide). Our results provide previously unavailable observations on remarkable changes in red cell cytoskeletal architecture and membrane stiffness due to oxidative damage. Furthermore, we also demonstrate that a pathogen that infects human blood cells, Plasmodium falciparum was unable to penetrate through the oxidant-exposed RBCs that have damaged cytoskeleton and stiffer membranes. This indicates the importance of bio-physical factors pertinent to aged RBCs and it's relevance to malaria infectivity.
In Vitro Study of Surface Modified Poly(ethylene glycol)-Impregnated Sintered Bovine Bone Scaffolds on Human Fibroblast Cells
Authors: Pramanik Sumit , Ataollahi Forough , Pingguan-Murphy Belinda , Oshkour Azim Ataollahi , Osman Noor Azuan Abu 
Published: May 2015

AbstractScaffold design from xenogeneic bone has the potential for tissue engineering (TE). However, major difficulties impede this potential, such as the wide range of properties in natural bone. In this study, sintered cortical bones from different parts of a bovine-femur impregnated with biodegradable poly(ethylene glycol) (PEG) binder by liquid phase adsorption were investigated. Flexural mechanical properties of the PEG-treated scaffolds showed that the scaffold is stiffer and stronger at a sintering condition of 1000°C compared with 900°C.In vitrocytotoxicity of the scaffolds evaluated by Alamar Blue assay and microscopic tests on human fibroblast cells is better at 1000°C compared with that at 900°C. Furthermore,in vitrobiocompatibility and flexural property of scaffolds derived from different parts of a femur depend on morphology and heat-treatment condition. Therefore, the fabricated scaffolds from the distal and proximal parts at 1000°C are potential candidates for hard and soft TE applications, respectively.
Layer-selective half-metallicity in bilayer graphene nanoribbons
Authors: Jeon Gi Wan , Lee Kyu Won , Lee Cheol Eui 
Published: May 2015

AbstractHalf-metallicity recently predicted in the zigzag-edge graphene nanoribbons (ZGNRs) and the hydrogenated carbon nanotubes (CNTs) enables fully spin-polarized electric currents, providing a basis for carbon-based spintronics. In both carbon systems, the half-metallicity arises from the edge-localized electron states under an electric field, lowering the critical electric field Dc for the half-metallicity being an issue in recent works on ZGNRs. A properly chosen direction of the electric field alone has been predicted to significantly reduce Dc in the hydrogenated CNTs, which in this work turned out to be the case in narrow bilayer ZGNRs (biZGNRs). Here, our simple model based on the electrostatic potential difference between the edges predicts that for wide biZGNRs of width greater than ~2.0 nm (10 zigzag carbon chains), only one layer of the biZGNRs becomes half-metallic leaving the other layer insulating as confirmed by our density functional theory (DFT) calculations. The electric field-induced switching of the spin-polarized current path is believed to open a new route to graphene-based spintronics applications.
Unfolding grain size effects in barium titanate ferroelectric ceramics
Authors: Tan Yongqiang , Zhang Jialiang , Wu Yanqing , Wang Chunlei , Koval Vladimir , Shi Baogui , Ye Haitao , McKinnon Ruth , Viola Giuseppe , Yan Haixue 
Published: May 2015

AbstractGrain size effects on the physical properties of polycrystalline ferroelectrics have been extensively studied for decades; however there are still major controversies regarding the dependence of the piezoelectric and ferroelectric properties on the grain size. Dense BaTiO3 ceramics with different grain sizes were fabricated by either conventional sintering or spark plasma sintering using micro- and nano-sized powders. The results show that the grain size effect on the dielectric permittivity is nearly independent of the sintering method and starting powder used. A peak in the permittivity is observed in all the ceramics with a grain size near 1 μm and can be attributed to a maximum domain wall density and mobility. The piezoelectric coefficient d33 and remnant polarization Pr show diverse grain size effects depending on the particle size of the starting powder and sintering temperature. This suggests that besides domain wall density, other factors such as back fields and point defects, which influence the domain wall mobility, could be responsible for the different grain size dependence observed in the dielectric and piezoelectric/ferroelectric properties. In cases where point defects are not the dominant contributor, the piezoelectric constant d33 and the remnant polarization Pr increase with increasing grain size.
Soret Fishnet Metalens Antenna
Authors: Orazbayev Bakhtiyar , Beruete Miguel , Pacheco-Peña Víctor , Crespo Gonzalo , Teniente Jorge , Navarro-Cía Miguel 
Published: May 2015

AbstractAt the expense of frequency narrowing, binary amplitude-only diffractive optical elements emulate refractive lenses without the need of large profiles. Unfortunately, they also present larger Fresnel reflection loss than conventional lenses. This is usually tackled by implementing unattractive cumbersome designs. Here we demonstrate that simplicity is not at odds with performance and we show how the fishnet metamaterial can improve the radiation pattern of a Soret lens. The building block of this advanced Soret lens is the fishnet metamaterial operating in the near-zero refractive index regime with one of the edge layers designed with alternating opaque and transparent concentric rings made of subwavelength holes. The hybrid Soret fishnet metalens retains all the merits of classical Soret lenses such as low profile, low cost and ease of manufacturing. It is designed for the W-band of the millimeter-waves range with a subwavelength focal length FL = 1.58 mm (0.5λ0) aiming at a compact antenna or radar systems. The focal properties of the lens along with its radiation characteristics in a lens antenna configuration have been studied numerically and confirmed experimentally, showing a gain improvement of ~2 dB with respect to a fishnet Soret lens without the fishnet metamaterial.
Metastatic breast cancer cells in lymph nodes increase nodal collagen density
Authors: Rizwan Asif , Bulte Camille , Kalaichelvan Anusha , Cheng Menglin , Krishnamachary Balaji , Bhujwalla Zaver M. , Jiang Lu , Glunde Kristine 
Published: May 2015

AbstractThe most life-threatening aspect of breast cancer is the occurrence of metastatic disease. The tumor draining lymph nodes typically are the first sites of metastasis in breast cancer. Collagen I fibers and the extracellular matrix have been implicated in breast cancer to form avenues for metastasis. In this study, we have investigated extracellular matrix molecules such as collagen I fibers in the lymph nodes of mice bearing orthotopic human breast cancer xenografts. The lymph nodes in mice with metastatic MDA-MB-231 and SUM159 tumor xenografts and tumor xenografts grown from circulating tumor cell lines displayed an increased collagen I density compared to mice with no tumor and mice with non-metastatic T-47D and MCF-7 tumor xenografts. These results suggest that cancer cells that have metastasized to the lymph nodes can modify the extracellular matrix components of these lymph nodes. Clinically, collagen density in the lymph nodes may be a good marker for identifying lymph nodes that have been invaded by breast cancer cells.
Derivation and characterization of human embryonic stem cells on human amnion epithelial cells
Authors: Lai Dongmei , Wang Yongwei , Sun Jian , Chen Yifei , Li Ting , Wu Yi , Guo Lihe , Wei Chunsheng 
Published: May 2015

AbstractCulture conditions that support the growth of undifferentiated human embryonic stem cells (hESCs) have already been established using primary human amnion epithelial cells (hAECs) as an alternative to traditional mitotically inactivated mouse embryonic fibroblasts (MEFs). In the present work, inner cell masses (ICM) were isolated from frozen embryos obtained as donations from couples undergoing in vitro fertilization (IVF) treatment and four new hESC lines were derived using hAECs as feeder cells. This feeder system was able to support continuous growth of what were, according to their domed shape and markers, undifferentiated naïve-like hESCs. Their pluripotent potential were also demonstrated by embryoid bodies developing to the expected three germ layers in vitro and the productions of teratoma in vivo. The cell lines retained their karyotypic integrity for over 35 passages. Transmission electron microscopy (TEM) indicated that these newly derived hESCs consisted mostly of undifferentiated cells with large nuclei and scanty cytoplasm. The new hESCs cultured on hAECs showed distinct undifferentiated characteristics in comparison to hESCs of the same passage maintained on MEFs. This type of optimized culture system may provide a useful platform for establishing clinical-grade hESCs and assessing the undifferentiated potential of hESCs.