bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of glycogen synthase kinase 3β promotes autophagy to protect mice from acute liver failure mediated by peroxisome proliferator-activated receptor α
Authors: Ren F , Zhang L , Zhang X , Shi H , Wen T , Bai L , Zheng S , Chen Y , Chen D , Li L , Duan Z
Published: March 2016

Our previous studies have demonstrated that inhibition of glycogen synthase kinase 3β (GSK3β) activity protects mice from acute liver failure (ALF), whereas its protective and regulatory mechanism remains elusive. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of the present study was to test the hypothesis that inhibition of GSK3β mediates autophagy to inhibit liver inflammation and protect against ALF. In ALF mice model induced by d-galactosamine (d-GalN) and lipopolysaccharide (LPS), autophagy was repressed compared with normal control, and d-GalN/LPS can directly induce autophagic flux in the progression of ALF mice. Autophagy activation by rapamycin protected against liver injury and its inhibition by 3-methyladenine (3-MA) or autophagy gene 7 (Atg7) small interfering RNA (siRNA) exacerbated liver injury. The protective effect of GSK3β inhibition on ALF mice model depending on the induction of autophagy, because that inhibition of GSK3β promoted autophagy in vitro and in vivo, and inhibition of autophagy reversed liver protection and inflammation of GSK3β inhibition. Furthermore, inhibition of GSK3β increased the expression of peroxisome proliferator-activated receptor α (PPARα), and the downregulated PPARα by siRNA decreased autophagy induced by GSK3β inhibition. More importantly, the expressions of autophagy-related gene and PPARα are significantly downregulated and the activity of GSK3β is significantly upregulated in liver of ALF patients with hepatitis B virus. Thus, we have demonstrated the new pathological mechanism of ALF that the increased GSK3β activity suppresses autophagy to promote the occurrence and development of ALF by inhibiting PPARα pathway.
miR-141 is involved in BRD7-mediated cell proliferation and tumor formation through suppression of the PTEN/AKT pathway in nasopharyngeal carcinoma
Authors: Liu Y , Zhao R , Wang H , Luo Y , Wang X , Niu W , Zhou Y , Wen Q , Fan S , Li X , Xiong W , Ma J , Li X , Tan M , Li G , Zhou M
Published: March 2016

Bromodomain containing 7 (BRD7) was identified as a nuclear transcriptional regulatory factor. BRD7 functions as a tumor suppressor in multiple cancers, including nasopharyngeal carcinoma (NPC). In this study, we reported a novel mechanism of BRD7 in NPC progression. We demonstrated that the expression of miR-141 was remarkably increased in NPC tissues and was negatively correlated with the expression of BRD7 and the survival rate of NPC patients. Decreased expression levels of miR-141, including the primary, the precursor and the mature forms of miR-141, were found in BRD7-overexpressing HEK293, 5-8F and HNE1 cells compared the control cells, while there was no obvious effect on the expression levels of the two critical enzymes Drosha and Dicer. BRD7 can negatively regulate the promoter activity of miR-141, while no obvious binding site of BRD7 was found in the potential promoter region of miR-141. Moreover, ectopic expression of miR-141 can significantly promote cell proliferation and inhibit apoptosis in NPC, and rescuing the expression of miR-141 in BRD7-overexpressing NPC cells could partially reverse the tumor suppressive effect of BRD7 on cell proliferation and tumor growth in vitro and in vivo. Furthermore, the activation of the PTEN/AKT pathway mediated by the overexpression of BRD7 could be inhibited by rescuing the expression of miR-141, which accordingly results in the partial restoration of cell proliferation and tumor growth. Our findings demonstrate that the BRD7/miR-141/PTEN/AKT axis has critical roles in the progression of NPC and provide some promising targets for the diagnosis and treatment of NPC.
Sodium–hydrogen exchanger NHA1 and NHA2 control sperm motility and male fertility
Authors: Chen Su-Ren , Chen M , Deng S-L , Hao X-X , Wang X-X , Liu Y-X
Published: March 2016

Our previous work identified NHA1, a testis-specific sodium–hydrogen exchanger, is specifically localized on the principal piece of mouse sperm flagellum. Our subsequent study suggested that the number of newborns and fertility rate of NHA1-vaccinated female mice are significantly stepped down. In order to define the physiological function of NHA1 in spermatozoa, we generated Nha1Fx/Fx, Zp3-Cre (hereafter called Nha1 cKO) mice and found that Nha1 cKO males were viable and subfertile with reduced sperm motility. Notably, cyclic AMP (cAMP) synthesis by soluble adenylyl cyclase (sAC) was attenuated in Nha1 cKO spermatozoa and cAMP analogs restored sperm motility. Similar to Nha1 cKO males, Nha2Fx/Fx, Zp3-Cre (hereafter called Nha2 cKO) male mice were subfertile, indicating these two Nha genes may be functionally redundant. Furthermore, we demonstrated that male mice lacking Nha1 and Nha2 genes (hereafter called Nha1/2 dKO mice) were completely infertile, with severely diminished sperm motility owing to attenuated sAC-cAMP signaling. Importantly, principal piece distribution of NHA1 in spermatozoa are phylogenetically conserved in spermatogenesis. Collectively, our data revealed that NHA1 and NHA2 function as a key sodium–hydrogen exchanger responsible for sperm motility after leaving the cauda epididymidis.
Understanding silicate hydration from quantitative analyses of hydrating tricalcium silicates
Authors: Pustovgar Elizaveta , Sangodkar Rahul P. , Andreev Andrey S. , Palacios Marta , Chmelka Bradley F. , Flatt Robert J. , d’Espinose de Lacaillerie Jean-Baptiste
Published: March 2016

Silicate hydration is prevalent in natural and technological processes, such as, mineral weathering, glass alteration, zeolite syntheses and cement hydration. Tricalcium silicate (Ca3SiO5), the main constituent of Portland cement, is amongst the most reactive silicates in water. Despite its widespread industrial use, the reaction of Ca3SiO5with water to form calcium-silicate-hydrates (C-S-H) still hosts many open questions. Here, we show that solid-state nuclear magnetic resonance measurements of29Si-enriched triclinic Ca3SiO5enable the quantitative monitoring of the hydration process in terms of transient local molecular composition, extent of silicate hydration and polymerization. This provides insights on the relative influence of surface hydroxylation and hydrate precipitation on the hydration rate. When the rate drops, the amount of hydroxylated Ca3SiO5decreases, thus demonstrating the partial passivation of the surface during the deceleration stage. Moreover, the relative quantities of monomers, dimers, pentamers and octamers in the C-S-H structure are measured.
Geometry-invariant resonant cavities
Authors: Liberal I. , Mahmoud A. M. , Engheta N.
Published: March 2016

Resonant cavities are one of the basic building blocks in various disciplines of science and technology, with numerous applications ranging from abstract theoretical modelling to everyday life devices. The eigenfrequencies of conventional cavities are a function of their geometry, and, thus, the size and shape of a resonant cavity is selected to operate at a specific frequency. Here we demonstrate theoretically the existence of geometry-invariant resonant cavities, that is, resonators whose eigenfrequencies are invariant with respect to geometrical deformations of their external boundaries. This effect is obtained by exploiting the unusual properties of zero-index metamaterials, such as epsilon-near-zero media, which enable decoupling of the temporal and spatial field variations in the lossless limit. This new class of resonators may inspire alternative design concepts, and it might lead to the first generation of deformable resonant devices.
VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread
Authors: Li Xiujuan , Padhan Narendra , Sjöström Elisabet O. , Roche Francis P. , Testini Chiara , Honkura Naoki , Sáinz-Jaspeado Miguel , Gordon Emma , Bentley Katie , Philippides Andrew , Tolmachev Vladimir , Dejana Elisabetta , Stan Radu V. , Vestweber Dietmar , Ballmer-Hofer Kurt , Betsholtz Christer , Pietras Kristian , Jansson Leif , Claesson-Welsh Lena
Published: March 2016

The specific role of VEGFA-induced permeability and vascular leakage in physiology and pathology has remained unclear. Here we show that VEGFA-induced vascular leakage depends on signalling initiated via the VEGFR2 phosphosite Y949, regulating dynamic c-Src and VE-cadherin phosphorylation. Abolished Y949 signalling in the mouse mutant Vegfr2Y949F/Y949F leads to VEGFA-resistant endothelial adherens junctions and a block in molecular extravasation. Vessels in Vegfr2Y949F/Y949F mice remain sensitive to inflammatory cytokines, and vascular morphology, blood pressure and flow parameters are normal. Tumour-bearing Vegfr2Y949F/Y949F mice display reduced vascular leakage and oedema, improved response to chemotherapy and, importantly, reduced metastatic spread. The inflammatory infiltration in the tumour micro-environment is unaffected. Blocking VEGFA-induced disassembly of endothelial junctions, thereby suppressing tumour oedema and metastatic spread, may be preferable to full vascular suppression in the treatment of certain cancer forms.
Implementation of quantum and classical discrete fractional Fourier transforms
Authors: Weimann Steffen , Perez-Leija Armando , Lebugle Maxime , Keil Robert , Tichy Malte , Gräfe Markus , Heilmann René , Nolte Stefan , Moya-Cessa Hector , Weihs Gregor , Christodoulides Demetrios N. , Szameit Alexander
Published: March 2016

Fourier transforms, integer and fractional, are ubiquitous mathematical tools in basic and applied science. Certainly, since the ordinary Fourier transform is merely a particular case of a continuous set of fractional Fourier domains, every property and application of the ordinary Fourier transform becomes a special case of the fractional Fourier transform. Despite the great practical importance of the discrete Fourier transform, implementation of fractional orders of the corresponding discrete operation has been elusive. Here we report classical and quantum optical realizations of the discrete fractional Fourier transform. In the context of classical optics, we implement discrete fractional Fourier transforms of exemplary wave functions and experimentally demonstrate the shift theorem. Moreover, we apply this approach in the quantum realm to Fourier transform separable and path-entangled biphoton wave functions. The proposed approach is versatile and could find applications in various fields where Fourier transforms are essential tools.
Roquin recognizes a non-canonical hexaloop structure in the 3′-UTR of Ox40
Authors: Janowski Robert , Heinz Gitta A. , Schlundt Andreas , Wommelsdorf Nina , Brenner Sven , Gruber Andreas R. , Blank Michael , Buch Thorsten , Buhmann Raymund , Zavolan Mihaela , Niessing Dierk , Heissmeyer Vigo , Sattler Michael
Published: March 2016

The RNA-binding protein Roquin is required to prevent autoimmunity. Roquin controls T-helper cell activation and differentiation by limiting the induced expression of costimulatory receptors such as tumor necrosis factor receptor superfamily 4 (Tnfrs4 or Ox40). A constitutive decay element (CDE) with a characteristic triloop hairpin was previously shown to be recognized by Roquin. Here we use SELEX assays to identify a novel U-rich hexaloop motif, representing an alternative decay element (ADE). Crystal structures and NMR data show that the Roquin-1 ROQ domain recognizes hexaloops in the SELEX-derived ADE and in an ADE-like variant present in the Ox40 3′-UTR with identical binding modes. In cells, ADE-like and CDE-like motifs cooperate in the repression of Ox40 by Roquin. Our data reveal an unexpected recognition of hexaloop cis elements for the posttranscriptional regulation of target messenger RNAs by Roquin.
Cortical contributions to the auditory frequency-following response revealed by MEG
Authors: Coffey Emily B. J. , Herholz Sibylle C. , Chepesiuk Alexander M. P. , Baillet Sylvain , Zatorre Robert J.
Published: March 2016

The auditory frequency-following response (FFR) to complex periodic sounds is used to study the subcortical auditory system, and has been proposed as a biomarker for disorders that feature abnormal sound processing. Despite its value in fundamental and clinical research, the neural origins of the FFR are unclear. Using magnetoencephalography, we observe a strong, right-asymmetric contribution to the FFR from the human auditory cortex at the fundamental frequency of the stimulus, in addition to signal from cochlear nucleus, inferior colliculus and medial geniculate. This finding is highly relevant for our understanding of plasticity and pathology in the auditory system, as well as higher-level cognition such as speech and music processing. It suggests that previous interpretations of the FFR may need re-examination using methods that allow for source separation.
Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA
Authors: Kettunen Johannes , Demirkan Ayşe , Würtz Peter , Draisma Harmen H.M. , Haller Toomas , Rawal Rajesh , Vaarhorst Anika , Kangas Antti J. , Lyytikäinen Leo-Pekka , Pirinen Matti , Pool René , Sarin Antti-Pekka , Soininen Pasi , Tukiainen Taru , Wang Qin , Tiainen Mika , Tynkkynen Tuulia , Amin Najaf , Zeller Tanja , Beekman Marian , Deelen Joris , van Dijk Ko Willems , Esko Tõnu , Hottenga Jouke-Jan , van Leeuwen Elisabeth M , Lehtimäki Terho , Mihailov Evelin , Rose Richard J. , de Craen Anton J.M. , Gieger Christian , Kähönen Mika , Perola Markus , Blankenberg Stefan , Savolainen Markku J. , Verhoeven Aswin , Viikari Jorma , Willemsen Gonneke , Boomsma Dorret I. , van Duijn Cornelia M. , Eriksson Johan , Jula Antti , Järvelin Marjo-Riitta , Kaprio Jaakko , Metspalu Andres , Raitakari Olli , Salomaa Veikko , Slagboom P. Eline , Waldenberger Melanie , Ripatti Samuli , Ala-Korpela Mika
Published: March 2016

Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk.
Age and gender specific estimation of visceral adipose tissue amounts from radiological images in morbidly obese patients
Authors: Linder Nicolas , Schaudinn Alexander , Garnov Nikita , Blüher Matthias , Dietrich Arne , Schütz Tatjana , Lehmann Stefanie , Retschlag Ulf , Karlas Thomas , Kahn Thomas , Busse Harald
Published: March 2016

Image-based quantifications of visceral adipose tissue (VAT) volumes from segmented VAT areas are increasingly considered for risk assessment in obese patients. The goal of this study was to determine the power of partial VAT areas to predict total VAT volume in morbidly obese patients (BMI > 40 kg/m2) as a function of gender, age and anatomical landmarks. 130 morbidly obese patients (mean BMI 46.5 kg/m2; 94 females) underwent IRB-approved MRI. Total VAT volumes were predicted from segmented VAT areas (of single or five adjacent slices) at common axial landmark levels and compared with the measured ones (VVAT-T, about 40 slices between diaphragm and pelvic floor). Standard deviations σ1 and σ5 of the respective VAT volume differences served as measures of agreement. Mean VVAT-T was 4.9 L for females and 8.1 L for males. Best predictions were found at intervertebral spaces L3-L4 for females (σ5 = 688 ml, σ1 = 832 ml) and L1-L2 for males (σ5 = 846 ml, σ1 = 992 ml), irrespective of age. In conclusion, VAT volumes in morbidly obese patients can be reliably predicted by multiplying the segmented VAT area at a gender-specific lumbar reference level with a fixed scaling factor and effective slice thickness.
Microsatellite alteration in head and neck squamous cell carcinoma patients from a betel quid-prevalent region
Authors: Lin Jin-Ching , Wang Chen-Chi , Jiang Rong-San , Wang Wen-Yi , Liu Shih-An
Published: March 2016

We investigated the frequency of microsatellite alteration and their impact on survival in head and neck squamous cell carcinoma patients from an endemic betel quid chewing area. We collected 116 head and neck squamous cell carcinoma specimens along with corresponding surgical margins which were confirmed by pathological examination. Ten oligonucleotide markers were chosen for the assessment of microsatellite alteration. The specimens were amplified by polymerase chain reaction followed by automatic fragment analysis. There were 44 specimens (37.9%) with microsatellite instability (MSI) in at least one marker while more than half of the specimens (n = 68, 58.6%) had loss of heterozygosity (LOH) in at least one marker. Though MSI/LOH was not correlated with the survival of head and neck squamous cell carcinoma patients, presence of MSI in the tumor-free surgical margins was associated with local recurrence (odds ratio: 15.14; 95% confidence interval: 6.451 ~ 35.53; P < 0.001). Genomic assessment of surgical margin can help surgeons to identify head and neck squamous cell carcinoma patients who are at risk of developing local recurrence in a betel quid-prevalent region.
From morphology to biochemical state – intravital multiphoton fluorescence lifetime imaging of inflamed human skin
Authors: Huck Volker , Gorzelanny Christian , Thomas Kai , Getova Valentina , Niemeyer Verena , Zens Katharina , Unnerstall Tim R. , Feger Julia S. , Fallah Mohammad A. , Metze Dieter , Ständer Sonja , Luger Thomas A. , Koenig Karsten , Mess Christian , Schneider Stefan W.
Published: March 2016

The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients’ bedsides. These ‘optical biopsies’ generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT-FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy.
Strengthened PAN-based carbon fibers obtained by slow heating rate carbonization
Authors: Kim Min-A , Jang Dawon , Tejima Syogo , Cruz-Silva Rodolfo , Joh Han-Ik , Kim Hwan Chul , Lee Sungho , Endo Morinobu
Published: March 2016

Large efforts have been made over the last 40 years to increase the mechanical strength of polyacrylonitrile (PAN)-based carbon fibers (CFs) using a variety of chemical or physical protocols. In this paper, we report a new method to increase CFs mechanical strength using a slow heating rate during the carbonization process. This new approach increases both the carbon sp3 bonding and the number of nitrogen atoms with quaternary bonding in the hexagonal carbon network. Theoretical calculations support a crosslinking model promoted by the interstitial carbon atoms located in the graphitic interlayer spaces. The improvement in mechanical performance by a controlled crosslinking between the carbon hexagonal layers of the PAN based CFs is a new concept that can contribute further in the tailoring of CFs performance based on the understanding of their microstructure down to the atomic scale.
Sn/Be Sequentially co-doped Hematite Photoanodes for Enhanced Photoelectrochemical Water Oxidation: Effect of Be2+ as co-dopant
Authors: Annamalai Alagappan , Lee Hyun Hwi , Choi Sun Hee , Lee Su Yong , Gracia-Espino Eduardo , Subramanian Arunprabaharan , Park Jaedeuk , Kong Ki-jeong , Jang Jum Suk
Published: March 2016

For ex-situ co-doping methods, sintering at high temperatures enables rapid diffusion of Sn4+ and Be2+ dopants into hematite (α–Fe2O3) lattices, without altering the nanorod morphology or damaging their crystallinity. Sn/Be co-doping results in a remarkable enhancement in photocurrent (1.7 mA/cm2) compared to pristine α–Fe2O3 (0.7 mA/cm2), and Sn4+ mono-doped α-Fe2O3 photoanodes (1.0 mA/cm2). From first-principles calculations, we found that Sn4+ doping induced a shallow donor level below the conduction band minimum, which does not contribute to increase electrical conductivity and photocurrent because of its localized nature. Additionally, Sn4+-doping induce local micro-strain and a decreased Fe-O bond ordering. When Be2+ was co-doped with Sn4+-doped α–Fe2O3 photoanodes, the conduction band recovered its original state, without localized impurities peaks, also a reduction in micro-strain and increased Fe-O bond ordering is observed. Also the sequence in which the ex-situ co-doping is carried out is very crucial, as Be/Sn co-doping sequence induces many under-coordinated O atoms resulting in a higher micro-strain and lower charge separation efficiency resulting undesired electron recombination. Here, we perform a detailed systematic characterization using XRD, FESEM, XPS and comprehensive electrochemical and photoelectrochemical studies, along with sophisticated synchrotron diffraction studies and extended X-ray absorption fine structure.
Integrating Epitaxial-Like Pb(Zr,Ti)O3 Thin-Film into Silicon for Next-Generation Ferroelectric Field-Effect Transistor
Authors: Park Jae Hyo , Kim Hyung Yoon , Jang Gil Su , Seok Ki Hwan , Chae Hee Jae , Lee Sol Kyu , Kiaee Zohreh , Joo Seung Ki
Published: March 2016

The development of ferroelectric random-access memory (FeRAM) technology with control of grain boundaries would result in a breakthrough for new nonvolatile memory devices. The excellent piezoelectric and electrical properties of bulk ferroelectrics are degraded when the ferroelectric is processed into thin films because the grain boundaries then form randomly. Controlling the nature of nucleation and growth are the keys to achieving a good crystalline thin-film. However, the sought after high-quality ferroelectric thin-film has so far been thought to be impossible to make, and research has been restricted to atomic-layer deposition which is extremely expensive and has poor reproducibility. Here we demonstrate a novel epitaxial-like growth technique to achieve extremely uniform and large rectangular-shaped grains in thin-film ferroelectrics by dividing the nucleation and growth phases. With this technique, it is possible to achieve 100-μm large uniform grains, even made available on Si, which is large enough to fabricate a field-effect transistor in each grain. The electrical and reliability test results, including endurance and retention test results, were superior to other FeRAMs reported so far and thus the results presented here constitute the first step toward the development of FeRAM using epitaxial-like ferroelectric thin-films.
Extract of Vernonia condensata, Inhibits Tumor Progression and Improves Survival of Tumor-allograft Bearing Mouse
Authors: Thomas Elizabeth , Gopalakrishnan Vidya , Somasagara Ranganatha R. , Choudhary Bibha , Raghavan Sathees C.
Published: March 2016

Medicinal plants are considered as one of the ideal sources for cancer therapy due to their bioactive contents and low toxicity to humans. Vernonia genus is one of the common medicinal plants, which has wide spread usage in food and medicine. However, there are limited studies to explore its anticancer properties. In the current study, we have used Vernonia condensata, to explore its anticancer activity using various approaches. Here, we show that extract prepared from Vernonia condensata (VCE) exhibits cytotoxic properties against various cancer cells in a dose- and time-dependent manner. Interestingly, when treated with VCE, there was no significant cytotoxicity in peripheral blood mononuclear cells (PBMCs). Flow cytometry analysis revealed that although VCE induced cell death, arrest was not observed. VCE treatment led to disruption of mitochondrial membrane potential in a concentration dependent manner resulting in activation of apoptosis culminating in cell death. Immunoblotting studies revealed that VCE activated intrinsic pathway of apoptosis. More importantly, VCE treatment resulted in tumor regression leading to significant enhancement in life span in treated mice, without showing any detectable side effects. Therefore, for the first time our study reveals the potential of extract from Vernonia condensata to be used as an anticancer agent.
Structure and dynamics of optically directed self-assembly of nanoparticles
Authors: Roy Debjit , Mondal Dipankar , Goswami Debabrata
Published: March 2016

Self-assembly of nanoparticles leading to the formation of colloidal clusters often serves as the representative analogue for understanding molecular assembly. Unravelling the in situ structure and dynamics of such clusters in liquid suspensions is highly challenging. Presently colloidal clusters are first isolated from their generating environment and then their structures are probed by light scattering methods. In order to measure the in situ structure and dynamics of colloidal clusters, we have generated them using the high-repetition-rate femtosecond laser pulse optical tweezer. Since the constituent of our dimer, trimer or tetramer clusters are 250 nm radius two-photon resonant fluorophore coated nanospheres under the optical trap, they inherently produce Two-Photon Fluorescence, which undergo intra-nanosphere Fluorescence Energy Transfer. This unique energy transfer signature, in turn, enables us to visualize structures and orientations of these colloidal clusters during the process of their formation and subsequent dynamics in a liquid suspension. We also show that due to shape-birefringence, orientation and structural control of these colloidal clusters are possible as the polarization of the trapping laser is changed from linear to circular. We thus report important progress in sampling the smallest possible aggregates of nanoparticles, dimers, trimers or tetramers, formed early in the self-assembly process.
Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive
Authors: Fiore Vincenzo G. , Rigoli Francesco , Stenner Max-Philipp , Zaehle Tino , Hirth Frank , Heinze Hans-Jochen , Dolan Raymond J.
Published: March 2016

Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model.
Constructive influence of the induced electron pairing on the Kondo state
Authors: Domański T. , Weymann I. , Barańska M. , Górski G.
Published: March 2016

Superconducting order and magnetic impurities are usually detrimental to each other. We show, however, that in nanoscopic objects the induced electron pairing can have constructive influence on the Kondo effect originating from the effective screening interactions. Such situation is possible at low temperatures in the quantum dots placed between the conducting and superconducting reservoirs, where the proximity induced electron pairing cooperates with the correlations amplifying the spin-exchange potential. The emerging Abrikosov-Suhl resonance, which is observable in the Andreev conductance, can be significantly enhanced by increasing the coupling to superconducting lead. We explain this intriguing tendency within the Anderson impurity model using: the generalized Schrieffer-Wolff canonical transformation, the second order perturbative treatment of the Coulomb repulsion and the nonperturbative numerical renormalization group calculations. We also provide hints for experimental observability of this phenomenon.
Amyloid formation of growth hormone in presence of zinc: Relevance to its storage in secretory granules
Authors: Jacob Reeba S. , Das Subhadeep , Ghosh Saikat , Anoop Arunagiri , Jha Narendra Nath , Khan Tuhin , Singru Praful , Kumar Ashutosh , Maji Samir K.
Published: March 2016

Amyloids are cross-β-sheet fibrillar aggregates, associated with various human diseases and native functions such as protein/peptide hormone storage inside secretory granules of neuroendocrine cells. In the current study, using amyloid detecting agents, we show that growth hormone (GH) could be stored as amyloid in the pituitary of rat. Moreover, to demonstrate the formation of GH amyloidin vitro, we studied various conditions (solvents, glycosaminoglycans, salts and metal ions) and found that in presence of zinc metal ions (Zn(II)), GH formed short curvy fibrils. The amyloidogenic nature of these fibrils was examined by Thioflavin T binding, Congo Red binding, transmission electron microscopy and X-ray diffraction. Our biophysical studies also suggest that Zn(II) initiates the early oligomerization of GH that eventually facilitates the fibrillation process. Furthermore, using immunofluorescence study of pituitary tissue, we show that GH in pituitary significantly co-localizes with Zn(II), suggesting the probable role of zinc in GH aggregation within secretory granules. We also found that GH amyloid formedin vitrois capable of releasing monomers. The study will help to understand the possible mechanism of GH storage, its regulation and monomer release from the somatotrophs of anterior pituitary.
N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release
Authors: Richter Frank , Koulen Peter , Kaja Simon
Published: March 2016

Cortical spreading depression (CSD), a wave of neuronal depolarization in the cerebral cortex following traumatic brain injury or cerebral ischemia, significantly aggravates brain damage. Here, we tested whether N-palmitoylethanolamine (PEA), a substance that effectively reduces lesion volumes and neurological deficits after ischemic stroke, influences CSD. CSD was elicited chemically in adult rats and occurrence, amplitude, duration and propagation velocity of CSD was determined prior to and for 6 hours after intraperitoneal injection of PEA. The chosen systemic administration of PEA stabilized the amplitude of CSD for at least four hours and prevented the run-down of amplitudes that is typically observed and was also seen in untreated controls. The propagation velocity of the CSD waves was unaltered indicating stable neuronal excitability. The stabilization of CSD amplitudes by PEA indicates that inhibition or prevention of CSD does not underlie PEA’s profound neuroprotective effect. Rather, PEA likely inhibits proinflammatory cytokine release thereby preventing the run-down of CSD amplitudes. This contribution of PEA to the maintenance of neuronal excitability in healthy tissue during CSD potentially adds to neuroprotection outside a damaged area, while other mechanisms control PEA-mediated neuroprotection in damaged tissue resulting from traumatic brain injury or cerebral ischemia.
Corneal Epithelium Thickness Profile in 614 Normal Chinese Children Aged 7–15 Years Old
Authors: Ma Yingyan , He Xiangui , Zhu Xiaofeng , Lu Lina , Zhu Jianfeng , Zou Haidong
Published: March 2016

The purpose of the study is to describe the values and distribution of corneal epithelium thickness (CET) in normal Chinese school-aged children, and to explore associated factors with CET. CET maps were measured by Fourier-domain optical coherence tomography (FD-OCT) in normal Chinese children aged 7 to 15 years old from two randomly selected schools in Shanghai, China. Children with normal intraocular pressure were further examined for cycloplegic autorefraction, corneal curvature radius (CCR) and axial length. Central (2-mm diameter area), para-central (2- to 5-mm diameter area), and peripheral (5- to 6-mm diameter area) CET in the superior, superotemporal, temporal, inferotemporal, inferior, inferonasal, nasal, superonasal cornea; minimum, maximum, range, and standard deviation of CET within the 5-mm diameter area were recorded. The CET was thinner in the superior than in the inferior and was thinner in the temporal than in the nasal. The maximum CET was located in the inferior zone, and the minimum CET was in the superior zone. A thicker central CET was associated with male gender (p = 0.009) and older age (p = 0.037) but not with CCR (p = 0.061), axial length (p = 0.253), or refraction (p = 0.351) in the multiple regression analyses. CCR, age, and gender were correlated with para-central and peripheral CET.
Paclitaxel-loaded phosphonated calixarene nanovesicles as a modular drug delivery platform
Authors: Mo Jingxin , Eggers Paul K. , Yuan Zhi-xiang , Raston Colin L. , Lim Lee Yong
Published: March 2016

A modular p-phosphonated calix[4]arene vesicle (PCV) loaded with paclitaxel (PTX) and conjugated with folic acid as a cancer targeting ligand has been prepared using a thin film-sonication method. It has a pH-responsive capacity to trigger the release of the encapsulated PTX payload under mildly acidic conditions. PTX-loaded PCV conjugated with alkyne-modified PEG-folic acid ligands prepared via click ligation (fP-PCVPTX) has enhanced potency against folate receptor (FR)-positive SKOV-3 ovarian tumour cells over FR-negative A549 lung tumour cells. Moreover, fP-PCVPTX is also four times more potent than the non-targeting PCVPTX platform towards SKOV-3 cells. Overall, as a delivery platform the PCVs have the potential to enhance efficacy of anticancer drugs by targeting a chemotherapeutic payload specifically to tumours and triggering the release of the encapsulated drug in the vicinity of cancer cells.
Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis
Authors: Ohta Tomokazu , Sugiyama Masanaka , Hemmi Hiroaki , Yamazaki Chihiro , Okura Soichiro , Sasaki Izumi , Fukuda Yuri , Orimo Takashi , Ishii Ken J. , Hoshino Katsuaki , Ginhoux Florent , Kaisho Tsuneyasu
Published: March 2016

Intestinal immune homeostasis requires dynamic crosstalk between innate and adaptive immune cells. Dendritic cells (DCs) exist as multiple phenotypically and functionally distinct sub-populations within tissues, where they initiate immune responses and promote homeostasis. In the gut, there exists a minor DC subset defined as CD103+CD11b− that also expresses the chemokine receptor XCR1. In other tissues, XCR1+ DCs cross-present antigen and contribute to immunity against viruses and cancer, however the roles of XCR1+ DCs and XCR1 in the intestine are unknown. We showed that mice lacking XCR1+ DCs are specifically deficient in intraepithelial and lamina propria (LP) T cell populations, with remaining T cells exhibiting an atypical phenotype and being prone to death and are also more susceptible to chemically-induced colitis. Mice deficient in either XCR1 or its ligand, XCL1, similarly possess diminished intestinal T cell populations and an accumulation of XCR1+ DCs in the gut. Combined with transcriptome and surface marker expression analysis, these observations lead us to hypothesise that T cell-derived XCL1 facilitates intestinal XCR1+ DC activation and migration and that XCR1+ DCs in turn provide support for T cell survival and function. Thus XCR1+ DCs and the XCR1/XCL1 chemokine axis have previously-unappreciated roles in intestinal immune homeostasis.
Ingestion of Bt corn pollen containing Cry1Ab/2Aj or Cry1Ac does not harm Propylea japonica larvae
Authors: Liu Yanmin , Liu Qingsong , Wang Yanan , Chen Xiuping , Song Xinyuan , Romeis Jörg , Li Yunhe , Peng Yufa
Published: March 2016

Propylea japonica(Thunberg) (Coleoptera: Coccinellidae) is a prevalent pollen consumer in corn fields and is therefore exposed to insecticidal proteins contained in the pollen of insect-resistant transgenic corn cultivars expressing Cry proteins derived fromBacillus thuringiensis(Bt). In the present study, the potential effect of Cry1Ab/2Aj- or Cry1Ac-containing transgenicBtcorn pollen on the fitness ofP. japonicalarvae was evaluated. The results show that the larval developmental time was significantly shorter whenP. japonicalarvae were fed pollen fromBtcorn cultivars rather than control pollen but that pupation rate, eclosion rate, and adult fresh weight were not significantly affected. In the feeding experiments, the stability of the Cry proteins in the food sources was confirmed. WhenBtcorn pollen passed through the gut ofP. japonica, 23% of Cry1Ab/2Aj was digested. The results demonstrate that consumption ofBtcorn pollen containing Cry1Ab/2Aj or Cry1Ac has no detrimental effect onP. japonicalarvae; the shortened developmental time of larvae that consumed these proteins was likely attributable to unknown differences in the nutritional composition between theBt-transgenic and control corn pollen.
The chemosensory receptors of codling moth Cydia pomonella–expression in larvae and adults
Authors: Walker William B. , Gonzalez Francisco , Garczynski Stephen F. , Witzgall Peter
Published: March 2016

Olfaction and gustation play critical roles in the life history of insects, mediating vital behaviors such as food, mate and host seeking. Chemosensory receptor proteins, including odorant receptors (ORs), gustatory receptors (GRs) and ionotropic receptors (IRs) function to interface the insect with its chemical environment. Codling moth, Cydia pomonella, is a worldwide pest of apple, pear and walnut and behavior-modifying semiochemicals are used for environmentally safe control. We produced an Illumina-based transcriptome from antennae of males and females as well as neonate head tissue, affording a qualitative and quantitative analysis of the codling moth chemosensory receptor repertoire. We identified 58 ORs, 20 GRs and 21 IRs and provide a revised nomenclature that is consistent with homologous sequences in related species. Importantly, we have identified several OR transcripts displaying sex-biased expression in adults, as well as larval-enriched transcripts. Our analyses have expanded annotations of the chemosensory receptor gene families and provide first-time transcript abundance estimates for codling moth. The results presented here provide a strong foundation for future work on codling moth behavioral physiology and ecology at the molecular level and may lead to the development of more precise biorational control strategies.
Miniature Compressive Ultra-spectral Imaging System Utilizing a Single Liquid Crystal Phase Retarder
Authors: August Isaac , Oiknine Yaniv , AbuLeil Marwan , Abdulhalim Ibrahim , Stern Adrian
Published: March 2016

Spectroscopic imaging has been proved to be an effective tool for many applications in a variety of fields, such as biology, medicine, agriculture, remote sensing and industrial process inspection. However, due to the demand for high spectral and spatial resolution it became extremely challenging to design and implement such systems in a miniaturized and cost effective manner. Using a Compressive Sensing (CS) setup based on a single variable Liquid Crystal (LC) retarder and a sensor array, we present an innovative Miniature Ultra-Spectral Imaging (MUSI) system. The LC retarder acts as a compact wide band spectral modulator. Within the framework of CS, a sequence of spectrally modulated images is used to recover ultra-spectral image cubes. Using the presented compressive MUSI system, we demonstrate the reconstruction of gigapixel spatio-spectral image cubes from spectral scanning shots numbering an order of magnitude less than would be required using conventional systems.
Weak, Quiet Magnetic Fields Seen in the Venus Atmosphere
Authors: Zhang T. L. , Baumjohann W. , Russell C. T. , Luhmann J. G. , Xiao S. D.
Published: March 2016

The existence of a strong internal magnetic field allows probing of the interior through both long term changes of and short period fluctuations in that magnetic field. Venus, while Earth’s twin in many ways, lacks such a strong intrinsic magnetic field, but perhaps short period fluctuations can still be used to probe the electrical conductivity of the interior. Toward the end of the Venus Express mission, an aerobraking campaign took the spacecraft below the ionosphere into the very weakly electrically conducting atmosphere. As the spacecraft descended from 150 to 140 km altitude, the magnetic field became weaker on average and less noisy. Below 140 km, the median field strength became steady but the short period fluctuations continued to weaken. The weakness of the fluctuations indicates they might not be useful for electromagnetic sounding of the atmosphere from a high altitude platform such as a plane or balloon, but possibly could be attempted on a lander.
Male Presence can Increase Body Mass and Induce a Stress-Response in Female Mice Independent of Costs of Offspring Production
Authors: Garratt Michael , Kee Anthony J. , Palme Rupert , Brooks Robert C.
Published: March 2016

Sexual reproduction in animals requires close interactions with the opposite sex. These interactions may generate costs of reproduction, because mates can induce detrimental physiological or physical effects on one another, due to their interest in maximising their own fitness. To understand how a male’s presence influences aspects of female physiology implicated in reproductive costs in mice, independent of offspring production, we paired females with vasectomised, castrated or intact males, or other females. Being paired with a male, irrespective of his gonadal status, increased female weight. This effect was transient in females paired with castrated males but more persistent in those with vasectomised males. Those paired with males also showed an increase in corticosterone, suggesting an increased stress response. However, this was dependent on the gonadal status of the male housing partner, since those housed with vasectomised males had lower corticosterone than those with castrated males. Altered energy metabolism was only detectable in pregnant females, and oxidative stress was not consistently affected by a female’s housing partner. These results suggest that a male’s presence alters female weight, and stresses associated with reproduction could be induced by simply the presence of a male, but reduced by mating and/or being solicited to mate.
Transcriptome analyses reveal molecular mechanism underlying tapping panel dryness of rubber tree (Hevea brasiliensis)
Authors: Li Dejun , Wang Xuncheng , Deng Zhi , Liu Hui , Yang Hong , He Guangming
Published: March 2016

Tapping panel dryness (TPD) is a serious threat to natural rubber yields from rubber trees, but the molecular mechanisms underlying TPD remain poorly understood. To identify TPD-related genes and reveal these molecular mechanisms, we sequenced and compared the transcriptomes of bark between healthy and TPD trees. In total, 57,760 assembled genes were obtained and analyzed in details. In contrast to healthy rubber trees, 5652 and 2485 genes were up- or downregulated, respectively, in TPD trees. The TPD-related genes were significantly enriched in eight GO terms and five KEGG pathways and were closely associated with ROS metabolism, programmed cell death and rubber biosynthesis. Our results suggest that rubber tree TPD is a complex process involving many genes. The observed lower rubber yield from TPD trees might result from lower isopentenyl diphosphate (IPP) available for rubber biosynthesis and from downregulation of the genes in post-IPP steps of rubber biosynthesis pathway. Our results not only extend our understanding of the complex molecular events involved in TPD but also will be useful for developing effective measures to control TPD of rubber trees.
Organic Pollutant Penetration through Fruit Polyester Skin: A Modified Three-compartment Diffusion Model
Authors: Li Yungui , Li Qingqing , Chen Baoliang
Published: March 2016

The surface of plants is covered by a continuous but heterogeneous cuticular membrane (CM). Serving as the first protective barrier, the uptake and transport behavior of organic pollutants at this interface continue to engage the research efforts of environmental chemist. To date, the contributions of cuticular components as a defense against the organic pollutants penetration remain unresolved. In this study, the unsteady-state penetration characteristics of phenanthrene (PHE) through isolated fruit CM was investigated. PHE penetration was differentiated by three cuticular compartments: epicuticular waxes (EW), cuticle proper (CP) and cuticular layer (CL). The driving force for PHE penetration was ascribed to the sharp concentration gradient built up endogenously by cuticular compartments with different lipophilic affinities. A modified penetration model was established and verified in terms of its general suitability for the hydrophobic chemicals and CMs of various plant species (apple, tomato and potato). The new three-compartment model demonstrates much higher accuracy in characterizing the uptake and transport behavior of semivolatile chemicals with fewer limitations in terms of environmental conditions and complexity (e.g., coexisting contaminants and temperature). This model could contribute to a more comprehensive understanding on the role of polymeric lipids in the organic pollutant sorption and transport into plants.