bluuebunny/crossref_metadata_2025 huggingface dataset:
‘I can't put that on paper.’ How medical professional values shape the content of death certificates
Authors: Leslie Myles
Published: June 2016

This paper follows collegiality, demonstrating how, as a central value of medically trained coroners, it can shape the content of death investigations and certificates. Drawing on ethnographic evidence from a 16-month-long study of the Office of the Chief Coroner (OCC) of Ontario, Canada, I argue that collegiality is an instrument of trust that both affords investigators tremendous access to information, and severely limits the flow of that information into the public domain that the OCC serves. The paper focuses on in-care death investigations, which are those where the OCC's medically qualified coroners find themselves investigating the quality of care delivered by professional colleagues. I show how professional expertise, experience and collegial values often combine to see instances of poor or even incompetent care dealt with privately (rather than publicly) or referred up the medical (rather than public safety) hierarchy. The burden of my argument is that collegial deference to the autonomy and skills of other physicians tends to see coroners expurgate the death certificates they produce. These expurgations obscure competence issues from public view and reduce the accuracy of the certificates. I close with a discussion of the benefits and drawbacks of medically qualified death investigators, as well as potential adjustments to improve the accuracy of in-care death investigations and certifications.
Spontaneous intrauterine growth restriction due to increased litter size in the guinea pig programmes postnatal growth, appetite and adult body composition
Authors: Horton D. M. , Saint D. A. , Owens J. A. , Kind K. L. , Gatford K. L.
Published: June 2016

Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in the programming of increased appetite, adiposity and cardiometabolic diseases. Guinea pigs provide an alternate small animal model to rodents to investigate mechanisms underlying prenatal programming, being relatively precocial at birth, with smaller litter sizes and undergoing neonatal catch-up growth after IUGR. The current study, therefore, investigated postnatal consequences of spontaneous IUGR due to varying litter size in this species. Size at birth, neonatal, juvenile (post-weaning, 30–60 days) and adolescent (60–90 days) growth, juvenile and adolescent food intake, and body composition of young adults (120 days) were measured in 158 male and female guinea pigs from litter sizes of one to five pups. Compared with singleton pups, birth weight of pups from litters of five was reduced by 38%. Other birth size measures were reduced to lesser degrees with head dimensions being relatively conserved. Pups from larger litters had faster fractional neonatal growth and faster absolute and fractional juvenile growth rates (P<0.005 for all). Relationships of post-weaning growth, feed intakes and adult body composition with size at birth and neonatal growth rate were sex specific, with neonatal growth rates strongly and positively correlated with adiposity in males only. In conclusion, spontaneous IUGR due to large litter sizes in the guinea pig causes many of the programmed sequelae of IUGR reported in other species, including human. This may therefore be a useful model to investigate the mechanisms underpinning perinatal programming of hyperphagia, obesity and longer-term metabolic consequences.
Stars and Swells Guide a Polynesian Canoe Around the World
Authors: Deatrick Elizabeth
Published: June 2016

Modern oceanographers and ancient navigators rely on similar waves to study the world's oceans.
Alix-mediated assembly of the actomyosin–tight junction polarity complex preserves epithelial polarity and epithelial barrier
Authors: Campos Yvan , Qiu Xiaohui , Gomero Elida , Wakefield Randall , Horner Linda , Brutkowski Wojciech , Han Young-Goo , Solecki David , Frase Sharon , Bongiovanni Antonella , d’Azzo Alessandra
Published: June 2016

Maintenance of epithelial cell polarity and epithelial barrier relies on the spatial organization of the actin cytoskeleton and proper positioning/assembly of intercellular junctions. However, how these processes are regulated is poorly understood. Here we reveal a key role for the multifunctional protein Alix in both processes. In a knockout mouse model of Alix, we identified overt structural changes in the epithelium of the choroid plexus and in the ependyma, such as asymmetrical cell shape and size, misplacement and abnormal beating of cilia, blebbing of the microvilli. These defects culminate in excessive cell extrusion, enlargement of the lateral ventricles and hydrocephalus. Mechanistically, we find that by interacting with F-actin, the Par complex and ZO-1, Alix ensures the formation and maintenance of the apically restricted actomyosin–tight junction complex. We propose that in this capacity Alix plays a role in the establishment of apical–basal polarity and in the maintenance of the epithelial barrier.
MicroRNA-125b-5p mimic inhibits acute liver failure
Authors: Yang Dakai , Yuan Qinggong , Balakrishnan Asha , Bantel Heike , Klusmann Jan-Henning , Manns Michael P. , Ott Michael , Cantz Tobias , Sharma Amar Deep
Published: June 2016

The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF.
Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases
Authors: Walport Louise J. , Hopkinson Richard J. , Chowdhury Rasheduzzaman , Schiller Rachel , Ge Wei , Kawamura Akane , Schofield Christopher J.
Published: June 2016

While the oxygen-dependent reversal of lysineNɛ-methylation is well established, the existence of bona fideNω-methylarginine demethylases (RDMs) is controversial. Lysine demethylation, as catalysed by two families of lysine demethylases (the flavin-dependent KDM1 enzymes and the 2-oxoglutarate- and oxygen-dependent JmjC KDMs, respectively), proceeds via oxidation of theN-methyl group, resulting in the release of formaldehyde. Here we report detailed biochemical studies clearly demonstrating that, in purified form, a subset of JmjC KDMs can also act as RDMs, both on histone and non-histone fragments, resulting in formaldehyde release. RDM catalysis is studied using peptides of wild-type sequences known to be arginine-methylated and sequences in which the KDM’s methylated target lysine is substituted for a methylated arginine. Notably, the preferred sequence requirements for KDM and RDM activity vary even with the same JmjC enzymes. The demonstration of RDM activity by isolated JmjC enzymes will stimulate efforts to detect biologically relevant RDM activity.
Integrated genetic and pharmacologic interrogation of rare cancers
Authors: Hong Andrew L. , Tseng Yuen-Yi , Cowley Glenn S. , Jonas Oliver , Cheah Jaime H. , Kynnap Bryan D. , Doshi Mihir B. , Oh Coyin , Meyer Stephanie C. , Church Alanna J. , Gill Shubhroz , Bielski Craig M. , Keskula Paula , Imamovic Alma , Howell Sara , Kryukov Gregory V. , Clemons Paul A. , Tsherniak Aviad , Vazquez Francisca , Crompton Brian D. , Shamji Alykhan F. , Rodriguez-Galindo Carlos , Janeway Katherine A. , Roberts Charles W. M. , Stegmaier Kimberly , van Hummelen Paul , Cima Michael J. , Langer Robert S. , Garraway Levi A. , Schreiber Stuart L. , Root David E. , Hahn William C. , Boehm Jesse S.
Published: June 2016

Identifying therapeutic targets in rare cancers remains challenging due to the paucity of established models to perform preclinical studies. As a proof-of-concept, we developed a patient-derived cancer cell line, CLF-PED-015-T, from a paediatric patient with a rare undifferentiated sarcoma. Here, we confirm that this cell line recapitulates the histology and harbours the majority of the somatic genetic alterations found in a metastatic lesion isolated at first relapse. We then perform pooled CRISPR-Cas9 and RNAi loss-of-function screens and a small-molecule screen focused on druggable cancer targets. Integrating these three complementary and orthogonal methods, we identify CDK4 and XPO1 as potential therapeutic targets in this cancer, which has no known alterations in these genes. These observations establish an approach that integrates new patient-derived models, functional genomics and chemical screens to facilitate the discovery of targets in rare cancers.
Cardiac sodium channel palmitoylation regulates channel availability and myocyte excitability with implications for arrhythmia generation
Authors: Pei Zifan , Xiao Yucheng , Meng Jingwei , Hudmon Andy , Cummins Theodore R.
Published: June 2016

Cardiac voltage-gated sodium channels (Nav1.5) play an essential role in regulating cardiac electric activity by initiating and propagating action potentials in the heart. Altered Nav1.5 function is associated with multiple cardiac diseases including long-QT3 and Brugada syndrome. Here, we show that Nav1.5 is subject to palmitoylation, a reversible post-translational lipid modification. Palmitoylation increases channel availability and late sodium current activity, leading to enhanced cardiac excitability and prolonged action potential duration. In contrast, blocking palmitoylation increases closed-state channel inactivation and reduces myocyte excitability. We identify four cysteines as possible Nav1.5 palmitoylation substrates. A mutation of one of these is associated with cardiac arrhythmia (C981F), induces a significant enhancement of channel closed-state inactivation and ablates sensitivity to depalmitoylation. Our data indicate that alterations in palmitoylation can substantially control Nav1.5 function and cardiac excitability and this form of post-translational modification is likely an important contributor to acquired and congenital arrhythmias.
Blood biomarker for Parkinson disease: peptoids
Authors: Yazdani Umar , Zaman Sayed , Hynan Linda S , Brown L Steven , Dewey Richard B , Karp David , German Dwight C
Published: June 2016

Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r=0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker.
Identification and characterization of a pathogenicity-related gene VdCYP1 from Verticillium dahliae
Authors: Zhang Dan-Dan , Wang Xin-Yan , Chen Jie-Yin , Kong Zhi-Qiang , Gui Yue-Jing , Li Nan-Yang , Bao Yu-Ming , Dai Xiao-Feng
Published: June 2016

Verticillium dahliae is a phytopathogenic fungus that causes vascular wilt disease in a wide variety of crop plants, thereby causing extensive economic loss. In present study, one V. dahliae T-DNA mutant M01C06 showed the pathogenicity loss on cotton, and the expression of a flanking gene encoding cytochrome P450 monooxygenase (P450, VdCYP1) was strongly repressed. P450s of fungi could affect the fungal pathogenicity by involving in the synthesis of secondary metabolites. However, there was no report about the pathogenic function of P450s in V. dahliae. VdCYP1 gene deletion and complementation experiments confirmed that VdCYP1 was the pathogenicity-related gene in V. dahliae. A comparison of culture supernatants of the VdCYP1 deletion mutants and wild-type strains indicates that at least 14 kinds of secondary metabolites syntheses were affected due to VdCYP1 gene deletion. One of these compounds, sulfacetamide, had the ability to induce the necrosis and wilting symptoms in cotton. Above results indicate that VdCYP1 could participate in pathogenesis by involving the secondary metabolism in V. dahliae, such as the compound sulfacetamide. In conclusion, VdCYP1 acts as an important pathogenicity-related factor to involve in secondary metabolism that likely contributes to the pathogenic process in V. dahliae.
Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model
Authors: Xu Shan , Tian Yuan , Hu Yili , Zhang Nijia , Hu Sheng , Song Dandan , Wu Zhengshun , Wang Yulan , Cui Yanfang , Tang Huiru
Published: June 2016

The effects of tumorigenesis and tumor growth on the non-involved organs remain poorly understood although many research efforts have already been made for understanding the metabolic phenotypes of various tumors. To better the situation, we systematically analyzed the metabolic phenotypes of multiple non-involved mouse organ tissues (heart, liver, spleen, lung and kidney) in an A549 lung cancer xenograft model at two different tumor-growth stages using the NMR-based metabonomics approaches. We found that tumor growth caused significant metabonomic changes in multiple non-involved organ tissues involving numerous metabolic pathways, including glycolysis, TCA cycle and metabolisms of amino acids, fatty acids, choline and nucleic acids. Amongst these, the common effects are enhanced glycolysis and nucleoside/nucleotide metabolisms. These findings provided essential biochemistry information about the effects of tumor growth on the non-involved organs.
Salivary total α-synuclein, oligomeric α-synuclein and SNCA variants in Parkinson’s disease patients
Authors: Kang Wenyan , Chen Wei , Yang Qiong , Zhang Lina , Zhang Linyuan , Wang Xiaoying , Dong Fangyi , Zhao Yang , Chen Shuai , Quinn Thomas J. , Zhang Jing , Chen Shengdi , Liu Jun
Published: June 2016

The present study was to evaluate the diagnostic value of salivary total and oligomeric α-synuclein levels in PD. Furthermore, we sought to explore the relationship between salivary total α-synuclein and α-synuclein SNP variants levels. 201 PD patients and 67 controls were recruited, of which there also had the genetic information of two positive α-synuclein (SNCA) loci. Salivary total α-synuclein was assayed using a highly sensitive Luminex assay and oligomeric α-synuclein was quantified by the combination of Gel filtration chromatography and Western blot, respectively. From our analysis,No difference in salivary total α-synuclein levels was found between PD patients and healthy controls, it decreased with age in PD patients and was closely associated with genotypic distribution of rs11931074 and rs894278 in PD, respectively. After controlled for age and genders, G allele of rs11931074 was correlated with lower salivary total α-synuclein levels, while G allele of rs894278 was also correlated with the higher levels. Simultaneously, the further study was shown that salivary oligomeric α-synuclein in PD patients significantly increased comparing to healthy controls. In conclusions,our study firstly demonstrated that salivary total α-synuclein levels could be manipulated by different α-synuclein SNPs and salivary oligomeric α-synuclein could be a potential diagnostic indicator of PD.
Light-trapping and recycling for extraordinary power conversion in ultra-thin gallium-arsenide solar cells
Authors: Eyderman Sergey , John Sajeev
Published: June 2016

We demonstrate nearly 30% power conversion efficiency in ultra-thin (~200 nm) gallium arsenide photonic crystal solar cells by numerical solution of the coupled electromagnetic Maxwell and semiconductor drift-diffusion equations. Our architecture enables wave-interference-induced solar light trapping in the wavelength range from 300–865 nm, leading to absorption of almost 90% of incoming sunlight. Our optimized design for 200 nm equivalent bulk thickness of GaAs, is a square-lattice, slanted conical-pore photonic crystal (lattice constant 550 nm, pore diameter 600 nm and pore depth 290 nm), passivated with AlGaAs, deposited on a silver back-reflector, with ITO upper contact and encapsulated with SiO2. Our model includes both radiative and non-radiative recombination of photo-generated charge carriers. When all light from radiative recombination is assumed to escape the structure, a maximum achievable photocurrent density (MAPD) of 27.6 mA/cm2 is obtained from normally incident AM 1.5 sunlight. For a surface non-radiative recombination velocity of 103 cm/s, this corresponds to a solar power conversion efficiency of 28.3%. When all light from radiative recombination is trapped and reabsorbed (complete photon recycling) the power conversion efficiency increases to 29%. If the surface recombination velocity is reduced to 10 cm/sec, photon recycling is much more effective and the power conversion efficiency reaches 30.6%.
Evaluation of right adrenal vein anatomy by Dyna computed tomography in patients with primary aldosteronism
Authors: Lee Bo-Ching , Chang Chin-Chen , Liu Kao-Lang , Chang Yeun-Chung , Wu Vin-Cent , Huang Kuo-How
Published: June 2016

Primary aldosteronism (PA) is the most common cause of secondary hypertension and consists up to 11% of patients with hypertension. Adrenal venous sampling (AVS) is the recommended procedure for diagnosis of PA, but the technique is difficult and the right adrenal vein is especially hard to catheterize. We retrospectively examined the clinically relevant anatomy of the right adrenal vein in a sample of 66 PA patients with technically successful AVS and distinctly-opacified right adrenal veins in Dyna computed tomography (CT). In the majority of cases: the right adrenal veins were catheterized when the catheter tilted posterior and rightward (57/66, 86.4%), the transverse direction of the right adrenal vein from the inferior vena cava (IVC) was posterior and rightward (55/66, 83.3%) and the vertical direction of the right adrenal vein from the IVC was caudal (52/66, 78.8%). This study shows that Dyna CT is able to provide detailed anatomical information to the course and direction of the right adrenal vein.
Depth-specific optogenetic control in vivo with a scalable, high-density μLED neural probe
Authors: Scharf Robert , Tsunematsu Tomomi , McAlinden Niall , Dawson Martin D. , Sakata Shuzo , Mathieson Keith
Published: June 2016

Controlling neural circuits is a powerful approach to uncover a causal link between neural activity and behaviour. Optogenetics has been widely adopted by the neuroscience community as it offers cell-type-specific perturbation with millisecond precision. However, these studies require light delivery in complex patterns with cellular-scale resolution, while covering a large volume of tissue at depth in vivo. Here we describe a novel high-density silicon-based microscale light-emitting diode (μLED) array, consisting of up to ninety-six 25 μm-diameter μLEDs emitting at a wavelength of 450 nm with a peak irradiance of 400 mW/mm2. A width of 100 μm, tapering to a 1 μm point, and a 40 μm thickness help minimise tissue damage during insertion. Thermal properties permit a set of optogenetic operating regimes, with ~0.5 °C average temperature increase. We demonstrate depth-dependent activation of mouse neocortical neurons in vivo, offering an inexpensive novel tool for the precise manipulation of neural activity.
The space of enzyme regulation in HeLa cells can be inferred from its intracellular metabolome
Authors: Diener Christian , Muñoz-Gonzalez Felipe , Encarnación Sergio , Resendis-Antonio Osbaldo
Published: June 2016

During the transition from a healthy state to a cancerous one, cells alter their metabolism to increase proliferation. The underlying metabolic alterations may be caused by a variety of different regulatory events on the transcriptional or post-transcriptional level whose identification contributes to the rational design of therapeutic targets. We present a mechanistic strategy capable of inferring enzymatic regulation from intracellular metabolome measurements that is independent of the actual mechanism of regulation. Here, enzyme activities are expressed by the space of all feasible kinetic constants (k-cone) such that the alteration between two phenotypes is given by their corresponding kinetic spaces. Deriving an expression for the transformation of the healthy to the cancer k-cone we identified putative regulated enzymes between the HeLa and HaCaT cell lines. We show that only a few enzymatic activities change between those two cell lines and that this regulation does not depend on gene transcription but is instead post-transcriptional. Here, we identify phosphofructokinase as the major driver of proliferation in HeLa cells and suggest an optional regulatory program, associated with oxidative stress, that affects the activity of the pentose phosphate pathway.
Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway
Authors: Chen Xu , Li Min , Li Li , Xu Song , Huang Dan , Ju Mei , Huang Ju , Chen Kun , Gu Heng
Published: June 2016

Trehalose is a natural disaccharide that is found in a diverse range of organisms but not in mammals. Autophagy is a process which mediates the sequestration, lysosomal delivery and degradation of proteins and organelles. Studies have shown that trehalose exerts beneficial effects through inducing autophagy in mammalian cells. However, whether trehalose or other saccharides can activate autophagy in keratinocytes is unknown. Here, we found that trehalose treatment increased the LC3-I to LC3-II conversion, acridine orange-stained vacuoles and GFP-LC3B (LC3B protein tagged with green fluorescent protein) puncta in the HaCaT human keratinocyte cell line, indicating autophagy induction. Trehalose-induced autophagy was also observed in primary keratinocytes and the A431 epidermal cancer cell line. mTOR signalling was not affected by trehalose treatment, suggesting that trehalose induced autophagy through an mTOR-independent pathway. mTOR-independent autophagy induction was also observed in HaCaT and HeLa cells treated with sucrose or raffinose but not in glucose, maltose or sorbitol treated HaCaT cells, indicating that autophagy induction was not a general property of saccharides. Finally, although trehalose treatment had an inhibitory effect on cell proliferation, it had a cytoprotective effect on cells exposed to UVB radiation. Our study provides new insight into the saccharide-mediated regulation of autophagy in keratinocytes.
Biochemical basis of synergism between pathogenic fungus Metarhizium anisopliae and insecticide chlorantraniliprole in Locusta migratoria (Meyen)
Authors: Jia Miao , Cao Guangchun , Li Yibo , Tu Xiongbing , Wang Guangjun , Nong Xiangqun , Whitman Douglas W. , Zhang Zehua
Published: June 2016

We challenged Locusta migratoria (Meyen) grasshoppers with simultaneous doses of both the insecticide chlorantraniliprole and the fungal pathogen, Metarhizium anisopliae. Our results showed synergistic and antagonistic effects on host mortality and enzyme activities. To elucidate the biochemical mechanisms that underlie detoxification and pathogen-immune responses in insects, we monitored the activities of 10 enzymes. After administration of insecticide and fungus, activities of glutathione-S-transferase (GST), general esterases (ESTs) and phenol oxidase (PO) decreased in the insect during the initial time period, whereas those of aryl acylamidase (AA) and chitinase (CHI) increased during the initial period and that of acetylcholinesterase (AChE) increased during a later time period. Activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) decreased at a later time period post treatment. Interestingly, treatment with chlorantraniliprole and M. anisopliae relieved the convulsions that normally accompany M. anisopliae infection. We speculate that locust mortality increased as a result of synergism via a mechanism related to Ca2+ disruption in the host. Our study illuminates the biochemical mechanisms involved in insect immunity to xenobiotics and pathogens as well as the mechanisms by which these factors disrupt host homeostasis and induce death. We expect this knowledge to lead to more effective pest control.
Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-α activated adipose derived mesenchymal stem cells in breast cancer model
Authors: Mohammadpour Hemn , Pourfathollah Ali Akbar , Nikougoftar Zarif Mahin , Shahbazfar Amir Ali
Published: June 2016

Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment in various types of cancer. Moreover, irradiation is usually applied as either a standard primary or adjuvant therapy. Here, we showed that the expression of TNF related apoptosis-inducing ligand (TRAIL) and Dickouf-3 (Dkk-3), the promising anticancer proteins, increased in murine adipose-derived mesenchymal stromal cells (AD-MSCs) following activation with TNF-α, resulting in the induction of apoptosis in cancer cells. Also, anticancer effects of TNF-α activated AD-MSCs were intensified with irradiation. In vivo results showed that TNF-α preactivated AD-MSCs combined with irradiation decreased tumor size and increased survival rate in tumor bearing mice. On the other hands, both TNF-α preactivated AD-MSCs with or without irradiation prevented metastasis in ling and liver, and increased apoptosis in tumor mass. Finally, flowcytometry assay demonstrated that naïve AD-MSCs combined with irradiation but not TNF-α activated MSCs with irradiation increased Treg population in lymph node and spleen. Altogether, obtained results suggest that TNF-α activated MSCs combined with irradiation therapy can serve as new strategy in breast cancer therapy.
Aerosol assisted chemical vapour deposition of gas sensitive SnO2 and Au-functionalised SnO2 nanorods via a non-catalysed vapour solid (VS) mechanism
Authors: Vallejos Stella , Selina Soultana , Annanouch Fatima Ezahra , Gràcia Isabel , Llobet Eduard , Blackman Chris
Published: June 2016

Tin oxide nanorods (NRs) are vapour synthesised at relatively lower temperatures than previously reported and without the need for substrate pre-treatment,viaa vapour-solid mechanism enabled using an aerosol-assisted chemical vapour deposition method. Results demonstrate that the growth of SnO2NRs is promoted by a compression of the nucleation rate parallel to the substrate and a decrease of the energy barrier for growth perpendicular to the substrate, which are controlled via the deposition conditions. This method provides both single-step formation of the SnO2NRs and their integration with silicon micromachined platforms, but also allows forin-situfunctionalization of the NRs with gold nanoparticlesviaco-deposition with a gold precursor. The functional properties are demonstrated for gas sensing, with microsensors using functionalised NRs demonstrating enhanced sensing properties towards H2compared to those based on non-functionalised NRs.
Spatially resolved photoresponse on individual ZnO nanorods: correlating morphology, defects and conductivity
Authors: Bandopadhyay K. , Mitra J.
Published: June 2016

Electrically active native point defects have a significant impact on the optical and electrical properties of ZnO nanostructures. Control of defect distribution and a detailed understanding of their physical properties are central to designing ZnO in novel functional forms and architecture, which ultimately decides device performance. Defect control is primarily achieved by either engineering nanostructure morphology by tailoring growth techniques or doping. Here, we report conducting atomic force microscopy studies of spatially resolved photoresponse properties on ZnO nanorod surfaces. The photoresponse for super-band gap, ultraviolet excitations show a direct correlation between surface morphology and photoactivity localization. Additionally, the system exhibits significant photoresponse with sub-bandgap, green illumination; the signature energy associated with the deep level oxygen vacancy states. While the local current-voltage characteristics provide evidence of multiple transport processes and quantifies the photoresponse, the local time-resolved photoresponse data evidences large variations in response times (90 ms–50 s), across the surface of a nanorod. The spatially varied photoconductance and the range in temporal response display a complex interplay of morphology, defects and connectivity that brings about the true colour of these ZnO nanostructures.
Responsiveness of soil nitrogen fractions and bacterial communities to afforestation in the Loess Hilly Region (LHR) of China
Authors: Ren Chengjie , Sun Pingsheng , Kang Di , Zhao Fazhu , Feng Yongzhong , Ren Guangxin , Han Xinhui , Yang Gaihe
Published: June 2016

In the present paper, we investigated the effects of afforestation on nitrogen fractions and microbial communities. A total of 24 soil samples were collected from farmland (FL) and three afforested lands, namely Robinia pseudoacacia L (RP), Caragana korshinskii Kom (CK), and abandoned land (AL), which have been arable for the past 40 years. Quantitative PCR and Illumina sequencing of 16S rRNA genes were used to analyze soil bacterial abundance, diversity, and composition. Additionally, soil nitrogen (N) stocks and fractions were estimated. The results showed that soil N stock, N fractions, and bacterial abundance and diversity increased following afforestation. Proteobacteria, Acidobacteria, and Actinobacteria were the dominant phyla of soil bacterial compositions. Overall, soil bacterial compositions generally changed from Actinobacteria (Acidobacteria)-dominant to Proteobacteria-dominant following afforestation. Soil N fractions, especially for dissolved organic nitrogen (DON), were significantly correlated with most bacterial groups and bacterial diversity, while potential competitive interactions between Proteobacteria (order Rhizobiales) and Cyanobacteria were suggested. In contrast, nitrate nitrogen (NO3−-N) influenced soil bacterial compositions less than other N fractions. Therefore, the present study demonstrated that bacterial diversity and specific species respond to farmland-to-forest conversion and hence have the potential to affect N dynamic processes in the Loess Plateau.
Concentrations of Radiocesium in Local Foods Collected in Kawauchi Village after the Accident at the Fukushima Dai-ichi Nuclear Power Station
Authors: Orita Makiko , Nakashima Kanami , Hayashida Naomi , Endo Yuuko , Yamashita Shunichi , Takamura Noboru
Published: June 2016

We evaluated the current concentrations of radiocesium in local foods collected in Kawauchi Village, which is located less than 30 km from Fukushima Daiichi Nuclear Power Station, to minimize public anxiety regarding internal radiation exposure through the consumption of locally produced foods after the 2011 Fukushima accident. The number of samples exceeding the regulatory radiocesium limit (100 Bq/kg for general foods) was five out of 4,080 vegetables (0.1%), 652 of 1,986 (32.8%) among edible wild plants and fungi, and eight of 647 (1.2%) in fruits. Our study confirmed that the internal radiation doses of ingesting these foods are acceptably low compared to the public dose limit, ranging from 24.4 to 42.7 μSv for males and from 21.7 to 43.4 μSv for females, although the potential for radiation exposure still exists. Long-term comprehensive follow-up should take place to clarify trends in radiocesium concentrations in local foods and the committed effective doses found in Fukushima-area residents. By constructing a system that allows residents to access information on radiocesium concentration in foods, a risk communication model between specialists and residents could be developed in the recovery phase after the Fukushima accident.
From non-covalent binding to irreversible DNA lesions: nile blue and nile red as photosensitizing agents
Authors: Gattuso Hugo , Besancenot Vanessa , Grandemange Stéphanie , Marazzi Marco , Monari Antonio
Published: June 2016

We report a molecular modeling study, coupled with spectroscopy experiments, on the behavior of two well known organic dyes, nile blue and nile red, when interacting with B-DNA. In particular, we evidence the presence of two competitive binding modes, for both drugs. However their subsequent photophysical behavior is different and only nile blue is able to induce DNA photosensitization via an electron transfer mechanism. Most notably, even in the case of nile blue, its sensitization capabilities strongly depend on the environment resulting in a single active binding mode: the minor groove. Fluorescence spectroscopy confirms the presence of competitive interaction modes for both sensitizers, while the sensitization via electron transfer, is possible only in the case of nile blue.
Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Nsp4 Cleaves VISA to Impair Antiviral Responses Mediated by RIG-I-like Receptors
Authors: Huang Chen , Du Yinping , Yu Zhibin , Zhang Qiong , Liu Yihao , Tang Jun , Shi Jishu , Feng Wen-hai
Published: June 2016

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most significant etiological agents in the swine industry worldwide. It has been reported that PRRSV infection can modulate host immune responses, and innate immune evasion is thought to play a vital role in PRRSV pathogenesis. In this study, we demonstrated that highly pathogenic PRRSV (HP-PRRSV) infection specifically down-regulated virus-induced signaling adaptor (VISA), a unique adaptor molecule that is essential for retinoic acid induced gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) signal transduction. Moreover, we verified that nsp4 inhibited IRF3 activation induced by signaling molecules, including RIG-I, MDA5, VISA, and TBK1, but not IRF3. Subsequently, we demonstrated that HP-PRRSV nsp4 down-regulated VISA and suppressed type I IFN induction. Importantly, VISA was cleaved by nsp4 and released from mitochondrial membrane, which interrupted the downstream signaling of VISA. However, catalytically inactive mutant of nsp4 abolished its ability to cleave VISA. Interestingly, nsp4 of typical PRRSV strain CH-1a had no effect on VISA. Taken together, these findings reveal a strategy evolved by HP-PRRSV to counteract anti-viral innate immune signaling, which complements the known PRRSV-mediated immune-evasion mechanisms.
Effects of the linker region on the structure and function of modular GH5 cellulases
Authors: Ruiz Diego M. , Turowski Valeria R. , Murakami Mario T.
Published: June 2016

The association of glycosyl hydrolases with catalytically inactive modules is a successful evolutionary strategy that is commonly used by biomass-degrading microorganisms to digest plant cell walls. The presence of accessory domains in these enzymes is associated with properties such as higher catalytic efficiency, extension of the catalytic interface and targeting of the enzyme to the proper substrate. However, the importance of the linker region in the synergistic action of the catalytic and accessory domains remains poorly understood. Thus, this study examined how the inter-domain region affects the structure and function of modular GH5 endoglucanases, by using cellulase 5A from Bacillus subtilis (BsCel5A) as a model. BsCel5A variants featuring linkers with different stiffnesses or sizes were designed and extensively characterized, revealing that changes in flexibility or rigidity in this region differentially affect kinetic behavior. Regarding the linker length, we found that precise inter-domain spacing is required to enable efficient hydrolysis because excessively long or short linkers were equally detrimental to catalysis. Together, these findings identify molecular and structural features that may contribute to the rational design of chimeric and multimodular glycosyl hydrolases.
R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5
Authors: Nakashima Hiroaki , Ohkawara Bisei , Ishigaki Shinsuke , Fukudome Takayasu , Ito Kenyu , Tsushima Mikito , Konishi Hiroyuki , Okuno Tatsuya , Yoshimura Toshiro , Ito Mikako , Masuda Akio , Sobue Gen , Kiyama Hiroshi , Ishiguro Naoki , Ohno Kinji
Published: June 2016

At the neuromuscular junction (NMJ), acetylcholine receptor (AChR) clustering is mediated by spinal motor neuron (SMN)-derived agrin and its receptors on the muscle, the low-density lipoprotein receptor-related protein 4 (LRP4) and muscle-specific receptor tyrosine kinase (MuSK). Additionally, AChR clustering is mediated by the components of the Wnt pathway. Laser capture microdissection of SMNs revealed that a secreted activator of Wnt signaling, R-spondin 2 (Rspo2), is highly expressed in SMNs. We found that Rspo2 is enriched at the NMJ and that Rspo2 induces MuSK phosphorylation and AChR clustering. Rspo2 requires Wnt ligands, but not agrin, for promoting AChR clustering in cultured myotubes. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), an Rspo2 receptor, is also accumulated at the NMJ and is associated with MuSK via LRP4. Lgr5 is required for Rspo2-mediated AChR clustering in myotubes. In Rspo2-knockout mice, the number and density of AChRs at the NMJ are reduced. The Rspo2-knockout diaphragm has an altered ultrastructure with widened synaptic clefts and sparse synaptic vesicles. Frequency of miniature endplate currents is markedly reduced in Rspo2-knockout mice. To conclude, we demonstrate that Rspo2 and its receptor Lgr5 are Wnt-dependent and agrin-independent regulators of AChR clustering at the NMJ.
PEDLA: predicting enhancers with a deep learning-based algorithmic framework
Authors: Liu Feng , Li Hao , Ren Chao , Bo Xiaochen , Shu Wenjie
Published: June 2016

Transcriptional enhancers are non-coding segments of DNA that play a central role in the spatiotemporal regulation of gene expression programs. However, systematically and precisely predicting enhancers remain a major challenge. Although existing methods have achieved some success in enhancer prediction, they still suffer from many issues. We developed a deep learning-based algorithmic framework named PEDLA (https://github.com/wenjiegroup/PEDLA), which can directly learn an enhancer predictor from massively heterogeneous data and generalize in ways that are mostly consistent across various cell types/tissues. We first trained PEDLA with 1,114-dimensional heterogeneous features in H1 cells, and demonstrated that PEDLA framework integrates diverse heterogeneous features and gives state-of-the-art performance relative to five existing methods for enhancer prediction. We further extended PEDLA to iteratively learn from 22 training cell types/tissues. Our results showed that PEDLA manifested superior performance consistency in both training and independent test sets. On average, PEDLA achieved 95.0% accuracy and a 96.8% geometric mean (GM) of sensitivity and specificity across 22 training cell types/tissues, as well as 95.7% accuracy and a 96.8% GM across 20 independent test cell types/tissues. Together, our work illustrates the power of harnessing state-of-the-art deep learning techniques to consistently identify regulatory elements at a genome-wide scale from massively heterogeneous data across diverse cell types/tissues.
Molecular descriptor data explain market prices of a large commercial chemical compound library
Authors: Polanski Jaroslaw , Kucia Urszula , Duszkiewicz Roksana , Kurczyk Agata , Magdziarz Tomasz , Gasteiger Johann
Published: June 2016

The relationship between the structure and a property of a chemical compound is an essential concept in chemistry guiding, for example, drug design. Actually, however, we need economic considerations to fully understand the fate of drugs on the market. We are performing here for the first time the exploration of quantitative structure-economy relationships (QSER) for a large dataset of a commercial building block library of over 2.2 million chemicals. This investigation provided molecular statistics that shows that on average what we are paying for is the quantity of matter. On the other side, the influence of synthetic availability scores is also revealed. Finally, we are buying substances by looking at the molecular graphs or molecular formulas. Thus, those molecules that have a higher number of atoms look more attractive and are, on average, also more expensive. Our study shows how data binning could be used as an informative method when analyzing big data in chemistry.
Wide and high resolution tension measurement using FRET in embryo
Authors: Yamashita Satoshi , Tsuboi Takashi , Ishinabe Nanako , Kitaguchi Tetsuya , Michiue Tatsuo
Published: June 2016

During embryonic development, physical force plays an important role in morphogenesis and differentiation. Stretch sensitive fluorescence resonance energy transfer (FRET) has the potential to provide non-invasive tension measurements inside living tissue. In this study, we introduced a FRET-based actinin tension sensor into Xenopus laevis embryos and demonstrated that this sensor captures variation of tension across differentiating ectoderm. The actinin tension sensor, containing mCherry and EGFP connected by spider silk protein, was validated in human embryonic kidney (HEK) cells and embryos. It co-localized with actin filaments and changed FRET efficiencies in response to actin filament destruction, myosin deactivation and osmotic perturbation. Time-lapse FRET analysis showed that the prospective neural ectoderm bears higher tension than the epidermal ectoderm during gastrulation and neurulation and cells morphogenetic behavior correlated with the tension difference. These data confirmed that the sensor enables us to measure tension across tissues concurrently and with high resolution.
Widespread ground motion distribution caused by rupture directivity during the 2015 Gorkha, Nepal earthquake
Authors: Koketsu Kazuki , Miyake Hiroe , Guo Yujia , Kobayashi Hiroaki , Masuda Tetsu , Davuluri Srinagesh , Bhattarai Mukunda , Adhikari Lok Bijaya , Sapkota Soma Nath
Published: June 2016

The ground motion and damage caused by the 2015 Gorkha, Nepal earthquake can be characterized by their widespread distributions to the east. Evidence from strong ground motions, regional acceleration duration, and teleseismic waveforms indicate that rupture directivity contributed significantly to these distributions. This phenomenon has been thought to occur only if a strike-slip or dip-slip rupture propagates to a site in the along-strike or updip direction, respectively. However, even though the earthquake was a dip-slip faulting event and its source fault strike was nearly eastward, evidence for rupture directivity is found in the eastward direction. Here, we explore the reasons for this apparent inconsistency by performing a joint source inversion of seismic and geodetic datasets, and conducting ground motion simulations. The results indicate that the earthquake occurred on the underthrusting Indian lithosphere, with a low dip angle, and that the fault rupture propagated in the along-strike direction at a velocity just slightly below the S-wave velocity. This low dip angle and fast rupture velocity produced rupture directivity in the along-strike direction, which caused widespread ground motion distribution and significant damage extending far eastwards, from central Nepal to Mount Everest.
Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits
Authors: Jing Da , Hao Xuguang , Xu Fang , Liu Jian , Xu Fei , Luo Erping , Meng Guolin
Published: June 2016

The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics.
Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications
Authors: Yassine Omar , Zaher Amir , Li Er Qiang , Alfadhel Ahmed , Perez Jose E. , Kavaldzhiev Mincho , Contreras Maria F. , Thoroddsen Sigurdur T. , Khashab Niveen M. , Kosel Jurgen
Published: June 2016

Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.