bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the cobalt requirement of beef cattle based on vitamin B12, folate, homocysteine and methylmalonic acid
Authors: Stangl G. I. , Schwarz F. J. , Müller H. , Kirchgessner M.
Published: January 2017

This investigation was designed to estimate the Co requirement of growing cattle on the basis of plasma and liver levels of vitamin B12and folate, plasma levels of homocysteine and methylmalonic acid (MMA) and haematological variables. For this purpose thirty-four male intact cattle of the German Simmental breed (236 kg) were assigned randomly to ten groups and were fed corn silage-based diets which contained 70, 90, 109, 147, 184, 257, 327, 421, 589 or 689 μg Co/kg DM for 40 weeks. One-slope broken-line model analysis and a quadratic model with plateau were used to estimate the Co requirement. The broken-line model estimated the dietary Co requirement of growing cattle to be 257 (SE 29) ΜG/KG DIETARY DM BASED ON PLASMA VITAMIN B12AS RESPONSE CRITERION. THE DIETARY CO LEVELS NEEDED TO MAXIMISE THE LIVER VITAMIN B12AND LIVER FOLATE WERE 236 (se 8) and 190 (se 8) μg/kg dietary DM respectively. Plasma folate did not show any response to the different Co levels. The dietary Co was inversely correlated with the plasma concentrations of homocysteine and MMA. Estimates of the dietary Co concentration required to minimise homocysteine were 161 (se 10) μg/kg DM. When MMA was used as response criterion, the linear model yielded a Co requirement of 124 (se 3) μg/kg dietary DM. The quadratic model did not provide a better closeness of regression fit and yielded similar requirements to the linear model. Haemoglobin concentration and haematocrit tended to have a slight response to increasing dietary Co and were only decreased in cattle on diets containing less than 100 μg Co/kg DM. On the basis of the present data, recommended levels of dietary Co for normal folate metabolism and minimum homocysteine and MMA levels can be set to be 150–200 μg/kg DM; for maximum vitamin B12levels, the desired Co content in the diet seems to be 250 μg/kg DM.
Contemplating the GANE model using an extreme case paradigm
Authors: Geva Ronny
Published: January 2017

Early experiences play a crucial role in programming brain function, affecting selective attention, learning, and memory. Infancy literature suggests an extension of the GANE (glutamate amplifies noradrenergic effects) model to conditions with minimal priority-map inputs, yet suggests qualifications by noting that its efficacy is increased when tonic levels of arousal are maintained in an optimal range, in manners that are age and exposure dependent.
Stagnant Ice at the Bed of White Glacier, Axel Heiberg Island. N.W.T., Canada
Authors: Blatter Heinz
Published: January 2017

A total of 400 soundings along 15 profiles were obtained on White Glacier, Axel Heiberg Island, N.W.T. with a monopulse radar equipment that was rebuilt according to a model of the US Geological Survey. The resulting data allowed maps to be compiled of the ice thickness for the glacier tongue, The radio echo-sounding data and englacial temperature measurements give some indication of the existence of stagnant ice in depressions of the glacier bed in the accumulation zone of White Glacier.
Maternal Anxiety and Depression and Development of Prematurely Born Infants in the First Year of Life
Authors: Carvalho Ana Emilia Vita , Martinez Francisco Eulógio , Linhares Maria Beatriz Martins
Published: January 2017

The purpose of this study was: (a) to assess and to compare anxiety and depression symptoms in mothers of pre-term neonates during hospitalization in the Neonatal Intensive Care Unit, after discharge, and at the end of the infants' first year of life; and (b) to assess the child's development at 12 months of chronological corrected age (CCA). Thirty-six mothers, with no psychiatric antecedents assessed with the SCID-NP, were evaluated by STAI and BDI. The infants were assessed with Bayley-II Scales. There was a significant decrease in clinical symptoms of state-anxiety in mothers (p = .008), comparing the period during hospitalization and after discharge of the infants. Clinical symptoms of anxiety and depression were observed in 20% of the mothers at the end of the infants' first year of age. The majority of the infants exhibited normal development on Bayley-II at 12 months CCA; however, 25% of the infants displayed cognitive problems and 40% motor problems. The mothers' anxiety and depression symptoms decreased at the end of the first year of life of the pre-term infants and the children showed predominately normal development at this phase.
Clouds Don't Reflect as Much Sunlight as Previously Thought
Authors: Underwood Emily
Published: January 2017

Icy clouds may actually increase, not decrease, the amount of solar energy that reaches Earth.
Tooth wear: a cross-sectional investigation of the prevalence and risk factors in Beijing, China
Authors: Sun Kan , Wang Wenhui , Wang Xiaozhe , Shi Xiangru , Si Yan , Zheng Shuguo
Published: January 2017

Objectives:

The aim of this study was to evaluate the epidemiology of tooth wear in Beijing and to establish appropriate preventive measures.

Materials and Methods:

This cross-sectional analysis involved a questionnaire survey conducted for 1,812 individuals aged 12–74 years in Beijing. Subjects were local residents living in the region for >6 months before the survey. Subjects were evaluated using clinical examinations with the basic erosive wear examination index and a self-administered questionnaire. Statistical analyses were performed using SPSS software.

Results:

The prevalence of maxillary tooth wear was 84.9% for the molars, 68.9% for the premolars, 74.1% for the canines and 97% for the incisors. In the mandible, the corresponding prevalence rates were 85.2%, 59.3%, 78.6% and 97.4%, respectively. The occlusal, incisal and cervical surfaces showed more frequent wear compared with the other surfaces. Age, acidic beverages, xerostomia and brushing habits were identified as risk factors for tooth wear (P<0.05).

Conclusions:

Tooth wear is common in Beijing. Specific preventive measures should be recommended for individuals reporting excessive consumption of fruits and/or acidic beverages, and those with xerostomia. In particular, incisor wear should be carefully monitored in individuals of all age groups.
Glia-derived ATP inversely regulates excitability of pyramidal and CCK-positive neurons
Authors: Tan Zhibing , Liu Yu , Xi Wang , Lou Hui-fang , Zhu Liya , Guo Zhifei , Mei Lin , Duan Shumin
Published: January 2017

Astrocyte responds to neuronal activity with calcium waves and modulates synaptic transmission through the release of gliotransmitters. However, little is known about the direct effect of gliotransmitters on the excitability of neuronal networks beyond synapses. Here we show that selective stimulation of astrocytes expressing channelrhodopsin-2 in the CA1 area specifically increases the firing frequency of CCK-positive but not parvalbumin-positive interneurons and decreases the firing rate of pyramidal neurons, phenomena mimicked by exogenously applied ATP. Further evidences indicate that ATP-induced increase and decrease of excitability are caused, respectively, by P2Y1 receptor-mediated inhibition of a two-pore domain potassium channel and A1 receptor-mediated opening of a G-protein-coupled inwardly rectifying potassium channel. Moreover, the activation of ChR2-expressing astrocytes reduces the power of kainate-induced hippocampal ex vivo gamma oscillation. Thus, through distinct receptor subtypes coupled with different K+ channels, astrocyte-derived ATP differentially modulates the excitability of different types of neurons and efficiently controls the activity of neuronal network.
A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes
Authors: Shu Lingling , Hoo Ruby L. C. , Wu Xiaoping , Pan Yong , Lee Ida P. C. , Cheong Lai Yee , Bornstein Stefan R , Rong Xianglu , Guo Jiao , Xu Aimin
Published: January 2017

The adipokine adipocyte fatty acid-binding protein (A-FABP) has been implicated in obesity-related cardio-metabolic complications. Here we show that A-FABP increases thermogenesis by promoting the conversion of T4 to T3 in brown adipocytes. We find that A-FABP levels are increased in both white (WAT) and brown (BAT) adipose tissues and the bloodstream in response to thermogenic stimuli. A-FABP knockout mice have reduced thermogenesis and whole-body energy expenditure after cold stress or after feeding a high-fat diet, which can be reversed by infusion of recombinant A-FABP. Mechanistically, A-FABP induces the expression of type-II iodothyronine deiodinase in BAT via inhibition of the nuclear receptor liver X receptor α, thereby leading to the conversion of thyroid hormone from its inactive form T4 to active T3. The thermogenic responses to T4 are abrogated in A-FABP KO mice, but enhanced by A-FABP. Thus, A-FABP acts as a physiological stimulator of BAT-mediated adaptive thermogenesis.
Probing dark exciton diffusion using photovoltage
Authors: Mullenbach Tyler K. , Curtin Ian J. , Zhang Tao , Holmes Russell J.
Published: January 2017

The migration of weakly and non-luminescent (dark) excitons remains an understudied subset of exciton dynamics in molecular thin films. Inaccessible via photoluminescence, these states are often probed using photocurrent methods that require efficient charge collection. Here we probe exciton harvesting in both luminescent and dark materials using a photovoltage-based technique. Transient photovoltage permits a real-time measurement of the number of charges in an organic photovoltaic cell, while avoiding non-geminate recombination losses. The extracted exciton diffusion lengths are found to be similar to those determined using photocurrent. For the luminescent material boron subphthalocyanine chloride, the photovoltage determined diffusion length is less than that extracted from photoluminescence. This indicates that while photovoltage circumvents non-geminate losses, geminate recombination at the donor–acceptor interface remains the primary recombination pathway. Photovoltage thus offers a general approach for extracting a device-relevant diffusion length, while also providing insight in to the dominant carrier recombination pathways.
Hexagonal tungsten oxide nanoflowers as enzymatic mimetics and electrocatalysts
Authors: Park Chan Yeong , Seo Ji Min , Jo Hongil , Park Juhyun , Ok Kang Min , Park Tae Jung
Published: January 2017

Tungsten oxide (WOx) has been widely studied for versatile applications based on its photocatalytic, intrinsic catalytic, and electrocatalytic properties. Among the several nanostructures, we focused on the flower-like structures to increase the catalytic efficiency on the interface with both increased substrate interaction capacities due to their large surface area and efficient electron transportation. Therefore, improved WOx nanoflowers (WONFs) with large surface areas were developed through a simple hydrothermal method using sodium tungstate and hydrogen chloride solution at low temperature, without any additional surfactant, capping agent, or reducing agent. Structural determination and electrochemical analyses revealed that the WONFs have hexagonal Na0.17WO3.085·0.17H2O structure and exhibit peroxidase-like activity, turning from colorless to blue by catalyzing the oxidation of a peroxidase substrate, such as 3,3′,5,5′-tetramethylbenzidine, in the presence of H2O2. Additionally, a WONF-modified glassy carbon electrode was adopted to monitor the electrocatalytic reduction of H2O2. To verify the catalytic efficiency enhancement by the unique shape and structure of the WONFs, they were compared with calcinated WONFs, cesium WOx nanoparticles, and other peroxidase-like nanomaterials. The results indicated that the WONFs showed a low Michaelis-Menten constant (km), high maximal reaction velocity (vmax), and large surface area.
Targeting osteoblastic casein kinase-2 interacting protein-1 to enhance Smad-dependent BMP signaling and reverse bone formation reduction in glucocorticoid-induced osteoporosis
Authors: Liu Jin , Lu Changwei , Wu Xiaohao , Zhang Zongkang , Li Jie , Guo Baosheng , Li Defang , Liang Chao , Dang Lei , Pan Xiaohua , Peng Songlin , Lu Aiping , Zhang Baoting , Zhang Ge
Published: January 2017

The underlying mechanism of the reduced bone formation during the development of glucocorticoid-induced osteoporosis (GIO) remains unclear. Here, we found that the highly expressed CKIP-1 together with lowly expressed total and phosphorylated Smad1/5 in bone samples was accompanied by either the reduced serum bone formation markers in GIO patients or the decreased bone formation in GIO mice. In vitro studies showed that the highly expressed CKIP-1 could promote Smad1 ubiquitination to suppress the Smad-dependent BMP signaling and inhibit osteogenic differentiation and mineral deposition in MC3T3-E1 cells during glucocorticoid treatment. Further, the reduced bone formation in GIO mice could not only be prevented by osteoblasts-specific Ckip-1 ablation, but also be attenuated after osteoblasts-specific Smad1 overexpression. Moreover, osteoblasts-targeting CKIP-1 siRNA treatment also attenuated the bone formation reduction in GIO mice. These study suggest that the highly expressed CKIP-1 in osteoblasts could suppress the Smad-dependent BMP signaling and contribute to the bone formation reduction in GIO. Targeting osteoblastic CKIP-1 would be a novel bone anabolic strategy for GIO patients.
Computational design of an epitope-specific Keap1 binding antibody using hotspot residues grafting and CDR loop swapping
Authors: Liu Xiaofeng , Taylor Richard D. , Griffin Laura , Coker Shu-Fen , Adams Ralph , Ceska Tom , Shi Jiye , Lawson Alastair D. G. , Baker Terry
Published: January 2017

Therapeutic and diagnostic applications of monoclonal antibodies often require careful selection of binders that recognize specific epitopes on the target molecule to exert a desired modulation of biological function. Here we present a proof-of-concept application for the rational design of an epitope-specific antibody binding with the target protein Keap1, by grafting pre-defined structural interaction patterns from the native binding partner protein, Nrf2, onto geometrically matched positions of a set of antibody scaffolds. The designed antibodies bind to Keap1 and block the Keap1-Nrf2 interaction in an epitope-specific way. One resulting antibody is further optimised to achieve low-nanomolar binding affinity by in silico redesign of the CDRH3 sequences. An X-ray co-crystal structure of one resulting design reveals that the actual binding orientation and interface with Keap1 is very close to the design model, despite an unexpected CDRH3 tilt and VH/VL interface deviation, which indicates that the modelling precision may be improved by taking into account simultaneous CDR loops conformation and VH/VL orientation optimisation upon antibody sequence change. Our study confirms that, given a pre-existing crystal structure of the target protein-protein interaction, hotspots grafting with CDR loop swapping is an attractive route to the rational design of an antibody targeting a pre-selected epitope.
RhBMP-2 loaded 3D-printed mesoporous silica/calcium phosphate cement porous scaffolds with enhanced vascularization and osteogenesis properties
Authors: Li Cuidi , Jiang Chuan , Deng Yuan , Li Tao , Li Ning , Peng Mingzheng , Wang Jinwu
Published: January 2017

A major limitation in the development of effective scaffolds for bone regeneration has been the limited vascularization of the regenerating tissue. Here, we propose the development of a novel calcium phosphate cement (CPC)-based scaffold combining the properties of mesoporous silica (MS) with recombinant human bone morphogenic protein-2 (rhBMP-2) to facilitate vascularization and osteogenesis. Specifically, the development of a custom MS/CPC paste allowed the three-dimensional (3D) printing of scaffolds with a defined macroporous structure and optimized silicon (Si) ions release profile to promote the ingrowth of vascular tissue at an early stage after implantation in support of tissue viability and osteogenesis. In addition, the scaffold microstructure allowed the prolonged release of rhBMP-2, which in turn significantly stimulated the osteogenesis of human bone marrow stromal cells in vitro and of bone regeneration in vivo as shown in a rabbit femur defect repair model. Thus, the combination MS/CPC/rhBMP-2 scaffolds might provide a solution to issues of tissue necrosis during the regeneration process and therefore might be able to be readily developed into a useful tool for bone repair in the clinic.
Effect of the KF post-deposition treatment on grain boundary properties in Cu(In, Ga)Se2 thin films
Authors: Nicoara N. , Lepetit Th. , Arzel L. , Harel S. , Barreau N. , Sadewasser S.
Published: January 2017

Significant power conversion efficiency improvements have recently been achieved for thin-film solar cells based on a variety of polycrystalline absorbers, including perovskites, CdTe, and Cu(In,Ga)Se2 (CIGS). The passivation of grain boundaries (GBs) through (post-deposition) treatments is a crucial step for this success. For the case of CIGS, the introduction of a potassium fluoride post-deposition treatment (KF-PDT) has boosted their power conversion efficiency to the best performance of all polycrystalline solar cells. Direct and indirect effects of potassium at the interface and interface-near region in the CIGS layer are thought to be responsible for this improvement. Here, we show that also the electronic properties of the GBs are beneficially modified by the KF-PDT. We used Kelvin probe force microscopy to study the effect of the KF-PDT on the CIGS surface by spatially resolved imaging of the surface potential. We find a clear difference for the GB electronic properties: the KF-PDT increases the band bending at GBs by about 70% and results in a narrower distribution of work function values at the GBs. This effect of the KF-PDT on the GB electronic properties is expected to contribute to the improved efficiency values observed for CIGS thin-film solar cells with KF-PDT.
Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse
Authors: Caldeira Vanessa , Dougherty Kimberly J. , Borgius Lotta , Kiehn Ole
Published: January 2017

Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.
Improved prediction of severe thunderstorms over the Indian Monsoon region using high-resolution soil moisture and temperature initialization
Authors: Osuri K. K. , Nadimpalli R. , Mohanty U. C. , Chen F. , Rajeevan M. , Niyogi D.
Published: January 2017

The hypothesis that realistic land conditions such as soil moisture/soil temperature (SM/ST) can significantly improve the modeling of mesoscale deep convection is tested over the Indian monsoon region (IMR). A high resolution (3 km foot print) SM/ST dataset prepared from a land data assimilation system, as part of a national monsoon mission project, showed close agreement with observations. Experiments are conducted with (LDAS) and without (CNTL) initialization of SM/ST dataset. Results highlight the significance of realistic land surface conditions on numerical prediction of initiation, movement and timing of severe thunderstorms as compared to that currently being initialized by climatological fields in CNTL run. Realistic land conditions improved mass flux, convective updrafts and diabatic heating in the boundary layer that contributed to low level positive potential vorticity. The LDAS run reproduced reflectivity echoes and associated rainfall bands more efficiently. Improper representation of surface conditions in CNTL run limit the evolution boundary layer processes and thereby failed to simulate convection at right time and place. These findings thus provide strong support to the role land conditions play in impacting the deep convection over the IMR. These findings also have direct implications for improving heavy rain forecasting over the IMR, by developing realistic land conditions.
On the Fractality of Complex Networks: Covering Problem, Algorithms and Ahlfors Regularity
Authors: Wang Lihong , Wang Qin , Xi Lifeng , Chen Jin , Wang Songjing , Bao Liulu , Yu Zhouyu , Zhao Luming
Published: January 2017

In this paper, we revisit the fractality of complex network by investigating three dimensions with respect to minimum box-covering, minimum ball-covering and average volume of balls. The first two dimensions are calculated through the minimum box-covering problem and minimum ball-covering problem. For minimum ball-covering problem, we prove its NP-completeness and propose several heuristic algorithms on its feasible solution, and we also compare the performance of these algorithms. For the third dimension, we introduce the random ball-volume algorithm. We introduce the notion of Ahlfors regularity of networks and prove that above three dimensions are the same if networks are Ahlfors regular. We also provide a class of networks satisfying Ahlfors regularity.
Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication
Authors: Aagaard Kjersti M. , Lahon Anismrita , Suter Melissa A. , Arya Ravi P. , Seferovic Maxim D. , Vogt Megan B. , Hu Min , Stossi Fabio , Mancini Michael A. , Harris R. Alan , Kahr Maike , Eppes Catherine , Rac Martha , Belfort Michael A. , Park Chun Shik , Lacorazza Daniel , Rico-Hesse Rebecca
Published: January 2017

Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.
Sensory and autonomic function and structure in footpads of a diabetic mouse model
Authors: Liu Ying , Sebastian Blessan , Liu Ben , Zhang Yiyue , Fissel John A. , Pan Baohan , Polydefkis Michael , Farah Mohamed H.
Published: January 2017

Sensory and autonomic neuropathy affects the majority of type II diabetic patients. Clinically, autonomic evaluation often focuses on sudomotor function yet this is rarely assessed in animal models. We undertook morphological and functional studies to assess large myelinated and small unmyelinated axons in the db/db type II diabetes mouse model. We observed that autonomic innervation of sweat glands in the footpads was significantly reduced in db/db mice compared to control db/+ mice and this deficit was greater compared to reductions in intraepidermal sensory innervation of adjacent epidermis. Additionally, db/db mice formed significantly fewer sweat droplets compared to controls as early as 6 weeks of age, a time when no statistical differences were observed electrophysiologically between db/db and db/+ mice studies of large myelinated sensory and motor nerves. The rate of sweat droplet formation was significantly slower and the sweat droplet size larger and more variable in db/db mice compared to controls. Whereas pilocarpine and glycopyrrolate increased and decreased sweating, respectively, in 6 month-old controls, db/db mice did not respond to pharmacologic manipulations. Our findings indicate autonomic neuropathy is an early and prominent deficit in the db/db model and have implications for the development of therapies for peripheral diabetic neuropathy.
The spleen microenvironment influences disease transformation in a mouse model of KITD816V-dependent myeloproliferative neoplasm
Authors: Pelusi Natalie , Kosanke Maike , Riedt Tamara , Rösseler Corinna , Seré Kristin , Li Jin , Gütgemann Ines , Zenke Martin , Janzen Viktor , Schorle Hubert
Published: January 2017

Activating mutations leading to ligand-independent signaling of the stem cell factor receptor KIT are associated with several hematopoietic malignancies. One of the most common alterations is the D816V mutation. In this study, we characterized mice, which conditionally express the humanized KITD816V receptor in the adult hematopoietic system to determine the pathological consequences of unrestrained KIT signaling during blood cell development. We found that KITD816V mutant animals acquired a myeloproliferative neoplasm similar to polycythemia vera, marked by a massive increase in red blood cells and severe splenomegaly caused by excessive extramedullary erythropoiesis. Moreover, we found mobilization of stem cells from bone marrow to the spleen. Splenectomy prior to KITD816V induction prevented expansion of red blood cells, but rapidly lead to a state of aplastic anemia and bone marrow fibrosis, reminiscent of post polycythemic myeloid metaplasia, the spent phase of polycythemia vera. Our results show that the extramedullary hematopoietic niche microenvironment significantly influences disease outcome in KITD816V mutant mice, turning this model a valuable tool for studying the interplay between functionally abnormal hematopoietic cells and their microenvironment during development of polycythemia vera-like disease and myelofibrosis.
Effect of Flow and Particle-Plastron Collision on the Longevity of Superhydrophobicity
Authors: Hokmabad Babak Vajdi , Ghaemi Sina
Published: January 2017

Among diverse methods for drag reduction, superhydrophobicity has shown considerable promise because it can produce a shear-free boundary without energy input. However, the plastron experiences a limited lifetime due to the dissolution of trapped air from surface cavities, into the surrounding water. The underwater longevity of the plastron, as it is influenced by environmental conditions, such as fine particles suspended in the water, must be studied in order to implement superhydrophobicity in practical applications. We present a proof-of-concept study on the kinetics of air loss from a plastron subjected to a canonical laminar boundary layer at Reδ = 1400 and 1800 (based on boundary layer thickness) with and without suspending 2 micron particles with density of 4 Kg/m3. To monitor the air loss kinetics, we developed an in situ non-invasive optical technique based on total internal reflection at the air-water interface. The shear flow at the wall is characterized by high resolution particle image velocimetry technique. Our results demonstrate that the flow-induced particle-plastron collision shortens the lifetime of the plastron by ~50%. The underlying physics are discussed and a theoretical analysis is conducted to further characterize the mass transfer mechanisms.
RNA helicase DDX3 maintains lipid homeostasis through upregulation of the microsomal triglyceride transfer protein by interacting with HNF4 and SHP
Authors: Tsai Tsung-Yuan , Wang Wei-Ting , Li Hao-Kang , Chen Wei-Ju , Tsai Yu-Hong , Chao Chi-Hong , Wu Lee Yan-Hwa
Published: January 2017

Multifunctional RNA helicase DDX3 participates in HCV infection, one of the major causes of hepatic steatosis. Here, we investigated the role of DDX3 in hepatic lipid metabolism. We found that HCV infection severely reduced DDX3 expression. Analysis of intracellular triglyceride and secreted ApoB indicated that lipid accumulations were increased while ApoB secretion were decreased in DDX3 knockdown HuH7 and HepG2 cell lines. Down-regulation of DDX3 significantly decreased protein and transcript expression of microsomal triglyceride transfer protein (MTP), a key regulator of liver lipid homeostasis. Moreover, DDX3 interacted with hepatocyte nuclear factor 4 (HNF4) and small heterodimer partner (SHP), and synergistically up-regulated HNF4-mediated transactivation of MTP promoter via its ATPase activity. Further investigation revealed that DDX3 interacted with CBP/p300 and increased the promoter binding affinity of HNF4 by enhancing HNF4 acetylation. Additionally, DDX3 partially relieved the SHP-mediated suppression on MTP promoter by competing with SHP for HNF4 binding which disrupted the inactive HNF4/SHP heterodimer while promoted the formation of the active HNF4 homodimer. Collectively, these results imply that DDX3 regulates MTP gene expression and lipid homeostasis through interplay with HNF4 and SHP, which may also reveal a novel mechanism of HCV-induced steatosis.
Design and fabrication of a passive droplet dispenser for portable high resolution imaging system
Authors: Kamal Tahseen , Watkins Rachel , Cen Zijian , Rubinstein Jaden , Kong Gary , Lee Woei Ming
Published: January 2017

Moldless lens manufacturing techniques using standard droplet dispensing technology often require precise control over pressure to initiate fluid flow and control droplet formation. We have determined a series of interfacial fluid parameters optimised using standard 3D printed tools to extract, dispense and capture a single silicone droplet that is then cured to obtain high quality lenses. The dispensing process relies on the recapitulation of liquid dripping action (Rayleigh-Plateau instability) and the capturing method uses the interplay of gravitational force, capillary forces and liquid pinning to control the droplet shape. The key advantage of the passive lens fabrication approach is rapid scale-up using 3D printing by avoiding complex dispensing tools. We characterise the quality of the lenses fabricated using the passive approach by measuring wavefront aberration and high resolution imaging. The fabricated lenses are then integrated into a portable imaging system; a wearable thimble imaging device with a detachable camera housing, that is constructed for field imaging. This paper provides the full exposition of steps, from lens fabrication to imaging platform, necessary to construct a standalone high resolution imaging system. The simplicity of our methodology can be implemented using a regular desktop 3D printer and commercially available digital imaging systems.
ComB proteins expression levels determine Helicobacter pylori competence capacity
Authors: Corbinais Christopher , Mathieu Aurélie , Damke Prashant P. , Kortulewski Thierry , Busso Didier , Prado-Acosta Mariano , Radicella J. Pablo , Marsin Stéphanie
Published: January 2017

Helicobacter pylori chronically colonises half of the world’s human population and is the main cause of ulcers and gastric cancers. Its prevalence and the increase in antibiotic resistance observed recently reflect the high genetic adaptability of this pathogen. Together with high mutation rates and an efficient DNA recombination system, horizontal gene transfer through natural competence makes of H. pylori one of the most genetically diverse bacteria. We show here that transformation capacity is enhanced in strains defective for recN, extending previous work with other homologous recombination genes. However, inactivation of either mutY or polA has no effect on DNA transformation, suggesting that natural competence can be boosted in H. pylori by the persistence of DNA breaks but not by enhanced mutagenesis. The transformation efficiency of the different DNA repair impaired strains correlates with the number of transforming DNA foci formed on the cell surface and with the expression of comB8 and comB10 competence genes. Overexpression of the comB6-B10 operon is sufficient to increase the transformation capacity of a wild type strain, indicating that the ComB complex, present in the bacterial wall and essential for DNA uptake, can be a limiting factor for transformation efficiency.
Photodegradation of octylisothiazolinone and semi-field emissions from facade coatings
Authors: Bollmann Ulla E. , Minelgaite Greta , Schlüsener Michael , Ternes Thomas A. , Vollertsen Jes , Bester Kai
Published: January 2017

Amongst others, 2-octyl-isothiazol-3(2 H)-one (OIT) is used as film preservative in water-based polymer resin paints and renders to prevent the growth of moulds and bacteria. It is known that biocides leach from facades with rainwater and end up in the environment via stormwater runoff. In the present study the leaching and fate of OIT used in facade coatings was determined under natural conditions. Potential phototransformation products were initially identified in laboratory experiments using UV-light. Afterwards, the leaching of OIT and seven degradation products were studied on artificial walls equipped with organic top coatings formulated with OIT. A mass balance, including the leached and remaining amounts of OIT and its seven transformation products, can explain up to 40% of the initial amount of OIT. The OIT remaining in the material after 1.5 yr is by far the largest fraction. The study shows that in the assessment of biocides in coating material, transformation products need to be taken into account both in leachate and remaining in the material. Furthermore, in case of volatile degradation products, the emissions to air might be relevant.
Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains
Authors: Hora Manuel , Carballo-Pacheco Martin , Weber Benedikt , Morris Vanessa K. , Wittkopf Antje , Buchner Johannes , Strodel Birgit , Reif Bernd
Published: January 2017

Antibody light chain amyloidosis is a rare disease caused by fibril formation of secreted immunoglobulin light chains (LCs). The huge variety of antibody sequences puts a serious challenge to drug discovery. The green tea polyphenol epigallocatechin-3-gallate (EGCG) is known to interfere with fibril formation in general. Here we present solution- and solid-state NMR studies as well as MD simulations to characterise the interaction of EGCG with LC variable domains. We identified two distinct EGCG binding sites, both of which include a proline as an important recognition element. The binding sites were confirmed by site-directed mutagenesis and solid-state NMR analysis. The EGCG-induced protein complexes are unstructured. We propose a general mechanistic model for EGCG binding to a conserved site in LCs. We find that EGCG reacts selectively with amyloidogenic mutants. This makes this compound a promising lead structure, that can handle the immense sequence variability of antibody LCs.
RNA sequencing of synaptic and cytoplasmic Upf1-bound transcripts supports contribution of nonsense-mediated decay to epileptogenesis
Authors: Mooney Claire M. , Jimenez-Mateos Eva M. , Engel Tobias , Mooney Catherine , Diviney Mairead , Venø Morten T. , Kjems Jørgen , Farrell Michael A. , O’Brien Donncha F. , Delanty Norman , Henshall David C.
Published: January 2017

The nonsense mediated decay (NMD) pathway is a critical surveillance mechanism for identifying aberrant mRNA transcripts. It is unknown, however, whether the NMD system is affected by seizuresin vivoand whether changes confer beneficial or maladaptive responses that influence long-term outcomes such the network alterations that produce spontaneous recurrent seizures. Here we explored the responses of the NMD pathway to prolonged seizures (status epilepticus) and investigated the effects of NMD inhibition on epilepsy in mice. Status epilepticus led to increased protein levels of Up-frameshift suppressor 1 homolog (Upf1) within the mouse hippocampus. Upf1 protein levels were also higher in resected hippocampus from patients with intractable temporal lobe epilepsy. Immunoprecipitation of Upf1-bound RNA from the cytoplasmic and synaptosomal compartments followed by RNA sequencing identified unique populations of NMD-associated transcripts and altered levels after status epilepticus, including known substrates such asArcas well as novel targets includingInhbaandNpas4. Finally, long-term video-EEG recordings determined that pharmacologic interference in the NMD pathway after status epilepticus reduced the later occurrence of spontaneous seizures in mice. These findings suggest compartment-specific recruitment and differential loading of transcripts by NMD pathway components may contribute to the process of epileptogenesis.
Association between underweight and tooth loss among Korean adults
Authors: Song In-Seok , Han Kyungdo , Ryu Jae-Jun , Park Jun-Beom
Published: January 2017

There is growing interest in the relationship between body mass index and oral health. Previous study showed that being underweight was significantly associated with having lower masticatory performance. This study was performed to assess the relationship between an underweight body mass index lower than 18.5 and the number of natural teeth using nationally representative data. Initially, a total of 25,534 individuals were candidates in the Korean National Health and Nutrition Examination Survey. The analysis in this study was confined to 17,870 subjects who were 19 years or older and without missing values for outcome variables. Body mass index and number of natural teeth were evaluated. Multiple regression analysis was used to evaluate the risk of tooth loss in relation to body mass index. Adjusted odds ratios and their 95% confidence intervals for chewing discomfort in individuals who were underweight, normal, overweight, obese, and extremely obese were 1.712(1.156–2.535), 1.111(0.939–1.315), 1(reference), 0.949(0.798–1.128), and 1.172(0.807–1.700), respectively, after adjustment. The association between underweight and tooth loss was proven by multiple logistic regression analyses after adjusting for confounding factors. Underweight may be considered a potential risk indicator for tooth loss in Korean adults.
Emergent Properties of Giant Vesicles Formed by a Polymerization-Induced Self-Assembly (PISA) Reaction
Authors: Albertsen Anders N. , Szymański Jan K. , Pérez-Mercader Juan
Published: January 2017

Giant micrometer sized vesicles are of obvious interest to the natural sciences as well as engineering, having potential application in fields ranging from drug delivery to synthetic biology. Their formation often requires elaborate experimental techniques and attempts to obtain giant vesicles from chemical media in a one-pot fashion have so far led to much smaller nanoscale structures. Here we show that a tailored medium undergoing controlled radical polymerization is capable of forming giant polymer vesicles. Using a protocol which allows for an aqueous reaction under mild conditions, we observe the macroscale consequences of amphiphilic polymer synthesis and the resulting molecular self-assembly using fluorescence microscopy. The polymerization process is photoinitiated by blue light granting complete control of the reaction, including on the microscope stage. The self-assembly process leads to giant vesicles with radii larger than 10 microns, exhibiting several emergent properties, including periodic growth and collapse as well as phototaxis.
Mastoid vibration affects dynamic postural control during gait in healthy older adults
Authors: Chien Jung Hung , Mukherjee Mukul , Kent Jenny , Stergiou Nicholas
Published: January 2017

Vestibular disorders are difficult to diagnose early due to the lack of a systematic assessment. Our previous work has developed a reliable experimental design and the result shows promising results that vestibular sensory input while walking could be affected through mastoid vibration (MV) and changes are in the direction of motion. In the present paper, we wanted to extend this work to older adults and investigate how manipulating sensory input through mastoid vibration (MV) could affect dynamic postural control during walking. Three levels of MV (none, unilateral, and bilateral) applied via vibrating elements placed on the mastoid processes were combined with the Locomotor Sensory Organization Test (LSOT) paradigm to challenge the visual and somatosensory systems. We hypothesized that the MV would affect sway variability during walking in older adults. Our results revealed that MV significantly not only increased the amount of sway variability but also decreased the temporal structure of sway variability only in anterior-posterior direction. Importantly, the bilateral MV stimulation generally produced larger effects than the unilateral. This is an important finding that confirmed our experimental design and the results produced could guide a more reliable screening of vestibular system deterioration.
Physiological performance of the intertidal Manila clam (Ruditapes philippinarum) to long-term daily rhythms of air exposure
Authors: Yin Xuwang , Chen Peng , Chen Hai , Jin Wen , Yan Xiwu
Published: January 2017

Intertidal organisms, especially the sessile species, often experience long-term periodic air exposure during their lives. Learning the biochemical and physiological responses of intertidal organisms to long-term periodic air exposure and the relationship to duration of air exposure provides insight into adaptation to this variably stressful environment. We studied the Manila clam, Ruditapes philippinarum, an important species in world aquaculture, as a model to evaluate survival, growth, lipid composition, oxygen consumption, oxidative damage, and antioxidant enzyme activity in relation to the duration of air exposure in a long-term (60 days) laboratory study of varying durations of periodic emersion and re-immersion. Our results show: (1) clams undergoing a longer period of air exposure had lower survival and growth compared to those given a shorter exposure, (2) levels of oxidative damage and activities of antioxidant enzymes were higher in all air exposure treatments, but did not increase with duration of air exposure, and (3) the content of docosahexaenoic acid increased with duration of air exposure. Our results can largely be interpreted in the context of the energy expenditure by the clams caused by aerobic metabolism during the daily cycle of emersion and re-immersion and the roles of docosahexaenoic acid against oxidative stress.
Graphene Oxide Dysregulates Neuroligin/NLG-1-Mediated Molecular Signaling in Interneurons in Caenorhabditis elegans
Authors: Chen He , Li Huirong , Wang Dayong
Published: January 2017

Graphene oxide (GO) can be potentially used in many medical and industrial fields. Using assay system of Caenorhabditis elegans, we identified the NLG-1/Neuroligin-mediated neuronal signaling dysregulated by GO exposure. In nematodes, GO exposure significantly decreased the expression of NLG-1, a postsynaptic cell adhesion protein. Loss-of-function mutation of nlg-1 gene resulted in a susceptible property of nematodes to GO toxicity. Rescue experiments suggested that NLG-1 could act in AIY interneurons to regulate the response to GO exposure. In the AIY interneurons, PKC-1, a serine/threonine protein kinase C (PKC) protein, was identified as the downstream target for NLG-1 in the regulation of response to GO exposure. LIN-45, a Raf protein in ERK signaling pathway, was further identified as the downstream target for PKC-1 in the regulation of response to GO exposure. Therefore, GO may dysregulate NLG-1-mediated molecular signaling in the interneurons, and a neuronal signaling cascade of NLG-1-PKC-1-LIN-45 was raised to be required for the control of response to GO exposure. More importantly, intestinal RNAi knockdown of daf-16 gene encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the resistant property of nematodes overexpressing NLG-1 to GO toxicity, suggesting the possible link between neuronal NLG-1 signaling and intestinal insulin signaling in the regulation of response to GO exposure.
Unleashing the Power of Semi-Synthesis: The Discovery of Torisel®
Authors: Skotnicki Jerauld S. , Abou-Gharbia Magid A.
Published: January 2017

Natural products offer unique and creative opportunities for drug discovery. With their complex architecture and multi-faceted functionality, these secondary metabolites often display exquisite pharmacological profiles and properties. Accordingly, natural products provide versatile and innovative starting points to apply the tenets of medicinal chemistry. Rapamycin (Rapamune®) is a potent, polyketide immunosuppressive agent, produced by Streptomyces hygroscopicus. Rapamycin forms a complex with FKBP and mTOR that elicits its unique mechanism of action, central in a number of biological processes. It is approved for the treatment of transplantation rejection. As part of a programme aimed at the identification of novel rapamycin analogues, we have explored systematic semi-synthetic point modifications to functional groups at essential regions of the molecule. The medicinal chemistry design rationale and strategy is highlighted, culminating in the discovery of CCI-779 (temsirolimus, Torisel®). Torisel® was approved (USA, May 2007) for the treatment of advanced renal cell carcinoma.
Recent Advances in Topical Applications for a New Anti-Aging Drug
Authors: Cantecor B. , Savelli M. P. , Marti-Mestres G. , Bonniol V. , Mostefa Side Larbi M. A. , Piccerelle P.
Published: January 2017

The human life span has more than doubled over the last two centuries. With this increase in life expectancy, a significant segment of the aging population will seek to improve their quality of life including the ability to preserve a more youthful appearance for as long as possible. Skin is notably sensitive to aging because it is affected by both intrinsic (genetically determined) and extrinsic (sun radiation, stress, pollution, etc.) processes. In response to consumer demand, numerous laboratories have developed new topical anti-aging formulas labeled as “innovative” but containing common active ingredients (alpha-hydroxy acids, antioxidants, depigmenting agents, etc.) which represent nothing revolutionary because they have been used for many years to reduce signs of ageing.
Section Editorial–Regulatory and Toxicology
Authors: Chilcott R. P.
Published: January 2017

Regulatory guidelines are generally written with great attention to detail in order to promote an unambiguous understanding of requirements. However, the necessarily comprehensive and rigorous nature of such documentation can paradoxically lead to misinterpretation and, consequently, submissions which may not meet the expectations of regulatory organisations.