bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonzero Berry phase in quantum oscillations from giant Rashba-type spin splitting in LaTiO3/SrTiO3 heterostructures
Authors: Veit M. J. , Arras R. , Ramshaw B. J. , Pentcheva R. , Suzuki Y.
Published: April 2018

The manipulation of the spin degrees of freedom in a solid has been of fundamental and technological interest recently for developing high-speed, low-power computational devices. There has been much work focused on developing highly spin-polarized materials and understanding their behavior when incorporated into so-called spintronic devices. These devices usually require spin splitting with magnetic fields. However, there is another promising strategy to achieve spin splitting using spatial symmetry breaking without the use of a magnetic field, known as Rashba-type splitting. Here we report evidence for a giant Rashba-type splitting at the interface of LaTiO3 and SrTiO3. Analysis of the magnetotransport reveals anisotropic magnetoresistance, weak anti-localization and quantum oscillation behavior consistent with a large Rashba-type splitting. It is surprising to find a large Rashba-type splitting in 3d transition metal oxide-based systems such as the LaTiO3/SrTiO3 interface, but it is promising for the development of a new kind of oxide-based spintronics.
Water-stress induced downsizing of light-harvesting antenna complex protects developing rice seedlings from photo-oxidative damage
Authors: Dalal Vijay K. , Tripathy Baishnab C.
Published: April 2018

The impact of water-stress on chloroplast development was studied by applying polyethylene glycol 6000 to the roots of 5-day-old etiolated rice (Oryza sativa) seedlings that were subsequently illuminated up to 72 h. Chloroplast development in drought environment led to down-regulation of light-harvesting Chl-proteins. Photosynthetic proteins of Photosystem II (PSII) and oxygen evolving complex i.e., Cytb559, OEC16, OEC23 and OEC33 as well as those of PSI such as PSI-III, PSI-V, and PSI-VI, decreased in abundance. Consequently, due to reduced light absorption by antennae, the electron transport rates of PSII and PSI decreased by 55% and 25% respectively. Further, seedling development in stress condition led to a decline in the ratio of variable (Fv) to maximum (Fm) Chl a fluorescence, as well in the quantum yield of PSII photochemistry. Addition of Mg2+ to the thylakoid membranes suggested that Mg2+-induced grana stacking was not affected by water deficit. Proteomic analysis revealed the down-regulation of proteins involved in electron transport and in carbon reduction reactions, and up-regulation of antioxidative enzymes. Our results demonstrate that developing seedlings under water deficit could downsize their light-harvesting capacity and components of photosynthetic apparatus to prevent photo-oxidative stress, excess ROS generation and membrane lipid peroxidation.
Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells
Authors: Cheng Shengnan , Lu Ying , Li Yuanyuan , Gao Luyan , Shen Huaying , Song Kai
Published: April 2018

Peritoneal fibrosis (PS) determines the long-term outcome of peritoneal dialysis (PD). We previous confirmed that hydrogen sulfide (H2S) inhibited PS, but its cellular mechanism was not fully elucidated. Epithelial-mesenchymal transition (EMT) of mesothelial cells (MCs) is an important cellular event of PS, we therefore investigated whether EMT can be affected by H2S in MCs. Rats were treated with 4.25% -glucose PD fluids plus lipopolysaccharide for 28 days to produce PS, and NaHS (56 μg/kg.d) was given simultaneously. NaHS (56 μg/kg.d) reduced the deposition of collagen in the submesothelial zone compared with the PS group. In primarily cultured rat MCs, 4.25% -glucose PD fluid induced EMT in MCs featured as loss of ZO-1 and Cytokeratin, and increase of α-SMA, plasminogen activator inhibitor 1, fibronectin and TGF-β1 proteins. PD fluid also increased IL-6 and monocyte chemotactic protein-1 mRNA expressions as well as the phosphorylation of Smad2/3 and Smad3. NaHS (50–300 μmol/L) reversed the above alterations with the optimal dose at 100 μmol/L. Thus, exogenous H2S improves PS by inhibiting EMT in MCs. The anti-EMT effect of H2S is associated with the inhibition of inflammation and TGF-β1-Smad signal pathway.
Effects of green tea on miRNA and microbiome of oral epithelium
Authors: Adami Guy R. , Tangney Christy C. , Tang Jessica L. , Zhou Yalu , Ghaffari Saba , Naqib Ankur , Sinha Saurabh , Green Stefan J. , Schwartz Joel L.
Published: April 2018

Consumption of green tea (GT) extracts or purified catechins has shown the ability to prevent oral and other cancers and inhibit cancer progression in rodent models, but the evidence for this in humans is mixed. Working with humans, we sought to understand the source of variable responses to GT by examining its effects on oral epithelium. Lingual epithelial RNA and lingual and gingival microbiota were measured before and after 4 weeks of exposure in tobacco smokers, whom are at high risk of oral cancer. GT consumption had on average inconsistent effects on miRNA expression in the oral epithelium. Only analysis that examined paired miRNAs, showing changed and coordinated expression with GT exposure, provided evidence for a GT effect on miRNAs, identifying miRNAs co-expressed with two hubs, miR-181a-5p and 301a-3p. An examination of the microbiome on cancer prone lingual mucosa, in contrast, showed clear shifts in the relative abundance of Streptococcus and Staphylococcus, and other genera after GT exposure. These data support the idea that tea consumption can consistently change oral bacteria in humans, which may affect carcinogenesis, but argue that GT effects on oral epithelial miRNA expression in humans vary between individuals.
Author Correction: Microplastics in Spanish Table Salt
Authors: Iñiguez Maria E. , Conesa Juan A. , Fullana Andres
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Publisher Correction: Predictors of chronic kidney disease in type 1 diabetes: a longitudinal study from the AMD Annals initiative
Authors: Piscitelli Pamela , Viazzi Francesca , Fioretto Paola , Giorda Carlo , Ceriello Antonio , Genovese Stefano , Russo Giuseppina , Guida Pietro , Pontremoli Roberto , De Cosmo Salvatore
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Spin-dependent magneto-thermopower of narrow-gap lead chalcogenide quantum wells
Authors: Sengupta Parijat , Wen Yu , Shi Junxia
Published: April 2018

A semi-classical analysis of magneto-thermopower behaviour, namely, the Seebeck and Nernst effect (NE) in quantum wells of IV-VI lead salts with significant extrinsic Rashba spin-orbit coupling (RSOC) is performed in this report. In addition to the spin-dependent Seebeck effect that has been observed before, we also theoretically predict a similar spin-delineated behavior for its magneto-thermal analog, the spin-dependent NE. The choice of lead salts follows from a two-fold advantage they offer, in part, to their superior thermoelectric properties, especially PbTe, while their low band gaps and high spin-orbit coupling make them ideal candidates to study RSOC governed effects in nanostructures. The calculations show a larger longitudinal magneto-thermopower for the spin-up electrons while the transverse components are nearly identical. In contrast, for a magnetic field free case, the related power factor calculations reveal a significantly higher contribution from the spin-down ensemble and suffer a reduction with an increase in the electron density. We also discuss qualitatively the limitations of the semi-classical approach for the extreme case of a high magnetic field and allude to the observed thermopower behaviour when the quantum Hall regime is operational. Finally, techniques to modulate the thermopower are briefly outlined.
Development of a mouse model for the visual and quantitative assessment of lymphatic trafficking and function by in vivo imaging
Authors: Yamaji Yoshihisa , Akita Shinsuke , Akita Hidetaka , Miura Naoya , Gomi Masaki , Manabe Ichiro , Kubota Yoshitaka , Mitsukawa Nobuyuki
Published: April 2018

Methods for quantitative analysis of long distance lymphatic transport of nanoparticles in live animals are yet to be established. We established a mouse model for analysis of time-dependent transport just beneath the abdominal skin to investigate lymph node-to-lymph node trafficking by in vivo imaging. For this purpose, popliteal lymph nodes (PLNs) as well as efferent and afferent lymphatic vessels, marginal veins, and feeding blood vessels were surgically resected to change the lymphatic flow from footpad injections. Using this model, we observed a novel lymphatic flow from the footpad to the proper axillary lymph node (ALN) via the inguinal lymph node (ILN). This drainage pathway was maintained over 12 weeks. Time-dependent transportation of 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide-labelled liposomes from the footpad to the ILN was successfully quantified by an in vivo imaging system. Moreover, congestion and development of a new collateral lymphatic route was visualised under a lymphedema status. Histological analysis of abdominal skin tissues of this model revealed that PLN resection had no effect on the abdominal lymphatic system between the ILN and ALN. These data indicate that this model might be useful to clarify the mechanisms of lymphedema and study direct transportation of lymph or other substances between lymph nodes.
Differential effect of morphine on gastrointestinal transit, colonic contractions and nerve-evoked relaxations in Toll-Like Receptor deficient mice
Authors: Beckett Elizabeth A. H. , Staikopoulos Vasiliki , Hutchinson Mark R.
Published: April 2018

Toll-like receptors (TLRs) are expressed in enteric neurons, glia, gastrointestinal (GI) smooth muscle and mucosa, yet their functional roles in the GI tract are not fully understood. TLRs have been linked to many of the undesirable central effects of chronic opioid administration including hyperalgesia and dependence via activation of central microglia. Opioid-induced bowel dysfunction (OIBD) remains a primary reason for the reduction or withdrawal of opioid analgesics. Morphine-induced inhibition of colonic motility was assessed in vivo by GI transit studies and in vitro using isolated colons from wildtype (WT) and TLR deficient mice. Morphine slowed movement of ingested content in WT but this retardation effect was attenuated in TLR4
−/−
and TLR2/4
−/−
. In isolated colons, morphine reduced amplitude and frequency colonic migrating motor contractions in both WT and TLR2/4
−/−
. Electrical field stimulation elicited distal colon relaxation that was potentiated by morphine in WT but not in TLR2/4
−/−
. Inhibitory junction potentials were of similar amplitude and kinetics in WT and TLR2/4
−/−
distal colon and not altered by morphine. Enteric nerve density and proportion of nitrergic nerves were similar in WT and TLR2/4
−/−
distal colon. These data suggest an involvement of TLRs in opioid pharmacodynamics and thus a potential interventional target for OIBD.
Author Correction: Remodeling of the Actin/Spectrin Membrane-associated Periodic Skeleton, Growth Cone Collapse and F-Actin Decrease during Axonal Degeneration
Authors: Unsain Nicolas , Bordenave Martin D. , Martinez Gaby F. , Jalil Sami , von Bilderling Catalina , Barabas Federico M. , Masullo Luciano A. , Johnstone Aaron D. , Barker Philip A. , Bisbal Mariano , Stefani Fernando D. , Cáceres Alfredo O.
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper
Nucleosomes of polyploid trophoblast giant cells mostly consist of histone variants and form a loose chromatin structure
Authors: Hayakawa Koji , Terada Kanae , Takahashi Tomohiro , Oana Hidehiro , Washizu Masao , Tanaka Satoshi
Published: April 2018

Trophoblast giant cells (TGCs) are one of the cell types that form the placenta and play multiple essential roles in maintaining pregnancy in rodents. TGCs have large, polyploid nuclei resulting from endoreduplication. While previous studies have shown distinct gene expression profiles of TGCs, their chromatin structure remains largely unknown. An appropriate combination of canonical and non-canonical histones, also known as histone variants, allows each cell to exert its cell type-specific functions. Here, we aimed to reveal the dynamics of histone usage and chromatin structure during the differentiation of trophoblast stem cells (TSCs) into TGCs. Although the expression of most genes encoding canonical histones was downregulated, the expression of a few genes encoding histone variants such as H2AX, H2AZ, and H3.3 was maintained at a relatively high level in TGCs. Both the micrococcal nuclease digestion assay and nucleosome stability assay using a microfluidic device indicated that chromatin became increasingly loose as TSCs differentiated. Combinatorial experiments involving H3.3-knockdown and -overexpression demonstrated that variant H3.3 resulted in the formation of loose nucleosomes in TGCs. In conclusion, our study revealed that TGCs possessed loose nucleosomes owing to alterations in their histone composition during differentiation.
Exchange-torque-induced excitation of perpendicular standing spin waves in nanometer-thick YIG films
Authors: Qin Huajun , Hämäläinen Sampo J. , van Dijken Sebastiaan
Published: April 2018

Spin waves in ferrimagnetic yttrium iron garnet (YIG) films with ultralow magnetic damping are relevant for magnon-based spintronics and low-power wave-like computing. The excitation frequency of spin waves in YIG is rather low in weak external magnetic fields because of its small saturation magnetization, which limits the potential of YIG films for high-frequency applications. Here, we demonstrate how exchange-coupling to a CoFeB film enables efficient excitation of high-frequency perpendicular standing spin waves (PSSWs) in nanometer-thick (80 nm and 295 nm) YIG films using uniform microwave magnetic fields. In the 295-nm-thick YIG film, we measure intense PSSW modes up to 10th order. Strong hybridization between the PSSW modes and the ferromagnetic resonance mode of CoFeB leads to characteristic anti-crossing behavior in broadband spin-wave spectra. We explain the excitation of PSSWs by exchange coupling between forced magnetization precessions in the YIG and CoFeB layers. If the amplitudes of these precessions are different, a dynamic exchange torque is generated, causing the emission of spin waves from the interface. PSSWs form when the wave vector of the spin waves matches a perpendicular confinement condition. PSSWs are not excited if exchange coupling between YIG and CoFeB is eliminated by a 10 nm Ta spacer layer. Micromagnetic simulations confirm the exchange-torque-driven mechanism.
Al-Coated Conductive Fiber Filters for High-Efficiency Electrostatic Filtration: Effects of Electrical and Fiber Structural Properties
Authors: Choi Dong Yun , An Eun Jeong , Jung Soo-Ho , Song Dong Keun , Oh Yong Suk , Lee Hyung Woo , Lee Hye Moon
Published: April 2018

Through the direct decomposition of an Al precursor ink AlH3{O(C4H9)2}, we fabricated an Al-coated conductive fiber filter for the efficient electrostatic removal of airborne particles (>99%) with a low pressure drop (~several Pascals). The effects of the electrical and structural properties of the filters were investigated in terms of collection efficiency, pressure drop, and particle deposition behavior. The collection efficiency did not show a significant correlation with the extent of electrical conductivity, as the filter is electrostatically charged by the metallic Al layers forming electrical networks throughout the fibers. Most of the charged particles were collected via surface filtration by Coulombic interactions; consequently, the filter thickness had little effect on the collection efficiency. Based on simulations of various fiber structures, we found that surface filtration can transition to depth filtration depending on the extent of interfiber distance. Therefore, the effects of structural characteristics on collection efficiency varied depending on the degree of the fiber packing density. This study will offer valuable information pertaining to the development of a conductive metal/polymer composite air filter for an energy-efficient and high-performance electrostatic filtration system.
Invasive Rosa rugosa populations outperform native populations, but some populations have greater invasive potential than others
Authors: Zhang Shuping , Isermann Maike , Gan Wenhao , Breed Martin
Published: April 2018

Increased performance of invasive plant species in their introduced range vs. their native range has been previously documented. However, performance differences among invasive populations have rarely been explored, despite this information being central to understanding the evolution of invasiveness as well as being a useful basis to inform management of invasive species. To examine variation in performance among populations of Rosa rugosa in its introduced range, and whether introduced populations perform better than native populations, we quantified growth and reproductive traits in five invasive populations in northwest Europe and two native and declining populations in China. Overall, we found that the introduced R. rugosa populations we sampled performed significantly better than the sampled native populations for growth and reproductive traits (2 to 4 fold increase). However, there was significant variation for most traits among the five invasive populations, demonstrating that some introduced populations we sampled were more successful invaders than others. Our findings provide a useful foundation for management of invasive R. rugosa in Europe, and support the recent call for more intra-species research in invasive species biology.
On the wrong track: ocean acidification attracts larval fish to irrelevant environmental cues
Authors: Rossi Tullio , Pistevos Jennifer C. A. , Connell Sean D. , Nagelkerken Ivan
Published: April 2018

Population replenishment of marine life largely depends on successful dispersal of larvae to suitable adult habitat. Ocean acidification alters behavioural responses to physical and chemical cues in marine animals, including the maladaptive deterrence of settlement-stage larval fish to odours of preferred habitat and attraction to odours of non-preferred habitat. However, sensory compensation may allow fish to use alternative settlement cues such as sound. We show that future ocean acidification reverses the attraction of larval fish (barramundi) to their preferred settlement sounds (tropical estuarine mangroves). Instead, acidification instigates an attraction to unfamiliar sounds (temperate rocky reefs) as well as artificially generated sounds (white noise), both of which were ignored by fish living in current day conditions. This finding suggests that by the end of the century, following a business as usual CO2 emission scenario, these animals might avoid functional environmental cues and become attracted to cues that provide no adaptive advantage or are potentially deleterious. This maladaptation could disrupt population replenishment of this and other economically important species if animals fail to adapt to elevated CO2 conditions.
Changing patterns of human migrations shaped the global population structure of Mycobacterium tuberculosis in France
Authors: Barbier Maxime , Dumitrescu Oana , Pichat Catherine , Carret Gérard , Ronnaux-Baron Anne-Sophie , Blasquez Ghislaine , Godin-Benhaim Christine , Boisset Sandrine , Carricajo Anne , Jacomo Véronique , Fredenucci Isabelle , Pérouse de Montclos Michèle , Genestet Charlotte , Flandrois Jean-Pierre , Ader Florence , Supply Philip , Lina Gérard , Wirth Thierry , Rasigade Jean-Philippe
Published: April 2018

Mycobacterium tuberculosis (Mtb) exhibits a structured phylogeographic distribution worldwide linked with human migrations. We sought to infer how the interactions between distinct human populations shape the global population structure of Mtb on a regional scale. We applied the recently described timescaled haplotypic density (THD) technique on 638 minisatellite-based Mtb genotypes from French tuberculosis patients. THD with a long-term (200 y) timescale indicated that Mtb population in France had been mostly influenced by interactions with Eastern and Southern Europe and, to a lesser extent, Northern and Middle Africa, consistent with historical migrations favored by geographic proximity or commercial exchanges with former French colonies. Restricting the timescale to 20 y, THD identified a sustained influence of Northern Africa, but not Europe where tuberculosis incidence decreased sharply. Evolving interactions between human populations, thus, measurably influence the local population structure of Mtb. Relevant information on such interactions can be inferred using THD from Mtb genotypes.
Regimes of Flow over Complex Structures of Endothelial Glycocalyx: A Molecular Dynamics Simulation Study
Authors: Jiang Xi Zhuo , Feng Muye , Ventikos Yiannis , Luo Kai H.
Published: April 2018

Flow patterns on surfaces grafted with complex structures play a pivotal role in many engineering and biomedical applications. In this research, large-scale molecular dynamics (MD) simulations are conducted to study the flow over complex surface structures of an endothelial glycocalyx layer. A detailed structure of glycocalyx has been adopted and the flow/glycocalyx system comprises about 5,800,000 atoms. Four cases involving varying external forces and modified glycocalyx configurations are constructed to reveal intricate fluid behaviour. Flow profiles including temporal evolutions and spatial distributions of velocity are illustrated. Moreover, streamline length and vorticity distributions under the four scenarios are compared and discussed to elucidate the effects of external forces and glycocalyx configurations on flow patterns. Results show that sugar chain configurations affect streamline length distributions but their impact on vorticity distributions is statistically insignificant, whilst the influence of the external forces on both streamline length and vorticity distributions are trivial. Finally, a regime diagram for flow over complex surface structures is proposed to categorise flow patterns.
Dietary and Physical Activity Interventions for Colorectal Cancer Survivors: A Randomized Controlled Trial
Authors: Lee C. F. , Ho Judy W. C. , Fong Daniel Y. T. , Macfarlane Duncan J. , Cerin Ester , Lee Antoinette M. , Leung Sharron , Chan Wynnie Y. Y. , Leung Ivy P. F. , Lam Sharon H. S. , Chu Natural , Taylor Aliki J. , Cheng Kar-keung
Published: April 2018

There has been evidence on the protective effects of diets high in fiber and low in red and processed meat (RPM), and physical activity (PA) against colorectal cancer (CRC) development, but that against CRC recurrence has been limited. This study evaluated the efficacy of a behavioral program comprising dietary and PA interventions in improving Chinese CRC survivors’ lifestyle. A 2 × 2 factorial randomized controlled trial of 223 CRC patients (82 females, mean age 65), randomly assigned to receive dietary, PA or both interventions, or usual care for 12 months, and assessed every 6 months for 24 months. Primary outcomes included two dietary and two PA targets. Secondary outcomes included changes in dietary consumptions and PA levels. Dietary interventions significantly increased the odds of achieving the targets of consuming less RPM at all time-points (OR 3.22–4.57, all p < 0.01) and refined grain (RG) at months 6 (OR 3.13, p = 0.002) and 24 (OR 2.19, p = 0.039), and reduced RPM (2.49–3.48 servings/week, all p < 0.01) and RG (0.31–0.5 servings/day, all p < 0.01) consumptions. Patients receiving PA interventions potentially spent more time on moderate-to-vigorous PA. This study demonstrated the efficacy of a behavioral program in improving dietary habits of Chinese CRC survivors.
Genetic homogeneity of goat malaria parasites in Asia and Africa suggests their expansion with domestic goat host
Authors: Kaewthamasorn Morakot , Takeda Mika , Saiwichai Tawee , Gitaka Jesse N. , Tiawsirisup Sonthaya , Imasato Yuhei , Mossaad Ehab , Sarani Ali , Kaewlamun Winai , Channumsin Manun , Chaiworakul Suchart , Katepongpun Wichit , Teeveerapunya Surapong , Panthong Jarus , Mureithi Dominic K. , Bawm Saw , Htun Lat Lat , Win Mar Mar , Ismail Ahmed Ali , Ibrahim Abdalla Mohamed , Suganuma Keisuke , Hakimi Hassan , Nakao Ryo , Katakura Ken , Asada Masahito , Kaneko Osamu
Published: April 2018

Plasmodium was first identified in a goat in Angola in 1923, and only recently characterized by DNA isolation from a goat blood sample in Zambia. Goats were first domesticated in the Fertile Crescent approximately 10,000 years ago, and are now globally distributed. It is not known if the Plasmodium identified in African goats originated from parasites circulating in the local ungulates, or if it co-evolved in the goat before its domestication. To address this question, we performed PCR-based surveillance using a total of 1,299 goat blood samples collected from Sudan and Kenya in Africa, Iran in west Asia, and Myanmar and Thailand in southeast Asia. Plasmodium DNA was detected from all locations, suggesting that the parasite is not limited to Africa, but widely distributed. Whole mitochondrial DNA sequences revealed that there was only one nucleotide substitution between Zambian/Kenyan samples and others, supporting the existence of a goat-specific Plasmodium species, presumably Plasmodium caprae, rather than infection of goats by local ungulate malaria parasites. We also present the first photographic images of P. caprae, from one Kenyan goat sample.
Zn-based eutectic mixture as anolyte for hybrid redox flow batteries
Authors: Wang Yiyu , Niu Zhihui , Zheng Qi , Zhang Changkun , Ye Jing , Dai Gaole , Zhao Yu , Zhang Xiaohong
Published: April 2018

Developing greener batteries with new chemistries is a formidable challenge, and a major focus for years to come. Redox flow batteries are receiving increasing research interest for grid-scale electrochemical energy storage owing to their unique architecture. However, challenges still remain by their low energy density as well as corrosive and/or toxic electrolytes. An anolyte based on aprotic Zn deep-eutectic-solvent, which uses low cost, abundant and environmentally benign materials, exhibits a utilizable concentration of Zn2+ ca. 1.7 M, resulting in a reversible volumetric capacity of ca. 90 A h·L−1. Combined with high efficiencies and relatively low redox potential of −1.12 V vs. Ag/AgCl, such an anolyte provides an alternative way to explore a family of anolytes using new chemistries for rechargeable Zn batteries that meet the criteria for grid-scale electrical energy storage.
Low-dose tributyltin exposure induces an oxidative stress-triggered JNK-related pancreatic β-cell apoptosis and a reversible hypoinsulinemic hyperglycemia in mice
Authors: Huang Chun-Fa , Yang Ching-Yao , Tsai Jing-Ren , Wu Cheng-Tien , Liu Shing-Hwa , Lan Kuo-Cheng
Published: April 2018

Tributyltin (TBT), an endocrine disrupting chemical, can be found in food (particular in fish and seafood) and drinking water by contamination. Here, we elucidated the effects and possible mechanisms of low-dose TBT on the growth and function of pancreatic β-cells and glucose metabolism in mice. Submicromolar-concentration of TBT significantly induced β-cell cytotoxicity and apoptosis, which were accompanied by poly (ADP-ribose) polymerase cleavage and mitogen-activated protein kinases-JNK and ERK1/2 phosphorylation. TBT could also suppress the glucose-stimulated insulin secretion in β-cells and isolated mouse islets. TBT increased reactive oxygen species production. TBT-induced β-cell cytotoxicity and apoptosis were significantly prevented by antioxidant N-acetylcysteine (NAC) and JNK inhibitor SP600125, but not ERK1/2 inhibitor PD98059 and p38 inhibitor SB203580. Both NAC and SP600125 inhibited JNK phosphorylation and reduced cell viability in TBT-treated β-cells. Four-week exposure of TBT (0.25 mg/kg) to mice revealed the decreased plasma insulin, increased blood glucose and plasma malondialdehyde, suppressed islet insulin secretion, and increased islet caspase-3 activity, which could be reversed by NAC treatment. After removing the TBT exposure for 2 weeks, the TBT-induced glucose metabolism alteration was significantly reversed. These results suggest that low-dose TBT can induce β-cell apoptosis and interfere with glucose homeostasis via an oxidative stress-related pathway.
Endothelial Cell Phenotypes are Maintained During Angiogenesis in Cultured Microvascular Networks
Authors: Motherwell Jessica M. , Anderson Christopher R. , Murfee Walter L.
Published: April 2018

A challenge in tissue engineering biomimetic models for studying angiogenesis is building the physiological complexity of real microvascular networks. Our laboratory recently introduced the rat mesentery culture model as an ex vivo experimental platform for investigating multicellular dynamics involved in angiogenesis within intact microvascular networks. The objective of this study was to compare endothelial cell phenotypes along capillary sprouts in cultured ex vivo rat mesentery microvascular networks to in vivo endothelial cell phenotypes. For Day 3 (Ex Vivo) tissues, adult rat mesentery tissues were cultured for three days in media supplemented with 10% serum. For Day 3 (In Vivo) tissues, adult rats were anesthetized and the mesentery was exteriorized for twenty minutes to induce angiogenesis. Microvascular networks from Day 3 (Ex Vivo) and Day 3 (In Vivo) groups were angiogenic, characterized by an increase in vessel density, capillary sprouting, and identification of similar BrdU-positive endothelial cell distributions along sprouts. Endothelial cells in both groups extended pseudopodia at the distal edge of capillary sprouts and displayed similar endothelial cell UNC5b, VEGFR-2, and CD36 labeling patterns. The results from this study support the physiological relevance of the rat mesentery culture model and highlight its novelty as a biomimetic tool for angiogenesis research.
Transverse dielectrophoretic-based DNA nanoscale confinement
Authors: Mahshid Sara , Lu Jia , Abidi Abrar A. , Sladek Robert , Reisner Walter W. , Ahamed Mohammed Jalal
Published: April 2018

Confinement of single molecules within nanoscale environments is crucial in a range of fields, including biomedicine, genomics, and biophysics. Here, we present a method that can concentrate, confine, and linearly stretch DNA molecules within a single optical field of view using dielectrophoretic (DEP) force. The method can convert an open surface into one confining DNA molecules without a requirement for bonding, hydrodynamic or mechanical components. We use a transverse DEP field between a top coverslip and a bottom substrate, both of which are coated with a transparent conductive material. Both layers are attached using double-sided tape, defining the chamber. The nanofeatures lie at the “floor” and do not require any bonding. With the application of an alternating (AC) electric field (2 Vp-p) between the top and bottom electrodes, a DEP field gradient is established and used to concentrate, confine and linearly extend DNA in nanogrooves as small as 100-nm in width. We also demonstrate reversible loading/unloading of DNA molecules into nanogrooves and nanopits by switching frequency (between 10 kHz to 100 kHz). The technology presented in this paper provides a new method for single-molecule trapping and analysis.
Serpine1 Knockdown Enhances MMP Activity after Flexor Tendon Injury in Mice: Implications for Adhesions Therapy
Authors: Freeberg Margaret A. T. , Farhat Youssef M. , Easa Anas , Kallenbach Jacob G. , Malcolm Dominic W. , Buckley Mark R. , Benoit Danielle S. W. , Awad Hani A.
Published: April 2018

Injuries to flexor tendons can be complicated by fibrotic adhesions, which severely impair the function of the hand. Adhesions have been associated with TGF-β1, which causes upregulation of PAI-1, a master suppressor of protease activity, including matrix metalloproteinases (MMP). In the present study, the effects of inhibiting PAI-1 in murine zone II flexor tendon injury were evaluated utilizing knockout (KO) mice and local nanoparticle-mediated siRNA delivery. In the PAI-1 KO murine model, reduced adherence of injured tendon to surrounding subcutaneous tissue and accelerated recovery of normal biomechanical properties compared to wild type controls were observed. Furthermore, MMP activity was significantly increased in the injured tendons of the PAI-1 KO mice, which could explain their reduced adhesions and accelerated remodeling. These data demonstrate that PAI-1 mediates fibrotic adhesions in injured flexor tendons by suppressing MMP activity. In vitro siRNA delivery to silence Serpine1 expression after treatment with TGF-β1 increased MMP activity. Nanoparticle-mediated delivery of siRNA targeting Serpine1 in injured flexor tendons significantly reduced target gene expression and subsequently increased MMP activity. Collectively, the data demonstrate that PAI-1 can be a druggable target for treating adhesions and accelerating the remodeling of flexor tendon injuries.
DNA-release by Streptococcus pneumoniae autolysin LytA induced Krueppel-like factor 4 expression in macrophages
Authors: Herta Toni , Bhattacharyya Aritra , Bollensdorf Christian , Kabus Christin , García Pedro , Suttorp Norbert , Hippenstiel Stefan , Zahlten Janine
Published: April 2018

The recruitment of myeloid cells to the lung is of utmost importance for the elimination of invading pathogens. We investigated the Streptococcus pneumoniae-dependent induction mechanism of KLF4 in macrophages as a potential regulator of the macrophage immune response. We demonstrated that only viable pneumococci, which have direct contact to the host cells and release LytA-dependent DNA, induced KLF4. Exogenous supplementation of pneumococcal, other bacterial, eukaryotic foreign (human) or self (mouse) DNA to autolysis-deficient pneumococci restored (at least in part) pneumococci-related KLF4 induction. Experiments using TLR9, TRIF and MyD88 knockout macrophages revealed that TLR9, TRIF and MyD88 were partly involved in the S. pneumoniae-induced KLF4 expression. BMMs missing important DNA receptor related molecules (ASC−/−, STING−/−) showed no differences in pneumococci-related KLF4 expression. Similar results were observed with IFNAR−/− BMMs and Type I IFN stimulated cells. LyzMcre mediated knockdown of KLF4 in BMMs resulted in a decreased secretion of proinflammatory cytokines and enhanced IL-10 release. In summary, we showed that pneumococci-related KLF4 induction in macrophages is mediated via a PAMP-DAMP induction mechanism involving a hitherto unknown host cell DNA sensor leading to a more proinflammatory macrophage phenotype.
An investigation of the mechanical and microstructural evolution of a TiNbZr alloy with varied ageing time
Authors: Biesiekierski Arne , Lin Jixing , Munir Khurram , Ozan Sertan , Li Yuncang , Wen Cuie
Published: April 2018

Alloys comprised of the highly biocompatible elements titanium, niobium and zirconium have been a major focus in recent years in the field of metallic biomaterials. To contribute to the corpus of data in this field, the current paper presents results from a thorough microstructural and mechanical investigation of Ti-32Nb-6Zr subjected to a variety of ageing treatments. The presented alloy was stabilized to the higher temperature, body-centred cubic phase, showing only minimal precipitation on prolonged ageing, despite the presence of nanoscaled spinodal segregation arising from the Nb-Zr interaction. It further showed excellent mechanical properties, with tensile yield stresses as high as 820 MPa and Young’s moduli as low as 53 GPa. This leads to the ratio of strength to modulus, also known as the admissible strain, reaching a maximum of 1.3% after 6 hours ageing. These results are further supported by similar measurements from nanoindentation analysis.
The C-terminal HRET sequence of Kv1.3 regulates gating rather than targeting of Kv1.3 to the plasma membrane
Authors: Voros Orsolya , Szilagyi Orsolya , Balajthy András , Somodi Sándor , Panyi Gyorgy , Hajdu Péter
Published: April 2018

Kv1.3 channels are expressed in several cell types including immune cells, such as T lymphocytes. The targeting of Kv1.3 to the plasma membrane is essential for T cell clonal expansion and assumed to be guided by the C-terminus of the channel. Using two point mutants of Kv1.3 with remarkably different features compared to the wild-type Kv1.3 (A413V and H399K having fast inactivation kinetics and tetraethylammonium-insensitivity, respectively) we showed that both Kv1.3 channel variants target to the membrane when the C-terminus was truncated right after the conserved HRET sequence and produce currents identical to those with a full-length C-terminus. The truncation before the HRET sequence (NOHRET channels) resulted in reduced membrane-targeting but non-functional phenotypes. NOHRET channels did not display gating currents, and coexpression with wild-type Kv1.3 did not rescue the NOHRET-A413V phenotype, no heteromeric current was observed. Interestingly, mutants of wild-type Kv1.3 lacking HRET(E) (deletion) or substituted with five alanines for the HRET(E) motif expressed current indistinguishable from the wild-type. These results demonstrate that the C-terminal region of Kv1.3 immediately proximal to the S6 helix is required for the activation gating and conduction, whereas the presence of the distal region of the C-terminus is not exclusively required for trafficking of Kv1.3 to the plasma membrane.
A retrospective study on association between obesity and cardiovascular risk diseases with aging in Chinese adults
Authors: Sun Jie , Zhou Weihong , Gu Tianwei , Zhu Dalong , Bi Yan
Published: April 2018

This study aimed to investigate the prevalence of overweight and obesity and its relationship with cardiovascular risk diseases among different sex and age groups in an urban Chinese adult population. A retrospective analysis was performed on 384,061 Chinese adults aged 20 years and older in Nanjing. The age-standardized prevalence of overweight and obesity was 42.8% and 13.2% in men and 23.9% and 6.6% in women. A gradually increasing trend was observed in the prevalence of overweight and obesity from 2008 to 2016, especially in individuals aged 20~39 years. Overweight and obesity were significantly associated with increased risks of dyslipidemia, diabetes mellitus, hypertension, and hyperuricemia. Age weakened such relationship for both genders, which spiked in individuals aged 20~39 years. For men and women aged 20~39 years, the OR (95% CI) of obesity reached 4.23 (4.01–4.47) and 5.29 (4.63–6.04) for dyslipidemia, 3.70 (2.97–4.60) and 6.38 (3.86–10.55) for diabetes mellitus, 6.19 (5.76–6.64) and 9.36 (7.86–11.13) for hypertension, and 3.66 (3.45–3.88) and 6.65 (5.70–7.74) for hyperuricemia, respectively. The increasing trend in the epidemic of overweight and obesity is a risk factor for cardiovascular risk diseases in Chinese adults, especially in individuals aged 20~39 years.
Author Correction: REM sleep respiratory behaviours match mental content in narcoleptic lucid dreamers
Authors: Oudiette Delphine , Dodet Pauline , Ledard Nahema , Artru Emilie , Rachidi Inès , Similowski Thomas , Arnulf Isabelle
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features
Authors: El-Sherbiny Y. M. , Psarras A. , Md Yusof M. Y. , Hensor E. M. A. , Tooze R. , Doody G. , Mohamed A. A. A , McGonagle D. , Wittmann M. , Emery P. , Vital E. M.
Published: April 2018

Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity of the ISG transcriptome, cell-specific expression, response to IFN-subtypes and bimodality of expression. We developed and clinically validated a 2-score system (IFN-Score-A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN-annotated modules. We evaluated these scores using in-vitro IFN stimulation as well as in sorted cells then clinically validated in a cohort of 328 autoimmune disease patients and healthy controls. ISGs varied in response to IFN-subtypes and both scores varied between cell subsets. IFN-Score-A differentiated Systemic Lupus Erythematosus (SLE) from both Rheumatoid Arthritis (RA) and Healthy Controls (HC) (both p < 0.001), while IFN-Score-B differentiated SLE and RA from HC (both p < 0.001). In SLE, both scores were associated with cutaneous and hematological (all p < 0.05) but not musculoskeletal disease activity. Comparing with bimodal (IFN-high/low) classification, significant differences in IFN-scores were found between diagnostic groups within the IFN-high group. Our continuous 2-score system is more clinically relevant than a simple bimodal classification of IFN status. This system should allow improvement in diagnosis, stratification, and therapy in IFN-mediated autoimmunity.
Hedgehog Interacting Protein Promotes Fibrosis and Apoptosis in Glomerular Endothelial Cells in Murine Diabetes
Authors: Zhao Xin-Ping , Chang Shiao-Ying , Liao Min-Chun , Lo Chao-Sheng , Chenier Isabelle , Luo Hongyu , Chiasson Jean-Louis , Ingelfinger Julie R. , Chan John S. D. , Zhang Shao-Ling
Published: April 2018

We investigated whether renal hedgehog interacting protein (Hhip) expression contributes to the progression of diabetic nephropathy (DN) and studied its related mechanism(s) in vivo and in vitro. Here, we show that Hhip expression is highly elevated in glomerular endothelial cells of adult type 1 diabetic (T1D) Akita and T2D db/db mouse kidneys as compared to non-diabetic control littermates. Hyperglycemia enhances reactive oxygen species (ROS) generation via NADPH oxidase 4 (Nox4) activation and stimulates renal Hhip gene expression, and that elevated renal Hhip gene expression subsequently activates the TGFβ1- Smad2/3 cascade and promotes endothelial to mesenchymal transition associated with endothelial cell fibrosis/apoptosis in vivo and in vitro. Furthermore, kidneys of low-dose streptozotocin-induced diabetic heterozygous Hhip deficient (Hhip+/−) mice displayed a normal albumin/creatinine ratio with fewer features of DN (glomerulosclerosis/fibrosis and podocyte apoptosis/loss) and less evidence of renal compensation (glomerular hypertrophy and hyperfiltration) as compared to diabetic wild type controls (Hhip+/+). Thus, our studies demonstrated that renal Hhip expression is associated with nephropathy development in diabetes and that hyperglycemia-induced renal Hhip expression may mediate glomerular endothelial fibrosis and apoptosis in diabetes, a novel finding.
The role of stabilizing and communicating symptoms given overlapping communities in psychopathology networks
Authors: Blanken Tessa F. , Deserno Marie K. , Dalege Jonas , Borsboom Denny , Blanken Peter , Kerkhof Gerard A. , Cramer Angélique O. J.
Published: April 2018

Network theory, as a theoretical and methodological framework, is energizing many research fields, among which clinical psychology and psychiatry. Fundamental to the network theory of psychopathology is the role of specific symptoms and their interactions. Current statistical tools, however, fail to fully capture this constitutional property. We propose community detection tools as a means to evaluate the complex network structure of psychopathology, free from its original boundaries of distinct disorders. Unique to this approach is that symptoms can belong to multiple communities. Using a large community sample and spanning a broad range of symptoms (Symptom Checklist-90-Revised), we identified 18 communities of interconnected symptoms. The differential role of symptoms within and between communities offers a framework to study the clinical concepts of comorbidity, heterogeneity and hallmark symptoms. Symptoms with many and strong connections within a community, defined as stabilizing symptoms, could be thought of as the core of a community, whereas symptoms that belong to multiple communities, defined as communicating symptoms, facilitate the communication between problem areas. We propose that defining symptoms on their stabilizing and/or communicating role within and across communities accelerates our understanding of these clinical phenomena, central to research and treatment of psychopathology.
Shorter sleep duration and better sleep quality are associated with greater tissue density in the brain
Authors: Takeuchi Hikaru , Taki Yasuyuki , Nouchi Rui , Yokoyama Ryoichi , Kotozaki Yuka , Nakagawa Seishu , Sekiguchi Atsushi , Iizuka Kunio , Yamamoto Yuki , Hanawa Sugiko , Araki Tsuyoshi , Miyauchi Carlos Makoto , Shinada Takamitsu , Sakaki Kohei , Nozawa Takayuki , Ikeda Shigeyuki , Yokota Susumu , Daniele Magistro , Sassa Yuko , Kawashima Ryuta
Published: April 2018

Poor sleep quality is associated with unfavorable psychological measurements, whereas sleep duration has complex relationships with such measurements. The aim of this study was to identify the associations between microstructural properties of the brain and sleep duration/sleep quality in a young adult. The associations between mean diffusivity (MD), a measure of diffusion tensor imaging (DTI), and sleep duration/sleep quality were investigated in a study cohort of 1201 normal young adults. Positive correlations between sleep duration and MD of widespread areas of the brain, including the prefrontal cortex (PFC) and the dopaminergic systems, were identified. Negative correlations between sleep quality and MD of the widespread areas of the brain, including the PFC and the right hippocampus, were also detected. Lower MD has been previously associated with more neural tissues in the brain. Further, shorter sleep duration was associated with greater persistence and executive functioning (lower Stroop interference), whereas good sleep quality was associated with states and traits relevant to positive affects. These results suggest that bad sleep quality and longer sleep duration were associated with aberrant neurocognitive measurements in the brain in healthy young adults.
A new way of producing pediocin in Pediococcus acidilactici through intracellular stimulation by internalized inulin nanoparticles
Authors: Kim Whee-Soo , Lee Jun-Yeong , Singh Bijay , Maharjan Sushila , Hong Liang , Lee Sang-Mok , Cui Lian-Hua , Lee Ki-June , Kim GiRak , Yun Cheol-Heui , Kang Sang-Kee , Choi Yun-Jaie , Cho Chong-Su
Published: April 2018

One of the most challenging aspects of probiotics as a replacement for antibiotics is to enhance their antimicrobial activity against pathogens. Given that prebiotics stimulate the growth and/or activity of probiotics, we developed phthalyl inulin nanoparticles (PINs) as prebiotics and observed their effects on the cellular and antimicrobial activities of Pediococcus acidilactici (PA). First, we assessed the internalization of PINs into PA. The internalization of PINs was largely regulated by glucose transporters in PA, and the process was energy-dependent. Once internalized, PINs induced PA to produce substantial amounts of antimicrobial peptide (pediocin), which is effective against both Gram-positive (Salmonella Gallinarum) and Gram-negative (Listeria monocytogenes) pathogens. When treated with small-sized PINs, PA witnessed a nine-fold increase in antimicrobial activity. The rise in pediocin activity in PA treated with PINs was accompanied by enhanced expression of stress response genes (groEL, groES, dnaK) and pediocin biosynthesis genes (pedA, pedD). Although the mechanism is not clear, it appears that the internalization of PINs by PA causes mild stress to activate the PA defense system, leading to increased production of pediocin. Overall, we identified a prebiotic in nanoparticle form for intracellular stimulation of probiotics, demonstrating a new avenue for the biological production of antimicrobial peptides.