bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian preference towards morningness is associated with lower slow sleep spindle amplitude and intensity in adolescents
Authors: Merikanto Ilona , Kuula Liisa , Makkonen Tommi , Bódizs Róbert , Halonen Risto , Heinonen Kati , Lahti Jari , Räikkönen Katri , Pesonen Anu-Katriina
Published: October 2017

Individual circadian preference types and sleep EEG patterns related to spindle characteristics, have both been associated with similar cognitive and mental health phenotypes. However, no previous study has examined whether sleep spindles would differ by circadian preference. Here, we explore if spindle amplitude, density, duration or intensity differ by circadian preference and whether these associations are moderated by spindle location, frequency, and time distribution across the night. The participants (N = 170, 59% girls; mean age = 16.9, SD = 0.1 years) filled in the shortened 6-item Horne-Östberg Morningness-Eveningness Questionnaire. We performed an overnight sleep EEG at the homes of the participants. In linear mixed model analyses, we found statistically significant lower spindle amplitude and intensity in the morning as compared to intermediate (P < 0.001) and evening preference groups (P < 0.01; P > 0.06 for spindle duration and density). Spindle frequency moderated the associations (P < 0.003 for slow (<13 Hz); P > 0.2 for fast (>13 Hz)). Growth curve analyses revealed a distinct time distribution of spindles across the night by the circadian preference: both spindle amplitude and intensity decreased more towards morning in the morning preference group than in other groups. Our results indicate that circadian preference is not only affecting the sleep timing, but also associates with sleep microstructure regarding sleep spindle phenotypes.
Prognostic role of plasma fibrinogen in patients with uterine leiomyosarcoma – a multicenter study
Authors: Bekos Christine , Grimm Christoph , Brodowicz Thomas , Petru Edgar , Hefler Lukas , Reimer Daniel , Koch Horst , Reinthaller Alexander , Polterauer Stephan , Polterauer Mariella
Published: October 2017

Fibrinogen has an important pathophysiological role in tumor cell progression and development of metastases in different types of cancer. The present study aimed to evaluate the role of pre-treatment fibrinogen plasma concentrations as a biomarker for tumor biology and prognosis in patients with uterine leiomyosarcoma (ULMS). Clinical data of patients with ULMS were assessed in this multi-center study Pre-therapeutic fibrinogen plasma concentrations were evaluated. We investigated the association between fibrinogen plasma levels and clinico-pathological parameters and performed univariate and multivariable survival analyses. In total, 70 women with ULMS were included into the analysis. Mean (SD) pre-treatment fibrinogen plasma levels were 480.2 (172.3) mg/dL. Patients with advanced tumor stage, increased tumor size and higher histological grading had higher fibrinogen levels (p = 0.02, p = 0.013, and p = 0.029, respectively). In ULMS patients with increased fibrinogen levels 5-year overall survival (OS) rates were 25.0% compared to 52.9% in ULMS patients with normal fibrinogen, respectively. Univariate survival analyses revealed that elevated fibrinogen plasma levels (p = 0.030), advanced tumor stage (p < 0.001) and undifferentiated histology (p = 0.003) showed association with unfavorable OS. In multivariable analysis, histological grade (p = 0.03) and tumor stage (0.02) were independently associated with survival. Elevated fibrinogen plasma levels were associated with aggressive tumor biology and poor prognosis in women with ULMS. Fibrinogen might be useful as a novel biomarker in ULMS.
T cells upon activation promote endothelin 1 production in monocytes via IFN-γ and TNF-α
Authors: Shinagawa Shoshi , Okazaki Takahiro , Ikeda Mari , Yudoh Kazuo , Kisanuki Yaz Y. , Yanagisawa Masashi , Kawahata Kimito , Ozaki Shoichi
Published: October 2017

Endothelin 1 (ET-1), mainly produced from vascular endothelial cells, induces vasoconstriction in physiological conditions. The endothelin receptor antagonist is among the most effective agents for pulmonary hypertension. However, little is known about the production source of ET-1 in inflammation and immunity. Here, we studied whether T cell-mediated ET-1 production system exists and operates independent of the production system in vascular endothelial cells. ET-1 production was readily detectable in the culture supernatant of human PBMCs and murine spleen cells stimulated with anti-CD3 antibody. Immunocytostaining showed that ET-1-producing cells emerged only in PBMCs stimulated with anti-CD3 antibody. Using the Transwell system, both murine and human monocytes sorted with magnetic beads in the inner chamber produced ET-1 when T cells were activated with antigen or anti-CD3 antibody in the outer chamber. This ET-1 production was inhibited by anti-IFN-γ and/or TNF-α antibody. Furthermore, monocytes purified from ETflox/flox;Tie2-Cre( + ) mice, which conditionally lack ET-1 in hematopoietic stem cells and vascular endothelial cells, did not produce ET-1 even when stimulated by antigen-specific T cell activation. This study demonstrates the existence of an immune-mediated ET-1 production induced by T cells upon activation through IFN-γ and TNF-α.
Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors
Authors: Bhattacharyya Sagnik , Egerton Alice , Kim Euitae , Rosso Lula , Riano Barros Daniela , Hammers Alexander , Brammer Michael , Turkheimer Federico E. , Howes Oliver D. , McGuire Philip
Published: October 2017

Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man. Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10 mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [11C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors.
Hydrogen storage and stability properties of Pd–Pt solid-solution nanoparticles revealed via atomic and electronic structure
Authors: Kumara Loku Singgappulige Rosantha , Sakata Osami , Kobayashi Hirokazu , Song Chulho , Kohara Shinji , Ina Toshiaki , Yoshimoto Toshiki , Yoshioka Satoru , Matsumura Syo , Kitagawa Hiroshi
Published: October 2017

Bimetallic Pd1−xPt
x
solid-solution nanoparticles (NPs) display charging/discharging of hydrogen gas, which has relevance for fuel cell technologies; however, the constituent elements are immiscible in the bulk phase. We examined these material systems using high-energy synchrotron X-ray diffraction, X-ray absorption fine structure and hard X-ray photoelectron spectroscopy techniques. Recent studies have demonstrated the hydrogen storage properties and catalytic activities of Pd-Pt alloys; however, comprehensive details of their structural and electronic functionality at the atomic scale have yet to be reported. Three-dimensional atomic-scale structure results obtained from the pair distribution function (PDF) and reverse Monte Carlo (RMC) methods suggest the formation of a highly disordered structure with a high cavity-volume-fraction for low-Pt content NPs. The NP conduction band features, as extracted from X-ray absorption near-edge spectra at the Pd and Pt L
III
-edge, suggest that the Pd conduction band is filled by Pt valence electrons. This behaviour is consistent with observations of the hydrogen storage capacity of these NPs. The broadening of the valence band width and the down-shift of the d-band centre away from the Fermi level upon Pt substitution also provided evidence for enhanced stability of the hydride (ΔH) features of the Pd1−xPt
x
solid-solution NPs with a Pt content of 8-21 atomic percent.
Active contours driven by difference of Gaussians
Authors: Akram Farhan , Garcia Miguel Angel , Puig Domenec
Published: October 2017

In this paper, a novel edge-based active contour method is proposed based on the difference of Gaussians (DoG) to segment intensity inhomogeneous images. DoG is known as a feature enhancement tool, which can enhance the edges of an image. However, in the proposed energy functional it is used as an edge-indicator parameter, which acts like a balloon force during the level-set curve evolution process. In the proposed formulation, the internal energy term penalizes the deviation of the level-set function from a signed distance function and external energy term evolves the contour towards the boundaries of the objects. There are three main advantages of the proposed method. First, image difference computed using the DoG function provides the global structure of an image, which helps to segment the image globally that the traditional edge-based methods are unable to do. Second, it has a low time complexity compared to the state-of-the-art active contours developed in the context of intensity inhomogeneity. Third, it is not sensitive to the initial position of contour. Experimental results using both synthetic and real brain magnetic resonance (MR) images show that the proposed method yields better segmentation results compared to the state-of-the-art.
Reactivity and sensitivity of commercially available influenza rapid diagnostic tests in Japan
Authors: Sakai-Tagawa Yuko , Yamayoshi Seiya , Kawakami Chiharu , Le Mai Q. , Uchida Yuko , Saito Takehiko , Nidom Chairul A. , Humaira Ira , Toohey-Kurth Kathy , Arafa Abdel-Satar , Liu Ming-Tsan , Shu Yuelong , Kawaoka Yoshihiro
Published: October 2017

Seasonal influenza virus routinely causes epidemic infections throughout the world. Sporadic infections by H5N1, H5N6, and H7N9 viruses are also reported. To treat patients suffering from such viral infections, broadly reactive and highly sensitive influenza rapid diagnostic tests (IRDTs) are required. Here, we examined the reactivity and sensitivity of 25 IRDTs available in Japan for the detection of seasonal H1N1pdm09, H3N2, and type B viruses, as well as highly pathogenic H5 and H7 viruses. All of the IRDTs tested detected the seasonal viruses and H5 and H7 viruses albeit with different sensitivities. Several IRDTs detected the H5 and H7 viruses and the seasonal viruses with similar (high) sensitivity.
Application of Lysine-specific Labeling to Detect Transient Interactions Present During Human Lysozyme Amyloid Fibril Formation
Authors: Ahn Minkoo , Waudby Christopher A. , Bernardo-Gancedo Ana , De Genst Erwin , Dhulesia Anne , Salvatella Xavier , Christodoulou John , Dobson Christopher M. , Kumita Janet R.
Published: October 2017

Populating transient and partially unfolded species is a crucial step in the formation and accumulation of amyloid fibrils formed from pathogenic variants of human lysozyme linked with a rare but fatal hereditary systemic amyloidosis. The partially unfolded species possess an unstructured β-domain and C-helix with the rest of the α-domain remaining native-like. Here we use paramagnetic relaxation enhancement (PRE) measured by NMR spectroscopy to study the transient intermolecular interactions between such intermediate species. Nitroxide spin labels, introduced specifically at three individual lysine residues, generate distinct PRE profiles, indicating the presence of intermolecular interactions between residues within the unfolded β-domain. This study describes the applicability to PRE NMR measurements of selective lysine labeling, at different sites within a protein, as an alternative to the introduction of spin labels via engineered cysteine residues. These results reveal the importance of the β-sheet region of lysozyme for initiating self-assembly into amyloid fibrils.
Marine heatwave causes unprecedented regional mass bleaching of thermally resistant corals in northwestern Australia
Authors: Le Nohaïc Morane , Ross Claire L. , Cornwall Christopher E. , Comeau Steeve , Lowe Ryan , McCulloch Malcolm T. , Schoepf Verena
Published: October 2017

In 2015/16, a marine heatwave associated with a record El Niño led to the third global mass bleaching event documented to date. This event impacted coral reefs around the world, including in Western Australia (WA), although WA reefs had largely escaped bleaching during previous strong El Niño years. Coral health surveys were conducted during the austral summer of 2016 in four bioregions along the WA coast (~17 degrees of latitude), ranging from tropical to temperate locations. Here we report the first El Niño-related regional-scale mass bleaching event in WA. The heatwave primarily affected the macrotidal Kimberley region in northwest WA (~16°S), where 4.5–9.3 degree heating weeks (DHW) resulted in 56.6–80.6% bleaching, demonstrating that even heat-tolerant corals from naturally extreme, thermally variable reef environments are threatened by heatwaves. Some heat stress (2.4 DHW) and bleaching (<30%) also occurred at Rottnest Island (32°01’S), whereas coral communities at Ningaloo Reef (23°9’S) and Bremer Bay (34°25’S) were not impacted. The only other major mass bleaching in WA occurred during a strong La Niña event in 2010/11 and primarily affected reefs along the central-to-southern coast. This suggests that WA reefs are now at risk of severe bleaching during both El Niño and La Niña years.
Exfoliated WS2-Nafion Composite based Electromechanical Actuators
Authors: Loeian Masoud S. , Ziolkowska Dominika A. , Khosravi Farhad , Jasinski Jacek B. , Panchapakesan Balaji
Published: October 2017

The ability to convert electrical energy into mechanical motion is of significant interest in many energy conversion technologies. Here, we demonstrate the first liquid phase exfoliated WS2-Nafion nanocomposite based electro-mechanical actuators. Highly exfoliated layers of WS2 mixed with Nafion solution, solution cast and doped with Li+ was studied as electromechanical actuators. Resonant Raman spectroscopy, X-ray photo-electron-spectroscopy, differential scanning calorimetry, dynamic mechanical analysis, and AC impedance spectroscopy were used to study the structure, photoluminescence, water uptake, mechanical and electromechanical actuation properties of the exfoliated nanocomposites. A 114% increase in elastic modulus (dry condition), 160% increase in proton conductivity, 300% increase in water uptake, cyclic strain amplitudes of ~0.15% for 0.1 Hz excitation frequency, tip displacements greater than nanotube-Nafion and graphene-Nafion actuators and continuous operation for more than 5 hours is observed for TMD-Nafion actuators. The mechanism behind the increase in water uptake is a result of oxygen atoms occupying the vacancies in the hydrophilic exfoliated flakes and subsequently bonding with water, not possible in Nafion composites based on carbon nanotube and graphene.
Antibiotics induce polarization of pleural macrophages to M2-like phenotype in patients with tuberculous pleuritis
Authors: Wang Sisi , Zhang Jian , Sui Liyan , Xu Hao , Piao Qianling , Liu Ying , Qu Xinglong , Sun Ying , Song Lei , Li Dan , Peng Liping , Hua Shucheng , Hu Guangan , Chen Jianzhu
Published: October 2017

Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural macrophages change in phenotype, transcription and function following antibiotics treatment in patients with tuberculous pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic treatment in the pleural effusions and pleural macrophages up-regulated markers characteristic of M2 macrophages such as CD163 and CD206. Differential expression analysis of transcriptomes from four paired samples before and after treatment identified 230 treatment-specific responsive genes in pleural macrophages. Functional analysis identified interferon-related pathway to be the most responsive genes and further confirmed macrophage polarization to M2-like phenotype. We further demonstrate that expression of a significant fraction of responsive genes was modulated directly by antibiotics in pleural macrophagesin vitro. Our results conclude that pleural macrophages polarize from M1-like to M2-like phenotype within a mean of 3.5 days post antibiotics treatment, which is dependent on both pleural cytokine environment and direct modulatory effects of antibiotics. The treatment-specific genes could be used to study the roles of pleural macrophages in the pathogenesis of tuberculous pleuritis and to monitor the response to antibiotics treatment.
Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model
Authors: Bauer Sophie , Wennberg Huldt Charlotte , Kanebratt Kajsa P. , Durieux Isabell , Gunne Daniela , Andersson Shalini , Ewart Lorna , Haynes William G. , Maschmeyer Ilka , Winter Annika , Ämmälä Carina , Marx Uwe , Andersson Tommy B.
Published: October 2017

Human in vitro physiological models studying disease and drug treatment effects are urgently needed as more relevant tools to identify new drug targets and therapies. We have developed a human microfluidic two-organ-chip model to study pancreatic islet–liver cross-talk based on insulin and glucose regulation. We have established a robust co-culture of human pancreatic islet microtissues and liver spheroids maintaining functional responses up to 15 days in an insulin-free medium. Functional coupling, demonstrated by insulin released from the islet microtissues in response to a glucose load applied in glucose tolerance tests on different days, promoted glucose uptake by the liver spheroids. Co-cultures maintained postprandial glucose concentrations in the circulation whereas glucose levels remained elevated in both single cultures. Thus, insulin secreted into the circulation stimulated glucose uptake by the liver spheroids, while the latter, in the absence of insulin, did not consume glucose as efficiently. As the glucose concentration fell, insulin secretion subsided, demonstrating a functional feedback loop between the liver and the insulin-secreting islet microtissues. Finally, inter-laboratory validation verified robustness and reproducibility. Further development of this model using tools inducing impaired glucose regulation should provide a unique in vitro system emulating human type 2 diabetes mellitus.
Trabecular bone anisotropy imaging with a compact laser-undulator synchrotron x-ray source
Authors: Jud Christoph , Braig Eva , Dierolf Martin , Eggl Elena , Günther Benedikt , Achterhold Klaus , Gleich Bernhard , Rummeny Ernst , Noël Peter , Pfeiffer Franz , Muenzel Daniela
Published: October 2017

Conventional x-ray radiography is a well-established standard in diagnostic imaging of human bones. It reveals typical bony anatomy with a strong surrounding cortical bone and trabecular structure of the inner part. However, due to limited spatial resolution, x-ray radiography cannot provide information on the microstructure of the trabecular bone. Thus, microfractures without dislocation are often missed in initial radiographs, resulting in a lack or delay of adequate therapy. Here we show that x-ray vector radiography (XVR) can overcome this limitation and allows for a deeper insight into the microstructure with a radiation exposure comparable to standard radiography. XVR senses x-ray ultrasmall-angle scattering in addition to the attenuation contrast and thereby reveals the mean scattering strength, its degree of anisotropy and the orientation of scattering structures. Corresponding to the structural characteristics of bones, there is a homogenous mean scattering signal of the trabecular bone but the degree of anisotropy is strongly affected by variations in the trabecular structure providing more detailed information on the bone microstructure. The measurements were performed at the Munich Compact Light Source, a novel type of x-ray source based on inverse Compton scattering. This laboratory-sized source produces highly brilliant quasi-monochromatic x-rays with a tunable energy.
Conventional and unconventional secretory proteins expressed with silkworm bombyxin signal peptide display functional fidelity
Authors: Park Sungjo , Arrell D. Kent , Reyes Santiago , Park Enoch Y. , Terzic Andre
Published: October 2017

Growth factors are signaling molecules which orchestrate cell growth, proliferation and differentiation. The majority are secreted proteins, exported through the classical endoplasmic reticulum (ER)/Golgi-dependent pathway, but a few are released by unconventional ER/Golgi-independent means. Human fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1), are canonical prototypes secreted by the unconventional and conventional pathway, respectively. We herein examined whether expression of these two growth factors in the Bombyx mori nucleopolyhedrovirus (BmNPV)-based silkworm expression system with its innate signal peptide, bombyxin, secures structural homogeneity at the signal peptide cleavage site regardless of the native secretory route. Proteomic analysis mapped structural microheterogeneity of signal peptide cleavage at the amino terminus of FGF2, whereas IGF1 displayed homogeneous amino-terminal cleavage with complete removal of the bombyxin signal peptide. A cell proliferation assay revealed potent functional activity of both FGF2 and IGF1, suggesting that FGF2 amino-terminal microheterogeneity does not alter mitogenic activity. These findings demonstrate that the occurrence of amino-terminal structural homogeneity may be associated with the original secretion mechanism of a particular growth factor. Furthermore, our results highlight the bombyxin signal peptide as a reliable secretion sequence applicable to mass production of functionally active secretory proteins in a silkworm-based expression platform.
Interactions Between Transfemoral Amputees and a Powered Knee Prosthesis During Load Carriage
Authors: Brandt Andrea , Wen Yue , Liu Ming , Stallings Jonathan , Huang He Helen
Published: October 2017

Machines and humans become mechanically coupled when lower limb amputees walk with powered prostheses, but these two control systems differ in adaptability. We know little about how they interact when faced with real-world physical demands (e.g. carrying loads). Here, we investigated how each system (i.e. amputee and powered prosthesis) responds to changes in the prosthesis mechanics and gravitational load. Five transfemoral amputees walked with and without load (i.e. weighted backpack) and a powered knee prosthesis with two pre-programmed controller settings (i.e. for load and no load). We recorded subjects’ kinematics, kinetics, and perceived exertion. Compared to the no load setting, the load setting reduced subjects’ perceived exertion and intact-limb stance time when they carried load. When subjects did not carry load, their perceived exertion and gait performance did not significantly change with controller settings. Our results suggest transfemoral amputees could benefit from load-adaptive powered knee controllers, and controller adjustments affect amputees more when they walk with (versus without) load. Further understanding of the interaction between powered prostheses, amputee users, and various environments may allow researchers to expand the utility of prostheses beyond simple environments (e.g. firm level ground without load) that represent only a subset of real-world environments.
Ecological and sanitary impacts of bacterial communities associated to biological invasions in African commensal rodent communities
Authors: Diagne Christophe , Galan Maxime , Tamisier Lucie , d’Ambrosio Jonathan , Dalecky Ambroise , Bâ Khalilou , Kane Mamadou , Niang Youssoupha , Diallo Mamoudou , Sow Aliou , Gauthier Philippe , Tatard Caroline , Loiseau Anne , Piry Sylvain , Sembène Mbacké , Cosson Jean-François , Charbonnel Nathalie , Brouat Carine
Published: October 2017

Changes in host-parasite ecological interactions during biological invasion events may affect both the outcome of invasions and the dynamics of exotic and/or endemic infections. We tested these hypotheses, by investigating ongoing house mouse (Mus musculus domesticus) and black rat (Rattus rattus) invasions in Senegal (West Africa). We used a 16S gene rRNA amplicon sequencing approach to study potentially zoonotic bacterial communities in invasive and native rodents sampled along two well-defined independent invasion routes. We found that individual host factors (body mass and sex) were important drivers of these bacterial infections in rodents. We observed that the bacterial communities varied along invasion routes and differed between invasive and native rodents, with native rodents displaying higher overall bacterial diversity than invasive rodents. Differences in prevalence levels for some bacterial Operational Taxonomic Units (OTUs) provided support for ecological processes connecting parasitism and invasion success. Finally, our results indicated that rodent invasions may lead to the introduction of exotic bacterial genera and/or to changes in the prevalence of endemic ones. This study illustrates the difficulty of predicting the relationship between biodiversity and disease risks, and advocate for public health prevention strategies based on global pathogen surveillance followed by accurate characterization of potential zoonotic agents.
Puerarin attenuates diabetic kidney injury through the suppression of NOX4 expression in podocytes
Authors: Li Xueling , Cai Weijing , Lee Kyung , Liu Bohan , Deng Yueyi , Chen Yiping , Zhang Xianwen , He John Cijiang , Zhong Yifei
Published: October 2017

Radix puerariae, a traditional Chinese herbal medication, has been used to treat patients with diabetic nephropathy (DN). Several studies demonstrated that puerarin, the active compound of radix puerariae, reduces diabetic injury in streptozotocin (STZ)-induced diabetic rodent models. However, as STZ injection alone results in mild kidney injury, the therapeutic benefit afforded by puerarin in DN remained inconclusive. Thus we sought to clarify the role of puerarin by employing an accelerated DN model, STZ-induced diabetes in the endothelial nitric oxide synthase-null (eNOS−/−) mice. Puerarin treatment of diabetic eNOS−/− mice significantly attenuated albuminuria and diabetic kidney injury, which were associated with reduced oxidative stress and reduced NAPDH oxidase 4 (NOX4) in glomeruli of diabetic eNOS−/− mice. Puerarin treatment of murine podocytes culture in high glucose conditions led to reduced superoxide production and NOX4 expression. We further determined that that puerarin treatment increased both mRNA and protein levels of SIRT1 in podocytes and that puerarin led to SIRT1-mediated deacetylation of NF-κB and suppression of NOX4 expression. Our findings confirm the renoprotective effects of puerarin in an experimental model of advanced DN and provide a molecular mechanism by which puerarin exerts the anti-oxidative effects in podocytes  in the diabetic milieu.
Surface engineering of perovskite films for efficient solar cells
Authors: Wang Jin-Feng , Zhu Lei , Zhao Ben-Guang , Zhao Yu-Long , Song Jian , Gu Xiu-Quan , Qiang Ying-Huai
Published: October 2017

It is critical to prepare smooth and dense perovskite films for the fabrication of high efficiency perovskite solar cells. However, solution casting process often results in films with pinhole formation and incomplete surface coverage. Herein, we demonstrate a fast and efficient vacuum deposition method to optimize the surface morphology of solution-based perovskite films. The obtained planar devices exhibit an average power conversion efficiency (PCE) of 13.42% with a standard deviation of ±2.15% and best efficiency of 15.57%. Furthermore, the devices also show excellent stability of over 30 days with a slight degradation <9% when stored under ambient conditions. We also investigated the effect of vacuum deposition thickness on the electron transportation and overall performance of the devices. This work provides a versatile approach to prepare high-quality perovskite films and paves a way for high-performance and stable perovskite photovoltaic devices.
Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain
Authors: Anderson Christopher S. , Ortega Sandra , Chaves Francisco A. , Clark Amelia M. , Yang Hongmei , Topham David J. , DeDiego Marta L.
Published: October 2017

The induction of antibodies specific for the influenza HA protein stalk domain is being pursued as a universal strategy against influenza virus infections. However, little work has been done looking at natural or induced antigenic variability in this domain and the effects on viral fitness. We analyzed human H1 HA head and stalk domain sequences and found substantial variability in both, although variability was highest in the head region. Furthermore, using human immune sera from pandemic A/California/04/2009 immune subjects and mAbs specific for the stalk domain, viruses were selectedin vitrocontaining mutations in both domains that partially contributed to immune evasion. Recombinant viruses encoding amino acid changes in the HA stalk domain replicated wellin vitro, and viruses incorporating two of the stalk mutations retained pathogenicityin vivo. These findings demonstrate that the HA protein stalk domain can undergo limited drift under immune pressure and the viruses can retain fitness and virulencein vivo, findings which are important to consider in the context of vaccination targeting this domain.
Shifts in microbial communities in soil, rhizosphere and roots of two major crop systems under elevated CO2 and O3
Authors: Wang Peng , Marsh Ellen L. , Ainsworth Elizabeth A. , Leakey Andrew D. B. , Sheflin Amy M. , Schachtman Daniel P.
Published: October 2017

Rising atmospheric concentrations of CO2 and O3 are key features of global environmental change. To investigate changes in the belowground bacterial community composition in response to elevated CO2 and O3 (eCO2 and eO3) the endosphere, rhizosphere and soil were sampled from soybeans under eCO2 and maize under eO3. The maize rhizosphere and endosphere α-diversity was higher than soybean, which may be due to a high relative abundance of Rhizobiales. Only the rhizosphere microbiome composition of the soybeans changed in response to eCO2, associated with an increased abundance of nitrogen fixing microbes. In maize, the microbiome composition was altered by the genotype and linked to differences in root exudate profiles. The eO3 treatment did not change the microbial communities in the rhizosphere, but altered the soil communities where hybrid maize was grown. In contrast to previous studies that focused exclusively on the soil, this study provides new insights into the effects of plant root exudates on the composition of the belowground microbiome in response to changing atmospheric conditions. Our results demonstrate that plant species and plant genotype were key factors driving the changes in the belowground bacterial community composition in agroecosystems that experience rising levels of atmospheric CO2 and O3.
Comparative transcriptome analysis reveals potentially novel roles of Homeobox genes in adipose deposition in fat-tailed sheep
Authors: Kang Danju , Zhou Guangxian , Zhou Shiwei , Zeng Jie , Wang Xiaolong , Jiang Yu , Yang Yuxin , Chen Yulin
Published: October 2017

Adipose tissues are phenotypically, metabolically and functionally heterogeneous based on the sites of their deposition. Undesirable fat deposits in the body are often detrimental to animal and human health. To unravel the potential underlying mechanisms governing accumulation of adipose tissues in various regions of the body, i.e., subcutaneous (SAT), visceral (VAT) and tail (TAT), we profiled transcriptomes from Tan sheep, a Chinese indigenous breed with notable fat tail using RNA-seq. Upon comparison, we identified a total of 1,058 differentially expressed genes (DEGs) between the three adipose types (218, 324, and 795 in SAT/VAT, SAT/TAT, and VAT/TAT, respectively), from which several known key players were identified that are involved in lipid metabolic process, Wnt signals, Vitamin A metabolism, and transcriptional regulation of adipocyte differentiation. We also found that many elevated genes in VAT were notably enriched for key biological processes such as cytokine secretion, signaling molecule interaction and immune systems. Several developmental genes including HOXC11, HOXC12 and HOXC13, and adipose-expressed genes in the tail region, such as HOTAIR_2, HOTAIR_3 and SP9 were specially highlighted, indicating their strong associations with tail fat development in fat-tailed sheep. Our results provide new insight into exploring the specific fat deposition in tail, also contribute to the understanding of differences between adipose depots.
Plasma amino acid profile associated with fatty liver disease and co-occurrence of metabolic risk factors
Authors: Yamakado Minoru , Tanaka Takayuki , Nagao Kenji , Imaizumi Akira , Komatsu Michiharu , Daimon Takashi , Miyano Hiroshi , Tani Mizuki , Toda Akiko , Yamamoto Hiroshi , Horimoto Katsuhisa , Ishizaka Yuko
Published: October 2017

Fatty liver disease (FLD) increases the risk of diabetes, cardiovascular disease, and steatohepatitis, which leads to fibrosis, cirrhosis, and hepatocellular carcinoma. Thus, the early detection of FLD is necessary. We aimed to find a quantitative and feasible model for discriminating the FLD, based on plasma free amino acid (PFAA) profiles. We constructed models of the relationship between PFAA levels in 2,000 generally healthy Japanese subjects and the diagnosis of FLD by abdominal ultrasound scan by multiple logistic regression analysis with variable selection. The performance of these models for FLD discrimination was validated using an independent data set of 2,160 subjects. The generated PFAA-based model was able to identify FLD patients. The area under the receiver operating characteristic curve for the model was 0.83, which was higher than those of other existing liver function-associated markers ranging from 0.53 to 0.80. The value of the linear discriminant in the model yielded the adjusted odds ratio (with 95% confidence intervals) for a 1 standard deviation increase of 2.63 (2.14–3.25) in the multiple logistic regression analysis with known liver function-associated covariates. Interestingly, the linear discriminant values were significantly associated with the progression of FLD, and patients with nonalcoholic steatohepatitis also exhibited higher values.
Dissipative generation of significant amount of mechanical entanglement in a coupled optomechanical system
Authors: Chen Rong-Xin , Liao Chang-Geng , Lin Xiu-Min
Published: October 2017

We propose an approach for generating steady-state mechanical entanglement in a coupled optomechanical system. By applying four-tone driving lasers with weighted amplitudes and specific frequencies, we obtain an effective Hamiltonian that couples the delocalized Bogoliubov modes of the two mechanical oscillators to the cavity modes via beam-splitter-like interactions. When the mechanical decay rate is small, the Bogoliubov modes can be effectively cooled by the dissipative dynamics of the cavity modes, generating steady-state entanglement of the mechanical modes. The mechanical entanglement obtained in the stationary regime is strongly dependent on the values of the ratio of the effective optomechanical coupling strengths. Numerical simulation with the full linearized Hamiltonian shows that significant amount of mechanical entanglement can indeed be obtained by balancing the opposing effects of varying the ratio and by carefully avoiding the system parameters that may lead to amplified oscillations of the mechanical mean values detrimental to the entanglement generation.
Organosolv-Water Cosolvent Phase Separation on Cellulose and its Influence on the Physical Deconstruction of Cellulose: A Molecular Dynamics Analysis
Authors: Smith Micholas Dean , Cheng Xiaolin , Petridis Loukas , Mostofian Barmak , Smith Jeremy C.
Published: October 2017

Deconstruction of cellulose is crucial for the chemical conversion of lignocellulose into fuel/bioproduct precursors. Recently, a water-organosolv cosolvent system (THF-water) has been shown to both phase-separate on cellulose surfaces and partially deconstruct Avicel  (cellulose) in the absence of acid. Here we employ molecular dynamics simulations to determine whether other common water-organosolv cosolvent systems (acetone, ethanol, and γ-valerolactone) exhibit phase separation at cellulose surface and whether this alters a purely physical cellulose dissociation pathway. Despite finding varied degrees of phase-separation of organosolv on cellulose surfaces, physical dissociation is not enhanced. Interestingly, however, the total amount the median water-cellulose contact lifetimes increases for the cosolvent systems in the order of THF > acetone > ethanol > γ-valerolactone. Together our results indicate two points: a purely physical process for deconstruction of cellulose is unlikely for these cosolvents, and in THF-water, unlike γ-valerolactone- (and some concentrations of acetone and ethanol) water cosolvents, a significant fraction of surface water is slowed. This slowing may be of importance in enhancing chemical deconstruction of cellulose, as it permits an increase in potential THF-water-cellulose reactions, even while the amount of water near cellulose is decreased.
Development and Validation of a Multi-Algorithm Analytic Platform to Detect Off-Target Mechanical Ventilation
Authors: Adams Jason Y. , Lieng Monica K. , Kuhn Brooks T. , Rehm Greg B. , Guo Edward C. , Taylor Sandra L. , Delplanque Jean-Pierre , Anderson Nicholas R.
Published: October 2017

Healthcare-specific analytic software is needed to process the large volumes of streaming physiologic waveform data increasingly available from life support devices such as mechanical ventilators. Detection of clinically relevant events from these data streams will advance understanding of critical illness, enable real-time clinical decision support, and improve both clinical outcomes and patient experience. We used mechanical ventilation waveform data (VWD) as a use case to address broader issues of data access and analysis including discrimination between true events and waveform artifacts. We developed an open source data acquisition platform to acquire VWD, and a modular,multi-algorithmanalyticplatform (ventMAP) to enable automated detection of off-target ventilation (OTV) delivery in critically-ill patients. We tested the hypothesis that use of artifact correction logic would improve the specificity of clinical event detection without compromising sensitivity. We showed that ventMAP could accurately detect harmful forms of OTV including excessive tidal volumes and common forms of patient-ventilator asynchrony, and that artifact correction significantly improved the specificity of event detection without decreasing sensitivity. Our multi-disciplinary approach has enabled automated analysis of high-volume streaming patient waveform data for clinical and translational research, and will advance the study and management of critically ill patients requiring mechanical ventilation.
Low dose nitrite improves reoxygenation following renal ischemia in rats
Authors: Cantow Kathleen , Flemming Bert , Ladwig-Wiegard Mechthild , Persson Pontus B. , Seeliger Erdmann
Published: October 2017

In hypoxic and acidic tissue environments, nitrite is metabolised to nitric oxide, thus, bringing about novel therapeutic options in myocardial infarction, peripheral artery disease, stroke, and hypertension. Following renal ischemia, reperfusion of the kidney remains incomplete and tissue oxygenation is reduced for several minutes to hours. Thus, in renal ischemia-reperfusion injury, providing nitrite may have outstanding therapeutic value. Here we demonstrate nitrite’s distinct potential to rapidly restore tissue oxygenation in the renal cortex and medulla after 45 minutes of complete unilateral kidney ischemia in the rat. Notably, tissue oxygenation was completely restored, while tissue perfusion did not fully reach pre-ischemia levels within 60 minutes of reperfusion. Nitrite was infused intravenously in a dose, which can be translated to the human. Specifically, methaemoglobin did not exceed 3%, which is biologically negligible. Hypotension was not observed. Providing nitrite well before ischemia and maintaining nitrite infusion throughout the reperfusion period prevented the increase in serum creatinine by ischemia reperfusion injury. In conclusion, low-dose nitrite restores renal tissue oxygenation in renal ischemia reperfusion injury and enhances regional kidney post-ischemic perfusion. As nitrite provides nitric oxide predominantly in hypoxic tissues, it may prove a specific measure to reduce renal ischemia reperfusion injury.
Intra-colony disease progression induces fragmentation of coral fluorescent pigments
Authors: Caldwell Jamie M. , Ushijima Blake , Couch Courtney S. , Gates Ruth D.
Published: October 2017

As disease spreads through living coral, it can induce changes in the distribution of coral’s naturally fluorescent pigments, making fluorescence a potentially powerful non-invasive intrinsic marker of coral disease. Here, we show the usefulness of live-imaging laser scanning confocal microscopy to investigate coral health state. We demonstrate that the Hawaiian coral Montipora capitata consistently emits cyan and red fluorescence across a depth gradient in reef habitats, but the micro-scale spatial distribution of those pigments differ between healthy coral and coral affected by a tissue loss disease. Naturally diseased and laboratory infected coral systematically exhibited fragmented fluorescent pigments adjacent to the disease front as indicated by several measures of landscape structure (e.g., number of patches) relative to healthy coral. Histology results supported these findings. Pigment fragmentation indicates a disruption in coral tissue that likely impedes translocation of energy within a colony. The area of fragmented fluorescent pigments in diseased coral extended 3.03 mm ± 1.80 mm adjacent to the disease front, indicating pathogenesis was highly localized rather than systemic. Our study demonstrates that coral fluorescence can be used as a proxy for coral health state, and, such patterns may help refine hypotheses about modes of pathogenesis.
Association between Ideal Cardiovascular Health Metrics and Suboptimal Health Status in Chinese Population
Authors: Wang Youxin , Liu Xiaoxue , Qiu Jing , Wang Hao , Liu Di , Zhao Zhongyao , Song Manshu , Song Qiaofeng , Wang Xizhu , Zhou Yong , Wang Wei
Published: October 2017

Suboptimal health status (SHS) is a physical state between health and illness, and previous studies suggested that SHS is associated with majority components of cardiovascular health metrics defined by American Heart Association (AHA). We investigated the association between SHS and cardiovascular health metrics in a cross-sectional analysis of China suboptimal health cohort study (COACS) consisting of 4313 participants (60.30% women) aged from 18 to 65 years old. The respective prevalence of SHS is 7.10%, 9.18%, 10.04% and 10.62% in the first, second, third and fourth quartiles of ideal cardiovascular health (CVH) metrics (P for trend = 0.012). Participants in the largest quartile of ideal CVH metrics show a lower likelihood of having optimal SHS score compared to those in the smallest quartile (odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32–0.59), after adjusting for age, gender, marital status, alcohol consumption, income level and education. Four metrics (smoking, physical inactivity, poor dietary intake and ideal control of blood pressure are significantly correlated with the risk of SHS. The present study suggests that ideal CVH metrics are associated with a lower prevalence of SHS, and the combined evaluation of SHS and CVH metrics allows the risk classification of cardiovascular disease, and thus consequently contributes to the prevention of cardiovascular diseases.
Particles of different sizes and shapes induce neutrophil necroptosis followed by the release of neutrophil extracellular trap-like chromatin
Authors: Desai Jyaysi , Foresto-Neto Orestes , Honarpisheh Mohsen , Steiger Stefanie , Nakazawa Daigo , Popper Bastian , Buhl Eva Miriam , Boor Peter , Mulay Shrikant R. , Anders Hans-Joachim
Published: October 2017

The human body is exposed to a wide range of particles of industrial, environmental or internal origin such as asbestos, alum, silica or crystals of urate, calcium phosphate, calcium oxalate, cystine or cholesterol. Phagocytic clearance of such particles involves neutrophils and macrophages. Here we report that neutrophils encountering such particles of diverse sizes and shapes undergo necrotic cell death, a process associated with the formation of neutrophil extracellular trap (NET)-like extracellular DNA. In human neutrophils receptor-interacting protein kinase (RIPK)-1 inhibition with necrostatin-1s or mixed lineage kinase domain-like (MLKL) inhibition with necrosulfonamide abrogated cell death and associated-neutrophil extracellular DNA release induced by all of the aforementioned particles. Similar results were obtained with Mlkl-deficient mice neutrophils for all particles in vitro. Furthermore, Mlkl-deficient mice lacked tophus formation upon injection of MSU crystals into subcutaneous air pouches. These findings imply that nano- or microparticle-induced neutrophil extracellular DNA release is the consequence of neutrophil necroptosis, a regulated form of cell necrosis defined by RIPK1-RIPK3-MLKL signaling. Interestingly, this finding was consistent across different particle sizes and shapes. The RIPK1-RIPK3-MLKL signaling pathway may represent a potential therapeutic target in nano- or microparticle-related diseases (crystallopathies).
Atomic-scale analysis of cation ordering in reduced calcium titanate
Authors: Li Luying , Hu Xiaokang , Jiang Fan , Jing Wenkui , Guo Cong , Jia Shuangfeng , Gao Yihua , Wang Jianbo
Published: October 2017

The phenomenon of cation ordering is closely related to certain physical properties of complex oxides, which necessitates the search of underlying structure-property relationship at atomic resolution. Here we study the superlattices within reduced calcium titanate single crystal micro-pillars, which are unexpected from the originally proposed atomic model. Bright and dark contrasts at alternating Ti double layers perpendicular to b axis are clearly observed, but show no signs in corresponding image simulations based on the proposed atomic model. The multi-dimensional chemical analyses at atomic resolution reveal periodic lower Ti concentrations at alternating Ti double layers perpendicular to b axis. The following in-situ heating experiment shows no phase transition at the reported Tc and temperature independence of the superlattices. The dimerization of the Ti-Ti bonds at neighboring double rutile-type chains within Ti puckered sheets are directly observed, which is found to be not disturbed by the cation ordering at alternating Ti double layers. The characterization of cation ordering of complex oxides from chemical and structural point of view at atomic resolution, and its reaction to temperature variations are important for further understanding their basic physical properties and exploiting potential applications.