bluuebunny/crossref_metadata_2025 huggingface dataset:
MAIT cells protect against pulmonary Legionella longbeachae infection
Authors: Wang Huimeng , D’Souza Criselle , Lim Xin Yi , Kostenko Lyudmila , Pediongco Troi J. , Eckle Sidonia B. G. , Meehan Bronwyn S. , Shi Mai , Wang Nancy , Li Shihan , Liu Ligong , Mak Jeffrey Y. W. , Fairlie David P. , Iwakura Yoichiro , Gunnersen Jennifer M. , Stent Andrew W. , Godfrey Dale I. , Rossjohn Jamie , Westall Glen P. , Kjer-Nielsen Lars , Strugnell Richard A. , McCluskey James , Corbett Alexandra J. , Hinks Timothy S. C. , Chen Zhenjun
Published: August 2018

Mucosal associated invariant T (MAIT) cells recognise conserved microbial metabolites from riboflavin synthesis. Striking evolutionary conservation and pulmonary abundance implicate them in antibacterial host defence, yet their functions in protection against clinically important pathogens are unknown. Here we show that mouse Legionellalongbeachae infection induces MR1-dependent MAIT cell activation and rapid pulmonary accumulation of MAIT cells associated with immune protection detectable in immunocompetent host animals. MAIT cell protection is more evident in mice lacking CD4+ cells, and adoptive transfer of MAIT cells rescues immunodeficient Rag2−/−γC−/− mice from lethal Legionella infection. Protection is dependent on MR1, IFN-γ and GM-CSF, but not IL-17A, TNF or perforin, and enhanced protection is detected earlier after infection of mice antigen-primed to boost MAIT cell numbers before infection. Our findings define a function for MAIT cells in protection against a major human pathogen and indicate a potential role for vaccination to enhance MAIT cell immunity.
Photo-generated dinuclear {Eu(II)}2 active sites for selective CO2 reduction in a photosensitizing metal-organic framework
Authors: Yan Zhi-Hao , Du Ming-Hao , Liu Junxue , Jin Shengye , Wang Cheng , Zhuang Gui-Lin , Kong Xiang-Jian , Long La-Sheng , Zheng Lan-Sun
Published: August 2018

Photocatalytic reduction of CO2 is a promising approach to achieve solar-to-chemical energy conversion. However, traditional catalysts usually suffer from low efficiency, poor stability, and selectivity. Here we demonstrate that a large porous and stable metal-organic framework featuring dinuclear Eu(III)2 clusters as connecting nodes and Ru(phen)3-derived ligands as linkers is constructed to catalyze visible-light-driven CO2 reduction. Photo-excitation of the metalloligands initiates electron injection into the nodes to generate dinuclear {Eu(II)}2 active sites, which can selectively reduce CO2 to formate in a two-electron process with a remarkable rate of 321.9 μmol h−1 mmolMOF−1. The electron transfer from Ru metalloligands to Eu(III)2 catalytic centers are studied via transient absorption and theoretical calculations, shedding light on the photocatalytic mechanism. This work highlights opportunities in photo-generation of highly active lanthanide clusters stabilized in MOFs, which not only enables efficient photocatalysis but also facilitates mechanistic investigation of photo-driven charge separation processes.
Multiplexed storage and real-time manipulation based on a multiple degree-of-freedom quantum memory
Authors: Yang Tian-Shu , Zhou Zong-Quan , Hua Yi-Lin , Liu Xiao , Li Zong-Feng , Li Pei-Yun , Ma Yu , Liu Chao , Liang Peng-Jun , Li Xue , Xiao Yi-Xin , Hu Jun , Li Chuan-Feng , Guo Guang-Can
Published: August 2018

The faithful storage and coherent manipulation of quantum states with matter-systems would enable the realization of large-scale quantum networks based on quantum repeaters. To achieve useful communication rates, highly multimode quantum memories are required to construct a multiplexed quantum repeater. Here, we present a demonstration of on-demand storage of orbital-angular-momentum states with weak coherent pulses at the single-photon-level in a rare-earth-ion-doped crystal. Through the combination of this spatial degree-of-freedom (DOF) with temporal and spectral degrees of freedom, we create a multiple-DOF memory with high multimode capacity. This device can serve as a quantum mode converter with high fidelity, which is a fundamental requirement for the construction of a multiplexed quantum repeater. This device further enables essentially arbitrary spectral and temporal manipulations of spatial-qutrit-encoded photonic pulses in real time. Therefore, the developed quantum memory can serve as a building block for scalable photonic quantum information processing architectures.
Vti1a/b regulate synaptic vesicle and dense core vesicle secretion via protein sorting at the Golgi
Authors: Emperador-Melero Javier , Huson Vincent , van Weering Jan , Bollmann Christian , Fischer von Mollard Gabriele , Toonen Ruud F. , Verhage Matthijs
Published: August 2018

The SNAREs Vti1a/1b are implicated in regulated secretion, but their role relative to canonical exocytic SNAREs remains elusive. Here, we show that synaptic vesicle and dense-core vesicle (DCV) secretion is indeed severely impaired in Vti1a/b-deficient neurons. The synaptic levels of proteins that mediate secretion were reduced, down to 50% for the exocytic SNARE SNAP25. The delivery of SNAP25 and DCV-cargo into axons was decreased and these molecules accumulated in the Golgi. These defects were rescued by either Vti1a or Vti1b expression. Distended Golgi cisternae and clear vacuoles were observed in Vti1a/b-deficient neurons. The normal non-homogeneous distribution of DCV-cargo inside the Golgi was lost. Cargo trafficking out of, but not into the Golgi, was impaired. Finally, retrograde Cholera Toxin trafficking, but not Sortilin/Sorcs1 distribution, was compromised. We conclude that Vti1a/b support regulated secretion by sorting secretory cargo and synaptic secretion machinery components at the Golgi.
Interfacing with silica boosts the catalysis of copper
Authors: Xu Chaofa , Chen Guangxu , Zhao Yun , Liu Pengxin , Duan Xinping , Gu Lin , Fu Gang , Yuan Youzhu , Zheng Nanfeng
Published: August 2018

Metal-support interaction is one of the most important parameters in controlling the catalysis of supported metal catalysts. Silica, a widely used oxide support, has been rarely reported as an effective support to create active metal-support interfaces for promoting catalysis. In this work, by coating Cu microparticles with mesoporous SiO2, we discover that Cu/SiO2 interface creates an exceptional effect to promote catalytic hydrogenation of esters. Both computational and experimental studies reveal that Cu–Hδ− and SiO–Hδ+ species would be formed at the Cu–O–SiOx interface upon H2 dissociation, thus promoting the ester hydrogenation by stablizing the transition states. Based on the proposed catalytic mechanism, encapsulting copper phyllosilicate nanotubes with mesoporous silica followed by hydrogen reduction is developed as an effective method to create a practical Cu nanocatalyst with abundant Cu-O-SiOx interfaces. The catalyst exhibits the best performance in the hydrogenation of dimethyl oxalate to ethylene glycol among all reported Cu catalysts.
Accelerated discovery of stable lead-free hybrid organic-inorganic perovskites via machine learning
Authors: Lu Shuaihua , Zhou Qionghua , Ouyang Yixin , Guo Yilv , Li Qiang , Wang Jinlan
Published: August 2018

Rapidly discovering functional materials remains an open challenge because the traditional trial-and-error methods are usually inefficient especially when thousands of candidates are treated. Here, we develop a target-driven method to predict undiscovered hybrid organic-inorganic perovskites (HOIPs) for photovoltaics. This strategy, combining machine learning techniques and density functional theory calculations, aims to quickly screen the HOIPs based on bandgap and solve the problems of toxicity and poor environmental stability in HOIPs. Successfully, six orthorhombic lead-free HOIPs with proper bandgap for solar cells and room temperature thermal stability are screened out from 5158 unexplored HOIPs and two of them stand out with direct bandgaps in the visible region and excellent environmental stability. Essentially, a close structure-property relationship mapping the HOIPs bandgap is established. Our method can achieve high accuracy in a flash and be applicable to a broad class of functional material design.
Memory B cells are reactivated in subcapsular proliferative foci of lymph nodes
Authors: Moran Imogen , Nguyen Akira , Khoo Weng Hua , Butt Danyal , Bourne Katherine , Young Clara , Hermes Jana R. , Biro Maté , Gracie Gary , Ma Cindy S. , Munier C. Mee Ling , Luciani Fabio , Zaunders John , Parker Andrew , Kelleher Anthony D. , Tangye Stuart G. , Croucher Peter I. , Brink Robert , Read Mark N. , Phan Tri Giang
Published: August 2018

Vaccine-induced immunity depends on the generation of memory B cells (MBC). However, where and how MBCs are reactivated to make neutralising antibodies remain unknown. Here we show that MBCs are prepositioned in a subcapsular niche in lymph nodes where, upon reactivation by antigen, they rapidly proliferate and differentiate into antibody-secreting plasma cells in the subcapsular proliferative foci (SPF). This novel structure is enriched for signals provided by T follicular helper cells and antigen-presenting subcapsular sinus macrophages. Compared with contemporaneous secondary germinal centres, SPF have distinct single-cell molecular signature, cell migration pattern and plasma cell output. Moreover, SPF are found both in human and mouse lymph nodes, suggesting that they are conserved throughout mammalian evolution. Our data thus reveal that SPF is a seat of immunological memory that may be exploited to rapidly mobilise secondary antibody responses and improve vaccine efficacy.
Early cellular innate immune responses drive Zika viral persistence and tissue tropism in pigtail macaques
Authors: O’Connor Megan A. , Tisoncik-Go Jennifer , Lewis Thomas B. , Miller Charlene J. , Bratt Debra , Moats Cassie R. , Edlefsen Paul T. , Smedley Jeremy , Klatt Nichole R. , Gale Michael , Fuller Deborah Heydenburg
Published: August 2018

The immunological and virological events that contribute to the establishment of Zika virus (ZIKV) infection in humans are unclear. Here, we show that robust cellular innate immune responses arising early in the blood and tissues in response to ZIKV infection are significantly stronger in males and correlate with increased viral persistence. In particular, early peripheral blood recruitment of plasmacytoid dendritic cells and higher production of monocyte chemoattractant protein (MCP-1) correspond with greater viral persistence and tissue dissemination. We also identify non-classical monocytes as primary in vivo targets of ZIKV infection in the blood and peripheral lymph node. These results demonstrate the potential differences in ZIKV pathogenesis between males and females and a key role for early cellular innate immune responses in the blood in viral dissemination and ZIKV pathogenesis.
Hydrophobic gating in BK channels
Authors: Jia Zhiguang , Yazdani Mahdieh , Zhang Guohui , Cui Jianmin , Chen Jianhan
Published: August 2018

The gating mechanism of transmembrane ion channels is crucial for understanding how these proteins control ion flow across membranes in various physiological processes. Big potassium (BK) channels are particularly interesting with large single-channel conductance and dual regulation by membrane voltage and intracellular Ca2+. Recent atomistic structures of BK channels failed to identify structural features that could physically block the ion flow in the closed state. Here, we show that gating of BK channels does not seem to require a physical gate. Instead, changes in the pore shape and surface hydrophobicity in the Ca2+-free state allow the channel to readily undergo hydrophobic dewetting transitions, giving rise to a large free energy barrier for K+ permeation. Importantly, the dry pore remains physically open and is readily accessible to quaternary ammonium channel blockers. The hydrophobic gating mechanism is also consistent with scanning mutagenesis studies showing that modulation of pore hydrophobicity is correlated with activation properties.
PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma
Authors: Liu Tianrun , Ma Wenjuan , Xu Haineng , Huang Menggui , Zhang Duo , He Zhenqiang , Zhang Lin , Brem Steven , O’Rourke Donald M. , Gong Yanqing , Mou Yonggao , Zhang Zhenfeng , Fan Yi
Published: August 2018

Angiogenesis is a hallmark of cancer. However, most malignant solid tumors exhibit robust resistance to current anti-angiogenic therapies that primarily target VEGF pathways. Here we report that endothelial-mesenchymal transformation induces glioblastoma (GBM) resistance to anti-angiogenic therapy by downregulating VEGFR-2 expression in tumor-associated endothelial cells (ECs). We show that VEGFR-2 expression is markedly reduced in human and mouse GBM ECs. Transcriptome analysis verifies reduced VEGFR-2 expression in ECs under GBM conditions and shows increased mesenchymal gene expression in these cells. Furthermore, we identify a PDGF/NF-κB/Snail axis that induces mesenchymal transformation and reduces VEGFR-2 expression in ECs. Finally, dual inhibition of VEGFR and PDGFR eliminates tumor-associated ECs and improves animal survival in GBM-bearing mice. Notably, EC-specific knockout of PDGFR-β sensitizes tumors to VEGF-neutralizing treatment. These findings reveal an endothelial plasticity-mediated mechanism that controls anti-angiogenic therapy resistance, and suggest that vascular de-transformation may offer promising opportunities for anti-vascular therapy in cancer.
Transfer printing techniques for flexible and stretchable inorganic electronics
Authors: Linghu Changhong , Zhang Shun , Wang Chengjun , Song Jizhou
Published: August 2018

Transfer printing is an emerging deterministic assembly technique for micro-fabrication and nano-fabrication, which enables the heterogeneous integration of classes of materials into desired functional layouts. It creates engineering opportunities in the area of flexible and stretchable inorganic electronics with equal performance to conventional wafer-based devices but the ability to be deformed like a rubber, where prefabricated inorganic semiconductor materials or devices on the donor wafer are required to be transfer-printed onto unconventional flexible substrates. This paper provides a brief review of recent advances on transfer printing techniques for flexible and stretchable inorganic electronics. The basic concept for each transfer printing technique is overviewed. The performances of these transfer printing techniques are summarized and compared followed by the discussions of perspectives and challenges for future developments and applications.
A quantitative analysis linking sea turtle mortality and plastic debris ingestion
Authors: Wilcox Chris , Puckridge Melody , Schuyler Qamar A , Townsend Kathy , Hardesty Britta Denise
Published: August 2018

Plastic in the marine environment is a growing environmental issue. Sea turtles are at significant risk of ingesting plastic debris at all stages of their lifecycle with potentially lethal consequences. We tested the relationship between the amount of plastic a turtle has ingested and the likelihood of death, treating animals that died of known causes unrelated to plastic ingestion as a statistical control group. We utilized two datasets; one based on necropsies of 246 sea turtles and a second using 706 records extracted from a national strandings database. Animals dying of known causes unrelated to plastic ingestion had less plastic in their gut than those that died of either indeterminate causes or due to plastic ingestion directly (e.g. via gut impaction and perforation). We found a 50% probability of mortality once an animal had 14 pieces of plastic in its gut. Our results provide the critical link between recent estimates of plastic ingestion and the population effects of this environmental threat.
Physicochemical properties and toxic elements in bus stop dusts from Qingyang, NW China
Authors: Wu Yongfu , Lu Xinwei
Published: August 2018

To appraise the content and pollution level of cadmium (Cd), arsenic (As), mercury (Hg), nickel (Ni) and lead (Pb) in bus stop dusts, representative samples (n = 53) were collected from the city of Qingyang in Gansu province, NW China. The Cd, As, Hg, Ni, and Pb contents and physicochemical properties (particle size, organic matter, pH and magnetic properties) of the bus stop dusts were investigated. Pollution levels were evaluated by the Nemero synthesis pollution index (NSPI) and geoaccumulation index (Igeo). The results indicate that the magnetic susceptibilities of the bus stop dusts were higher than those in the local soils. Cd, As, Ni, and Pb contents ranged from 0.4 to 3.1, 7.1 to 16.3, 12.7 to 151.3, and 20.1 to 96.2 mg kg−1, with average values of 1.2, 10.1, 22.2, and 44.9 mg kg−1, while Hg content ranged from 4.5 to 1357.7 µg kg−1 with an average of 214.0 µg kg−1. The mean contents of Cd, As, Hg, Ni, and Pb were 12.0, 0.8, 10.0, 0.6, and 2.4 times the local soil background value, respectively. Cd, Hg and Pb in approximately 96%, 62% and 19% of the bus stop dusts were above the “moderately polluted” level in terms of Igeo. As and Ni were defined as “practically unpolluted” in all of the bus stop dusts. The NSPI values of all of the bus stop dust samples exceeded 3, which reveals overall serious contamination of harmful elements.
Readout-segmented echo-planar diffusion-weighted MR for the evaluation of aggressive characteristics of rectal cancer
Authors: Xia Chun-chao , Pu Jin , Zhang Jin-ge , Peng Wan-lin , Li Lei , Zhao Fei , Zhang Kai , Li Yu-ming , Liu Ke-ling , Meng Wen-jian , Deng Xiang-bing , Zhou Xiao-yue , Li Zhen-lin
Published: August 2018

To evaluate whether aggressive characteristics of rectal cancer can be predicted by the apparent diffusion coefficient (ADC) obtained using readout-segmented echo-planar imaging (rs-EPI) diffusion-weighted magnetic resonance. We enrolled one hundred and fifteen patients. The image quality of ADC maps by rs-EPI was compared with that by traditional single-shot echo-planar imaging (ss-EPI), and ADC measurement was performed on the rs-EPI based ADC maps. Differences in ADC values of tumors grouped according to differentiation grade, clinical T stage and plasmatic carcinoembryonic antigen (CEA) level were tested. The correlation between each aggressive characteristic and the corresponding ADC values was evaluated. The image quality of ADC maps obtained by rs-EPI was superior toss-EPI (P < 0.05). The ADC values of tumor were categorized based on the following differentiation grades: poor (0.89 ± 0.12 × 10−3 mm2/s), moderate (1.13 ± 0.25 × 10−3 mm2/s), and good (1.31 ± 0.19 × 10−3 mm2/s); P < 0.001. Tumors with lower differentiation grades corresponded to lower ADC values (r = 0.59, P < 0.001). However, ADC differences were not observed in different clinical T stage (P = 0.22) and plasmatic CEA level (P = 0.38). Rs-EPI sequence-based ADC values represent a potential imaging marker for the aggressive rectal cancer characteristics.
Predicting changes to INa from missense mutations in human SCN5A
Authors: Clerx Michael , Heijman Jordi , Collins Pieter , Volders Paul G. A.
Published: August 2018

Mutations in SCN5A can alter the cardiac sodium current INa and increase the risk of potentially lethal conditions such as Brugada and long-QT syndromes. The relation between mutations and their clinical phenotypes is complex, and systems to predict clinical severity of unclassified SCN5A variants perform poorly. We investigated if instead we could predict changes to INa, leaving the link from INa to clinical phenotype for mechanistic simulation studies. An exhaustive list of nonsynonymous missense mutations and resulting changes to INa was compiled. We then applied machine-learning methods to this dataset, and found that changes to INa could be predicted with higher sensitivity and specificity than most existing predictors of clinical significance. The substituted residues’ location on the protein correlated with channel function and strongly contributed to predictions, while conservedness and physico-chemical properties did not. However, predictions were not sufficiently accurate to form a basis for mechanistic studies. These results show that changes to INa, the mechanism through which SCN5A mutations create cardiac risk, are already difficult to predict using purely in-silico methods. This partly explains the limited success of systems to predict clinical significance of SCN5A variants, and underscores the need for functional studies of INa in risk assessment.
From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β
Authors: Plou J. , Juste-Lanas Y. , Olivares V. , del Amo C. , Borau C. , García-Aznar J. M.
Published: August 2018

Cancer cells have the ability to migrate from the primary (original) site to other places in the body. The extracellular matrix affects cancer cell migratory capacity and has been correlated with tissue-specific spreading patterns. However, how the matrix orchestrates these behaviors remains unclear. Here, we investigated how both higher collagen concentrations and TGF-β regulate the formation of H1299 cell (a non-small cell lung cancer cell line) spheroids within 3D collagen-based matrices and promote cancer cell invasive capacity. We show that at low collagen concentrations, tumor cells move individually and have moderate invasive capacity, whereas when the collagen concentration is increased, the formation of cell clusters is promoted. In addition, when the concentration of TGF-β in the microenvironment is lower, most of the clusters are aggregates of cancer cells with a spheroid-like morphology and poor migratory capacity. In contrast, higher concentrations of TGF-β induced the formation of clusters with a notably higher invasive capacity, resulting in clear strand-like collective cell migration. Our results show that the concentration of the extracellular matrix is a key regulator of the formation of tumor clusters that affects their development and growth. In addition, chemical factors create a microenvironment that promotes the transformation of idle tumor clusters into very active, invasive tumor structures. These results collectively demonstrate the relevant regulatory role of the mechano-chemical microenvironment in leading the preferential metastasis of tumor cells to specific tissues with high collagen concentrations and TFG-β activity.
An Adult Zebrafish Model Reveals that Mucormycosis Induces Apoptosis of Infected Macrophages
Authors: López-Muñoz Azucena , Nicolás Francisco E. , García-Moreno Diana , Pérez-Oliva Ana B. , Navarro-Mendoza María I. , Hernández-Oñate Miguel A. , Herrera-Estrella Alfredo , Torres-Martínez Santiago , Ruiz-Vázquez Rosa M. , Garre Victoriano , Mulero Victoriano
Published: August 2018

Mucormycosis is a life-threatening fungal infection caused by various ubiquitous filamentous fungi of the Mucorales order, althoughRhizopusspp. andMucorspp. are the most prevalent causal agents. The limited therapeutic options available together with a rapid progression of the infection and a difficult early diagnosis produce high mortality. Here, we developed an adult zebrafish model ofMucor circinelloidesinfection which allowed us to confirm the link between sporangiospore size and virulence. Transcriptomic studies revealed a local, strong inflammatory response of the host elicited after sporangiospore germination and mycelial tissue invasion, while avirulent and UV-killed sporangiospores failed to induce inflammation and were rapidly cleared. Of the 857 genes modulated by the infection, those encoding cytokines, complement factors, peptidoglycan recognition proteins, and iron acquisition are particularly interesting. Furthermore, neutrophils and macrophages were similarly recruited independently of sporangiospore virulence and viability, which results in a robust depletion of both cell types in the hematopoietic compartment. Strikingly, our model also reveals for the first time the ability of mucormycosis to induce the apoptosis of recruited macrophages but not neutrophils. The induction of macrophage apoptosis, therefore, might represent a key virulence mechanism of these fungal pathogens, providing novel targets for therapeutic intervention in this lethal infection.
Nucleation of superfluid-light domains in a quenched dynamics
Authors: Figueroa Joaquín , Rogan José , Valdivia Juan Alejandro , Kiwi Miguel , Romero Guillermo , Torres Felipe
Published: August 2018

Strong correlation effects emerge from light-matter interactions in coupled resonator arrays, such as the Mott-insulator to superfluid phase transition of atom-photon excitations. We demonstrate that the quenched dynamics of a finite-sized complex array of coupled resonators induces a first-order like phase transition. The latter is accompanied by domain nucleation that can be used to manipulate the photonic transport properties of the simulated superfluid phase; this in turn leads to an empirical scaling law. This universal behavior emerges from the light-matter interaction and the topology of the array. The validity of our results over a wide range of complex architectures might lead to a promising device for use in scaled quantum simulations.
A healthy lifestyle attenuates the effect of polypharmacy on total and cardiovascular mortality: a national prospective cohort study
Authors: Martinez-Gomez David , Guallar-Castillon Pilar , Higueras-Fresnillo Sara , Banegas Jose R. , Sadarangani Kabir P. , Rodriguez-Artalejo Fernando
Published: August 2018

This work examines whether the increased all-cause and cardiovascular disease (CVD) mortality associated with polypharmacy could be offset by a healthy lifestyle. We included a prospective cohort of 3,925 individuals representative of the Spanish population aged ≥60 years, who were recruited in 2000–2001 and followed up through 2014. Polypharmacy was defined as treatment with ≥5 medications. The following lifestyle behaviors were considered healthy: not smoking, eating a healthy diet, being physically active, moderate alcohol consumption, low sitting time, and adequate sleep duration. Individuals were classified into three lifestyle categories s: unfavorable (0–2), intermediate (3–4) favorable (5–6). Over a median 13.8-y follow-up, 1,822 all-cause and 675 CVD deaths occurred. Among individuals with polypharmacy, intermediate and favorable lifestyles were associated with an all-cause mortality reduction (95% confidence interval [CI]) of 47% (34–58%) and 54% (37–66%), respectively; 37% (9–56%) and 60% (33–76%) for CVD death, respectively. The theoretical adjusted hazard ratio (95%CI) associated with replacing 1 medication with 1 healthy lifestyle behavior was 0.73 (0.66–0.81) for all-cause death and 0.69 (0.59–0.82) for CVD death. The theoretical adjusted hazard ratio (95%CI) for all-cause and CVD mortality associated with simply reducing 1 medication was 0.88 (0.83–0.94) and 0.83 (0.76–0.91), respectively. Hence, adherence to a healthy lifestyle behavior can reduce mortality risk associated with polypharmacy in older adults.
Unfavourable gender effect of high body mass index on brain metabolism and connectivity
Authors: Malpetti Maura , Sala Arianna , Vanoli Emilia Giovanna , Gianolli Luigi , Luzi Livio , Perani Daniela
Published: August 2018

The influence of Body Mass Index (BMI) on neurodegeneration in dementia has yet to be elucidated. We aimed at exploring the effects of BMI levels on cerebral resting-state metabolism and brain connectivity, as crucial measures of synaptic function and activity, in a large group of patients with Alzheimer’s Dementia (AD) (n = 206), considering gender. We tested the correlation between BMI levels and brain metabolism, as assessed by18F-FDG-PET, and the modulation of the resting-state functional networks by BMI. At comparable dementia severity, females with high BMI can withstand a lower degree of brain metabolism dysfunction, as shown by a significant BMI-brain metabolism correlation in the temporal-parietal regions, which are typically vulnerable to AD pathology (R = 0.269, p = 0.009). Of note, high BMI was also associated with reduced connectivity in frontal and limbic brain networks, again only in AD females (p < 0.05 FDR-corrected, k = 100 voxels). This suggests a major vulnerability of neural systems known to be selectively involved in brain compensatory mechanisms in AD females. These findings indicate a strong gender effect of high BMI and obesity in AD, namely reducing the available reserve mechanisms in female patients. This brings to considerations for medical practice and health policy.
Author Correction: Structural and functional studies on Pseudomonas aeruginosa DspI: implications for its role in DSF biosynthesis
Authors: Liu Li , Li Tao , Cheng Xing-Jun , Peng Cui-Ting , Li Chang-Cheng , He Li-Hui , Ju Si-Min , Wang Ning-Yu , Ye Ting-Hong , Lian Mao , Xiao Qing-Jie , Song Ying-Jie , Zhu Yi-Bo , Yu Luo-Ting , Wang Zhen-Ling , Bao Rui
Published: August 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.
Tidal Records as Liquid Climate Archives for Large-Scale Interior Mediterranean Variability
Authors: Rubino Angelo , Zanchettin Davide , Androsov Alexey , Voltzinger Naum E.
Published: August 2018

Characterization of interior ocean variability is necessary for understanding climate. Water mass evolution shapes ocean-atmosphere interactions and contributes to determine timescales for global and regional climate variability. However, a robust assessment of past state and variability of the ocean interior is prevented by sparseness/shortness of historical subsurface observations and uncertainties affecting proxy-based reconstructions. Here, we propose a novel approach to infer past large-scale interior ocean variability with unprecedented accuracy and temporal resolution. It exploits links between stratification determined by “large-scale” water mass distributions and local dynamics. We characterize interannual interior ocean variability in the Mediterranean Sea in the early 20th century contained in tidal measurements in the Strait of Messina, and demonstrate the general applicability of our method, paving the way to a new approach to analyze historical oceanographic records: Regions where different water masses are known to collide can thus act as magnifying glasses for basin-scale interior ocean variability, hence providing “liquid archives” for climatology.
Identification of beagle food taking patterns and protocol for food effects evaluation on bioavailability
Authors: Zhang Guoqing , Wang Caifen , Wu Li , Xu Jian , Hu Xiaoxiao , Shakya Shailendra , He Yuanzhi , Ren Xiaohong , Chen Weidong , Zhang Jiwen
Published: August 2018

Food is a known primary role to the exposure of the drugs orally administered. Since each animal may have unique food taking pattern and it is difficult to manipulate the food taking to animals, there lacks rationalized protocol for the food effects in pre-clinic study. The objective of this study was to identify the beagle food taking patterns and demonstrate their effects on bioavailability in valsartan. Herein, four types of food taking patterns of beagle were identified via inter-day and intra-day analysis, and named as Persisting, Pulsing, Postponing, Pushing (“4P Modes”), respectively, which were also validated by principal component analysis (PCA). Interestingly, food intake resulted in a reduced area under the concentration-time curve (AUC0–12h), maximum concentration (Cmax) and absorption rate, whilst the reduction varied in “4P Modes” of food taking. General considerations in the design of experiment for food effect to the bioavailability in beagles have been established as: to recognize the food taking patterns in each animal, to confirm the inter-day stability of the food taking behaviors, to trace the food taking patterns in parallel with plasma sampling. In conclusion, the right animals with proper food taking patterns should be assessed and selected for pre-clinic bioavailability evaluations.
Numerical and Experimental Investigation of the Hemodynamic Performance of Bifurcated Stent Grafts with Various Torsion Angles
Authors: Liu Ming , Sun Anqiang , Deng Xiaoyan
Published: August 2018

The “crossed limbs” strategy for bifurcated stent grafts (BSGs) is widely employed when abdominal aortic aneurysm (AAA) patients have unfavorable neck or highly splayed iliac arteries. Helical flow is regarded as a typical flow pattern within the human arterial system and is believed to have the positive physiological effects of inhibiting thrombosis formation and atherosclerosis. The “crossed limbs” strategy may induce helical flow and improve the stent graft outcome. To verify the performance of this strategy by considering hemodynamics, we constructed a series of idealized BSGs with various torsion angles and evaluated the hemodynamic performance, including the helical strength, time-averaged wall shear stress (TAWSS), oscillatory shear index, relative resident time (RRT), and displacement force. Our numerical results indicate that an increased torsion angle enhances the helicity strength at the iliac outlets. However, with increasing torsion angle, the TAWSS in the iliac graft decreases and the RRT increases. In addition, our numerical simulations and in vitro experiments reveal that the displacement force increases gradually with increasing torsion angle. In summary, the “crossed limbs” strategy may have benefits for AAA treatment in terms of helical flow, but because of the unfavorable hemodynamic performance verified by analyzing the hemodynamic indicators, the risk of stent graft migration increases with increasing torsion angle. Therefore, the “crossed limbs” strategy should be carefully employed in surgical AAA treatment.
Novel gene encoding a unique luciferase from the fireworm Odontsyllis undecimdonta
Authors: Mitani Yasuo , Yasuno Rie , Isaka Minato , Mitsuda Nobutaka , Futahashi Ryo , Kamagata Yoichi , Ohmiya Yoshihiro
Published: August 2018

Luciferases identified or engineered so far emit violet, blue, blue-green, green, yellow, red or near infra-red light. The unique and beautiful bluish-green bioluminescence of fireworms Odontosyllis spp. has attracted particular interest, however, their molecular basis is totally unknown partly due to the difficulty of animal collection. Here we report a novel type of luciferase gene from the Japanese fireworm O. undecimdonta. The major SDS-PAGE band of the luminous mucus showed luciferase activity. A highly sensitive mass spectrometry analysis in combination with RNA sequencing technique revealed that this band was product of a single gene with no homology to any other sequences in public databases. The recombinant protein of this putative luciferase gene expressed in mammalian cells produced the same unique bluish-green emission peak as the fireworm crude extract, indicating that this novel gene is the genuine fireworm luciferase with an evolutionary different origin from other luciferases previously described. Our findings extend the repertoire of luciferin/luciferase system to previously unavailable wavelength range.
Characterization of membrane penetration and cytotoxicity of C9orf72-encoding arginine-rich dipeptides
Authors: Kanekura Kohsuke , Harada Yuichiro , Fujimoto Mao , Yagi Takuya , Hayamizu Yuhei , Nagaoka Kentaro , Kuroda Masahiko
Published: August 2018

Cell-penetrating peptides (CPPs) including arginine-rich peptides are attracting a lot of attention due to their potential as a novel intracellular drug delivery tool without substantial toxicity. On the other hand, disease-associated arginine-rich CPPs, such as poly-PR and poly-GR translated from C9orf72 gene, also efficiently enter neuronal cells and then kill them. Although both non-harmful CPPs and harmful poly-PR/GR penetrate the plasma membrane using same arginine residues, little is known about the factors which determine the toxicity of the pathogenic CPPs. Here, we show that poly-PR and poly-GR, but not other Arg-rich CPPs, specifically distributed to nucleolus via interaction with RNA. Importantly, C9orf72-dipeptides, but not other Arg-rich CPPs, caused inhibition of protein translation and cell death. Raising extracellular pH enhanced the cell penetration of poly-PR. The repeat number of (PR) affected the secondary structure and determined the intracellular delivery rate and neurotoxicity, and enforced intracellular delivery of non-penetrating short poly-PR peptide caused cell death, suggesting that modulation of extracellular environment to inhibit the uptake of Arg-rich dipeptides might be a drug target against poly-PR/GR-mediated neurotoxicity.
Evaluating Tumor Evolution via Genomic Profiling of Individual Tumor Spheroids in a Malignant Ascites
Authors: Kim Sungsik , Kim Soochi , Kim Jinhyun , Kim Boyun , Kim Se Ik , Kim Min A. , Kwon Sunghoon , Song Yong Sang
Published: August 2018

Epithelial ovarian cancer (EOC) is a silent but mostly lethal gynecologic malignancy. Most patients present with malignant ascites and peritoneal seeding at diagnosis. In the present study, we used a laser-aided isolation technique to investigate the clonal relationship between the primary tumor and tumor spheroids found in the malignant ascites of an EOC patient. Somatic alteration profiles of ovarian cancer-related genes were determined for eight spatially separated samples from primary ovarian tumor tissues and ten tumor spheroids from the malignant ascites using next-generation sequencing. We observed high levels of intra-tumor heterogeneity (ITH) in copy number alterations (CNAs) and single-nucleotide variants (SNVs) in the primary tumor and the tumor spheroids. As a result, we discovered that tumor cells in the primary tissues and the ascites were genetically different lineages. We categorized the CNAs and SNVs into clonal and subclonal alterations according to their distribution among the samples. Also, we identified focal amplifications and deletions in the analyzed samples. For SNVs, a total of 171 somatic mutations were observed, among which 66 were clonal mutations present in both the primary tumor and the ascites, and 61 and 44 of the SNVs were subclonal mutations present in only the primary tumor or the ascites, respectively. Based on the somatic alteration profiles, we constructed phylogenetic trees and inferred the evolutionary history of tumor cells in the patient. The phylogenetic trees constructed using the CNAs and SNVs showed that two branches of the tumor cells diverged early from an ancestral tumor clone during an early metastasis step in the peritoneal cavity. Our data support the monophyletic spread of tumor spheroids in malignant ascites.
Selection scan reveals three new loci related to high altitude adaptation in Native Andeans
Authors: Jacovas Vanessa C. , Couto-Silva Cainã M. , Nunes Kelly , Lemes Renan B. , de Oliveira Marcelo Z. , Salzano Francisco M. , Bortolini Maria Cátira , Hünemeier Tábita
Published: August 2018

The Andean Altiplano has been occupied continuously since the late Pleistocene, ~12,000 years ago, which places the Andean natives as one of the most ancient populations living at high altitudes. In the present study, we analyzed genomic data from Native Americans living a long-time at Andean high altitude and at Amazonia and Mesoamerica lowland areas. We have identified three new candidate genes - SP100, DUOX2 and CLC - with evidence of positive selection for altitude adaptation in Andeans. These genes are involved in the TP53 pathway and are related to physiological routes important for high-altitude hypoxia response, such as those linked to increased angiogenesis, skeletal muscle adaptations, and immune functions at the fetus-maternal interface. Our results, combined with other studies, showed that Andeans have adapted to the Altiplano in different ways and using distinct molecular strategies as compared to those of other natives living at high altitudes.
Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment
Authors: Kumar Parvin , Efstathopoulos Paschalis , Millischer Vincent , Olsson Eric , Wei Ya Bin , Brüstle Oliver , Schalling Martin , Villaescusa J. Carlos , Ösby Urban , Lavebratt Catharina
Published: August 2018

Mitochondrial pathology has been implicated in the pathogenesis of psychotic disorders. A few studies have proposed reduced leukocyte mitochondrial DNA (mtDNA) copy number in schizophrenia and bipolar disorder type I, compared to healthy controls. However, it is unknown if mtDNA copy number alteration is driven by psychosis, comorbidity or treatment. Whole blood mtDNA copy number was determined in 594 psychosis patients and corrected for platelet to leukocyte count ratio (mtDNAcnres). The dependence of mtDNAcnres on clinical profile, metabolic comorbidity and antipsychotic drug exposure was assessed. mtDNAcnres was reduced with age (β = −0.210, p < 0.001), use of clozapine (β = −0.110,p = 0.012) and risperidone (β = −0.109,p = 0.014), dependent on prescribed dosage (p = 0.006 and p = 0.026, respectively), and the proportion of life on treatment (p = 0.006). Clozapine (p = 0.0005) and risperidone (p = 0.0126) had a reducing effect on the mtDNA copy number also in stem cell-derived human neurons in vitro at therapeutic plasma levels. For patients not on these drugs, psychosis severity had an effect (β = −0.129, p = 0.017), similar to age (β = −0.159, p = 0.003) and LDL (β = −0.119, p = 0.029) on whole blood mtDNAcnres. Further research is required to determine if mtDNAcnres reflects any psychosis-intrinsic mitochondrial changes.
Assessment of the ability of open- and closed-loop cueing to improve turning and freezing in people with Parkinson’s disease
Authors: Mancini Martina , Smulders Katrijn , Harker Graham , Stuart Samuel , Nutt John G.
Published: August 2018

Turning impairments are common in Parkinson’s disease (PD) and can elicit freezing of gait (FoG). Extensive examination of open-loop cueing interventions has demonstrated that they can ameliorate gait deficits in PD; less is known about efficacy to improve turning. Here, we investigate the immediate effectiveness of open- and closed-loop cueing in improving turning characteristics in people with PD. Twenty-five subjects with and 18 subjects without FoG participated in the study. Subjects turned in place for one minute under single- and dual-task for 3 randomized conditions: (i) Baseline; (ii) Turning to the beat of a metronome (open-loop); and (iii) Turning with phase-dependent tactile biofeedback (closed-loop). Objective measures of freezing, such as % time spent freezing and FoG-ratio, significantly improved when turning with both open-loop and closed-loop cueing compared to baseline. Dual-tasking did not worsen FoG in freezers, but significantly slowed down turns in both groups. Both cueing modalities significantly improved turning smoothness in both groups, but reduced turning velocity and number of turns compared to baseline. Both open and closed-loop cueing markedly improved turning in people with PD. These preliminary observations warrant further exploration of vibrotactile closed-loop cueing to improve mobility in everyday life.
Prevention of posterior capsule opacification through intracapsular hydrogen peroxide or distilled water treatment in human donor tissue
Authors: D’Antin Justin Christopher , Barraquer Rafael I. , Tresserra Francisco , Michael Ralph
Published: August 2018

In order to determine whether posterior capsule opacification after cataract surgery, could be delayed or inhibited through the application of hydrogen peroxide (H2O2) or distilled water (H2Od),we extracted lens capsules from 25 human donor eye globes. Samples were treated for 5 min with either 30 mM H2O2 or H2Od or used as controls, and cultured for one month, during which dark field and tilt illumination photos were taken. These were used to observe and quantify, time until cellular growth and confluence on the posterior capsule. After culture, histological sections were stained for H&E, α-SMA, Ki-67 and vimentin and evaluated. We prevented cellular growth in 50% of H2Od and 58% H2O2 of treated samples. The overall prevention of cell growth compared to cultured controls was significant for both treatments while there was no significant difference between them. In the cases where cellular growth was not prevented, both treatments significantly delay cellular growth. Until day 28 none of the treated samples of either type that had shown growth reached total confluence. All cultured controls reached total confluence before treated samples (median = day 11.5). Also, histologically, there was a clear morphological difference between cultured controls and treated samples.
Characterization and induction of prophages in human gut-associated Bifidobacterium hosts
Authors: Mavrich Travis N. , Casey Eoghan , Oliveira Joana , Bottacini Francesca , James Kieran , Franz Charles M. A. P. , Lugli Gabriele Andrea , Neve Horst , Ventura Marco , Hatfull Graham F. , Mahony Jennifer , van Sinderen Douwe
Published: August 2018

In the current report, we describe the identification of three genetically distinct groups of prophages integrated into three different chromosomal sites of human gut-associated Bifidobacterium breve and Bifidobacterium longum strains. These bifidobacterial prophages are distantly related to temperate actinobacteriophages of several hosts. Some prophages, integrated within the dnaJ2 gene, are competent for induction, excision, replication, assembly and lysis, suggesting that they are fully functional and can generate infectious particles, even though permissive hosts have not yet been identified. Interestingly, several of these phages harbor a putative phase variation shufflon (the Rin system) that generates variation of the tail-associated receptor binding protein (RBP). Unlike the analogous coliphage-associated shufflon Min, or simpler Cin and Gin inversion systems, Rin is predicted to use a tyrosine recombinase to promote inversion, the first reported phage-encoded tyrosine-family DNA invertase. The identification of bifidobacterial prophages with RBP diversification systems that are competent for assembly and lysis, yet fail to propagate lytically under laboratory conditions, suggests dynamic evolution of bifidobacteria and their phages in the human gut.
An eco-friendly synthesized mesoporous-silica particle combined with WSe2-graphene-TiO2 by self-assembled method for photocatalytic dye decomposition and hydrogen production
Authors: Zhu Lei , Nguyen Dinh Cung Tien , Woo Jung-Hun , Zhang Qinfang , Cho Kwang Youn , Oh Won-Chun
Published: August 2018

To address the limitations of titanium dioxide (TiO2) and expand the applicability of the photocatalytic activity of TiO2,WSe2 and silica, an eco-friendly, self-assembled method for combining a silica precursor with a WSe2-graphene-TiO2 composite with cetyltrimethylammonium bromide (CTAB) as surface active agents is proposed. Firstly, for the main target, the photocatalytic degradation of organic dye solutions with different initial pH levels and catalyst dosages under visible light irradiation was surveyed. The as-synthesized sample exhibited highly efficient photocatalytic effects for the treatment of the SO dye solution in the optimal conditions of this study, which included a solution with a pH level of 11 and 0.05-gram dosage of the catalyst. Secondly, previous photocatalytic hydrogen production studies reported markedly better outcomes with SiO2/WSe2-graphene-TiO2 than with the binary WSe2-graphene and ternary WSe2-graphene-TiO2 composites under ambient conditions with and without 20% methanol sacrificing reagents. The SiO2/WSe2-graphene-TiO2 composite is promising to become a potential candidate for photocatalytic performance that performs excellently as well as offer an efficient heterosystem for hydrogen production.