bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding how excess lead iodide precursor improves halide perovskite solar cell performance
Authors: Park Byung-wook , Kedem Nir , Kulbak Michael , Lee Do Yoon , Yang Woon Seok , Jeon Nam Joong , Seo Jangwon , Kim Geonhwa , Kim Ki Jeong , Shin Tae Joo , Hodes Gary , Cahen David , Seok Sang Il
Published: August 2018

The presence of excess lead iodide in halide perovskites has been key for surpassing 20% photon-to-power conversion efficiency. To achieve even higher power conversion efficiencies, it is important to understand the role of remnant lead iodide in these perovskites. To that end, we explored the mechanism facilitating this effect by identifying the impact of excess lead iodide within the perovskite film on charge diffusion length, using electron-beam-induced current measurements, and on film formation properties, from grazing-incidence wide-angle X-ray scattering and high-resolution transmission electron microscopy. Based on our results, we propose that excess lead iodide in the perovskite precursors can reduce the halide vacancy concentration and lead to formation of azimuthal angle-oriented cubic α-perovskite crystals in-between 0° and 90°. We further identify a higher perovskite carrier concentration inside the nanostructured titanium dioxide layer than in the capping layer. These effects are consistent with enhanced lead iodide-rich perovskite solar cell performance and illustrate the role of lead iodide.
AIP1 and cofilin ensure a resistance to tissue tension and promote directional cell rearrangement
Authors: Ikawa Keisuke , Sugimura Kaoru
Published: August 2018

In order to understand how tissue mechanics shapes animal body, it is critical to clarify how cells respond to and resist tissue stress when undergoing morphogenetic processes, such as cell rearrangement. Here, we address the question in the Drosophila wing epithelium, where anisotropic tissue tension orients cell rearrangements. We found that anisotropic tissue tension localizes actin interacting protein 1 (AIP1), a cofactor of cofilin, on the remodeling junction via cooperative binding of cofilin to F-actin. AIP1 and cofilin promote actin turnover and locally regulate the Canoe-mediated linkage between actomyosin and the junction. This mechanism is essential for cells to resist the mechanical load imposed on the remodeling junction perpendicular to the direction of tissue stretching. Thus, the present study delineates how AIP1 and cofilin achieve an optimal balance between resistance to tissue tension and morphogenesis.
Emerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance to the first-line antimalarial piperaquine
Authors: Ross Leila S. , Dhingra Satish K. , Mok Sachel , Yeo Tomas , Wicht Kathryn J. , Kümpornsin Krittikorn , Takala-Harrison Shannon , Witkowski Benoit , Fairhurst Rick M. , Ariey Frederic , Menard Didier , Fidock David A.
Published: August 2018

The widely used antimalarial combination therapy dihydroartemisinin + piperaquine (DHA + PPQ) has failed in Cambodia. Here, we perform a genomic analysis that reveals a rapid increase in the prevalence of novel mutations in the Plasmodium falciparum chloroquine resistance transporter PfCRT following DHA + PPQ implementation. These mutations occur in parasites harboring the K13 C580Y artemisinin resistance marker. By introducing PfCRT mutations into sensitive Dd2 parasites or removing them from resistant Cambodian isolates, we show that the H97Y, F145I, M343L, or G353V mutations each confer resistance to PPQ, albeit with fitness costs for all but M343L. These mutations sensitize Dd2 parasites to chloroquine, amodiaquine, and quinine. In Dd2 parasites, multicopy plasmepsin 2, a candidate molecular marker, is not necessary for PPQ resistance. Distended digestive vacuoles were observed in pfcrt-edited Dd2 parasites but not in Cambodian isolates. Our findings provide compelling evidence that emerging mutations in PfCRT can serve as a molecular marker and mediator of PPQ resistance.
Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high-throughput mutagenesis
Authors: Braun Simon , Enculescu Mihaela , Setty Samarth T. , Cortés-López Mariela , de Almeida Bernardo P. , Sutandy F. X.  Reymond , Schulz Laura , Busch Anke , Seiler Markus , Ebersberger Stefanie , Barbosa-Morais Nuno L. , Legewie Stefan , König Julian , Zarnack Kathi
Published: August 2018

Mutations causing aberrant splicing are frequently implicated in human diseases including cancer. Here, we establish a high-throughput screen of randomly mutated minigenes to decode thecis-regulatory landscape that determines alternative splicing of exon 11 in the proto-oncogeneMST1R(RON). Mathematical modelling of splicing kinetics enables us to identify more than 1000 mutations affectingRONexon 11 skipping, which corresponds to the pathological isoform RON∆165. Importantly, the effects correlate withRONalternative splicing in cancer patients bearing the same mutations. Moreover, we highlight heterogeneous nuclear ribonucleoprotein H (HNRNPH) as a key regulator ofRONsplicing in healthy tissues and cancer. Using iCLIP and synergy analysis, we pinpoint the functionally most relevant HNRNPH binding sites and demonstrate how cooperative HNRNPH binding facilitates a splicing switch ofRONexon 11. Our results thereby offer insights into splicing regulation and the impact of mutations on alternative splicing in cancer.
Galectin-9 binds IgM-BCR to regulate B cell signaling
Authors: Cao Anh , Alluqmani Nouf , Buhari Fatima Hifza Mohammed , Wasim Laabiah , Smith Logan K. , Quaile Andrew T. , Shannon Michael , Hakim Zaki , Furmli Hossai , Owen Dylan M. , Savchenko Alexei , Treanor Bebhinn
Published: August 2018

The galectin family of secreted lectins have emerged as important regulators of immune cell function; however, their role in B-cell responses is poorly understood. Here we identify IgM-BCR as a ligand for galectin-9. Furthermore, we show enhanced BCR microcluster formation and signaling in galectin-9-deficient B cells. Notably, treatment with exogenous recombinant galectin-9 nearly completely abolishes BCR signaling. We investigated the molecular mechanism for galectin-9-mediated inhibition of BCR signaling using super-resolution imaging and single-particle tracking. We show that galectin-9 merges pre-existing nanoclusters of IgM-BCR, immobilizes IgM-BCR, and relocalizes IgM-BCR together with the inhibitory molecules CD45 and CD22. In resting naive cells, we use dual-color super-resolution imaging to demonstrate that galectin-9 mediates the close association of IgM and CD22, and propose that the loss of this association provides a mechanism for enhanced activation of galectin-9-deficient B cells.
Conditional control of fluorescent protein degradation by an auxin-dependent nanobody
Authors: Daniel Katrin , Icha Jaroslav , Horenburg Cindy , Müller Doris , Norden Caren , Mansfeld Jörg
Published: August 2018

The conditional and reversible depletion of proteins by auxin-mediated degradation is a powerful tool to investigate protein functions in cells and whole organisms. However, its wider applications require fusing the auxin-inducible degron (AID) to individual target proteins. Thus, establishing the auxin system for multiple proteins can be challenging. Another approach for directed protein degradation are anti-GFP nanobodies, which can be applied to GFP stock collections that are readily available in different experimental models. Here, we combine the advantages of auxin and nanobody-based degradation technologies creating an AID-nanobody to degrade GFP-tagged proteins at different cellular structures in a conditional and reversible manner in human cells. We demonstrate efficient and reversible inactivation of the anaphase promoting complex/cyclosome (APC/C) and thus provide new means to study the functions of this essential ubiquitin E3 ligase. Further, we establish auxin degradation in a vertebrate model organism by employing AID-nanobodies in zebrafish.
Ultrafast and highly sensitive infrared photodetectors based on two-dimensional oxyselenide crystals
Authors: Yin Jianbo , Tan Zhenjun , Hong Hao , Wu Jinxiong , Yuan Hongtao , Liu Yujing , Chen Cheng , Tan Congwei , Yao Fengrui , Li Tianran , Chen Yulin , Liu Zhongfan , Liu Kaihui , Peng Hailin
Published: August 2018

Infrared light detection and sensing is deeply embedded in modern technology and human society and its development has always been benefitting from the discovery of various photoelectric materials. The rise of two-dimensional materials, thanks to their distinct electronic structures, extreme dimensional confinement and strong light–matter interactions, provides a material platform for next-generation infrared photodetection. Ideal infrared detectors should have fast respond, high sensitivity and air-stability, which are rare to meet at the same time in one two-dimensional material. Herein we demonstrate an infrared photodetector based on two-dimensional Bi2O2Se crystal, whose main characteristics are outstanding in the whole two-dimensional family: high sensitivity of 65 AW−1 at 1200 nm and ultrafast photoresponse of ~1 ps at room temperature, implying an intrinsic material-limited bandwidth up to 500 GHz. Such great performance is attributed to the suitable electronic bandgap and high carrier mobility of two-dimensional oxyselenide.
Large networks of rational agents form persistent echo chambers
Authors: Madsen Jens Koed , Bailey Richard M , Pilditch Toby D.
Published: August 2018

Echo chambers (ECs) are enclosed epistemic circles where like-minded people communicate and reinforce pre-existing beliefs. It remains unclear if cognitive errors are necessarily required for ECs to emerge, and then how ECs are able to persist in networks with available contrary information. We show that ECs can theoretically emerge amongst error-free Bayesian agents, and that larger networks encourage rather than ameliorate EC growth. This suggests that the network structure itself contributes to echo chamber formation. While cognitive and social biases might exacerbate EC emergence, they are not necessary conditions. In line with this, we test stylized interventions to reduce EC formation, finding that system-wide truthful ‘educational’ broadcasts ameliorate the effect, but do not remove it entirely. Such interventions are shown to be more effective on agents newer to the network. Critically, this work serves as a formal argument for the responsibility of system architects in mitigating EC formation and retention.
A centuries-long delay between a paleo-ice-shelf collapse and grounding-line retreat in the Whales Deep Basin, eastern Ross Sea, Antarctica
Authors: Bart Philip J. , DeCesare Matthew , Rosenheim Brad E. , Majewski Wojceich , McGlannan Austin
Published: August 2018

Recent thinning and loss of Antarctic ice shelves has been followed by near synchronous acceleration of ice flow that may eventually lead to sustained deflation and significant contraction in the extent of grounded and floating ice. Here, we present radiocarbon dates from foraminifera that constrain the time elapsed between a previously described paleo-ice-shelf collapse and the subsequent major grounding-line retreat in the Whales Deep Basin (WDB) of eastern Ross Sea. The dates indicate that West Antarctic Ice Sheet (WAIS) grounding-line retreat from the continental shelf edge was underway prior to 14.7 ± 0.4 cal kyr BP. A paleo-ice-shelf collapse occurred at 12.3 ± 0.2 cal kyr BP. The grounding position was maintained on the outer-continental shelf until at least 11.5 ± 0.3 cal kyr BP before experiencing a 200-km retreat. Given the age uncertainties, the major grounding-line retreat lagged ice-shelf collapse by at least two centuries and by as much as fourteen centuries. In the WDB, the centuries-long delay in the retreat of grounded ice was partly due to rapid aggradational stacking of an unusually large volume of grounding-zone-wedge sediment as ice-stream discharge accelerated following ice-shelf collapse. This new deglacial reconstruction shows that ongoing changes to ice shelves may trigger complex dynamics whose consequences are realized only after a significant lag.
Quantitative prediction of long-term molecular response in TKI-treated CML – Lessons from an imatinib versus dasatinib comparison
Authors: Glauche Ingmar , Kuhn Matthias , Baldow Christoph , Schulze Philipp , Rothe Tino , Liebscher Hendrik , Roy Amit , Wang Xiaoning , Roeder Ingo
Published: August 2018

Longitudinal monitoring of BCR-ABL transcript levels in peripheral blood of CML patients treated with tyrosine kinase inhibitors (TKI) revealed a typical biphasic response. Although second generation TKIs like dasatinib proved more efficient in achieving molecular remission compared to first generation TKI imatinib, it is unclear how individual responses differ between the drugs and whether mechanisms of drug action can be deduced from the dynamic data. We use time courses from the DASISION trial to address statistical differences in the dynamic response between first line imatinib vs. dasatinib treatment cohorts and we analyze differences between the cohorts by fitting an established mathematical model of functional CML treatment to individual time courses. On average, dasatinib-treated patients show a steeper initial response, while the long-term response only marginally differed between the treatments. Supplementing each patient time course with a corresponding confidence region, we illustrate the consequences of the uncertainty estimate for the underlying mechanisms of CML remission. Our model suggests that the observed BCR-ABL dynamics may result from different, underlying stem cell dynamics. These results illustrate that the perception and description of CML treatment response as a dynamic process on the level of individual patients is a prerequisite for reliable patient-specific response predictions and treatment optimizations.
Patterns of early primary school-based literacy interventions among Pacific children from a nationwide health screening programme of 4 year olds
Authors: Schluter Philip J. , Kokaua Jesse , Tautolo El-Shadan , Richards Rosalina , Taleni Tufulasi , Kim Hyun M. , Audas Richard , McNeill Brigid , Taylor Barry , Gillon Gail
Published: August 2018

Literacy success is critical to unlocking a child’s potential and enhancing their future wellbeing. Thus, the early identification and redressing of literacy needs is vital. Pacific children have, on average, the lowest literacy achievement levels in New Zealand. However, this population is very diverse. This study sought to determine whether the current national health screening programme of pre-school children could be used as an early detection tool of Pacific children with the greatest literacy needs. Time-to-event analyses of literacy intervention data for Pacific children born in years 2005–2011 were employed. A multivariable Cox proportional hazard model was fitted, and predictive assessment made using training and test datasets. Overall, 59,760 Pacific children were included, with 6,861 (11.5%) receiving at least one literacy intervention. Tongan (hazard ratio [HR]: 1.33; 95% confidence interval [CI]: 1.23, 1.45) and Cook Island Māori (HR: 1.33; 95% CI: 1.21, 1.47) children were more likely to receive an intervention than Samoan children; whereas those children with both Pacific and non-Pacific ethnic identifications were less likely. However, the multivariable model lacked reasonable predictive power (Harrell’s c-statistic: 0.592; 95% CI: 0.583, 0.602). Regardless, important Pacific sub-populations emerged who would benefit from targeted literacy intervention or policy implementation.
3D Bioprinted Human Skeletal Muscle Constructs for Muscle Function Restoration
Authors: Kim Ji Hyun , Seol Young-Joon , Ko In Kap , Kang Hyun-Wook , Lee Young Koo , Yoo James J. , Atala Anthony , Lee Sang Jin
Published: August 2018

A bioengineered skeletal muscle tissue as an alternative for autologous tissue flaps, which mimics the structural and functional characteristics of the native tissue, is needed for reconstructive surgery. Rapid progress in the cell-based tissue engineering principle has enabled in vitro creation of cellularized muscle-like constructs; however, the current fabrication methods are still limited to build a three-dimensional (3D) muscle construct with a highly viable, organized cellular structure with the potential for a future human trial. Here, we applied 3D bioprinting strategy to fabricate an implantable, bioengineered skeletal muscle tissue composed of human primary muscle progenitor cells (hMPCs). The bioprinted skeletal muscle tissue showed a highly organized multi-layered muscle bundle made by viable, densely packed, and aligned myofiber-like structures. Our in vivo study presented that the bioprinted muscle constructs reached 82% of functional recovery in a rodent model of tibialis anterior (TA) muscle defect at 8 weeks of post-implantation. In addition, histological and immunohistological examinations indicated that the bioprinted muscle constructs were well integrated with host vascular and neural networks. We demonstrated the potential of the use of the 3D bioprinted skeletal muscle with a spatially organized structure that can reconstruct the extensive muscle defects.
Coupled Transmembrane Substrate Docking and Helical Unwinding in Intramembrane Proteolysis of Amyloid Precursor Protein
Authors: Clemente Nicolina , Abdine Alaa , Ubarretxena-Belandia Iban , Wang Chunyu
Published: August 2018

Intramembrane-cleaving proteases (I-CLiPs) play crucial roles in physiological and pathological processes, such as Alzheimer’s disease and cancer. However, the mechanisms of substrate recognition by I-CLiPs remain poorly understood. The aspartic I-CLiP presenilin is the catalytic subunit of the γ-secretase complex, which releases the amyloid-β peptides (Aβs) through intramembrane proteolysis of the transmembrane domain of the amyloid precursor protein (APPTM). Here we used solution NMR to probe substrate docking of APPTM to the presenilin homologs (PSHs) MCMJR1 and MAMRE50, which cleaved APPTM in the NMR tube. Chemical shift perturbation (CSP) showed juxtamembrane regions of APPTM mediate its docking to MCMJR1. Binding of the substrate to I-CLiP decreased the magnitude of amide proton chemical shifts δH at the C-terminal half of the substrate APPTM, indicating that the docking to the enzyme weakens helical hydrogen bonds and unwinds the substrate transmembrane helix around the initial ε-cleavage site. The APPTM V44M substitution linked to familial AD caused more CSP and helical unwinding around the ε-cleavage site. MAMRE50, which cleaved APPTM at a higher rate, also caused more CSP and helical unwinding in APPTM than MCMJR1. Our data suggest that docking of the substrate transmembrane helix and helical unwinding is coupled in intramembrane proteolysis and FAD mutation modifies enzyme/substrate interaction, providing novel insights into the mechanisms of I-CLiPs and AD drug discovery.
Invasive meningococcal disease in Shanghai, China from 1950 to 2016: implications for serogroup B vaccine implementation
Authors: Chen Mingliang , Rodrigues Charlene M. C. , Harrison Odile B. , Zhang Chi , Tan Tian , Chen Jian , Zhang Xi , Chen Min , Maiden Martin C. J.
Published: August 2018

Serogroup B invasive meningococcal disease (IMD) is increasing in China, but little is known about the causative meningococci. Here, IMD and carriage isolates in Shanghai characterised and the applicability of different vaccines assessed. Seven IMD epidemic periods have been observed in Shanghai since 1950, with 460 isolates collected including 169 from IMD and 291 from carriage. Analyses were divided according to the period of meningococcal polysaccharide vaccine (MPV) introduction: (i) pre-MPV-A, 1965–1980; (ii) post-MPV-A, 1981–2008; and (iii) post-MPV-A + C, 2009–2016. Over this period, IMD incidence decreased from 55.4/100,000 to 0.71 then to 0.02, corresponding to successive changes in meningococcal type from serogroup A ST-5 complex (MenA:cc5) to MenC:cc4821, and finally MenB:cc4821. MenB IMD became predominant (63.2%) in the post-MPV-A + C period, and 50% of cases were caused by cc4821, with the highest incidence in infants (0.45/100,000) and a case-fatality rate of 9.5%. IMD was positively correlated with population carriage rates. Using the Bexsero Antigen Sequence Type (BAST) system, fewer than 25% of MenB isolates in the post-MPV-A + C period contained exact or predicted cross reactive matches to the vaccines Bexsero, Trumenba, or an outer membrane vesicle (OMV)-based vaccine, NonaMen. A unique IMD epidemiology was seen in China, changing periodically from epidemic to hyperepidemic and low-level endemic disease. At the time of writing, MenB IMD dominated IMD in Shanghai, with isolates potentially beyond coverage with licenced OMV- and protein-based MenB vaccines.
AIEC infection triggers modification of gut microbiota composition in genetically predisposed mice, contributing to intestinal inflammation
Authors: Bretin Alexis , Lucas Cécily , Larabi Anaïs , Dalmasso Guillaume , Billard Elisabeth , Barnich Nicolas , Bonnet Richard , Nguyen Hang Thi Thu
Published: August 2018

A high prevalence of adherent-invasive E. coli (AIEC) in the intestinal mucosa of Crohn’s disease patients has been shown. AIEC colonize the intestine and induce inflammation in genetically predisposed mouse models including CEABAC10 transgenic (Tg) mice expressing human CEACAM6-receptor for AIEC and eif2ak4−/− mice exhibiting autophagy defect in response to AIEC infection. Here, we aimed at investigating whether gut microbiota modification contributes to AIEC-induced intestinal inflammation in these mouse models. For this, eif2ak4+/+ and eif2ak4−/− mice or CEABAC10 Tg mice invalidated for Eif2ak4 gene (Tg/eif2ak4−/−) or not (Tg/eif2ak4+/+) were infected with the AIEC reference strain LF82 or the non-pathogenic E. coli K12 MG1655 strain. In all mouse groups, LF82 colonized the gut better and longer than MG1655. No difference in fecal microbiota composition was observed in eif2ak4+/+ and eif2ak4−/− mice before infection and at day 1 and 4 post-infection. LF82-infected eif2ak4−/− mice exhibited altered fecal microbiota composition at day 14 and 21 post-infection and increased fecal lipocalin-2 level at day 21 post-infection compared to other groups, indicating that intestinal inflammation developed after microbiota modification. Similar results were obtained for LF82-infected Tg/eif2ak4−/− mice. These results suggest that in genetically predisposed hosts, AIEC colonization might induce chronic intestinal inflammation by altering the gut microbiota composition.
A 200-year annually laminated stalagmite record of precipitation seasonality in southeastern China and its linkages to ENSO and PDO
Authors: Zhang Haiwei , Cheng Hai , Spötl Christoph , Cai Yanjun , Sinha Ashish , Tan Liangcheng , Yi Liang , Yan Hong , Kathayat Gayatri , Ning Youfeng , Li Xianglei , Zhang Fan , Zhao Jingyao , Edwards R. Lawrence
Published: August 2018

In southeastern China (SEC), the precipitation amount produced by the East Asian summer monsoon (EASM) is almost equivalent to that during the non-summer monsoon (NSM) period, both of them significantly affecting agriculture and socioeconomy. Here, we present a seasonally-resolved stalagmite δ18O record (δ18Os) for the interval 1810–2009 AD from E’mei cave, Jiangxi Province, SEC. The comparison between δ18Os and instrumental data indicates that the δ18Os variability is primarily controlled by the precipitation seasonality (i.e., the ratio of EASM/NSM precipitation) modulated by the El Niño/Southern Oscillation (ENSO) on interannual to interdecadal timescales. Higher (lower) δ18Os values thereby correspond to lower (higher) EASM/NSM ratios associated with El Niño (La Niña) events. Significant correlations with ENSO and the Pacific Decadal Oscillation (PDO) indicate that the precipitation seasonality in SEC is remarkably influenced by ocean-atmosphere interactions, with lower (higher) EASM/NSM ratios during warm (cold) phases of ENSO/PDO. The progressive increase in δ18Os since 2005 AD may reflect a strengthening of the central Pacific El Niño under continued anthropogenic global warming. The relationship between seasonal precipitation and δ18Os with ENSO/PDO requires further studies.
Locus Coeruleus atrophy doesn’t relate to fatigue in Parkinson’s disease
Authors: Solopchuk Oleg , Sebti Moustapha , Bouvy Céline , Benoit Charles-Etienne , Warlop Thibault , Jeanjean Anne , Zénon Alexandre
Published: August 2018

Fatigue is a frequent complaint among healthy population and one of the earliest and most debilitating symptoms in Parkinson’s disease (PD). Earlier studies have examined the role of dopamine and serotonin in pathogenesis of fatigue, but the plausible role of noradrenalin (NA) remains underexplored. We investigated the relationship between fatigue in Parkinsonian patients and the extent of degeneration of Locus Coeruleus (LC), the main source of NA in the brain. We quantified LC and Substantia Nigra (SN) atrophy using neuromelanin-sensitive imaging, analyzed with a novel, fully automated algorithm. We also assessed patients’ fatigue, depression, sleep disturbance and vigilance. We found that LC degeneration correlated with the levels of depression and vigilance but not with fatigue, while fatigue correlated weakly with atrophy of SN. These results indicate that LC degeneration in Parkinson’s disease is unlikely to cause fatigue, but may be involved in mood and vigilance alterations.
Oral Delivery of a DNA Vaccine Expressing the PrM and E Genes: A Promising Vaccine Strategy against Flavivirus in Ducks
Authors: Huang Juan , Jia Renyong , Shen Haoyue , Wang Mingshu , Zhu Dekang , Chen Shun , Liu Mafeng , Zhao Xinxin , Wu Ying , Yang Qiao , Yin Zhongqiong , Cheng Anchun
Published: August 2018

A flavivirus, named duck tembusu virus (DTMUV), emerged in China in 2010. This virus has caused great economic losses in the poultry industry in China and may pose a threat to public health. As a safe, efficient and convenient vaccine development strategy, DNA-based vaccines have become a popular approach for both human and veterinary applications. Attenuated bacteria have been widely used as vehicles to deliver heterologous antigens to the immune system. Thus, an efficient and low-cost oral delivery DNA vaccine SL7207 (pVAX1-SME) based on envelope proteins (prM and E) of DTMUV and attenuated Salmonella typhimurium aroA- strain SL7207 was developed and evaluated in this study. The prM and E antigen proteins were successfully expressed from the vaccine SL7207 (pVAX1-SME) both in vitro and in vivo. High titers of the specific antibody against the DTMUV-E protein and the neutralizing antibody against the DTMUV virus were both detected after vaccination with SL7207 (pVAX1-SME). Ducks orally vaccinated with the SL7207 (pVAX-SME) vaccine were efficiently protected from lethal DTMUV infection in this study. Taken together, we demonstrated that prM and E proteins of DTMUV possess strong immunogenicity against the DTMUV infection. Moreover, an oral delivery of the DNA vaccine SL7207 (pVAX1-SME) utilizing Salmonella SL7207 was an efficient way to protect the ducks against DTMUV infection and provides an economic and fast vaccine delivery strategy for a large-scale clinical use.
Subwavelength Interferometric Control of Absorption in Three-port Acoustic Network
Authors: Richoux O. , Achilleos V. , Theocharis G. , Brouzos I.
Published: August 2018

Utilizing the effect of losses, we show that symmetric 3-port devices exhibit coherent perfect absorption of waves and we provide the corresponding conditions on the reflection and transmission coefficients. Infinite combinations of asymmetric inputs with different amplitudes and phase at each port as well as a completely symmetric input, are found to be perfectly absorbed. To illustrate the above we study an acoustic 3-port network operating in a subwavelength frequency both theoretically and experimentally. In addition we show how the output from a 3-port network is altered, when conditions of perfect absorption are met but the input waves phase and amplitude vary. In that regard, we propose optimized structures which feature both perfect absorption and perfect transmission at the same frequency by tuning the amplitudes and phases of the input waves.
Hyperuricemia is associated with atrial fibrillation prevalence in very elderly - a community based study in Chengdu, China
Authors: Huang Gang , Xu Rong-hua , Xu Jun-bo , liu Ya , Liu Zhao-hui , Xie Xue , Zhang Ting-jie
Published: August 2018

Hyperuricemia is a risk factor for cardiovascular diseases. However, in very elderly, the relationship between hyperuricemia and the prevalence of atrial fibrillation (AF) is not clear. This study aimed to investigate hyperuricemia and the risk of AF in community very elderly. In this cross-sectional study, 1056 very elderly in community were enrolled. Serum uric acid (SUA) were measured and rest 12-lead electrocardiogram was performed. Multiple logistic regression models were used to explore risk factors for AF in very elderly. Finally, 1038 participants were included in analysis and the mean age of the study participants were 83.6 ± 3.4 years (age range 80–100 years). The mean SUA level was 350.1 ± 84.5 µmol/L. The estimated prevalence of AF was 5.3%, and there was no significant sex difference (5.8% for men and 4.8% for women, p = 0.401). Multiple logistic regression found that participants with hyperuricemia (SUA >416 µmol/L in men and >357 µmol/L in women) had a higher risk (odds ratio: 2.080, 95% confidence interval: 1.103–4.202, P = 0.007) of suffering AF in very elderly Chinese. In conclusion, AF is relatively frequent in this community very elderly Chinese in Chengdu. Hyperuricemia is associated with the prevalence of AF in general very elderly.
COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin activation
Authors: Youn Seock-Won , Lee Hyun-Chae , Lee Sae-Won , Lee Jaewon , Jang Hyunduk , Lee Eun Ju , Kim Hyo-Soo
Published: August 2018

Angiopoietin-1 modulates vascular stability via Tie2 on endothelial cells. In our previous study, we also showed it acts as an inhibitor of cardiomyocyte death. However, it remains poorly understood how Ang1 regulates myogenesis during muscle regeneration. Here we found that COMP-Ang1 (cAng1) enhances muscle regeneration through N-cadherin activation. Muscle fiber regeneration after limb muscle damage by ischemic injury was enhanced with cAng1 treatment. Mechanistically cAng1 directly bound to N-cadherin on the myoblast surface in a Ca2+ dependent manner. The interaction enhanced N-cadherin activation via N-cadherin/p120-catenin complex formation, which in turn activated p38MAPK (but not AKT or ERK) and myogenin expression (but not myoD) as well as increasing myogenin+ cells in/ex vivo. After transplantation of GFP-expressing myoblasts (GFP-MB), we showed an increased generation of GFP+ myotubes with adenovirus cAng1 (Adv-cAng1) injection. Adv-cAng1, however, could not stimulate myotube formation in N-cadherin-depleted GFP-MB. Taken together, this study uncovers the mechanism of how cAng1 promotes myoblast differentiation and muscle regeneration through the N-cadherin/p120-catenin/p38MAPK/myogenin axis.
Neck-specific exercise may reduce radiating pain and signs of neurological deficits in chronic whiplash - Analyses of a randomized clinical trial
Authors: Landén Ludvigsson Maria , Peterson Gunnel , Peolsson Anneli
Published: August 2018

Up to 90% of people with neurological deficits following a whiplash injury do not recover and cervical muscle dysfunction is common. The aim of this multicentre, randomized controlled trial was to examine whether two versions of neck-specific exercise or prescription of physical activity (PPA) can improve radiating arm pain and clinical signs that can be associated with neurological deficits in people with chronic whiplash associated disorders (WAD). Participants with chronic WAD, arm symptoms and signs associated with neurological deficits (n = 171) were randomized to: 12 weeks of neck-specific exercise without (NSE) or with a behavioural approach (NSEB), or PPA. Pain/bothersomeness frequency, six measures of arm pain/paraesthesia (VAS scales), and four clinical neurological tests were evaluated after 3 months. The NSE group reported the lowest frequency and lowest levels of arm pain, the highest proportion of participants with at least 50% pain reduction and the highest proportion of normal arm muscle force. The NSEB group reported increased normal tendon reflexes. No improvements were recorded for the PPA group. Neck-specific exercise may improve arm pain and decrease signs of neurological deficits, but the addition of a behavioural approach does not seem to be of additional benefit.
Klebsiella oxytoca expands in cancer cachexia and acts as a gut pathobiont contributing to intestinal dysfunction
Authors: Pötgens Sarah A. , Brossel Hélène , Sboarina Martina , Catry Emilie , Cani Patrice D. , Neyrinck Audrey M. , Delzenne Nathalie M. , Bindels Laure B.
Published: August 2018

Cancer cachexia is a complex multi-organ syndrome characterized by body weight loss, weakness, muscle atrophy and fat depletion. With a prevalence of 1 million people in Europe and only limited therapeutic options, there is a high medical need for new approaches to treat cachexia. Our latest results highlighted microbial dysbiosis, characterized by a bloom inEnterobacteriaceaeand altered gut barrier function in preclinical models of cancer cachexia. They also demonstrated the potential of targeting the gut microbial dysbiosis in this pathology. However, the exact mechanisms underlying the gut microbiota-host crosstalk in cancer cachexia remain elusive. In this set of studies, we identifiedKlebsiella oxytocaas one of the mainEnterobacteriaceaespecies increased in cancer cachexia and we demonstrated that this bacteria acts as a gut pathobiont by altering gut barrier function in cachectic mice. Moreover, we propose a conceptual framework for the lower colonization resistance toK.oxytocain cancer cachexia that involves altered host gut epithelial metabolism and host-derived nitrate boosting the growth of the gut pathobiont. This set of studies constitutes a strong progression in the field of gut microbiota in cancer cachexia, by dissecting the mechanism of emergence of one bacterium,K.oxytoca, and establishing its role as a gut pathobiont in this severe disease.
Hybrid optical-electronic convolutional neural networks with optimized diffractive optics for image classification
Authors: Chang Julie , Sitzmann Vincent , Dun Xiong , Heidrich Wolfgang , Wetzstein Gordon
Published: August 2018

Convolutional neural networks (CNNs) excel in a wide variety of computer vision applications, but their high performance also comes at a high computational cost. Despite efforts to increase efficiency both algorithmically and with specialized hardware, it remains difficult to deploy CNNs in embedded systems due to tight power budgets. Here we explore a complementary strategy that incorporates a layer of optical computing prior to electronic computing, improving performance on image classification tasks while adding minimal electronic computational cost or processing time. We propose a design for an optical convolutional layer based on an optimized diffractive optical element and test our design in two simulations: a learned optical correlator and an optoelectronic two-layer CNN. We demonstrate in simulation and with an optical prototype that the classification accuracies of our optical systems rival those of the analogous electronic implementations, while providing substantial savings on computational cost.
Quantifying emergence and self-organisation of Enterobacter cloacae microbial communities
Authors: Balaban Valeriu , Lim Sean , Gupta Gaurav , Boedicker James , Bogdan Paul
Published: August 2018

From microbial communities to cancer cells, many such complex collectives embody emergent and self-organising behaviour. Such behaviour drives cells to develop composite features such as formation of aggregates or expression of specific genes as a result of cell-cell interactions within a cell population. Currently, we lack universal mathematical tools for analysing the collective behaviour of biological swarms. To address this, we propose a multifractal inspired framework to measure the degree of emergence and self-organisation from scarce spatial (geometric) data and apply it to investigate the evolution of the spatial arrangement of Enterobacter cloacae aggregates. In a plate of semi-solid media, Enterobacter cloacae form a spatially extended pattern of high cell density aggregates. These aggregates nucleate from the site of inoculation and radiate outward to fill the entire plate. Multifractal analysis was used to characterise these patterns and calculate dynamics changes in emergence and self-organisation within the bacterial population. In particular, experimental results suggest that the new aggregates align their location with respect to the old ones leading to a decrease in emergence and increase in self-organisation.
Humpback whale migrations to Antarctic summer foraging grounds through the southwest Pacific Ocean
Authors: Andrews-Goff V. , Bestley S. , Gales N. J. , Laverick S. M. , Paton D. , Polanowski A. M. , Schmitt N. T. , Double M. C.
Published: August 2018

Humpback whale (Megaptera novaeangliae) populations typically undertake seasonal migrations, spending winters in low latitude breeding grounds and summers foraging in high latitude feeding grounds. Until recently, a broad scale understanding of whale movement has been derived from whaling records, Discovery marks, photo identification and genetic analyses. However, with advances in satellite tagging technology and concurrent development of analytical methodologies we can now detail finer scale humpback whale movement, infer behavioural context and examine how these animals interact with their physical environment. Here we describe the temporal and spatial characteristics of migration along the east Australian seaboard and into the Southern Ocean by 30 humpback whales satellite tagged over three consecutive austral summers. We characterise the putative Antarctic feeding grounds and identify supplemental foraging within temperate, migratory corridors. We demonstrate that Antarctic foraging habitat is associated with the marginal ice zone, with key predictors of inferred foraging behaviour including distance from the ice edge, ice melt rate and variability in ice concentration two months prior to arrival. We discuss the highly variable ice season within the putative foraging habitat and the implications that this and other environmental factors may have on the continued strong recovery of this humpback whale population.
Interaction of septin 7 and DOCK8 in equine lymphocytes reveals novel insights into signaling pathways associated with autoimmunity
Authors: Schauer Melanie , Kleinwort Kristina J. H. , Degroote Roxane L. , Wiedemann Carmen , Kremmer Elisabeth , Hauck Stefanie M. , Deeg Cornelia A.
Published: August 2018

The GTP-binding protein septin 7 is involved in various cellular processes, including cytoskeleton organization, migration and the regulation of cell shape. Septin 7 function in lymphocytes, however, is poorly characterized. Since the intracellular signaling role of septin 7 is dependent on its interaction network, interaction proteomics was applied to attain novel knowledge about septin 7 function in hematopoietic cells. Our previous finding of decreased septin 7 expression in blood-derived lymphocytes in ERU, a spontaneous animal model for autoimmune uveitis in man, extended the role of septin 7 to a potential key player in autoimmunity. Here, we revealed novel insights into septin 7 function by identification of DOCK8 as an interaction partner in primary blood-derived lymphocytes. Since DOCK8 is associated with important immune functions, our finding of significantly decreased DOCK8 expression and altered DOCK8 interaction network in ERU might explain changes in immune response and shows the contribution of DOCK8 in pathomechanisms of spontaneous autoimmune diseases. Moreover, our analyses revealed insights in DOCK8 function, by identifying the signal transducer ILK as a DOCK8 interactor in lymphocytes. Our finding of the enhanced enrichment of ILK in ERU cases indicates a deviant influence of DOCK8 on inter- and intracellular signaling in autoimmune disease.
Invisible Flashes Alter Perceived Sound Location
Authors: Delong Patrycja , Aller Máté , Giani Anette S. , Rohe Tim , Conrad Verena , Watanabe Masataka , Noppeney Uta
Published: August 2018

Information integration across the senses is fundamental for effective interactions with our environment. The extent to which signals from different senses can interact in the absence of awareness is controversial. Combining the spatial ventriloquist illusion and dynamic continuous flash suppression (dCFS), we investigated in a series of two experiments whether visual signals that observers do not consciously perceive can influence spatial perception of sounds. Importantly, dCFS obliterated visual awareness only on a fraction of trials allowing us to compare spatial ventriloquism for physically identical flashes that were judged as visible or invisible. Our results show a stronger ventriloquist effect for visible than invisible flashes. Critically, a robust ventriloquist effect emerged also for invisible flashes even when participants were at chance when locating the flash. Collectively, our findings demonstrate that signals that we are not aware of in one sensory modality can alter spatial perception of signals in another sensory modality.
Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA
Authors: Miyagi-Shiohira Chika , Nakashima Yoshiki , Kobayashi Naoya , Saitoh Issei , Watanabe Masami , Noguchi Hirofumi
Published: August 2018

Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. Furthermore, our recent study demonstrated the generation of induced tissue-specific stem (iTS) cells by transient overexpression of the reprogramming factors using a plasmid combined with tissue-specific selection. In this study, we were able to generate RNA-based iTS cells that utilize a single, synthetic, self-replicating VEE-RF RNA replicon expressing four reprogramming factors (OCT4, KLF4, SOX2, and GLIS1). A single VEE-RF RNA transfection into mouse pancreatic tissue resulted in efficient generation of iTS cells from pancreas (iTS-P cells) with genetic markers of endoderm and pancreatic progenitors and differentiation into insulin-producing cells more efficiently than ES cells. Subcutaneous transplantation of iTS-P cells into immunodeficient mice resulted in no teratoma formation. Bisulfite genomic sequencing demonstrated that the promoters of Oct4 and Nanog remained partially methylated in iTS-P cells. We compared the global gene-expression profiles of ES cells, iTS-P cells, and pancreatic islets. Microarray analyses confirmed that the iTS-P cells were similar but not identical to ES cells compared with islets. These data suggest that iTS-P cells are cells that inherit numerous components of epigenetic memory from pancreas cells and acquire self-renewal potential. The generation of iTS cells may have important implications for the clinical application of stem cells.
Extracellular vesicles protect glucuronidase model enzymes during freeze-drying
Authors: Frank Julia , Richter Maximilian , de Rossi Chiara , Lehr Claus-Michael , Fuhrmann Kathrin , Fuhrmann Gregor
Published: August 2018

Extracellular vesicles (EVs) are natural nanoparticles that play important roles in intercellular communication and are increasingly studied for biosignalling, pathogenesis and therapy. Nevertheless, little is known about optimal conditions for their transfer and storage, and the potential impact on preserving EV-loaded cargoes. We present the first comprehensive stability assessment of different widely available types of EVs during various storage conditions including −80 °C, 4 °C, room temperature, and freeze-drying (lyophilisation). Lyophilisation of EVs would allow easy handling at room temperature and thus significantly enhance their expanded investigation. A model enzyme, β-glucuronidase, was loaded into different types of EVs derived from mesenchymal stem cells, endothelial cells and cancer cells. Using asymmetric flow field-flow fractionation we proved that the model enzyme is indeed stably encapsulated into EVs. When assessing enzyme activity as indicator for EV stability, and in comparison to liposomes, we show that EVs are intrinsically stable during lyophilisation, an effect further enhanced by cryoprotectants. Our findings provide new insight for exploring lyophilisation as a novel storage modality and we create an important basis for standardised and advanced EV applications in biomedical research.
Polarization-sensitive tunable absorber in visible and near-infrared regimes
Authors: Lee Dasol , Han Sung Yong , Jeong Yeonggyo , Nguyen Duc Minh , Yoon Gwanho , Mun Jungho , Chae Jeonghoon , Lee Jae Hyuk , Ok Jong G. , Jung Gun Young , Park Hui Joon , Kim Kyunghoon , Rho Junsuk
Published: August 2018

A broadband tunable absorber is designed and fabricated. The tunable absorber is comprised of a dielectric-metal-dielectric multilayer and plasmonic grating. A large size of tunable absorber device is fabricated by nano-imprinting method. The experimental results show that over 90% absorption can be achieved within visible and near-infrared regimes. Moreover, the high absorption can be controlled by changing the polarization of incident light. This polarization-sensitive tunable absorber can have practical applications such as high-efficiency polarization detectors and transmissive polarizer.
Density functional theory study of the role of benzylic hydrogen atoms in the antioxidant properties of lignans
Authors: Vo Quan V. , Nam Pham Cam , Bay Mai Van , Thong Nguyen Minh , Cuong Nguyen Duc , Mechler Adam
Published: August 2018

Antioxidants are a diverse group of chemicals with proven health benefits and thus potential preventive medicine and therapeutic applications. While most of these compounds are natural products, determining their mechanism of radical scavenging and common motifs that contribute to antioxidant activity would allow the rational design of novel antioxidants. Here the origins of the antioxidant properties of ten natural products of the lignan family were studied in silico by calculating their thermochemical properties by using ROB3LYP/6-311++G(2df,2p)//B3LYP/6-311G(d,p) model chemistry. Three conditions were modelled: gas phase, ethanol and water solvents. The results allowed assigning the antioxidant activity to specific moieties and structural features of these compounds. It was found that the benzylic hydrogen atoms are the most likely to be abstracted to form radicals and hence define antioxidant properties in most of the studied compounds. The results also suggested that the most likely mechanism of HOO• radical scavenging differs by the key moiety: it is hydrogen atom transfer in case the benzylic C-H bonds, however it is proton coupled electron transfer in case of the compounds where O-H bonds are responsible for radical scavenging.