bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular edge effects in the Endangered golden-brown mouse lemurMicrocebus ravelobensis
Authors: Radespiel U. , Schulte J. , Burke R. J. , Lehman S. M.
Published: July 2018

Habitat fragmentation creates habitat edges, and ecological edge effects can cause major changes in the ecology and distribution of many taxa. However, these ecological changes may in turn influence animal movements and lead to molecular edge effects and edge-related genetic structure, matters that are largely unexplored. This study aims to infer molecular edge effects and to test three possible underlying mechanisms in the Endangered golden-brown mouse lemurMicrocebus ravelobensis, a nocturnal species in the dry deciduous forest of the Ankarafantsika National Park in north-western Madagascar. Mouse lemurs were sampled in one edge and two interior habitats in close proximity to each other (500–1,400 m) in a continuous forest. A total of 41 mouse lemur samples were genotyped with seven nuclear microsatellites, and a fragment of the mitochondrial control region was sequenced for all samples. The overall genetic diversity (allelic richness, heterozygosity, haplotype richness, nucleotide diversity) was lower in the edge habitat compared to the two interior sites and all subpopulations showed signals of relatively low genetic exchange and significant genetic differentiation between them despite the short geographical distances, supporting the local preference model. These findings can be interpreted as preliminary signals of a molecular edge effect and suggest the potential for local adaptation. They are highly relevant for the conservation of fragmented populations, because a further subdivision of already small populations may increase their vulnerability to stochastic demographic changes and collapse.
The effectiveness and cost-effectiveness of the Incredible Years®Teacher Classroom Management programme in primary school children: results of the STARS cluster randomised controlled trial
Authors: Ford Tamsin , Hayes Rachel , Byford Sarah , Edwards Vanessa , Fletcher Malcolm , Logan Stuart , Norwich Brahm , Pritchard Will , Allen Kate , Allwood Matthew , Ganguli Poushali , Grimes Katie , Hansford Lorraine , Longdon Bryony , Norman Shelley , Price Anna , Ukoumunne Obioha C.
Published: July 2018

Background

We evaluated the effectiveness and cost-effectiveness of the Incredible Years®Teacher Classroom Management (TCM) programme as a universal intervention, given schools’ important influence on child mental health.

Methods

A two-arm, pragmatic, parallel group, superiority, cluster randomised controlled trial recruited three cohorts of schools (clusters) between 2012 and 2014, randomising them to TCM (intervention) or Teaching As Usual (TAU-control). TCM was delivered to teachers in six whole-day sessions, spread over 6 months. Schools and teachers were not masked to allocation. The primary outcome was teacher-reported Strengths and Difficulties Questionnaire (SDQ) Total Difficulties score. Random effects linear regression and marginal logistic regression models using Generalised Estimating Equations were used to analyse the outcomes. Trial registration: ISRCTN84130388.

Results

Eighty schools (2075 children) were enrolled; 40 (1037 children) to TCM and 40 (1038 children) to TAU. Outcome data were collected at 9, 18, and 30-months for 96, 89, and 85% of children, respectively. The intervention reduced the SDQ-Total Difficulties score at 9 months (mean (s.d.):5.5 (5.4) in TCMv.6.2 (6.2) in TAU; adjusted mean difference = −1.0; 95% CI−1.9 to −0.1;p= 0.03) but this did not persist at 18 or 30 months. Cost-effectiveness analysis suggested that TCM may be cost-effective compared with TAU at 30-months, but this result was associated with uncertainty so no firm conclusions can be drawn. A priori subgroup analyses suggested TCM is more effective for children with poor mental health.

Conclusions

TCM provided a small, short-term improvement to children's mental health particularly for children who are already struggling.
Change in Cognitive Performance From Midlife Into Old Age: Findings from the Midlife in the United States (MIDUS) Study
Authors: Hughes Matthew L. , Agrigoroaei Stefan , Jeon Minjeong , Bruzzese Molly , Lachman Margie E.
Published: July 2018

Objectives:A substantial body of research has documented age-related declines in cognitive abilities among adults over 60, yet there is much less known about changes in cognitive abilities during midlife. The goal was to examine longitudinal changes in multiple cognitive domains from early midlife through old age in a large national sample, the Midlife in the United States (MIDUS) study.Methods:The Brief Test of Adult Cognition by Telephone (BTACT) was administered on two occasions (MIDUS 2, MIDUS 3), an average of 9 years apart. At MIDUS 3, those with the cognitive assessment (N=2518) ranged in age from 42 to 92 years (M=64.30;SD=11.20) and had a mean education of 14.68 years (SD=2.63). The BTACT includes assessment of key aging-sensitive cognitive domains: immediate and delayed free recall, number series, category fluency, backward digit span, processing speed, and reaction time for attention switching and inhibitory control, which comprise two factors: episodic memory and executive functioning.Results:As predicted, all cognitive subtests and factors showed very small but significant declines over 9 years, with differences in the timing and extent of change. Processing speed showed the earliest and steepest decrements. Those with higher educational attainment scored better on all tests except reaction time. Men had better executive functioning and women performed better on episodic memory.Conclusions:Examining cognitive changes in midlife provides opportunities for early detection of cognitive impairments and possibilities for preventative interventions. (JINS, 2018,24, 805–820)
Anesthetists’ Heart Rate Variability as an Indicator of Performance During Induction of General Anesthesia and Simulated Critical Incidents
Authors: Schneider Frederick , Martin Jan , Skrzypczak Matthias , Hinzmann Dominik , Jordan Denis , Wagner Klaus J. , Schulz Christian M.
Published: July 2018

Abstract. In the environment of anesthesia, good performance describes the absence of threat for the patient as well as a quick reaction to challenging and possibly life-threatening circumstances. Elsewhere, performance and cognitive function have been linked to indicators of vagally-mediated heart rate variability (HRV). This exploratory study examines the correlation between anesthetists’ HRV and their performance during uneventful induction of general anesthesia and during a simulated critical incident. For this study electrocardiograms (ECG) were obtained from two different groups of anesthetists providing general anesthesia in uneventful real cases in the operation room (OR, n = 38) and during the management of a hypotension scenario in a high-fidelity human patient simulator environment (SIM, n = 23). Frequency, time domain, and nonlinear HRV metrics were calculated from 5-min ECG recordings. To separate high performing (HP) and low performing (LP) individuals, the time needed for induction (in the OR setting) and the length and depth of hypotension (in the SIM setting) were used as performance correlates. The Mann-Whitney- U-test was used to assess differences in HRV within the groups. In both settings (OR and SIM), linear and nonlinear HRV metrics did not differ significantly between the HP and LP group. Also, the anesthetists’ work experience and sex were not related to performance. While providing general anesthesia and during a simulated critical incident, high and low performing individuals do not differ with respect to HRV metrics, sex, and work experience. Further research including the HRV under resting conditions is necessary.
Characterizing Ion Flows Across a Magnetotail Dipolarization Jet
Authors: Arnold H. , Swisdak M. , Drake J. F.
Published: July 2018

The structure of dipolarization jets with finite width in the dawn‐dusk direction relevant to magnetic reconnection in the Earth's magnetotail is explored with particle‐in‐cell simulations. We carry out Riemann simulations of the evolution of the jet in the dawn‐dusk, north‐south plane to investigate the dependence of the jet structure on the jet width in the dawn‐dusk direction. We find that the magnetic field and Earth‐directed ion flow structure depend on the dawn‐dusk width. A reversal in the usual Hall magnetic field near the center of the current sheet on the duskside of larger jets is observed. For small widths, the maximum velocity of the earthward flow is significantly reduced below the theoretical limit of the upstream Alfvén speed. However, the ion flow speed approaches this limit once the width exceeds the ion Larmor radius based on the normal magnetic field, Bz.
Fabrication and testing of polymer-based capacitive micromachined ultrasound transducers for medical imaging
Authors: Gerardo Carlos D. , Cretu Edmond , Rohling Robert
Published: July 2018

The ultrasonic transducer industry is dominated by piezoelectric materials. As an emerging alternative, capacitive micromachined ultrasound transducers (CMUTs) offer wider bandwidth, better integration with electronics, and ease of fabricating large arrays. CMUTs have a sealed cavity between a fixed electrode and a suspended metalized membrane. Manufacturing cost and sensitivity are limiting factors in current CMUTs that depend on the fabrication equipment and, especially, on the materials used. For widespread use of CMUTs, a much lower fabrication cost that uses inexpensive materials, which maintain or improve upon existing sensitivity, is needed. Herein, a new fabrication process is described for polymer-based CMUTs (polyCMUTs) using the photopolymer SU-8 and Omnicoat. The first ultrasound B-mode image of a wire phantom created with a 64-element linear array using synthetic aperture beamforming techniques is presented. A 12 VAC signal superimposed on a 10 VDC signal was used on the transmission side, and only a bias-tee, with no amplifiers, was used on the receiving side. The low operational voltage and high sensitivity of this device can be partially attributed to a pre-biasing condition on the membrane. By using a novel sacrificial layer combined with a top electrode embedded inside the membrane, we demonstrated that SU-8 can be used to manufacture CMUTs inexpensively. Moreover, the fabrication used relatively simple equipment, and the number of fabrication steps was reduced compared to traditional CMUT fabrication. This new fabrication process has the potential to increase the use of CMUTs in the ultrasound market, including the market for wearable transducers.
Crosstalk between hepatic tumor cells and macrophages via Wnt/β-catenin signaling promotes M2-like macrophage polarization and reinforces tumor malignant behaviors
Authors: Yang Yang , Ye Yu-Chen , Chen Yan , Zhao Jun-Long , Gao Chun-Chen , Han Hua , Liu Wen-Chao , Qin Hong-Yan
Published: July 2018

Tumor-associated macrophages (TAMs) are a major component of tumor microenvironment (TME) and play pivotal roles in the progression of hepatocellular carcinoma (HCC). Wnt signaling is evolutionarily conserved and participates in liver tumorigenesis. Several studies have shown that macrophage-derived Wnt ligands can activate Wnt signaling in tumor cells. However, whether Wnt ligands secreted by tumor cells can trigger Wnt signaling in macrophages is still elusive. In this study, we first verified that canonical Wnt/β-catenin signaling was activated during monocyte-to-macrophage differentiation and in M2-polarized macrophages. Knockdown of β-catenin in M2 macrophages exhibited stronger antitumor characteristics when cocultured with Hepa1-6 HCC cells in a series of experiments. Activation of Wnt signaling promoted M2 macrophage polarization through c-Myc. Moreover, co-culturing naïve macrophages with Hepa1-6 HCC cells in which Wnt ligands secretion was blocked by knockdown of Wntless inhibited M2 polarization in vitro. Consistently, the growth of HCC tumor orthotopically inoculated with Wntless-silenced Hepa1-6 cells was impeded, and the phenotype of M2-like TAMs was abrogated due to attenuated Wnt/β-catenin signaling in TAMs, leading to subverted immunosuppressive TME. Finally, we confirmed the correlation between M2 macrophage polarization and nuclear β-catenin accumulation in CD68+ macrophages in human HCC biopsies. Taken together, our study indicates that tumor cells-derived Wnt ligands stimulate M2-like polarization of TAMs via canonical Wnt/β-catenin signaling, which results in tumor growth, migration, metastasis, and immunosuppression in HCC. To block Wnts secretion from tumor cells and/or Wnt/β-catenin signal activation in TAMs may be potential strategy for HCC therapy in future.
NIR-II nanoprobes in-vivo assembly to improve image-guided surgery for metastatic ovarian cancer
Authors: Wang Peiyuan , Fan Yong , Lu Lingfei , Liu Lu , Fan Lingling , Zhao Mengyao , Xie Yang , Xu Congjian , Zhang Fan
Published: July 2018

Local recurrence is a common cause of treatment failure for patients with solid tumors. Tumor-specific intraoperative fluorescence imaging may improve staging and debulking efforts in cytoreductive surgery and, thereby improve prognosis. Here, we report in vivo assembly of the second near-infrared window (NIR-II) emitting downconversion nanoparticles (DCNPs) modified with DNA and targeting peptides to improve the image-guided surgery for metastatic ovarian cancer. The NIR-II imaging quality with DCNPs is superior to that of clinically approved ICG with good photostability and deep tissue penetration (8 mm). Stable tumor retention period experienced 6 h by in vivo assembly of nanoprobes can be used for precise tumor resection. Superior tumor-to-normal tissue ratio is successfully achieved to facilitate the abdominal ovarian metastases surgical delineation. Metastases with ≤1 mm can be completely excised under NIR-II bioimaging guidance. This novel technology provides a general new basis for the future design of nanomaterials for medical applications.
Femtosecond formation dynamics of the spin Seebeck effect revealed by terahertz spectroscopy
Authors: Seifert Tom S. , Jaiswal Samridh , Barker Joseph , Weber Sebastian T. , Razdolski Ilya , Cramer Joel , Gueckstock Oliver , Maehrlein Sebastian F. , Nadvornik Lukas , Watanabe Shun , Ciccarelli Chiara , Melnikov Alexey , Jakob Gerhard , Münzenberg Markus , Goennenwein Sebastian T. B. , Woltersdorf Georg , Rethfeld Baerbel , Brouwer Piet W. , Wolf Martin , Kläui Mathias , Kampfrath Tobias
Published: July 2018

Understanding the transfer of spin angular momentum is essential in modern magnetism research. A model case is the generation of magnons in magnetic insulators by heating an adjacent metal film. Here, we reveal the initial steps of this spin Seebeck effect with <27 fs time resolution using terahertz spectroscopy on bilayers of ferrimagnetic yttrium iron garnet and platinum. Upon exciting the metal with an infrared laser pulse, a spin Seebeck current js arises on the same ~100 fs time scale on which the metal electrons thermalize. This observation highlights that efficient spin transfer critically relies on carrier multiplication and is driven by conduction electrons scattering off the metal–insulator interface. Analytical modeling shows that the electrons’ dynamics are almost instantaneously imprinted onto js because their spins have a correlation time of only ~4 fs and deflect the ferrimagnetic moments without inertia. Applications in material characterization, interface probing, spin-noise spectroscopy and terahertz spin pumping emerge.
Publisher Correction: Operando monitoring the lithium spatial distribution of lithium metal anodes
Authors: Lv Shasha , Verhallen Tomas , Vasileiadis Alexandros , Ooms Frans , Xu Yaolin , Li Zhaolong , Li Zhengcao , Wagemaker Marnix
Published: July 2018

The original HTML version of this Article omitted to list Zhengcao Li as a corresponding author. Correspondingly, the original PDF version of this Article incorrectly stated that ‘Correspondence and requests for materials should be addressed to M.W. (email: m.wagemaker@tudelft.nl)’, instead of the correct ‘Correspondence and requests for materials should be addressed to Z.L. (email: zcli@tsinghua.edu.cn) or to M.W. (email: m.wagemaker@tudelft.nl)’. This has been corrected in both the PDF and HTML versions of the Article.
North China Plain threatened by deadly heatwaves due to climate change and irrigation
Authors: Kang Suchul , Eltahir Elfatih A. B.
Published: July 2018

North China Plain is the heartland of modern China. This fertile plain has experienced vast expansion of irrigated agriculture which cools surface temperature and moistens surface air, but boosts integrated measures of temperature and humidity, and hence enhances intensity of heatwaves. Here, we project based on an ensemble of high-resolution regional climate model simulations that climate change would add significantly to the anthropogenic effects of irrigation, increasing the risk from heatwaves in this region. Under the business-as-usual scenario of greenhouse gas emissions, North China Plain is likely to experience deadly heatwaves with wet-bulb temperature exceeding the threshold defining what Chinese farmers may tolerate while working outdoors. China is currently the largest contributor to the emissions of greenhouse gases, with potentially serious implications to its own population: continuation of the current pattern of global emissions may limit habitability in the most populous region, of the most populous country on Earth.
Interferon gene therapy reprograms the leukemia microenvironment inducing protective immunity to multiple tumor antigens
Authors: Escobar Giulia , Barbarossa Luigi , Barbiera Giulia , Norelli Margherita , Genua Marco , Ranghetti Anna , Plati Tiziana , Camisa Barbara , Brombin Chiara , Cittaro Davide , Annoni Andrea , Bondanza Attilio , Ostuni Renato , Gentner Bernhard , Naldini Luigi
Published: July 2018

Immunotherapy is emerging as a new pillar of cancer treatment with potential to cure. However, many patients still fail to respond to these therapies. Among the underlying factors, an immunosuppressive tumor microenvironment (TME) plays a major role. Here we show that monocyte-mediated gene delivery of IFNα inhibits leukemia in a mouse model. IFN gene therapy counteracts leukemia-induced expansion of immunosuppressive myeloid cells and imposes an immunostimulatory program to the TME, as shown by bulk and single-cell transcriptome analyses. This reprogramming promotes T-cell priming and effector function against multiple surrogate tumor-specific antigens, inhibiting leukemia growth in our experimental model. Durable responses are observed in a fraction of mice and are further increased combining gene therapy with checkpoint blockers. Furthermore, IFN gene therapy strongly enhances anti-tumor activity of adoptively transferred T cells engineered with tumor-specific TCR or CAR, overcoming suppressive signals in the leukemia TME. These findings warrant further investigations on the potential development of our gene therapy strategy towards clinical testing.
Characterization of domain distributions by second harmonic generation in ferroelectrics
Authors: Zhang Yuan , Zhang Yi , Guo Quan , Zhong Xiangli , Chu Yinghao , Lu Haidong , Zhong Gaokuo , Jiang Jie , Tan Congbing , Liao Min , Lu Zhihui , Zhang Dongwen , Wang Jinbin , Yuan Jianmin , Zhou Yichun
Published: July 2018

Domain orientations and their volume ratios in ferroelectrics are recognized as a compelling topic recently for domain switching dynamics and domain stability in devices application. Here, an optimized second harmonic generation method has been explored for ferroelectric domain characterization. Combing a unique theoretical model with azimuth-polarization-dependent second harmonic generation response, the complex domain components and their distributions can be rigidly determined in ferroelectric thin films. Using the proposed model, the domain structures of rhombohedral BiFeO3 films with 71° and 109° domain wall, and, tetragonal BiFeO3, Pb(Zr0.2Ti0.8)O3, and BaTiO3 ferroelectric thin films are analyzed and the corresponding polarization variants are determined. This work could provide a powerful and all-optical method to track and evaluate the evolution of ferroelectric domains in the ferroelectric-based devices.
Complete elimination of information leakage in continuous-variable quantum communication channels
Authors: Jacobsen Christian S. , Madsen Lars S. , Usenko Vladyslav C. , Filip Radim , Andersen Ulrik L.
Published: July 2018

In all lossy communication channels realized to date, information is inevitably leaked to a potential eavesdropper. Here we present a communication protocol that does not allow for any information leakage to a potential eavesdropper in a purely lossy channel. By encoding information into a restricted Gaussian alphabet of squeezed states we show, both theoretically and experimentally, that the Holevo information between the eavesdropper and the intended recipient can be exactly zero in a purely lossy channel while minimized in a noisy channel. This result is of fundamental interest, but might also have practical implications in extending the distance of secure quantum key distribution.
Identification of novel transcripts and peptides in developing murine lens
Authors: Khan Shahid Y. , Ali Muhammad , Kabir Firoz , Chen Ruiqiang , Na Chan Hyun , Lee Mei-Chong W. , Pourmand Nader , Hackett Sean F. , Riazuddin S. Amer
Published: July 2018

We previously investigated the transcriptome and proteome profiles of the murine ocular lens at six developmental time points including two embryonic (E15 and E18) and four postnatal time points (P0, P3, P6, and P9). Here, we extend our analyses to identify novel transcripts and peptides in developing  mouse lens. We identified a total of 9,707 novel transcripts and 325 novel fusion genes in developing mouse lens. Additionally, we identified 13,281 novel alternative splicing (AS) events in mouse lens including 6,990 exon skipping (ES), 2,447 alternative 3′ splice site (A3SS), 1,900 alternative 5′ splice site (A5SS), 1,771 mutually exclusive exons (MXE), and 173 intron retention (IR). Finally, we integrated our OMIC (Transcriptome and Proteome) datasets identifying 20 novel peptides in mouse lens. All 20 peptides were validated through matching MS/MS spectra of synthetic peptides. To the best of our knowledge, this is the first report integrating OMIC datasets to identify novel peptides in developing murine lens.
Integrated Platform for Monitoring Single-cell MAPK Kinetics in Computer-controlled Temporal Stimulations
Authors: Ryu Hyunryul , Chung Minhwan , Song Jiyoung , Lee Sung Sik , Pertz Olivier , Jeon Noo Li
Published: July 2018

Extracellular response kinase (ERK) is one of the key regulator of cell fate, such as proliferation, differentiation and cell migration. Here, we propose a novel experimental pipeline to learn ERK kinetics by temporal growth factor (GF) stimulation. High signal-to-noise ratio of genetically encoded Fluorescence resonance energy transfer (FRET) biosensor enables to get a large number of single-cell ERK activity at each time point, while computer-controlled microfluidics fine-tune the temporal stimulation. Using this platform, we observed that static Epidermal growth factor (EGF) stimulation led to transient ERK activation with a significant cell-to-cell variation, while dynamic stimulation of 3′ EGF pulse led to faster adaptation kinetics with no discrepancy. Multiple EGF pulses retriggered ERK activity with respect to frequency of stimulation. We also observed oscillation of ERK activity of each cell at basal state. Introducing of Mitogen-activated protein kinase kinase (MEK) inhibitor, U0126, was not only dropping the average of basal activity for 7.5%, but also diminishing oscillatory behavior. Activity level raised up when inhibitor was removed, followed by transient peak of ERK kinetics. We expect this platform to probe Mitogen-associated protein kinase (MAPK) signaling network for systems biology research at single cellular level.
Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma
Authors: Halse H. , Colebatch A. J. , Petrone P. , Henderson M. A. , Mills J. K. , Snow H. , Westwood J. A. , Sandhu S. , Raleigh J. M. , Behren A. , Cebon J. , Darcy P. K. , Kershaw M. H. , McArthur G. A. , Gyorki D. E. , Neeson P. J.
Published: July 2018

A prospective study explored the heterogeneous nature of metastatic melanoma using Multiplex immunohistochemistry (IHC) and flow cytometry (FACS). Multiplex IHC data quantitated immune subset number present intra-tumoral (IT) vs the tumor stroma, plus distance of immune subsets from the tumor margin (TM). In addition, mIHC showed a close association between the presence of IT CD8+ T cells and PDL1 expression in melanoma, which was more prevalent on macrophages than on melanoma cells. In contrast, FACS provided more detailed information regarding the T cell subset differentiation, their activation status and expression of immune checkpoint molecules. Interestingly, mIHC detected significantly higher Treg numbers than FACS and showed preferential CD4+ T cell distribution in the tumor stroma. Based on the mIHC and FACS data, we provide a model which defines metastatic melanoma immune context into four categories using the presence or absence of PDL1+ melanoma cells and/or macrophages, and their location within the tumor or on the periphery, combined with the presence or absence of IT CD8+ T cells. This model interprets melanoma immune context as a spectrum of tumor escape from immune control, and provides a snapshot upon which interpretation of checkpoint blockade inhibitor (CBI) therapy responses can be built.
Publisher Correction: Bioprospecting on invasive plant species to prevent seed dispersal
Authors: Guzzetti Lorenzo , Galimberti Andrea , Bruni Ilaria , Magoni Chiara , Ferri Maura , Tassoni Annalisa , Sangiovanni Enrico , Dell’Agli Mario , Labra Massimo
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
A high-throughput imaging and nuclear segmentation analysis protocol for cleared 3D culture models
Authors: Boutin Molly E. , Voss Ty C. , Titus Steven A. , Cruz-Gutierrez Kennie , Michael Sam , Ferrer Marc
Published: July 2018

Imaging and subsequent segmentation analysis in three-dimensional (3D) culture models are complicated by the light scattering that occurs when collecting fluorescent signal through multiple cell and extracellular matrix layers. For 3D cell culture models to be usable for drug discovery, effective and efficient imaging and analysis protocols need to be developed that enable high-throughput data acquisition and quantitative analysis of fluorescent signal. Here we report the first high-throughput protocol for optical clearing of spheroids, fluorescent high-content confocal imaging, 3D nuclear segmentation, and post-segmentation analysis. We demonstrate nuclear segmentation in multiple cell types, with accurate identification of fluorescently-labeled subpopulations, and develop a metric to assess the ability of clearing to improve nuclear segmentation deep within the tissue. Ultimately this analysis pipeline allows for previously unattainable segmentation throughput of 3D culture models due to increased sample clarity and optimized batch-processing analysis.
Quad-mode functional and molecular photoacoustic microscopy
Authors: Liu Wei , Shcherbakova Daria M. , Kurupassery Neel , Li Yang , Zhou Qifa , Verkhusha Vladislav V. , Yao Junjie
Published: July 2018

A conventional photoacoustic microscopy (PAM) system typically has to make tradeoffs between its spatial resolution and penetration depth, by choosing a fixed configuration of optical excitation and acoustic detection. The single-scale imaging capability of PAM may limit its applications in biomedical studies. Here, we report a quad-mode photoacoustic microscopy (QM-PAM) system with four complementary spatial resolutions and maximum penetration depths. For this we first developed a ring-shaped focused ultrasound transducer that has two independent elements with respective central frequencies at 20 MHz and 40 MHz, providing complementary acoustically-determined spatial resolutions and penetration depths. To accommodate the dual-element ultrasound transducer, we implemented two optical excitation modes to provide tightly- and weakly-focused light illumination. The dual-element acoustic detection combined with the two optical focusing modes can thus provide four imaging scales in a single imaging device, with consistent contrast mechanisms and co-registered field of views. We have demonstrated the multiscale morphological, functional, and molecular imaging capability of QM-PAM in the mouse head, leg and ear in vivo. We expect the high scale flexibility of QM-PAM will enable broad applications in preclinical studies.
Natural and sexual selection drive multivariate phenotypic divergence along climatic gradients in an invasive fish
Authors: Ouyang Xu , Gao Jiancao , Xie Meifeng , Liu Binghua , Zhou Linjun , Chen Bojian , Jourdan Jonas , Riesch Rüdiger , Plath Martin
Published: July 2018

Invasive species that rapidly spread throughout novel distribution ranges are prime models to investigate climate-driven phenotypic diversification on a contemporary scale. Previous studies on adaptive diversification along latitudinal gradients in fish have mainly considered body size and reported either increased or decreased body size towards higher latitudes (i.e. Bergmann’s rule). Our study is the first to investigate phenotypic divergence in multiple traits, including sexually selected traits (size and shape of the male copulatory organ, the gonopodium) of invasive Gambusia affinis in China. We studied body size, life history traits and morphological variation across populations spanning 17 degrees of latitude and 16 degrees of longitude. Even though we found phenotypic variation along climatic gradients to be strongest in naturally selected traits, some sexually selected traits also showed systematic gradual divergence. For example, males from southern populations possessed wider gonopodia with increased armament. Generally, males and females diverged in response to different components of climatic gradients (latitudinal or longitudinal variation) and in different trait suites. We discuss that not only temperature regimes, but also indirect effects of increased resource and mate competition (as a function of different extrinsic overwinter mortality rates) alter the selective landscape along climatic gradients.
Quantifying Anharmonic Vibrations in Thermoelectric Layered Cobaltites and Their Role in Suppressing Thermal Conductivity
Authors: Fujii Susumu , Yoshiya Masato , Fisher Craig A. J.
Published: July 2018

Optimizing multiple materials properties which are simultaneously in competition with each other is one of the chief challenges in thermoelectric materials research. Introducing greater anharmonicity to vibrational modes is one strategy for suppressing phonon thermal transport in crystalline oxides without detrimentally affecting electronic conductivity, so that the overall thermoelectric efficiency can be improved. Based on perturbed molecular dynamics and associated numerical analyses, we show that CoO2 layers in layered cobaltite thermoelectrics NaxCoO2 and Ca3Co4O9 are responsible for most of the in-plane heat transport in these materials, and that the non-conducting intermediate layers in the two materials exhibit different kinds of anharmonicity. More importantly, thermal conduction is shown to be altered by modifying the structure of the intermediate layers. The simulation methods developed to quantify the effect of anharmonic atomic vibrations on thermal conductivity provide a new tool for the rational design of thermoelectric materials, and the insights gained should hasten the attainment of higher conversion efficiencies so that thermoelectrics can be put to widespread practical use.
Biscrolled Carbon Nanotube Yarn Structured Silver-Zinc Battery
Authors: Lee Jae Myeong , Choi Changsoon , Kim Ji Hwan , de Andrade Mônica Jung , Baughman Ray H. , Kim Seon Jeong
Published: July 2018

Flexible yarn- or fiber-based energy storing devices are attractive because of their small dimension, light weight, and suitability for integration into woven or textile application. Some Li-ion based yarn or fiber batteries were developed due to their performance advantages, realizing highly performing and practically safe wearable battery still remains a challenge. Here, high performance and safe yarn-based battery is demonstrated by embedding active materials into inner structure of yarn and using water based electrolyte. Thanks to biscrolling method, loading level of silver and zinc in yarn electrodes increased up to 99 wt%. Our high loaded Silver and Zinc yarn electrodes enables high linear capacity in liquid electrolyte (0.285 mAh/cm) and solid electrolyte (0.276 mAh/cm), which are significantly higher than previously reported fiber batteries. In additions, due to PVA-KOH based aqueous electrolyte, our yarn battery system is inflammable, non-explosive and safe. Consequently, these high-capacities enable our Silver-Zinc aqueous yarn battery to be applicable to the energy source of portable and wearable electronics like an electric watch.
Associations Between Nutrition, Gut Microbiome, and Health in A Novel Nonhuman Primate Model
Authors: Clayton Jonathan B. , Al-Ghalith Gabriel A. , Long Ha Thang , Tuan Bui Van , Cabana Francis , Huang Hu , Vangay Pajau , Ward Tonya , Minh Vo Van , Tam Nguyen Ai , Dat Nguyen Tat , Travis Dominic A. , Murtaugh Michael P. , Covert Herbert , Glander Kenneth E. , Nadler Tilo , Toddes Barbara , Sha John C. M. , Singer Randy , Knights Dan , Johnson Timothy J.
Published: July 2018

Red-shanked doucs (Pygathrix nemaeus) are endangered, foregut-fermenting colobine primates which are difficult to maintain in captivity. There are critical gaps in our understanding of their natural lifestyle, including dietary habits such as consumption of leaves, unripe fruit, flowers, seeds, and other plant parts. There is also a lack of understanding of enteric adaptations, including their unique microflora. To address these knowledge gaps, we used the douc as a model to study relationships between gastrointestinal microbial community structure and lifestyle. We analyzed published fecal samples as well as detailed dietary history from doucs with four distinct lifestyles (wild, semi-wild, semi-captive, and captive) and determined gastrointestinal bacterial microbiome composition using 16S rRNA sequencing. A clear gradient of microbiome composition was revealed along an axis of natural lifestyle disruption, including significant associations with diet, biodiversity, and microbial function. We also identified potential microbial biomarkers of douc dysbiosis, including Bacteroides and Prevotella, which may be related to health. Our results suggest a gradient-like shift in captivity causes an attendant shift to severe gut dysbiosis, thereby resulting in gastrointestinal issues.
Cytological analysis and structural quantification of FtsZ1-2 and FtsZ2-1 network characteristics in Physcomitrella patens
Authors: Özdemir Bugra , Asgharzadeh Pouyan , Birkhold Annette I. , Mueller Stefanie J. , Röhrle Oliver , Reski Ralf
Published: July 2018

Although the concept of the cytoskeleton as a cell-shape-determining scaffold is well established, it remains enigmatic how eukaryotic organelles adopt and maintain a specific morphology. TheFilamentousTemperatureSensitiveZ(FtsZ) protein family, an ancient tubulin, generates complex polymer networks, with striking similarity to the cytoskeleton, in the chloroplasts of the mossPhyscomitrella patens. Certain members of this protein family are essential for structural integrity and shaping of chloroplasts, while others are not, illustrating the functional diversity within the FtsZ protein family. Here, we apply a combination of confocal laser scanning microscopy and a self-developed semi-automatic computational image analysis method for the quantitative characterisation and comparison of network morphologies and connectivity features for two selected, functionally dissimilar FtsZ isoforms, FtsZ1-2 and FtsZ2-1. We show that FtsZ1-2 and FtsZ2-1 networks are significantly different for 8 out of 25 structural descriptors. Therefore, our results demonstrate that different FtsZ isoforms are capable of generating polymer networks with distinctive morphological and connectivity features which might be linked to the functional differences between the two isoforms. To our knowledge, this is the first study to employ computational algorithms in the quantitative comparison of different classes of protein networks in living cells.
Social Closure and the Evolution of Cooperation via Indirect Reciprocity
Authors: Righi Simone , Takács Károly
Published: July 2018

Direct and indirect reciprocity are good candidates to explain the fundamental problem of evolution of cooperation. We explore the conditions under which different types of reciprocity gain dominance and their performances in sustaining cooperation in the PD played on simple networks. We confirm that direct reciprocity gains dominance over indirect reciprocity strategies also in larger populations, as long as it has no memory constraints. In the absence of direct reciprocity, or when its memory is flawed, different forms of indirect reciprocity strategies are able to dominate and to support cooperation. We show that indirect reciprocity relying on social capital inherent in closed triads is the best competitor among them, outperforming indirect reciprocity that uses information from any source. Results hold in a wide range of conditions with different evolutionary update rules, extent of evolutionary pressure, initial conditions, population size, and density.
Synergistic antibacterial activity of silver with antibiotics correlating with the upregulation of the ROS production
Authors: Zou Lili , Wang Jun , Gao Yu , Ren Xiaoyuan , Rottenberg Martin E. , Lu Jun , Holmgren Arne
Published: July 2018

Thiol-dependent enzymes, including the thioredoxin (Trx) and glutathione (GSH) systems, have recently been found as promising bactericidal targets in multidrug-resistant (MDR) bacteria. We previously discovered that silver acted synergistically with ebselen in the inhibition of the Trx system and also resulted in a fast depletion of GSH in Gram-negative bacteria. Silver has been found by others to improve the sensitivity of bacteria to certain conventional antibiotics. Here, we found that the synergistic antibacterial effects of silver with four conventional antibiotics was correlated with the blockage of bacterial Trx system by silver. The synergistic antibacterial effect came along with the production of reactive oxygen species. All these results suggested that silver primarily enhanced the bactericidal activities of conventional antibiotics towards Gram-negative strains through the upregulation of ROS production.
Enhancing coevolution-based contact prediction by imposing structural self-consistency of the contacts
Authors: Kassem Maher M. , Christoffersen Lars B. , Cavalli Andrea , Lindorff-Larsen Kresten
Published: July 2018

Based on the development of new algorithms and growth of sequence databases, it has recently become possible to build robust higher-order sequence models based on sets of aligned protein sequences. Such models have proven useful inde novostructure prediction, where the sequence models are used to find pairs of residues that co-vary during evolution, and hence are likely to be in spatial proximity in the native protein. The accuracy of these algorithms, however, drop dramatically when the number of sequences in the alignment is small. We have developed a method that we termed CE-YAPP (CoEvolution-YAPP), that is based on YAPP (Yet Another Peak Processor), which has been shown to solve a similar problem in NMR spectroscopy. By simultaneously performing structure prediction and contact assignment, CE-YAPP uses structural self-consistency as a filter to remove false positive contacts. Furthermore, CE-YAPP solves another problem, namely how many contacts to choose from the ordered list of covarying amino acid pairs. We show that CE-YAPP consistently improves contact prediction from multiple sequence alignments, in particular for proteins that are difficult targets. We further show that the structures determined from CE-YAPP are also in better agreement with those determined using traditional methods in structural biology.
Optically reconfigurable polarized emission in Germanium
Authors: De Cesari Sebastiano , Bergamaschini Roberto , Vitiello Elisa , Giorgioni Anna , Pezzoli Fabio
Published: July 2018

Light polarization can conveniently encode information. Yet, the ability to tailor polarized optical fields is notably demanding but crucial to develop practical methods for data encryption and to gather fundamental insights into light-matter interactions. Here we demonstrate the dynamic manipulation of the chirality of light at telecom wavelengths. This unique possibility is enrooted in the multivalley nature of the conduction band of a conventional semiconductor, namely Ge. In particular, we demonstrate that optical pumping suffices to govern the kinetics of spin-polarized carriers and eventually the chirality of the radiative recombination. We found that the polarized component of the emission can be remarkably swept through orthogonal eigenstates without magnetic field control or phase shifter coupling. Our results provide insights into spin-dependent phenomena and offer guiding information for the future selection and design of spin-enhanced photonic functionalities of group IV semiconductors.
Evolutionary cell biology traces the rise of the exomer complex in Fungi from an ancient eukaryotic component
Authors: Ramirez-Macias Inmaculada , Barlow Lael D. , Anton Carlos , Spang Anne , Roncero Cesar , Dacks Joel B.
Published: July 2018

Cargo is transported from the trans-Golgi Network to the plasma membrane by adaptor complexes, which are pan-eukaryotic components. However, in yeast, cargo can also be exported by the exomer complex, a heterotetrameric protein complex consisting of two copies of Chs5, and any two members of four paralogous proteins (ChAPs). To understand the larger relevance of exomer, its phylogenetic distribution and function outside of yeast need to be explored. We find that the four ChAP proteins are derived from gene duplications after the divergence of Yarrowia from the remaining Saccharomycotina, with BC8 paralogues (Bch2 and Chs6) being more diverged relative to the BB8 paralogues (Bch1 and Bud7), suggesting neofunctionalization. Outside Ascomycota, a single preduplicate ChAP is present in nearly all Fungi and in diverse eukaryotes, but has been repeatedly lost. Chs5, however, is a fungal specific feature, appearing coincidentally with the loss of AP-4. In contrast, the ChAP protein is a wide-spread, yet uncharacterized, membrane-trafficking component, adding one more piece to the increasingly complex machinery deduced as being present in our ancient eukaryotic ancestor.
Chloroquine exposure triggers distinct cellular responses in sensitive versus resistant Plasmodium falciparum parasites
Authors: Reiling Sarah J. , Krohne Georg , Friedrich Oliver , Geary Timothy G. , Rohrbach Petra
Published: July 2018

Chloroquine (CQ) treatment failure in Plasmodium falciparum parasites has been documented for decades, but the pharmacological explanation of this phenotype is not fully understood. Current concepts attribute CQ resistance to reduced accumulation of the drug at a given external CQ concentration ([CQ]ex) in resistant compared to sensitive parasites. The implication of this explanation is that the mechanisms of CQ-induced toxicity in resistant and sensitive strains are similar once lethal internal concentrations have been reached. To test this hypothesis, we investigated the mechanism of CQ-induced toxicity in CQ-sensitive (CQS) versus CQ-resistant (CQR) parasites by analyzing the time-course of cellular responses in these strains after exposure to varying [CQ]ex as determined in 72 h toxicity assays. Parasite killing was delayed in CQR parasites for up to 10 h compared to CQS parasites when exposed to equipotent [CQ]ex. In striking contrast, brief exposure (1 h) to lethal [CQ]ex in CQS but not CQR parasites caused the appearance of hitherto undescribed hemozoin (Hz)-containing compartments in the parasite cytosol. Hz-containing compartments were very rarely observed in CQR parasites even after CQ exposures sufficient to cause irreversible cell death. These findings challenge current concepts that CQ killing of malaria parasites is solely concentration-dependent, and instead suggest that CQS and CQR strains fundamentally differ in the consequences of CQ exposure.
In vivo delineation of glioblastoma by targeting tumor-associated macrophages with near-infrared fluorescent silica coated iron oxide nanoparticles in orthotopic xenografts for surgical guidance
Authors: Lee Chaedong , Kim Ga Ram , Yoon Juhwan , Kim Sang Eun , Yoo Jung Sun , Piao Yuanzhe
Published: July 2018

Glioblastoma multiforme (GBM) is the most aggressive and lethal type of human brain cancer. Surgery is a current gold standard for GBM treatment but the complete surgical resection of GBM is almost impossible due to their diffusive characteristics into surrounded normal brain tissues. There is an urgent need to develop a sensitive imaging tool for accurate delineation of GBM in the operating room to guide surgeons. Here we illustrate the feasibility of using near-infrared fluorescent silica coated iron oxide nanoparticles (NF-SIONs) with high water dispersion capacity and strong fluorescence stability for intraoperative imaging of GBM by targeting tumor-associated macrophages. Abundant macrophage infiltration is a key feature of GBM margins and it is well associated with poor prognosis. We synthesized NF-SIONs of about 37 nm to maximize endocytosis activity for macrophage uptake. The NF-SIONs selectively visualized tumor-associated macrophage populations by in vitro live-cell imaging and in vivo fluorescence imaging. In the orthotopic GBM xenograft models, the NF-SIONs could successfully penetrate blood-brain barrier and delineated tumor burden specifically. Taken together, this study showcased the potential applications in GBM treatment for improved intraoperative staging and more radical surgery as well as dual modality benefit in order to circumvent previous clinical failure.
Faunal activity rhythms influencing early community succession of an implanted whale carcass offshore Sagami Bay, Japan
Authors: Aguzzi J. , Fanelli E. , Ciuffardi T. , Schirone A. , De Leo F. C. , Doya C. , Kawato M. , Miyazaki M. , Furushima Y. , Costa C. , Fujiwara Y.
Published: July 2018

Benthic community succession patterns at whale falls have been previously established by means of punctual submersible and ROV observations. The contribution of faunal activity rhythms in response to internal tides and photoperiod cues to that community succession dynamism has never been evaluated. Here, we present results from a high-frequency monitoring experiment of an implanted sperm whale carcass in the continental slope (500 m depth) offshore Sagami Bay, Japan. The benthic community succession was monitored at a high frequency in a prolonged fashion (i.e. 2-h intervals for 2.5 months) with a seafloor lander equipped with a time-lapse video camera and an acoustic Doppler profiler to concomitantly study current flow dynamics. We reported here for the first time, to the best of our knowledge, the occurrence of strong 24-h day-night driven behavioral rhythms of the most abundant species (Simenchelys parasitica; Macrocheira kaempferi, and Pterothrissus gissu). Those rhythms were detected in detriment of tidally-controlled ones. Evidence of a diel temporal niche portioning between scavengers and predators avoiding co-occurrence at the carcass, is also provided. The high-frequency photographic and oceanographic data acquisition also helped to precisely discriminate the transition timing between the successional stages previously described for whale falls’ attendant communities.