bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilingual lexical access: A dynamic operation modulated by word-status and individual differences in inhibitory control
Authors: SUDARSHAN ARUNA , BAUM SHARI R.
Published: May 2018

A question central to bilingualism research is whether representations from the contextually inappropriate language compete for lexical selection during language production. It has been argued recently that the extent of interference from the non-target language may be contingent on a host of factors. In two studies, we investigated whether factors such as word-type and individual differences in inhibitory control capacities influence lexical selection via a cross-modal picture-word interference task and a non-linguistic Simon task. Highly proficient French–English bilinguals named non-cognate and cognate target pictures in L2 (English) while ignoring auditory distractors in L1 (French) and L2. Taken together, our results demonstrated that lexical representations from L1 are active and compete for selection when naming in L2, even in highly proficient bilinguals. However, the extent of cross-language activation was modulated by both word-type and individual differences in inhibitory control capacities.
Reasonable Hope in Kant’s Ethics
Authors: Cureton Adam
Published: May 2018

The most apparent obstacles to a just, enlightened and peaceful social world are also, according to Kant, nature’s way of compelling us to realize those and other morally good ends. Echoing Adam Smith’s idea of the ‘invisible hand’, Kant thinks that selfishness, rivalry, quarrelsomeness, vanity, jealousy and self-conceit, along with the oppressive social inequalities they tend to produce, drive us to perfect our talents, develop culture, approach enlightenment and, through the strife and instability caused by our unsocial sociability, push us towards justice, political equality and the highest good. What are we to make of these arguments, which seem to rely on questionable empirical assumptions, invoke dubious claims about natural teleology and sit uncomfortably with fundamental aspects of Kant’s ethical framework? I suggest that the arguments reveal one of Kant’s deep and important insights about the moral life by partially describing what a good and virtuous person reasonably hopes for.
Kant on Fine Art, Genius and the Threat of Private Meaning
Authors: Reiter Aviv
Published: May 2018

Wittgenstein’s private language argument claims that language and meaning generally are public. It also contends with our appreciation of artworks and reveals the deep connection in our minds between originality and the temptation to think of original meaning as private. This problematic connection of ideas is found in Kant’s theory of fine art. For Kant conceives of the capacity of artistic genius for imaginatively envisioning original content as prior to and independent of finding the artistic means of communicating this content to others. This raises the question of whether we can conceive of art as both original and meaningful without succumbing to privacy.
Pattern of geometric changes of parotid gland in conventional and intensity-modulated radiotherapy in nasopharyngeal cancer patients
Authors: Zhang Yingting , Liu Xiaozhen , Lin Chengguang , Lee Shara W. Y. , Tam Shing-yau , Wu Vincent W. C.
Published: May 2018

Introduction

This study compared the pattern of radiation induced parotid changes between conventional (ConRT) and intensity modulated radiotherapy (IMRT) in nasopharyngeal carcinoma patients.

Methods

56 adult NPC patients treated with IMRT (n=28) and conventional radiotherapy (n=28) were recruited. CT scans were acquired before radiotherapy, at 10th, 20th and 30th fractions, and 3 months after treatment. Parotid gland was delineated in the corresponding CT slices and its mean dose was calculated. The volumetric and geometric changes of the parotid gland at various time intervals were compared against the pre-treatment structure set. The pattern of changes was compared between the two techniques.

Results

The mean parotid dose of IMRT (37.5±9.5 Gy) was significantly lower than ConRT (49.1±7.4 Gy). The parotid gland volume, DICE similarity coefficient and lateral dimension of patient head gradually decreased during the radiotherapy course and partially recovered in 3 months post-treatment. The differences between two groups were not significant until at 3 month after treatment, where IMRT showed significantly better volume recovery.

Conclusion

Similar parotid gland size and location changes were observed during the treatment course in both ConRT and IMRT. However IMRT demonstrated better parotid volume recovery after treatment.
Black Lives Matter: Evidence that Police-Caused Deaths Predict Protest Activity
Authors: Williamson Vanessa , Trump Kris-Stella , Einstein Katherine Levine
Published: May 2018

Since 2013, protests opposing police violence against Black people have occurred across a number of American cities under the banner of “Black Lives Matter.” We develop a new dataset of Black Lives Matter protests that took place in 2014–2015 and explore the contexts in which they emerged. We find that Black Lives Matter protests are more likely to occur in localities where more Black people have previously been killed by police. We discuss the implications of our findings in light of the literature on the development of social movements and recent scholarship on the carceral state’s impact on political engagement.
Development of understanding of DOHaD concepts in students during undergraduate health professional programs in Japan and New Zealand
Authors: Oyamada M. , Lim A. , Dixon R. , Wall C. , Bay J.
Published: May 2018

Evidence in support of the Developmental Origins of Health and Disease (DOHaD) hypothesis has reached the level where it can appropriately be used to inform practice. DOHaD informed interventions supporting primary noncommunicable disease risk reduction should target the pre- and periconceptional periods, pregnancy, lactation, childhood and adolescence. Such interventions are dependent on a health workforce (including dietitians, nurses, midwives, doctors, and nutrition teachers), that has a deep understanding of DOHaD concepts. This study assessed development of awareness of DOHaD concepts during undergraduate health professional training programs. Using a cross-sectional design, a standardized questionnaire was completed by Year 1–4 undergraduate students studying nutrition in Japan (n=309) and Year 1–3 nursing students in New Zealand (n=151). On entry to undergraduate study, most students had no awareness of the terms ‘DOHaD’ or ‘First 1000 Days’. While awareness reached 60% by Year 3 in courses that included DOHaD-related teaching, this remains inadequate. More than 95% of Year 1 undergraduates in both countries demonstrated an appreciation of associations between maternal nutrition and fetal health. However, awareness of associations between parental health status and/or nutritional environment and later-life health was low. While levels of awareness increased across program years, overall awareness was less than optimal. These results indicate evidence of some focus on DOHaD-related content in curricula. We argue that DOHaD principles should be one pillar around which health training curricula are built. This study indicates a need for the DOHaD community to engage with faculties in curriculum development.
Judicial Fact-Finding Initiatives in theSouth China Sea Arbitration
Authors: ESPENILLA Jacqueline Joyce F.
Published: May 2018

The historic Award in theSouth China Sea Arbitrationgave much-needed clarity to many of the complex legal issues lying at the heart of the Philippines-China maritime dispute. Often overlooked, however, is the procedural significance of the case. This Comment submits that theSouth China Sea Arbitrationrepresents a shift towards the use of judicial fact-finding initiatives as a means to overcome the adjudicatory challenges inherent to highly technical and scientific cases where one Party fails or refuses to participate. Even more striking, the Tribunal’s independently acquired facts appear to be the basis for the majority of its conclusions in the Award. This Comment highlights the appropriateness and practicality of the Tribunal’s actions in view of its extraordinary obligation under Article 9 of Annex VII of the UNCLOS to “satisfy itself” that the Philippines’ claims are “well-founded in fact and law”.
Calibrating SuperDARN Interferometers Using Meteor Backscatter
Authors: Chisham G.
Published: May 2018

Accurate geolocation of ionospheric backscatter measured by the Super Dual Auroral Radar Network (SuperDARN) high‐frequency radars is critical for the integrity of polar ionospheric convection maps, which involve combining SuperDARN line‐of‐sight velocity measurements originating from multiple locations. Geolocation requires estimation of the propagation paths of the high‐frequency radio signal to and from the scattering volume. The SuperDARN radars comprise both a main and interferometer antenna array to allow the estimation of the elevation angle of arrival of the returning signal, and hence its most likely propagation path. However, over the history of operation of SuperDARN (>20 years) elevation angle data have not been routinely used owing to problems with the calibration of phase difference measurements. Instead, virtual height models have been used to estimate the most likely propagation paths, and these are often of limited accuracy. Here we present a method for calibrating SuperDARN interferometer measurements using backscatter from meteor trails measured in the near field‐of‐view of the SuperDARN radars. We present estimates of calibration factors for the SuperDARN radar in Saskatoon, Canada, at different temporal resolutions: 3 months, 10 days, and 1 day. The calibration factor varies over the 9‐year interval studied, such that employing a single value for the whole interval would lead to significant errors in elevation angle measurements at times. The higher‐resolution results show the ability of the technique to determine the calibration factor routinely at a high time resolution.
Stopping Solar Geoengineering Through Technical Means: A Preliminary Assessment of Counter‐Geoengineering
Authors: Parker A. , Horton J. B. , Keith D. W.
Published: May 2018

Counter‐geoengineering is the idea that a country might seek or threaten to counteract the cooling effect of solar geoengineering through technical means. Although this concept has been mentioned with increasing frequency in commentary on geoengineering, it has received little scholarly attention. We offer a preliminary analysis. We begin by distinguishing two kinds of counter‐geoengineering: countervailing with a warming agent and neutralizing with a physical disruption. Based on this distinction, we review prior suggestions and describe novel methods by which either method might be accomplished, within the constraints imposed by deep technical uncertainties and substantial technical challenges. We then reflect on the strategic requirements and motivations for developing counter geoengineering and use a simple game‐theoretic framework to demonstrate how counter‐geoengineering might interact with the free‐driver dynamic of solar geoengineering to shape climate geopolitics. We find that any state that could credibly threaten counter‐geoengineering would effectively have a veto over the use of solar geoengineering, which could reduce the prospects of unilateral deployment. Alternatively, the development of geoengineering and counter‐geoengineering capabilities could lead to dangerous brinkmanship. We conclude that the development of counter‐geoengineering would face considerable practical obstacles and would signal continuing political failure to manage climate risks on a cooperative basis.
Using Microbes to Predict the Flow of Arctic Rivers
Authors: Underwood Emily
Published: May 2018

Bacterial DNA provides a good estimate of river discharge.
Volcano‐Tectonic Activity at Deception Island Volcano Following a Seismic Swarm in the Bransfield Rift (2014–2015)
Authors: Almendros J. , Carmona E. , Jiménez V. , Díaz‐Moreno A. , Lorenzo F.
Published: May 2018

In September 2014 there was a sharp increase in the seismic activity of the Bransfield Strait, Antarctica. More than 9,000 earthquakes with magnitudes up to 4.6 located SE of Livingston Island were detected over a period of 8 months. A few months after the series onset, local seismicity at the nearby (∼35 km) Deception Island volcano increased, displaying enhanced long‐period seismicity and several outbursts of volcano‐tectonic (VT) earthquakes. Before February 2015, VT earthquakes occurred mainly at 5–20 km SW of Deception Island. In mid‐February the numbers and sizes of VT earthquakes escalated, and their locations encompassed the whole volcanic edifice, suggesting a situation of generalized unrest. The activity continued in anomalously high levels at least until May 2015. Given the spatial and temporal coincidence, it is unlikely that the Livingston series and the Deception VT swarm were unrelated. We propose that the Livingston series may have produced a triggering effect on Deception Island volcano. Dynamic stresses associated to the seismic swarm may have induced overpressure in the unstable volcanic system, leading to a magmatic intrusion that may in turn have triggered the VT swarm. Alternatively, both the Livingston earthquakes and the VT swarm could be consequences of a magmatic intrusion at Deception Island. The Livingston series would be an example of precursory distal VT swarm, which seems to be a common feature preceding volcanic eruptions and magma intrusions in long‐dormant volcanoes.
Thermal and Energetic Ion Dynamics in Ganymede's Magnetosphere
Authors: Poppe A. R. , Fatemi S. , Khurana K. K.
Published: May 2018

Ganymede is the solar system's only known moon with an intrinsic, global magnetic field. This field is strong enough to stand off the incident Jovian magnetospheric flow to form a small, complex magnetosphere around the satellite. Ganymede's magnetosphere is thought to be responsible for variable surface weathering patterns, the production of a neutral exosphere, and the generation of UV aurorae near Ganymede's open‐closed field line boundaries; however, the exact details and underlying mechanisms are poorly understood. We use results from three‐dimensional hybrid models of Ganymede's magnetosphere and a three‐dimensional particle tracing model to quantify the dynamics of thermal and energetic Jovian ions as they interact with Ganymede's magnetosphere and precipitate to the surface. We identify the formation of quasi‐trapped ionic radiation belts in the model and variable surface weathering. Most of the particle precipitation occurs in Ganymede's polar caps, yet ions also precipitate onto Ganymede's equatorial region in lesser amounts due to particle shadowing of quasi‐trapped ions in Ganymede's ionic radiation belts. Model results predict that within Jupiter's central plasma sheet, total ion fluxes to Ganymede's polar, leading, and trailing hemispheres are 50 × 106, 10 × 106, and 0.06 × 106 cm−2 · s−1, respectively. Finally, convolution of incident ions fluxes with neutral sputtering yields for icy bodies predicts neutral sputtered fluxes in Ganymede's polar, leading, and trailing hemispheres of 1.3 × 109, 4.8 × 108, and 1.2 × 108 neutrals cm−2 · s−1, respectively. Together, we estimate that Ganymede loses 7.5 × 1026 neutral particles per second, or assuming a mean mass of 18 amu, approximately 23 kg/s, half that estimated for Europa.
Retrieval of Barometric Pressure from Satellite Passive Microwave Observations over the Oceans
Authors: Zhang Zijin , Dong Xiaolong , Liu Liling , He Jieying
Published: May 2018

Sea surface barometric pressure is one of the few key geophysical variables has not been derived from satellite observations. In this study, we investigate the retrieval of sea surface barometric pressure from passive microwave observations. The direct relationship between surface barometric pressure and upward‐emitted brightness temperature observed by a microwave radiometer is deduced and validated. A statistical retrieval algorithm based on the back‐propagation (BP) neural networks is proposed to estimate sea surface barometric pressure using the observations from the Advanced Technology Microwave Sounder (ATMS) onboard the Suomi‐National Polar‐Orbiting Operational Environmental Satellite System Preparatory Project (SNPP) satellite. In situ buoy measurements and reanalysis data are used to assess the retrieval performance. Experimental results show that the proposed retrieval algorithm can estimate sea surface barometric pressure over mid‐to‐low latitude areas (
) with the root mean square errors of less than 2.0, 3.0, and 3.5 hPa for clear‐sky, cloudy, and rainy conditions, respectively. Several tropical cyclone retrieval experiments also show that the proposed retrieval algorithm behaves well under high wind conditions (15 m/s < wind speed < 28 m/s).
Geomagnetically Induced Currents Caused by Interplanetary Shocks With Different Impact Angles and Speeds
Authors: Oliveira D. M. , Arel D. , Raeder J. , Zesta E. , Ngwira C. M. , Carter B. A. , Yizengaw E. , Halford A. J. , Tsurutani B. T. , Gjerloev J. W.
Published: May 2018

The occurrence of geomagnetically induced currents (GICs) poses serious threats to modern technological infrastructure. Large GICs result from sharp variations of the geomagnetic field (dB/dt) caused by changes of large‐scale magnetospheric and ionospheric currents. Intense dB/dt perturbations are known to occur often in high‐latitude regions as a result of storm time substorms. Magnetospheric compressions usually caused by interplanetary shocks increase the magnetopause current leading to dB/dt perturbations more evident in midlatitude to low‐latitude regions, while they increase the equatorial electrojet current leading to dB/dt perturbations in dayside equatorial regions. We investigate the effects of shock impact angles and speeds on the subsequent dB/dt perturbations with a database of 547 shocks observed at the L1 point. By adopting the threshold of dB/dt = 100 nT/min, identified as a risk factor to power systems, we find that dB/dt generally surpasses this threshold when following impacts of high‐speed and nearly frontal shocks in dayside high‐latitude locations. The same trend occurs at lower latitudes and for all nightside events but with fewer high‐risk events. Particularly, we found nine events in equatorial locations with dB/dt > 100 nT/min. All events were caused by high‐speed and nearly frontal shock impacts and were observed by stations located around noon local time. These high‐risk perturbations were caused by sudden strong and symmetric magnetospheric compressions, more effectively intensifying the equatorial electrojet current, leading to sharp dB/dt perturbations. We suggest that these results may provide insights for GIC forecasting aiming at preventing degradation of power systems due to GICs.
Deubiquitinase function of A20 maintains and repairs endothelial barrier after lung vascular injury
Authors: Soni Dheeraj , Wang Dong-Mei , Regmi Sushil C. , Mittal Manish , Vogel Stephen M. , Schlüter Dirk , Tiruppathi Chinnaswamy
Published: May 2018

Vascular endothelial cadherin (VE-cad) expression at endothelial adherens junctions (AJs) regulates vascular homeostasis. Here we show that endothelial A20 is required for VE-cad expression at AJs to maintain and repair the injured endothelial barrier. In endothelial cell (EC)-restricted Tnfaip3 (A20) knockout (A20
∆EC
) mice, LPS challenge caused uncontrolled lung vascular leak and persistent sequestration of polymorphonuclear neutrophil (PMNs). Importantly, A20
∆EC
mice exhibited drastically reduced VE-cad expression in lungs compared with wild-type counterparts. Endothelial expression of wild-type A20 but not the deubiquitinase-inactive A20 mutant (A20C103A) prevented VE-cad ubiquitination, restored VE-cad expression, and suppressed lung vascular leak in A20
∆EC
mice. Interestingly, IRAK-M-mediated nuclear factor-κB (NF-κB) signaling downstream of TLR4 was required for A20 expression in ECs. interleukin-1 receptor-associated kinase M (IRAK-M) knockdown suppressed basal and LPS-induced A20 expression in ECs. Further, in vivo silencing of IRAK-M in mouse lung vascular ECs through the CRISPR-Cas9 system prevented expression of A20 and VE-cad while augmenting lung vascular leak. These results suggest that targeting of endothelial A20 is a potential therapeutic strategy to restore endothelial barrier integrity in the setting of acute lung injury.
Plasma membrane LAT activation precedes vesicular recruitment defining two phases of early T-cell activation
Authors: Balagopalan Lakshmi , Yi Jason , Nguyen Tiffany , McIntire Katherine M. , Harned Adam S. , Narayan Kedar , Samelson Lawrence E.
Published: May 2018

The relative importance of plasma membrane-localized LAT versus vesicular LAT for microcluster formation and T-cell receptor (TCR) activation is unclear. Here, we show the sequence of events in LAT microcluster formation and vesicle delivery, using lattice light sheet microscopy to image a T cell from the earliest point of activation. A kinetic lag occurs between LAT microcluster formation and vesicular pool recruitment to the synapse. Correlative 3D light and electron microscopy show an absence of vesicles at microclusters at early times, but an abundance of vesicles as activation proceeds. Using TIRF-SIM to look at the activated T-cell surface with high resolution, we capture directed vesicle movement between microclusters on microtubules. We propose a model in which cell surface LAT is recruited rapidly and phosphorylated at sites of T-cell activation, while the vesicular pool is subsequently recruited and dynamically interacts with microclusters.
Cross-plane coherent acoustic phonons in two-dimensional organic-inorganic hybrid perovskites
Authors: Guo Peijun , Stoumpos Constantinos C. , Mao Lingling , Sadasivam Sridhar , Ketterson John B. , Darancet Pierre , Kanatzidis Mercouri G. , Schaller Richard D.
Published: May 2018

Two-dimensional Ruddlesden–Popper organic–inorganic hybrid layered perovskites (2D RPs) are solution-grown semiconductors with prospective applications in next-generation optoelectronics. The heat-carrying, low-energy acoustic phonons, which are important for heat management of 2D RP-based devices, have remained unexplored. Here we report on the generation and propagation of coherent longitudinal acoustic phonons along the cross-plane direction of 2D RPs, following separate characterizations of below-bandgap refractive indices. Through experiments on single crystals of systematically varied perovskite layer thickness, we demonstrate significant reduction in both group velocity and propagation length of acoustic phonons in 2D RPs as compared to the three-dimensional methylammonium lead iodide counterpart. As borne out by a minimal coarse-grained model, these vibrational properties arise from a large acoustic impedance mismatch between the alternating layers of perovskite sheets and bulky organic cations. Our results inform on thermal transport in highly impedance-mismatched crystal sub-lattices and provide insights towards design of materials that exhibit highly anisotropic thermal dissipation properties.
High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing
Authors: Zhang Peng , Xia Ji-Han , Zhu Jing , Gao Ping , Tian Yi-Jun , Du Meijun , Guo Yong-Chen , Suleman Sufyan , Zhang Qin , Kohli Manish , Tillmans Lori S. , Thibodeau Stephen N. , French Amy J. , Cerhan James R. , Wang Li-Dong , Wei Gong-Hong , Wang Liang
Published: May 2018

Functional characterization of disease-causing variants at risk loci has been a significant challenge. Here we report a high-throughput single-nucleotide polymorphisms sequencing (SNPs-seq) technology to simultaneously screen hundreds to thousands of SNPs for their allele-dependent protein-binding differences. This technology takes advantage of higher retention rate of protein-bound DNA oligos in protein purification column to quantitatively sequence these SNP-containing oligos. We apply this technology to test prostate cancer-risk loci and observe differential allelic protein binding in a significant number of selected SNPs. We also test a unique application of self-transcribing active regulatory region sequencing (STARR-seq) in characterizing allele-dependent transcriptional regulation and provide detailed functional analysis at two risk loci (RGS17 and ASCL2). Together, we introduce a powerful high-throughput pipeline for large-scale screening of functional SNPs at disease risk loci.
Super-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components
Authors: Yang T. Tony , Chong Weng Man , Wang Won-Jing , Mazo Gregory , Tanos Barbara , Chen Zhengmin , Tran Thi Minh Nguyet , Chen Yi-De , Weng Rueyhung Roc , Huang Chia-En , Jane Wann-Neng , Tsou Meng-Fu Bryan , Liao Jung-Chi
Published: May 2018

Distal appendages (DAPs) are nanoscale, pinwheel-like structures protruding from the distal end of the centriole that mediate membrane docking during ciliogenesis, marking the cilia base around the ciliary gate. Here we determine a super-resolved multiplex of 16 centriole-distal-end components. Surprisingly, rather than pinwheels, intact DAPs exhibit a cone-shaped architecture with components filling the space between each pinwheel blade, a new structural element we term the distal appendage matrix (DAM). Specifically, CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. By contrast, FBF1 marks the distal end of the DAM near the ciliary membrane. Strikingly, unlike CEP164, which is essential for ciliogenesis, FBF1 is required for ciliary gating of transmembrane proteins, revealing DAPs as an essential component of the ciliary gate. Our findings redefine both the structure and function of DAPs.
Point of care microspirometry to facilitate the COPD diagnostic process in primary care: a clustered randomised trial
Authors: Schermer Tjard R. , Vatsolaki Maria , Behr Robbert , Grootens Joke , Cretier Riet , Akkermans Reinier , Denis Joke , Poels Patrick , van den Bemt Lisette
Published: May 2018

We studied if pre-bronchodilator FEV1/FEV6 determinations with microspirometers by GPs improve the diagnostic process for COPD in a 6–8 month clustered randomised controlled trial in Dutch general practices (http://www.trialregister.nl: NTR4041). GPs allocated to microspirometry (MI) used COPD-6® microspirometers in patients ≥50 years old with a smoking history and respiratory complaints that could indicate undiagnosed COPD and ask to refer patients for full spirometry if MI was positive (FEV1/FEV6 <0.73). Introduction of the COPD-6® was postponed in the usual care (UC) group. GPs of both study arms were asked to list all patients that fulfilled study criteria and at the end of the study we screened the electronic medical record system for number of patients that fulfilled study criteria and visited their GP within the study period. Main end point was a documented diagnostic conclusion of COPD within 3 months after the patient’s visit. We used multilevel logistic regression with correction for relevant covariates. Next, we described the process of care. 21 practices (88 GPs) participated and 416 possible undiagnosed COPD patient visited these practices in the study period. 78 (of 192 visiting) subjects were listed by MI GPs and diagnostic conclusions were documented in 77%, compared to 61 listed (of 224 visiting) subjects and 44% with documented diagnostic conclusions by UC GPs (Odds Ratio: OR: 4.3, 95%CI: 1.6–11.5). Microspirometry improved the diagnostic process for possible underlying COPD in patients who consulted their GP with respiratory symptoms, but the majority of possible undiagnosed COPD patients remained unrecognised by GPs.
A novel extracellular vesicle-associated endodeoxyribonuclease helps Streptococcus pneumoniae evade neutrophil extracellular traps and is required for full virulence
Authors: Jhelum Hina , Sori Hema , Sehgal Devinder
Published: May 2018

Streptococcus pneumoniae (pneumococcus) is a major bacterial pathogen that causes pneumonia and septicemia in humans. Pneumococci are cleared from the host primarily by antibody dependent opsonophagocytosis by phagocytes like neutrophils. Neutrophils release neutrophil extracellular traps (NETs) on contacting pneumococci. NETs immobilize pneumococci and restrict its dissemination in the host. One of the strategies utilized by pneumococci to evade the host immune response involves use of DNase(s) to degrade NETs. We screened the secretome of autolysin deficient S. pneumoniae to identify novel DNase(s). Zymogram analysis revealed 3 bands indicative of DNase activity. Mass spectrometric analysis led to the identification of TatD as a potential extracellular DNase. Recombinant TatD showed nucleotide sequence-independent endodeoxyribonuclease activity. TatD was associated with extracellular vesicles. Pneumococcal secretome degraded NETs from human neutrophils. Extracellular vesicle fraction from tatD deficient strain showed little NET degrading activity. Recombinant TatD efficiently degraded NETs. tatD deficient pneumococci showed lower bacterial load in lungs, blood and spleen in a murine sepsis model compared to wildtype strain, and showed less severe lung pathology and compromised virulence. This study provides insights into the role of a novel extracellular DNase in evasion of the innate immune system.
Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-β load: A pilot study
Authors: Chatterjee Pratishtha , Goozee Kathryn , Lim Chai K. , James Ian , Shen Kaikai , Jacobs Kelly R. , Sohrabi Hamid R. , Shah Tejal , Asih Prita R. , Dave Preeti , ManYan Candice , Taddei Kevin , Lovejoy David B. , Chung Roger , Guillemin Gilles J. , Martins Ralph N.
Published: May 2018

The kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer’s disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-β load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65–90 y, were categorised into NAL+ (n = 35) and NAL− (n = 65) using a standard uptake value ratio cut-off = 1.35. Employing linear models adjusting for age and APOEε4, higher kynurenine and anthranilic acid (AA) in NAL+ versus NAL− participants were observed in females (kynurenine, p = 0.004; AA, p = 0.001) but not males (NALxGender, p = 0.001, 0.038, respectively). To evaluate the predictive potential of kynurenine or/and AA for NAL+ in females, logistic regressions with NAL+/− as outcome were carried out. After age and APOEε4 adjustment, kynurenine and AA were individually and jointly significant predictors (p = 0.007, 0.005, 0.0004, respectively). Areas under the receiver operating characteristic curves were 0.794 using age and APOEε4 as predictors, and 0.844, 0.866 and 0.871 when kynurenine, AA and both were added. Findings from the current study exhibit increased KP activation in NAL+ females and highlight the predictive potential of KP metabolites, AA and kynurenine, for NAL+. Additionally, the current study also provides insight into he influence of gender in AD pathogenesis.
Publisher Correction: Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport
Authors: Toba Shiori , Jin Mingyue , Yamada Masami , Kumamoto Kanako , Matsumoto Sakiko , Yasunaga Takuo , Fukunaga Yuko , Miyazawa Atsuo , Fujita Sakiko , Itoh Kyoko , Fushiki Shinji , Kojima Hiroaki , Wanibuchi Hideki , Arai Yoshiyuki , Nagai Takeharu , Hirotsune Shinji
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
The Diversity of Chemoprotective Glucosinolates in Moringaceae (Moringa spp.)
Authors: Fahey Jed W. , Olson Mark E. , Stephenson Katherine K. , Wade Kristina L. , Chodur Gwen M. , Odee David , Nouman Wasif , Massiah Michael , Alt Jesse , Egner Patricia A. , Hubbard Walter C.
Published: May 2018

Glucosinolates (GS) are metabolized to isothiocyanates that may enhance human healthspan by protecting against a variety of chronic diseases. Moringa oleifera, the drumstick tree, produces unique GS but little is known about GS variation within M. oleifera, and even less in the 12 other Moringa species, some of which are very rare. We assess leaf, seed, stem, and leaf gland exudate GS content of 12 of the 13 known Moringa species. We describe 2 previously unidentified GS as major components of 6 species, reporting on the presence of simple alkyl GS in 4 species, which are dominant in M. longituba. We document potent chemoprotective potential in 11 of 12 species, and measure the cytoprotective activity of 6 purified GS in several cell lines. Some of the unique GS rank with the most powerful known inducers of the phase 2 cytoprotective response. Although extracts of most species induced a robust phase 2 cytoprotective response in cultured cells, one was very low (M. longituba), and by far the highest was M. arborea, a very rare and poorly known species. Our results underscore the importance of Moringa as a chemoprotective resource and the need to survey and conserve its interspecific diversity.
A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses
Authors: Kasprowicz Richard , Rand Emma , O’Toole Peter J. , Signoret Nathalie
Published: May 2018

Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4+T cells and monocyte-derived macrophages (MDMs) forming functional conjugatesin vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4+T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells.
Giant photovoltaic response in band engineered ferroelectric perovskite
Authors: Pal Subhajit , Swain Atal Bihari , Biswas Pranab Parimal , Murali D. , Pal Arnab , Nanda B. Ranjit K. , Murugavel Pattukkannu
Published: May 2018

Recently the solar energy, an inevitable part of green energy source, has become a mandatory topics in frontier research areas. In this respect, non-centrosymmetric ferroelectric perovskites with open circuit voltage (VOC) higher than the bandgap, gain tremendous importance as next generation photovoltaic materials. Here a non-toxic co-doped Ba1−x(Bi0.5Li0.5)
x
TiO3 ferroelectric system is designed where the dopants influence the band topology in order to enhance the photovoltaic effect. In particular, at the optimal doping concentration (x
opt
 ~ 0.125) the sample reveals a remarkably high photogenerated field EOC = 320 V/cm (VOC = 16 V), highest ever reported in any bulk polycrystalline non-centrosymmetric systems. The band structure, examined through DFT calculations, suggests that the shift current mechanism is key to explain the large enhancement in photovoltaic effect in this family.
Ring quantum cascade lasers with twisted wavefronts
Authors: Szedlak Rolf , Hisch Thomas , Schwarz Benedikt , Holzbauer Martin , MacFarland Donald , Zederbauer Tobias , Detz Hermann , Andrews Aaron Maxwell , Schrenk Werner , Rotter Stefan , Strasser Gottfried
Published: May 2018

We demonstrate the on-chip generation of twisted light beams from ring quantum cascade lasers. A monolithic gradient index metamaterial is fabricated directly into the substrate side of the semiconductor chip and induces a twist of the light’s wavefront. This significantly influences the obtained beam pattern, which changes from a central intensity minimum to a maximum depending on the discontinuity count of the metamaterial. Our design principle provides an interesting alternative to recent implementations of microlasers operating at an exceptional point.
Microbial production of novel sulphated alkaloids for drug discovery
Authors: Matsumura Eitaro , Nakagawa Akira , Tomabechi Yusuke , Ikushiro Shinichi , Sakaki Toshiyuki , Katayama Takane , Yamamoto Kenji , Kumagai Hidehiko , Sato Fumihiko , Minami Hiromichi
Published: May 2018

Natural products from plants are useful as lead compounds in drug discovery. Plant benzylisoquinoline alkaloids (BIAs) exhibit various pharmaceutical activities. Although unidentified BIAs are expected to be of medicinal value, sufficient quantities of such BIAs, for biological assays, are sometimes difficult to obtain due to their low content in natural sources. Here, we showed that high productivity of BIAs in engineered Escherichia coli could be exploited for drug discovery. First, we improved upon the previous microbial production system producing (S)-reticuline, an important BIA intermediate, to obtain yields of around 160 mg/L, which was 4-fold higher than those of the previously reported highest production system. Subsequently, we synthesised non-natural BIAs (O-sulphated (S)-reticulines) by introducing human sulphotransferases into the improved (S)-reticuline production system. Analysis of human primary cells treated with these BIAs demonstrated that they affected a biomarker expression in a manner different from that by the parent compound (S)-reticuline, suggesting that simple side-chain modification altered the characteristic traits of BIA. These results indicated that highly productive microbial systems might facilitate the production of scarce or novel BIAs and enable subsequent evaluation of their biological activities. The system developed here could be applied to other rare natural products and might contribute to the drug-discovery process as a next-generation strategy.
A study of wound repair in Dictyostelium cells by using novel laserporation
Authors: Pervin Mst. Shaela , Itoh Go , Talukder Md. Shahabe Uddin , Fujimoto Koushiro , Morimoto Yusuke V. , Tanaka Masamitsu , Ueda Masahiro , Yumura Shigehiko
Published: May 2018

We examined the mechanism of cell membrane repair in Dictyostelium cells by using a novel laser-based cell poration method. The dynamics of wound pores opening and closing were characterized by live imaging of fluorescent cell membrane proteins, influx of fluorescent dye, and Ca2+ imaging. The wound closed within 2–4 sec, depending on the wound size. Cells could tolerate a wound size of less than 2.0 µm. In the absence of Ca2+ in the external medium, the wound pore did not close and cells ruptured. The release of Ca2+ from intracellular stores also contributed to the elevation of cytoplasmic Ca2+ but not to wound repair. Annexin C1 immediately accumulated at the wound site depending on the external Ca2+ concentration, and annexin C1 knockout cells had a defect in wound repair, but it was not essential. Dictyostelium cells were able to respond to multiple repeated wounds with the same time courses, in contrast to previous reports showing that the first wound accelerates the second wound repair in fibroblasts.
Glioblastoma single-cell microRaman analysis under stress treatments
Authors: Ricci Maria , Ragonese Francesco , Gironi Beatrice , Paolantoni Marco , Morresi Assunta , Latterini Loredana , Fioretti Bernard , Sassi Paola
Published: May 2018

Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor characterized by highly heterogeneous subpopulations. In order to reveal the heterogeneous cell response, single cell analysis is an essential requirement. In this study, optical microscopy and Raman microspectroscopy were used to follow the stress response of U251 single cells adherent on a silicon substrate. Cultured cells on silicon substrate were treated with hydrogen peroxide to promote apoptosis. Under these conditions expected changes occurred after a few hours and were revealed by the reduction of cytochrome c, lipid, nucleic acid and protein Raman signals: this ensured the possibility to analyse U251 cell line as grown on Si substrate, and to monitor the response of single cells to stress conditions. As a consequence, we used microRaman to monitor the effects induced by nutrient depletion: a fast change of Raman spectra showed two different sub-populations of sensible and resistant U251 cells. Furthermore, spectral variations after DMSO addition were associated to volume changes and confirmed by morphological analysis. Thus, our results highlight the sensitivity of Raman microspectroscopy to detect rapid variations of macromolecule concentration due to oxidative stress and/or cell volume changes at the single cell level.
Non-coding RNAs in Various Stages of Liver Disease Leading to Hepatocellular Carcinoma: Differential Expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs
Authors: Koduru Srinivas V. , Leberfinger Ashley N. , Kawasawa Yuka I. , Mahajan Milind , Gusani Niraj J. , Sanyal Arun J. , Ravnic Dino J.
Published: May 2018

Hepatocellular carcinoma (HCC) was the fifth leading cause of cancer death in men and eighth leading cause of death in women in the United States in 2017. In our study, we sought to identify sncRNAs in various stages of development of HCC. We obtained publicly available small RNA-seq data derived from patients with cirrhosis (n = 14), low-grade dysplastic nodules (LGDN, n = 9), high grade dysplastic nodules (HGDN, n = 6), early hepatocellular carcinoma (eHCC, n = 6), and advanced hepatocellular carcinoma (HCC, n = 20), along with healthy liver tissue samples (n = 9). All samples were analyzed for various types of non-coding RNAs using PartekFlow software. We remapped small RNA-seq to miRBase to obtain differential expressions of miRNAs and found 87 in cirrhosis, 106 in LGDN, 59 in HGDN, 80 in eHCC, and 133 in HCC. Pathway analysis of miRNAs obtained from diseased samples compared to normal samples showed signaling pathways in the microRNA dependent EMT, CD44, and others. Additionally, we analyzed the data sets for piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs. We validated the in silico data using human HCC samples with NanoString miRNA global expression. Our results suggest that publically available data is a valuable resource for sncRNA identification in HCC progression (FDR set to <0.05 for all samples) and that a data mining approach is useful for biomarker development.
An Intrinsic Role of Beta Oscillations in Memory for Time Estimation
Authors: Wiener Martin , Parikh Alomi , Krakow Arielle , Coslett H. Branch
Published: May 2018

The neural mechanisms underlying time perception are of vital importance to a comprehensive understanding of behavior and cognition. Recent work has suggested a supramodal role for beta oscillations in measuring temporal intervals. However, the precise function of beta oscillations and whether their manipulation alters timing has yet to be determined. To accomplish this, we first re-analyzed two, separate EEG datasets and demonstrate that beta oscillations are associated with the retention and comparison of a memory standard for duration. We next conducted a study of 20 human participants using transcranial alternating current stimulation (tACS), over frontocentral cortex, at alpha and beta frequencies, during a visual temporal bisection task, finding that beta stimulation exclusively shifts the perception of time such that stimuli are reported as longer in duration. Finally, we decomposed trialwise choice data with a drift diffusion model of timing, revealing that the shift in timing is caused by a change in the starting point of accumulation, rather than the drift rate or threshold. Our results provide evidence for the intrinsic involvement of beta oscillations in the perception of time, and point to a specific role for beta oscillations in the encoding and retention of memory for temporal intervals.
Multitasking of Hsp70 chaperone in the biogenesis of bacterial functional amyloids
Authors: Sugimoto Shinya , Arita-Morioka Ken-ichi , Terao Akari , Yamanaka Kunitoshi , Ogura Teru , Mizunoe Yoshimitsu
Published: May 2018

Biofilms are intricate communities of microorganisms embedded in a self-produced matrix of extracellular polymer, which provides microbes survival advantages in stressful environments and can cause chronic infections in humans. Curli are functional amyloids that assemble on the extracellular surface of enteric bacteria such asEscherichia coliduring biofilm development and colonization. The molecular chaperone DnaK, a bacterial Hsp70 homologue, promotes curli biogenesis via unknown mechanism(s). Here we show that DnaK increases the expression of CsgA and CsgB—the major and minor structural components of curli, respectively—via a quantity and quality control of RpoS, a stationary phase-specific alternative sigma factor regulating bacterial transcription, and CsgD, the master transcriptional regulator of curli formation. DnaK also keeps CsgA and CsgB in a translocation-competent state by binding to their signal peptides prone to aggregation. Our findings suggest that DnaK controls the homoeostasis of curli biogenesis at multiple stages to organize the biofilm matrix.
Folic acid-modified mesoporous silica nanoparticles with pH-responsiveness loaded with Amp for an enhanced effect against anti-drug-resistant bacteria by overcoming efflux pump systems
Authors: Chen Xu , Liu Yanan , Lin Ange , Huang Na , Long Liquan , Gang Ye , Liu Jie
Published: May 2018

Efflux pump system-mediated bacterial multidrug resistance is one of the main causes of antibiotic failure.
Suppression of dendritic lithium growth in lithium metal-based batteries
Authors: Li Linlin , Li Siyuan , Lu Yingying
Published: May 2018

We describe the challenges of high-energy lithium-metal batteries and outline the future directions that are expected to drive their progress.
Mild rhodium(iii)-catalyzed intramolecular annulation of benzamides with allylic alcohols to access azepinone derivatives
Authors: Peneau Augustin , Tricart Quentin , Guillou Catherine , Chabaud Laurent
Published: May 2018

A mild intramolecular Rh(iii)-catalyzed annulation by C–H activation to access azepinone derivatives has been developed.
Label-free and high-throughput bioluminescence detection of uracil-DNA glycosylase in cancer cells through tricyclic cascade signal amplification
Authors: Zhang Yan , Li Qing-nan , Li Chen-chen , Zhang Chun-yang
Published: May 2018

We develop a label-free and high-throughput bioluminescence method for the sensitive detection of uracil DNA glycosylase through tricyclic cascade signal amplification.
Spray drying of zeolitic imidazolate frameworks: investigation of crystal formation and properties
Authors: Chaemchuen Somboon , Zhou Kui , Mousavi Bibimaryam , Ghadamyari Marzieh , Heynderickx Philippe M. , Zhuiykov Serge , Yusubov Mekhman S. , Verpoort Francis
Published: May 2018

The mechanism of crystal growth for ZIFs (ZIF-67 and Zn/Co-ZIF) is explored for the first time using the spray-drying technique.