bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed Fluorinated/Hydrogenated Self‐Assembled Monolayer‐Protected Gold Nanoparticles: In Silico and In Vitro Behavior
Authors: Marson Domenico , Guida Filomena , Şologan Maria , Boccardo Silvia , Pengo Paolo , Perissinotto Fabio , Iacuzzi Valentina , Pellizzoni Elena , Polizzi Stefano , Casalis Loredana , Pasquato Lucia , Pacor Sabrina , Tossi Alessandro , Posocco Paola
Published: April 2019

Gold nanoparticles (AuNPs) covered with mixtures of immiscible ligands present potentially anisotropic surfaces that can modulate their interactions at complex nano–bio interfaces. Mixed, self‐assembled, monolayer (SAM)‐protected AuNPs, prepared with incompatible hydrocarbon and fluorocarbon amphiphilic ligands, are used here to probe the molecular basis of surface phase separation and disclose the role of fluorinated ligands on the interaction with lipid model membranes and cells, by integrating in silico and experimental approaches. These results indicate that the presence of fluorinated amphiphilic ligands enhances the membrane binding ability and cellular uptake of gold nanoparticles with respect to those coated only with hydrogenated amphiphilic ligands. For mixed monolayers, computational results suggest that ligand phase separation occurs on the gold surface, and the resulting anisotropy affects the number of contacts and adhesion energies with a membrane bilayer. This reflects in a diverse membrane interaction for NPs with different surface morphologies, as determined by surface plasmon resonance, as well as differential effects on cells, as observed by flow cytometry and confocal microscopy. Overall, limited changes in monolayer features can significantly affect NP surface interfacial properties, which, in turn, affect the interaction of SAM‐AuNPs with cellular membranes and subsequent effects on cells.
Representations of nature of science in U.S. science standards: A historical account with contemporary implications
Authors: Summers Ryan , Alameh Sahar , Brunner Jeanne , Maddux John M. , Wallon Robert C. , Abd‐El‐Khalick Fouad
Published: April 2019

This study evaluated the representations of nature of science (NOS) in U.S. state science standards, and examined the changes in these representations from documents advanced in the 1980s through 2016. Drawing from the consensus perspective on NOS and prior studies focusing on the analysis of textual content, documents were inspected for 10 target NOS aspects: the empirical, tentative, inferential, creative, theory‐driven, and social NOS, in addition to the myth of “The Scientific Method,” the nature of scientific theories and laws, and the social and cultural embeddedness of science. Ninety‐eight state documents from 48 states were analyzed and multiple editions were collected from 34 states. Additionally, relevant materials from the Next Generation Science Standards (NGSS) were assessed for their coverage of the same NOS aspects. Collected materials were scored as whole documents, including over 11,000 pages of text in total, on each target aspect, which reflected the treatment (naïve vs. informed) of NOS in text and the manner of presentation (explicit vs. implicit). Overall, surprisingly, state standards documents have improved very little with respect to their NOS coverage over the last 30 years. NOS standards documents remain silent on a majority of key aspects of NOS, and the number of aspects showing explicit, informed representations has held constant. The NGSS performed well compared to many contemporary documents, but they failed to address all target NOS aspects in a desirable manner. Further analysis raised concerns with the degree that states fully adopt and disseminate standards in manner consistent with the NGSS despite stated intentions, which may negatively impact NOS coverage in instructional resources and classroom enactments. To improve NOS representations in standards, recognizing the role these documents play in shaping instructional materials and teaching in the science classroom, exemplars from analyzed materials were highlighted with informed and explicit representations of multiple aspects.
On Whitham's conjecture of a highest cusped wave for a nonlocal dispersive equation
Authors: Ehrnström Mats , Wahlén Erik
Published: April 2019

We consider the Whitham equation

u_{t} + 2uu_{x} + Lu_{x} = 0

, where
L
is the nonlocal Fourier multiplier operator given by the symbol

m(\xi ) = \sqrt{\mathrm{\tanh }⁡\xi / \xi }

. G. B. Whitham conjectured that for this equation there would be a highest, cusped, travelling-wave solution. We find this wave as a limiting case at the end of the main bifurcation curve of
P
-periodic solutions, and give several qualitative properties of it, including its optimal

C^{1/ 2}

-regularity. An essential part of the proof consists in an analysis of the integral kernel corresponding to the symbol

m(\xi )

, and a following study of the highest wave. In particular, we show that the integral kernel corresponding to the symbol

m(\xi )

is completely monotone, and provide an explicit representation formula for it. Our methods may be generalised.
Questions of life and death: (De)constructing human rights norms through US public opinion surveys
Authors: Nylen Alexandria , Carpenter Charli
Published: April 2019

Public opinion polls on national security issues are often seen as indicators of the strength of international human rights norms. By contrast, we hypothesise that the very act of answering poll questions can weaken citizens’ understandings of important international human rights laws and norms in the very moment they are being measured. We ground this discussion empirically by analysing a new dataset of post-9/11 survey questions on two US national security policies at odds with international human rights norms: ‘enhanced interrogations’ and ‘targeted killing’. In so doing, we encourage a widened research agenda on how international legal and normative understandings are transmitted to the public through surveys. We conclude by highlighting substantive implications for norm scholars and policy implications for norm advocates.
The Ex-Factor: Attachment Anxiety and Social Comparisons Across Romantic Relationships
Authors: Hingorani Simran , Pinkus Rebecca T.
Published: April 2019

Individuals high in attachment anxiety often experience persistent negative self-perceptions and heightened sensitivity toward perceived relationship threats. These characteristics may extend into past romantic relationships. This study examined whether individual differences in attachment style predict self-evaluations and relationship social comparison frequency. Two hundred and fifty-nine individuals rated themselves, their partner, and their current partner's ex-partner (CPE) or their ex-partner's current partner (ECP) on several dimensions. Individuals high in attachment anxiety experienced more relationship uncertainty but were not less satisfied than individuals low in attachment anxiety. They also made more comparisons in general and to relationships involving an ex-partner, and viewed themselves less positively than they viewed their CPE/ECP. Findings are discussed with respect to the influence that past relationships might hold over anxiously attached individuals’ current relationships.
Wheeling and dealing behind closed doors: estimating the causal effect of transparency on policy evaluations using a survey experiment
Authors: Juhl Sebastian , Hilpert David
Published: April 2019

The Transatlantic Trade and Investment Partnership between the European Union and the US is highly technical. Still, the negotiations triggered large-scale protests among citizens with very diverse socioeconomic backgrounds. Why has a complex issue such an enormous mobilizing effect although the economic consequences are either unclear or favorable for the participating economies? We argue that the transparency of negotiations is an important consideration for people evaluating the negotiation outcome. Conducting a survey experiment, we show that non-transparent decision-making decreases citizens' appraisal of the agreementindependentof its outcome: A non-transparent negotiation is, on average, almost 16 percent less likely to find public approval than a transparent but otherwise identical agreement. Our findings have important implications for democratic decision-making.
A celebration of the twentieth anniversary of the Fluvial Archives Group (FLAG)
Authors: Briant Rebecca M. , Bridgland David R. , Cordier Stephane , Rixhon Gilles , van Balen Ronald
Published: April 2019

The Fluvial Archives Group (FLAG) was founded in 1996 to bring together researchers looking at the development of fluvial systems over multiple timescales and global spatial scales. Fluvial archives of various types are important not just because they provide insights into past landscape dynamics, e.g., driven by climate or crustal processes, but also because they frequently contain fossil or archaeological material for which they provide stratigraphic control. Since 1996, FLAG has evolved from a research group of the British Quaternary Research Association into an organisation with around 500 members in over 20 countries. The research group held 12 biennial meetings, comprising both presentations and field excursions, as well as multiple themed sessions at international conferences. These had resulted by 2017 in 19 journal special issues, all fully detailed by Cordier et al. (2017). The goals of FLAG are: provision of a community for discussion of key issues concerning fluvial archives, including organising the aforementioned biennial discussion/field meetings, sessions at relevant international conferences, and special issues of journals; continued promotion of the value of fluvial archives by means of readily accessible published information; and coordination of activity with other research groupings with overlapping interests, e.g., by co-convening sessions and collaborating on publications.
ON THE DIMENSION OF PERMUTATION VECTOR SPACES
Authors: REIS LUCAS
Published: April 2019

Let $K$ be a field that admits a cyclic Galois extension of degree $n\geq 2$. The symmetric group $S_{n}$ acts on $K^{n}$ by permutation of coordinates. Given a subgroup $G$ of $S_{n}$ and $u\in K^{n}$, let $V_{G}(u)$ be the $K$-vector space spanned by the orbit of $u$ under the action of $G$. In this paper we show that, for a special family of groups $G$ of affine type, the dimension of $V_{G}(u)$ can be computed via the greatest common divisor of certain polynomials in $K[x]$. We present some applications of our results to the cases $K=\mathbb{Q}$ and $K$ finite.
What Explains Credible Apologies? A Comment on Yap' ‘Non-Electoral Responsiveness Mechanisms’
Authors: LOWRY ROBERT C.
Published: April 2019

In a recent issue of this Journal Professor Yap asks whether and how governments in what she calls ‘less-democratic’ countries, that is those where elections are uncompetitive due to a lack of democratic safeguards or opposition parties, are held accountable for the effects of their policies on economic performance. She argues that governments in these countries have an interest in avoiding strife and inducing private actors to provide resources necessary for economic prosperity. Because of this, ‘when their economies are performing less than optimally, these governments tend to offer credible apologies in the same year to attenuate the potential labour disquiet and loss in production investment.’ Yap develops the concept of a credible apology as the joint occurrence of punishment of responsible actors or reparations to injured parties, and an increase in monitoring activity by non-government actors. She then presents evidence for South Korea for 1964–87 and Singapore and Malaysia for 1966–94 showing that, ceteris paribus, the tendency of production investment to decrease and strike activity to increase in years with high unemployment is offset if the government makes a credible apology.

Yap is quite clear that she assumes a causal arrow running from poor economic performance to credible apologies. Indeed, such a causal relationship is necessary for the concept of accountability; the events that Yap classifies as credible apologies must be made in response to unsatisfactory economic performance in order for us to say that these governments are being held (or are holding themselves) accountable for the consequences of their policies.
Maritime Migrations: Stewards of the African Grove
Authors: GONZALEZ ANITA
Published: April 2019

This essay discusses how maritime migrations contribute to movements of ideas across transnational ethnic communities. It focuses on actors from the African Grove, a New York City-based African American theatre company. Actors in this company worked as stewards on transatlantic packet ships where the architecture of the ship supported intercultural exchanges.
Performing Public Presence: African Migrant Women Create Uncomfortable Conversations in London
Authors: DELMENICO LESLEY
Published: April 2019

In 2017, a group of African women migrants and I devised Uncomfortable Conversations for FORWARD, a London NGO, to speak publicly about FGM and gendered marginalization. This article, braiding theories from Tompkins, Rancière and Kershaw, explores the effects on participating actors.
Lag effect of climatic variables on dengue burden in India
Authors: Kakarla Satya Ganesh , Caminade Cyril , Mutheneni Srinivasa Rao , Morse Andrew P , Upadhyayula Suryanaryana Murty , Kadiri Madhusudhan Rao , Kumaraswamy Sriram
Published: April 2019

Dengue is a widespread vector-borne disease believed to affect between 100 and 390 million people every year. The interaction between vector, host and pathogen is influenced by various climatic factors and the relationship between dengue and climatic conditions has been poorly explored in India. This study explores the relationship between El Niño Southern Oscillation (ENSO), the Indian Ocean Dipole (IOD) and dengue cases in India. Additionally, distributed lag non-linear model was used to assess the delayed effects of climatic factors on dengue cases. The weekly dengue cases reported by the Integrated Disease Surveillance Program (IDSP) over India during the period 2010–2017 were analysed. The study shows that dengue cases usually follow a seasonal pattern, with most cases reported in August and September. Both temperature and rainfall were positively associated with the number of dengue cases. The precipitation shows the higher transmission risk of dengue was observed between 8 and 15 weeks of lag. The highest relative risk (RR) of dengue was observed at 60 mm rainfall with a 12-week lag period when compared with 40 and 80 mm rainfall. The RR of dengue tends to increase with increasing mean temperature above 24 °C. The largest transmission risk of dengue was observed at 30 °C with a 0–3 weeks of lag. Similarly, the transmission risk increases more than twofold when the minimum temperature reaches 26 °C with a 2-week lag period. The dengue cases and El Niño were positively correlated with a 3–6 months lag period. The significant correlation observed between the IOD and dengue cases was shown for a 0–2 months lag period.
When blue is a disyllabic word: Perceptual epenthesis in the mental lexicon of second language learners
Authors: DARCY ISABELLE , THOMAS TRISHA
Published: April 2019

Word-initial obstruent-liquid clusters, frequent in English (e.g., blue), are prohibited in Korean. Korean learners of English perceptually repair illicit word-initial consonant sequences with an epenthetic vowel [ʊ]. Thus they might perceive blue as b[ʊ]lue, and, at least initially, also represent it lexically as a disyllabic word. We ask whether the sound sequences permitted in one's L1 influence the way L2 words are represented in the mental lexicon. If they do, we predict that in a lexical decision task, Korean learners will accept nonwords containing epenthetic vowels ([bʊˈluː] for blue) as real English words more often than English listeners. These predictions were confirmed: we observed high error rates on test nonwords ([bʊˈluː]) by the Korean participants only, accompanied by few errors on control nonwords ([bɪˈluː]), suggesting that learners’ lexical representations for familiar L2 words can be activated by nonwords that obey their L1 phonotactic grammar.
“Bonjour” Welcome to Québec City
Authors: Charest Pierre M.
Published: April 2019

The Microsopical Society of Canada and the LAC of Microscopy and
Microanalysis 2002 are very proud to welcome you in Québec City
for the MSA - MAS - MSC/SMC-IMS joint meeting that will take place for
the first time in Canada. This event will be a commemorative new experience
of science mixed with the “Joie de Vivre” of Québec
City. Founded in 1608 by French explorer Samuel de Champlain, Québec
City was the center of New France, which at the time extended from the St.
Lawrence River in the northeast right down to the Gulf of Mexico in the
south. By the end of the 19th century, Québec City had taken on many
of its current attributes: political capital, university town, center of
culture, tourist destination, and regional services and trade hub. The
city's old quarter was declared a world heritage site by UNESCO in
1985.

Come to Québec, an American-style City with a French Attitude!
Microscopy Society of America
Authors: Erlandsen Stanley L.
Published: April 2019

It is my pleasure to welcome you to Microscopy and Microanalysis
2002, jointly sponsored by the Microscopy Society of America,
Microbeam Analysis Society, Microscopy Society of
Canada/Société de Microscopie du Canada, and the
International Metallographic Society. An excellent program with
an outstanding list of invited speakers for symposia has been
assembled by the Program Committee consisting of the Chair,
Edgar Voelkl, and Co-Chairs, David Piston (MSA), Raynald Gauvin
(MAS/MSC), and Allan Lockley (IMS). Highlights of Microscopy
and Microanalysis 2002 include the world's largest display
of microscopes and related technologies together with outstanding
sessions on all aspects of microscopy and microanalysis. Symposia
will be held on 3-D electron microscopy of macromolecules and
cryo-electron microscopy of macromolecules, the quantitative
aspects of X-ray microscopy, confocal microscopy, biomaterials,
biological and materials specimen preparation. Special sessions
will be held on holography, phase imaging, deep tissue imaging,
(S)TEM instrumentation, developments in focused-ion beam
instruments and imaging, metallographic specimen preparation
from start to finish, and the changing role of atom probe
microscopes in the nanotechnology era. Advances in immunolabeling,
EELS, and detectors for X-ray microanalysis also will be presented.
A special analytical electron microscopy session honoring the
work of Elmar Zeitler is also scheduled. A pre-meetingworkshop
“Future of Materials Characterization of Charging
Materialsusing Microbeam Analysis” organized by Dr. Raynald
Gauvin will be held at McGill University in Montreal on August
2–3. The Local Arrangements Committee, headed by Pierre
Charest, has coordinated the scheduling of many local events
to complement the meeting.
Microbeam Analysis Society
Authors: Meeker Greg
Published: April 2019

The Microbeam Analysis Society (MAS) is a nonprofit organization
dedicated to the enhancement of microanalysis techniques and
instrumentation. The Society, founded in 1968, was originally
called the Electron Probe Analysis Society of America. In 1974
the name was changed to the Microbeam Analysis Society to reflect
the growing number of micro-analytical techniques of interest
to our members. Our members come from industry, academia and
government and have a broad range of scientific interests. MAS
serves the microanalysis community by providing a forum for
education, discussion and exchange of ideas in the field of
microanalysis.
International Metallographic Society
Authors: Ryan Richard
Published: April 2019

As president of IMS, I am pleased to welcome attendees to our 2002
meeting. We have a wonderful site for a great meeting city. Quebec is
full of things to see and we have a great Symposium and technical meeting
with lots to do and see.
North Atlantic Circulation Patterns Reveal Seas of Change
Authors: Morton Mary
Published: April 2019

New evidence suggests the eastern Atlantic may be the site of major overturning.
Ice Drove Past Indo-Pacific Climate Variance
Authors: Derouin Sarah
Published: April 2019

Researchers used both terrestrial and marine proxy data to reconstruct the dramatic and dynamic climatic changes.
Recent Weakening in the Stratospheric Planetary Wave Intensity in Early Winter
Authors: Hu Dingzhu , Guo Yipeng , Guan Zhaoyong
Published: April 2019

Previous studies have reported that the tropospheric climate shifted around the 2000s, but the recent trend in the stratospheric wave intensity (SWI) is still unclear. The results in this study show that the SWI in December during 2001–2015 weakens, which is opposite to that during 1979–2000, implying a shift around the 2000s. The weakened SWI is dominated by its wave number‐1 component, which is related to the wave propagation impeded by the decreased refractive index at high latitudes and the weakened wave activity in the troposphere. Changes in refractive index are mainly contributed by changes in the meridional potential vorticity gradient via the barotropic term. This shift in the wave number‐1 waves leads to a shift in the stratospheric Arctic temperature, that is, warming (cooling) during 1979–2000 (2001–2015), implying that similar shifting phenomena may appear regardless of the continued greenhouse gas emissions.
Extreme Convective Storms Over High‐Latitude Continental Areas Where Maximum Warming Is Occurring
Authors: Houze Robert A. , Wang Jingyu , Fan Jiwen , Brodzik Stacy , Feng Zhe
Published: April 2019

Deep convective storms play a key role in severe weather, the hydrological cycle, and the global atmospheric circulation. Historically, little attention has been paid to the intense convective storms in the high latitudes. These regions have been experiencing the largest increases of mean surface temperature over the last century. The Global Precipitation Measurement core satellite, which features a space‐borne Dual‐frequency Precipitation Radar providing near‐global coverage (65°S to 65°N), has made it possible to establish the occurrence of convective storms at high latitudes. Analysis of the three‐dimensional radar echoes seen by Global Precipitation Measurement over a 5‐year period (2014–2018) shows that extremely intense deep convective storms do occur often during the warm season (April–September) in the high‐latitude continents where the increase of surface temperature has been greatest. The associated thermodynamical environments suggest that high‐latitude extreme convection could be more common in a continually warming world.
A High‐Fidelity Benthic Stable Isotope Record of Late Cretaceous–Early Eocene Climate Change and Carbon‐Cycling
Authors: Barnet J. S. K. , Littler K. , Westerhold T. , Kroon D. , Leng M. J. , Bailey I. , Röhl U. , Zachos J. C.
Published: April 2019

The Late Cretaceous–Early Paleogene is the most recent period in Earth history that experienced sustained global greenhouse warmth on multimillion year timescales. Yet, knowledge of ambient climate conditions and the complex interplay between various forcing mechanisms are still poorly constrained. Here we present a 14.75 million‐year‐long, high‐resolution, orbitally tuned record of paired climate change and carbon‐cycling for this enigmatic period (~67–52 Ma), which we compare to an up‐to‐date compilation of atmospheric pCO2 records. Our climate and carbon‐cycling records, which are the highest resolution stratigraphically complete records to be constructed from a single marine site in the Atlantic Ocean, feature all major transient warming events (termed “hyperthermals”) known from this time period. We identify eccentricity as the dominant pacemaker of climate and the carbon cycle throughout the Late Maastrichtian to Early Eocene, through the modulation of precession. On average, changes in the carbon cycle lagged changes in climate by ~23,000 years at the long eccentricity (405,000‐year) band, and by ~3,000–4,500 years at the short eccentricity (100,000‐year) band, suggesting that light carbon was released as a positive feedback to warming induced by orbital forcing. Our new record places all known hyperthermals of the Late Maastrichtian–Early Eocene into temporal context with regards to evolving ambient climate of the time. We constrain potential carbon cycle influences of Large Igneous Province volcanism associated with the Deccan Traps and North Atlantic Igneous Province, as well as the sensitivity of climate and the carbon‐cycle to the 2.4 million‐year‐long eccentricity cycle.
Prognosis and improved outcomes in major depression: a review
Authors: Kraus Christoph , Kadriu Bashkim , Lanzenberger Rupert , Zarate Carlos A. , Kasper Siegfried
Published: April 2019

Treatment outcomes for major depressive disorder (MDD) need to be improved. Presently, no clinically relevant tools have been established for stratifying subgroups or predicting outcomes. This literature review sought to investigate factors closely linked to outcome and summarize existing and novel strategies for improvement. The results show that early recognition and treatment are crucial, as duration of untreated depression correlates with worse outcomes. Early improvement is associated with response and remission, while comorbidities prolong course of illness. Potential biomarkers have been explored, including hippocampal volumes, neuronal activity of the anterior cingulate cortex, and levels of brain-derived neurotrophic factor (BDNF) and central and peripheral inflammatory markers (e.g., translocator protein (TSPO), interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor alpha (TNFα)). However, their integration into routine clinical care has not yet been fully elucidated, and more research is needed in this regard. Genetic findings suggest that testing for CYP450 isoenzyme activity may improve treatment outcomes. Strategies such as managing risk factors, improving clinical trial methodology, and designing structured step-by-step treatments are also beneficial. Finally, drawing on existing guidelines, we outline a sequential treatment optimization paradigm for selecting first-, second-, and third-line treatments for acute and chronically ill patients. Well-established treatments such as electroconvulsive therapy (ECT) are clinically relevant for treatment-resistant populations, and novel transcranial stimulation methods such as theta-burst stimulation (TBS) and magnetic seizure therapy (MST) have shown promising results. Novel rapid-acting antidepressants, such as ketamine, may also constitute a paradigm shift in treatment optimization for MDD.
Author Correction: The role of Chinese Milk Vetch as cover crop in complex soil nitrogen dynamics in rice rotation system of South China
Authors: Xie Zhijian , Zhou Chunhuo , Shah Farooq , Iqbal Amjad , Ni GuoRong
Published: April 2019

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.
Differential Mobility Spectrometry of Ketones in Air at Extreme Levels of Moisture
Authors: Safaei Z. , Eiceman G. A. , Puton J. , Stone J. A. , Nasirikheirabadi M. , Anttalainen O. , Sillanpää M.
Published: April 2019

The performance of a differential mobility spectrometer was characterized at ambient pressure and ten values of water vapor concentration, from 1.0 × 102 to 1.7 × 104 ppm using a homologous series of seven ketones from acetone to 2-dodecanone. Dispersion plots at 30 °C with separation fields from 35 to 123 Td exhibited increased alpha functions for the hydrated proton, protonated monomers, and proton bound dimers with increased moisture levels. Increases in the level of moisture were accompanied by decreased quantitative response with progressive suppression in the formation of the proton bound dimer first and then protonated monomer. Product ions for 2-octanone at 7 ppb were not observed above a moisture level of 4.0 × 103 ppm, establishing a limit for observation of analyte ion formation. The observation limit increased from 1.1 × 103 ppm for acetone to 5.7 × 103 ppm for 2-dodecanone. These findings demonstrate that ketones can be determined with a differential mobility spectrometry (DMS) analyzer near room temperature in the presence of elevated levels of moisture expected with the use of membrane inlets or headspace sampling of surface or ground waters. Moisture levels entering this DMS analyzer employed as an environmental monitor should be kept at 1.0 × 103 ppm or below and quantitative studies for individual ketones should be made at a fixed moisture level.
Succession matters: Community shifts in moths over three decades increases multifunctionality in intermediate successional stages
Authors: Habel Jan Christian , Segerer Andreas H. , Ulrich Werner , Schmitt Thomas
Published: April 2019

Species composition strongly depends on time, place and resources. In this context, semi-natural grasslands belong to the most species-rich habitats of Europe, and succession may eventually cause local extinction of typical grassland species, but conversely increase species richness due to habitat diversification. Here, we analyse potential effects of succession of calcareous grasslands on moths. Our studied community, assessed over three decades in south-eastern Germany, comprised >1000 species. We compiled data on the ecology of each of these species, considering the larval and adult stages. We assigned Ellenberg indicator values to each main larval food plant species used by these lepidopterans. Changes in the community means of these indicators were applied to test for possible consequences of the changes in habitat structure and quality. Our data revealed increasing multifunctionality of community structure, higher variability of habitat association over time, the appearance of range expanding species, but also local extinction of various typical grassland moth species. These shifts in species composition mirror effects of succession, which frequently transform previously homogenous semi-natural grasslands into a heterogeneous habitat mosaic.
Optimization of the adipose-derived mesenchymal stem cell delivery time for radiation-induced lung fibrosis treatment in rats
Authors: Zhang Yang , Jiang Xinping , Ren Liqun
Published: April 2019

The present study attempts to identify the optimal time duration for the administration of Ad-MSCs, in order to maximize its therapeutic benefits, and compare the degree of fibrosis among three different administration time points using the RILF rat model system. Ad-MSCs were delivered to Sprague-Dawley rats through the tail vein at the following different time points after thorax irradiation: two hours, seven days, and two hours + seven days. Post Ad-MSCs transplantation and the histopathological analysis of the lungs were performed along with analysis of inflammatory cytokine levels, including interleukin (IL)-1, IL-2, IL-6, IL-10 and tumor necrosis factor-α (TNF-α). In particular, pro-fibrotic factors (TGF-β1 and α-SMA) were also evaluated in serum and lung tissues. In addition, it was also determined whether Ad-MSCs had any role in inhibiting the transition of type II alveolar epithelial cells into fibroblasts in the lungs of injured rats. The present results demonstrated that the intravenous delivery of Ad-MSCs twice at the 2-hour and 7-day (R + MSC2h+7d group) was effective in reducing lung fibrosis for long term durations, when compared with single delivery either at the two-hour or 7-day time points. In addition, a marked anti-inflammatory effect was also observed in RILF rats in the R + MSC2h+7d group, as indicated by the reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and increased levels of anti-inflammatory cytokines IL-10 and IL-2. Rats that were delivered twice with Ad-MSCs (R + MSC2h+7d group) exhibited significantly reduced TGF-β1 and α-SMA levels, in contrast to rats in the R + MSC7d or R + MSC2h groups, after four weeks. Furthermore, it was also noted that after four weeks, Ad-MSCs increased the number of lung epithelial cells (SP-C) and inhibited the lung fibroblastic cells (α-SMA) of rats in the R + MSC2h and R + MSC2h+7d groups. The present study concluded that two injections of Ad-MSCs (R + MSC2h+7d group) appear to be optimal for therapeutic efficacy and safety during RILF.
Reconciling cooperation, biodiversity and stability in complex ecological communities
Authors: Tu Chengyi , Suweis Samir , Grilli Jacopo , Formentin Marco , Maritan Amos
Published: April 2019

Empirical evidences show that ecosystems with high biodiversity can persist in time even in the presence of few types of resources and are more stable than low biodiverse communities. This evidence is contrasted by the conventional mathematical modeling, which predicts that the presence of many species and/or cooperative interactions are detrimental for ecological stability and persistence. Here we propose a modelling framework for population dynamics, which also include indirect cooperative interactions mediated by other species (e.g. habitat modification). We show that in the large system size limit, any number of species can coexist and stability increases as the number of species grows, if mediated cooperation is present, even in presence of exploitative or harmful interactions (e.g. antibiotics). Our theoretical approach thus shows that appropriate models of mediated cooperation naturally lead to a solution of the long-standing question about complexity-stability paradox and on how highly biodiverse communities can coexist.
Local Administration of GITR Agonistic Antibody Induces a Stronger Antitumor Immunity than Systemic Delivery
Authors: Narumi Kenta , Miyakawa Reina , Shibasaki Chihiro , Henmi Marina , Mizoguchi Yukihiro , Ueda Ryosuke , Hashimoto Hisayoshi , Hiraoka Nobuyoshi , Yoshida Teruhiko , Aoki Kazunori
Published: April 2019

An anti-glucocorticoid induced TNF receptor (GITR) agonistic antibody (Ab) induces an antitumor immunity with both stimulation of effector T cells and inhibition of regulatory T cell activity. To enhance GITR Ab-mediated tumor immunity, we focused on the intratumoral route, since a tumor-localized high concentration of Ab would confer activation of only tumor-infiltrating T cells. First, in a murine colon cancer model, we showed that the intratumoral delivery of Ab significantly increased the number of effector T cells infiltrated into tumors, and suppressed tumor growth more effectively than the intraperitoneal and intravenous injections did. Then, we found that the injection of Ab into the peritumoral area induced a systemic antitumor immunity at a similar level to the intratumoral injection. Therefore, we hypothesized that the transfer of locally administrated Ab into tumor-draining lymph nodes (TDLNs) plays an important role in inducing an effective immunity. In fact, intratumorally or peritumorally injected Ab was detected in TDLNs, and resection of Ab-injected TDLNs significantly reduced GITR Ab-mediated systemic tumor immunity. Intratumoral injection showed less number of auto-reactive T cells in the spleen than the intraperitoneal injection did. Intratumoral delivery of GITR Ab is a promising approach to induce an effective immunity compared to the systemic delivery.
A Pipeline for Faecal Host DNA Analysis by Absolute Quantification of LINE-1 and Mitochondrial Genomic Elements Using ddPCR
Authors: He Kuang , Fujiwara Hideaki , Zajac Cynthia , Sandford Erin , Reddy Pavan , Choi Sung Won , Tewari Muneesh
Published: April 2019

Stool contains DNA shed from cells of the gastrointestinal (GI) tract and has great potential as a bio-specimen for non-invasive, nucleic acid-based detection of GI diseases. Whereas methods for studying faecal microbiome DNA are plentiful, there is a lack of well-characterised procedures for stabilisation, isolation, and quantitative analysis of faecal host DNA. We report an optimised pipeline for faecal host DNA analysis from the point-of-collection to droplet digital PCR (ddPCR) absolute quantification of host-specific gene targets. We evaluated multiple methods for preservation and isolation of host DNA from stool to identify the highest performing methods. To quantify host DNA even if present in partially degraded form, we developed sensitive, human-specific short-amplicon ddPCR assays targeting repetitive nuclear genomic elements (LINE-1) and mitochondrial genes. We validated the ability of these optimised methods to perform absolute quantification of host DNA in 200 stool DNA extracts from samples that were serially collected from three healthy individuals and three hospitalised patients. These specimens allowed assessment of host DNA day-to-day variability in stool specimens with widely varying physical characteristics (i.e., Bristol scores). We further extended this approach to mouse stool analysis, to enable faecal host DNA studies in animal disease models as well.
Segmenting Mechanomyography Measures of Muscle Activity Phases Using Inertial Data
Authors: Woodward Richard B. , Stokes Maria J. , Shefelbine Sandra J. , Vaidyanathan Ravi
Published: April 2019

Electromyography (EMG) is the standard technology for monitoring muscle activity in laboratory environments, either using surface electrodes or fine wire electrodes inserted into the muscle. Due to limitations such as cost, complexity, and technical factors, including skin impedance with surface EMG and the invasive nature of fine wire electrodes, EMG is impractical for use outside of a laboratory environment. Mechanomyography (MMG) is an alternative to EMG, which shows promise in pervasive applications. The present study used an exerting squat-based task to induce muscle fatigue. MMG and EMG amplitude and frequency were compared before, during, and after the squatting task. Combining MMG with inertial measurement unit (IMU) data enabled segmentation of muscle activity at specific points: entering, holding, and exiting the squat. Results show MMG measures of muscle activity were similar to EMG in timing, duration, and magnitude during the fatigue task. The size, cost, unobtrusive nature, and usability of the MMG/IMU technology used, paired with the similar results compared to EMG, suggest that such a system could be suitable in uncontrolled natural environments such as within the home.
Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells
Authors: Costantini Daniele , Overi Diletta , Casadei Luca , Cardinale Vincenzo , Nevi Lorenzo , Carpino Guido , Di Matteo Sabina , Safarikia Samira , Valerio Mariacristina , Melandro Fabio , Bizzarri Mariano , Manetti Cesare , Berloco Pasquale Bartolomeo , Gaudio Eugenio , Alvaro Domenico
Published: April 2019

Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG). Self-replication and differentiation toward mature cells were determined by culturing hBTSCs in Kubota’s Medium (KM) and in hormonally defined medium (HDM) tailored for hepatocyte differentiation. The effects on the expression and cell exo-metabolome profiles of SMG versus NG cultures were analyzed. SMG promotes tridimensional (3D) cultures of hBTSCs and HepG2. Significative increase of stemness gene expression (p < 0.05) has been observed in hBTSCs cultured in SMG when compared to NG condition. At the same time, the expression of hepatocyte lineage markers in hBTSCs differentiated by HDM was significantly lower (p < 0.05) in SMG compared to NG, demonstrating an impaired capability of hBTSCs to differentiate in vitro toward mature hepatocytes when cultured in SMG condition. Furthermore, in HepG2 cells the SMG caused a lower (p < 0.05 vs controls) transcription of CYP3A4, a marker of late-stage (i.e. Zone 3) hepatocytes. Exo-metabolome NMR-analysis showed that both cell cultures consumed a higher amount of glucose and lower glutamate in SMG respect to NG (p < 0.05). Moreover, hBTSCs media cultures resulted richer of released fermentation (lactate, acetate) and ketogenesis products (B-hydroxybutyrate) in SGM (p < 0.05) than NG. While, HepG2 cells showed higher consumption of amino acids and release of ketoacids (3-Methyl-2-oxovalerate, 2-oxo-4-methyl-valerate) and formiate with respect to normogravity condition (p < 0.05). Based on our results, SMG could be helpful for developing hBTSCs-derived liver devices. In conclusion, SMG favored the formation of hBTSCs and HepG2 3D cultures and the maintenance of stemness contrasting cell differentiation; these effects being associated with stimulation of glycolytic metabolism. Interestingly, the impact of SMG on stem cell biology should be taken into consideration for workers involved in space medicine programs.
Combination of acid β-glucosidase mutation and Saposin C deficiency in mice reveals Gba1 mutation dependent and tissue-specific disease phenotype
Authors: Liou Benjamin , Zhang Wujuan , Fannin Venette , Quinn Brian , Ran Huimin , Xu Kui , Setchell Kenneth D. R. , Witte David , Grabowski Gregory A. , Sun Ying
Published: April 2019

Gaucher disease is caused by mutations in GBA1 encoding acid β-glucosidase (GCase). Saposin C enhances GCase activity and protects GCase from intracellular proteolysis. Structure simulations indicated that the mutant GCases, N370S (0 S), V394L (4L) and D409V(9V)/H(9H), had altered function. To investigate the in vivo function of Gba1 mutants, mouse models were generated by backcrossing the above homozygous mutant GCase mice into Saposin C deficient (C*) mice. Without saposin C, the mutant GCase activities in the resultant mouse tissues were reduced by ~50% compared with those in the presence of Saposin C. In contrast to 9H and 4L mice that have normal histology and life span, the 9H;C* and 4L;C* mice had shorter life spans. 9H;C* mice developed significant visceral glucosylceramide (GC) and glucosylsphingosine (GS) accumulation (GC»GS) and storage macrophages, but lesser GC in the brain, compared to 4L;C* mice that presents with a severe neuronopathic phenotype and accumulated GC and GS primarily in the brain. Unlike 9V mice that developed normally for over a year, 9V;C* pups had a lethal skin defect as did 0S;C* mice resembled that of 0S mice. These variant Gaucher disease mouse models presented a mutation specific phenotype and underscored the in vivo role of Saposin C in the modulation of Gaucher disease.
The role of the environment in the evolution of nest shape in Australian passerines
Authors: Medina Iliana
Published: April 2019

Avian nests present great variation in structure but, after excluding cavity nesters, probably the most obvious difference is that between open and domed nests. Some species lay their eggs in open structures, exposed to environmental variables, while other species build domed, enclosed nests with a roof, which are suggested to protect eggs and nestlings from weather conditions, high radiation levels, and predation. To date it is unclear which variables drove the evolution of different nest types. In this study, environmental and nest type information was extracted for continental Australian passerines, showing that species with open and closed nests are distributed in similar climates. However, species with open nests have larger ranges and are distributed in a wider variety of climatic conditions, suggesting open nests could be an evolutionary key innovation. This analysis was complemented with a detailed study of the evolution of particular nest traits in the largest Australasian avian radiation (Meliphagoidea), confirming that adult body size – but not environment – is an important factor in nest architecture, and larger species tend to build nests that are shallow and supported from underneath. Nest structure is a multidimensional trait that has probably evolved to match the phenotype of the nest owner, but that could also constrain or facilitate establishment in different environments.
Whole genome sequencing identifies bacterial factors affecting transmission of multidrug-resistant tuberculosis in a high-prevalence setting
Authors: Dixit Avika , Freschi Luca , Vargas Roger , Calderon Roger , Sacchettini James , Drobniewski Francis , Galea Jerome T. , Contreras Carmen , Yataco Rosa , Zhang Zibiao , Lecca Leonid , Kolokotronis Sergios-Orestis , Mathema Barun , Farhat Maha R.
Published: April 2019

Whole genome sequencing (WGS) can elucidate Mycobacterium tuberculosis (Mtb) transmission patterns but more data is needed to guide its use in high-burden settings. In a household-based TB transmissibility study in Peru, we identified a large MIRU-VNTR Mtb cluster (148 isolates) with a range of resistance phenotypes, and studied host and bacterial factors contributing to its spread. WGS was performed on 61 of the 148 isolates. We compared transmission link inference using epidemiological or genomic data and estimated the dates of emergence of the cluster and antimicrobial drug resistance (DR) acquisition events by generating a time-calibrated phylogeny. Using a set of 12,032 public Mtb genomes, we determined bacterial factors characterizing this cluster and under positive selection in other Mtb lineages. Four of the 61 isolates were distantly related and the remaining 57 isolates diverged ca. 1968 (95%HPD: 1945–1985). Isoniazid resistance arose once and rifampin resistance emerged subsequently at least three times. Emergence of other DR types occurred as recently as within the last year of sampling. We identified five cluster-defining SNPs potentially contributing to transmissibility. In conclusion, clusters (as defined by MIRU-VNTR typing) may be circulating for decades in a high-burden setting. WGS allows for an enhanced understanding of transmission, drug resistance, and bacterial fitness factors.
Coral Skeleton δ15N as a Tracer of Historic Nutrient Loading to a Coral Reef in Maui, Hawaii
Authors: Murray Joseph , Prouty Nancy G. , Peek Sara , Paytan Adina
Published: April 2019

Excess nutrient loading to nearshore environments has been linked to declining water quality and ecosystem health. Macro-algal blooms, eutrophication, and reduction in coral cover have been observed in West Maui, Hawaii, and linked to nutrient inputs from coastal submarine groundwater seeps. Here, we present a forty-year record of nitrogen isotopes (δ15N) of intra-crystalline coral skeletal organic matter in three coral cores collected at this site and evaluate the record in terms of changes in nitrogen sources. Our results show a dramatic increase in coral δ15N values after 1995, corresponding with the implementation of biological nutrient removal at the nearby Lahaina Wastewater Reclamation Facility (LWRF). High δ15N values are known to be strongly indicative of denitrification and sewage effluent, corroborating a previously suggested link between local wastewater injection and degradation of the reef environment. This record demonstrates the power of coral skeletal δ15N as a tool for evaluating nutrient dynamics within coral reef environments.