bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion ratios ofn-3 fatty acids between plasma and erythrocytes: a systematic review and meta-regression
Authors: Hu Xue Feng , Sandhu Simran K. , Harris William S. , Chan Hing Man
Published: May 2017

As biomarkers of dietary intake or disease risk factor,n-3 fatty acid (FA) can be measured in plasma phospholipids (PL), total lipids (TL) or erythrocytes. However, the numeric relationships betweenn-3 FA in these lipid pools are not clear. Our goal was to derive conversion ratios for plasma and erythrocyten-3 FA. Potential studies were identified through systematic literature search in PubMed, Embase and the Cochrane Library of Systematic reviews (1950 to October 2014). In all, fifty-six studies reportingn-3 in healthy individuals were included, of which thirty-four articles reported plasma PL and erythrocytes, and twenty-two reported plasma TL and erythrocytes. Meta-regressions were performed to quantify the ratio between plasma and erythrocyten-3 FA weight percentages, controlling for covariates including age, sex and study design. The conversion ratios from plasma PL to erythrocytes for EPA, DHA, DPA and totaln-3 PUFA are 0·75, 1·16, 2·32 and 1·22; the corresponding conversion ratios from plasma TL to erythrocytes are 1·00, 2·10, 3·85 and 2·08, respectively. The conversion ratios were validated using reported values from the literature and measured data from fifty individuals. The relative error of the predicted results were within 10 % of the mean reported values except for EPA, and the individual measured data except for DPA, in plasma TL. The conversion ratios between plasma PL and erythrocytes were more stable compared with plasma TL. Such conversion ratios will be useful for nutritionists or public health professionals to assess FA profiles of different populations using data collected with different methodologies.
Asia Treads the Nuclear Path, Unaware That Self-Assured Destruction Would Result from Nuclear War
Authors: Toon Owen B. , Robock Alan , Mills Michael , Xia Lili
Published: May 2017

Of the nine countries known to have nuclear weapons, six are located in Asia and another, the United States, borders the Pacific Ocean. Russia and China were the first Asian nations with nuclear weapons, followed by Israel, India, Pakistan, and North Korea. Most of the world's nuclear powers are reducing their arsenals or maintaining them at historic levels, but several of those in Asia—India, Pakistan, and North Korea—continue to pursue relentless and expensive programs of nuclear weapons development and production. Hopefully, the nuclear agreement reached in July 2015 between Iran, the European Union, and the five permanent members of the United Nations Security Council will be a step toward eliminating nuclear weapons throughout Asia and the rest of the world. As we will discuss below, any country possessing a nuclear arsenal is on a path leading toward self-assured destruction, and is a threat to people everywhere on Earth.
A review of bovine fasciolosis and other trematode infections in Nigeria
Authors: Elelu N. , Eisler M.C.
Published: May 2017

Trematode infections cause serious economic losses to livestock worldwide. Global production losses due to fasciolosis alone exceed US$3 billion annually. Many trematode infections are also zoonotic and thus a public health concern. The World Health Organization has estimated that about 56 million people worldwide are infected by at least one zoonotic trematode species, and up to 750 million people are at risk of infection. Fasciolosis caused by the flukeFasciola giganticais endemic in Nigeria and is one of the most common causes of liver condemnation in abattoirs. Total cattle losses fromFasciolainfection in Nigeria have been estimated to cost £32.5 million. Other trematode infections of cattle, including paramphistomosis, dicrocoeliasis and schistosomiasis, have all been reported in various parts of Nigeria, with varying prevalence. Most publications on trematode infections are limited to Nigerian local and national journals, with very few international reports. This paper therefore summarized the current data on distribution, control and zoonotic trematode infections in Nigeria and other African countries. We also identified research gaps and made recommendations for future research and areas for funding for policy/planning.
Autism risk following antidepressant medication during pregnancy
Authors: Viktorin A. , Uher R. , Reichenberg A. , Levine S. Z. , Sandin S.
Published: May 2017

Background

Previous studies have examined if maternal antidepressant medication during pregnancy increase the risk of autism spectrum disorder (ASD) in the offspring, but the results have been conflicting.

Methods

In a population-based cohort of 179 007 children born in 2006 and 2007 and followed through 2014 when aged 7 and 8, we estimated relative risks (RRs) of ASD and 95% confidence intervals (CIs) from Cox regression in children exposed to any antidepressant medication during pregnancy, and nine specific antidepressant drugs. Analyses were adjusted for potential confounders and were conducted in the full population sample, and in a clinically relevant sub-sample of mothers with at least one diagnosis of depression or anxiety during life.

Results

The adjusted RR of ASD in children of mothers who used antidepressant medication during pregnancy was estimated at 1.23 (95% CI 0.96–1.57), and at 1.07 (95% CI 0.80–1.43) in women with a history of depression or anxiety. Analyses of specific antidepressants initially revealed increased RRs of offspring ASD confined to citalopram and escitalopram (RR: 1.47; 95% CI 0.92–2.35) and clomipramine (RR: 2.86; 95% CI 1.04–7.82).

Conclusion

Medication with antidepressants during pregnancy does not appear to be causally associated with an increased risk of ASD in the offspring. Instead, the results suggest that the association is explained by factors related to the underlying susceptibility to psychiatric disorders. Based on these findings, the risk of ASD in the offspring should not be a consideration to withhold treatment with commonly used antidepressant drugs from pregnant women.
‘MONS MANUFACTUS’: ROME'S MAN-MADE MOUNTAINS BETWEEN HISTORY AND NATURAL HISTORY (c. 1100–1700)
Authors: Donkin Lucy
Published: May 2017

Rome's man-made mounds occupy a position between built antiquities and natural features. In the Middle Ages and early modern period, particular attention was paid to Monte Testaccio, the Mausoleum of Augustus, and the related ‘mons omnis terra’. Debate focused on the origins and composition of the mounds, thought to contain either earth brought to Rome as symbolic tribute, pottery used to hold monetary tribute, or pottery produced locally. Developing over time in different genres of writing on the city, these interpretations were also employed in works on historical, religious and geological themes. The importation of material, expressive of relations between Rome and the wider world in antiquity, was used to draw positive and negative comparisons with present-day rulers and the papacy, and to associate Rome with Babylon. The growth of the mounds and the presence of ceramics were invoked in discussions of the formation of mountains and montane fossils. If the mounds' ambiguities facilitated their incorporation into other debates, the terms in which they are discussed reflect ongoing engagement with literature on the city. The reception of these monuments thus offers a distinctive perspective on the significance of Rome to connections between spheres of knowledge in this period.
WHY PATIENTS SHOULD BE INVOLVED IN HEALTH TECHNOLOGY ASSESSMENT
Authors: Wale Janet , Scott Anna Mae , Hofmann Bjørn , Garner Sarah , Low Eric , Sansom Lloyd
Published: May 2017

Objectives: Some countries make considerable effort to involve patients and patient groups in their health technology assessment (HTA) processes; others are only just considering or are yet to consider patient involvement in HTA.

Methods: This commentary offers four arguments why patient involvement should be prioritized by those HTA agencies that do not yet involve patients: (1) from a patients’ rights perspective, (2) based on patient and community values, (3) centering on evidentiary contributions, and (4) from a methodological perspective.

Results: The first argument builds on the Alma-Ata Declaration, which holds that patients have a right and duty to have a say in the planning and delivery of their health care, individually and collectively. Where HTA is used to determine access to technologies and services, we argue that patients have a right to be heard. The second argues that decisions about treatments and services need to be aligned with the core values and morals of the patients whom the health system serves. The third argues that patients have unique knowledge and insights about living with a health condition and their needs for services and treatments regarding that condition, which can add to the knowledge base and value of the HTA process. The fourth argues that involvement of patients can facilitate methodological advancement of HTA, in areas such as early scientific advice and managed entry with evidence development.

Conclusions: An HTA process that includes patient perspectives can, therefore, provide added value to patients, policy makers and healthcare professionals alike.
Unveiling Neoliberal Dynamics: Government Purchase (goumai) of Social Work Services in Shenzhen's Urban Periphery
Authors: Cho Mun Young
Published: May 2017

How has social work, which has emerged as a distinct profession in the PRC with the full support of the party-state, come to produce neoliberal outcomes similar to those found in other, capitalist countries? In this article, I draw attention to the government purchase (goumai) of social work services, which is commonly considered as confirmation of state capacity and leadership rather than the passing on of state responsibilities to civil sectors with tight budgets. Ethnographic research on the actual social work practices in Shenzhen's Foxconn town reveals how neoliberal-style outsourcing has converged with diverse historical legacies, thus creating precarious labour conditions for frontline social workers. Neoliberal dynamics end up filling most of these social work positions with migrant youth from the countryside, reproducing and perpetuating China's rural–urban divide. Institutional efforts at social care may not only reduce the existing inequalities but may also rely upon and even reinforce them.
Persistent infections support maintenance of a coronavirus in a population of Australian bats (Myotis macropus)
Authors: JEONG J. , SMITH C. S. , PEEL A. J. , PLOWRIGHT R. K. , KERLIN D. H. , MCBROOM J. , MCCALLUM H.
Published: May 2017

Understanding viral transmission dynamics within populations of reservoir hosts can facilitate greater knowledge of the spillover of emerging infectious diseases. While bat-borne viruses are of concern to public health, investigations into their dynamics have been limited by a lack of longitudinal data from individual bats. Here, we examine capture–mark–recapture (CMR) data from a species of Australian bat (Myotis macropus) infected with a putative novel Alphacoronavirus within a Bayesian framework. Then, we developed epidemic models to estimate the effect of persistently infectious individuals (which shed viruses for extensive periods) on the probability of viral maintenance within the study population. We found that the CMR data analysis supported grouping of infectious bats into persistently and transiently infectious bats. Maintenance of coronavirus within the study population was more likely in an epidemic model that included both persistently and transiently infectious bats, compared with the epidemic model with non-grouping of bats. These findings, using rare CMR data from longitudinal samples of individual bats, increase our understanding of transmission dynamics of bat viral infectious diseases.
Hybrid PDE solver for data-driven problems and modern branching
Authors: BERNAL FRANCISCO , DOS REIS GONÇALO , SMITH GREIG
Published: May 2017

The numerical solution of large-scale PDEs, such as those occurring in data-driven applications, unavoidably require powerful parallel computers and tailored parallel algorithms to make the best possible use of them. In fact, considerations about the parallelization and scalability of realistic problems are often critical enough to warrant acknowledgement in the modelling phase. The purpose of this paper is to spread awareness of the Probabilistic Domain Decomposition (PDD) method, a fresh approach to the parallelization of PDEs with excellent scalability properties. The idea exploits the stochastic representation of the PDE and its approximation via Monte Carlo in combination with deterministic high-performance PDE solvers. We describe the ingredients of PDD and its applicability in the scope of data science. In particular, we highlight recent advances in stochastic representations for non-linear PDEs using branching diffusions, which have significantly broadened the scope of PDD. We envision this work as a dictionary giving large-scale PDE practitioners references on the very latest algorithms and techniques of a non-standard, yet highly parallelizable, methodology at the interface of deterministic and probabilistic numerical methods. We close this work with an invitation to the fully non-linear case and open research questions.
A framework for learner agency in online spoken interaction tasks
Authors: Knight Janine , Barbera Elena , Appel Christine
Published: May 2017

Learner agency, the capability of individual human beings to make choices and act on these choices in a way that makes a difference in their lives (Martin, 2004), is instrumental in second language learning because attainment is only arrived at by learner choice (Pavlenko & Lantolf, 2000). If attainment is understood as learner engagement in synchronous, collaborative, spoken interaction which is thought to lead to gains in second language acquisition (SLA), then design considerations that harness learners’ agency towards that end is important. This study explores the relationship between learner agency and two different task types, namely an information-gap task and an opinion-sharing task in two peer-to-peer synchronous computer-mediated communication (SCMC) spoken interaction events. Students’ choices and how students act on these choices during tasks are analysed using a discourse analysis approach. Audio recordings of four dyads as cases were examined using three analytical dimensions: language functions of verbal interaction, cognitive processing and social processing. The results show that most learners used their agency to reconfigure the tasks from spontaneous to planned interaction, with some choices and actions relating to technology impacting detrimentally on interaction time in the target language. The different tasks were found to filter and channel different types of agency that learners could exercise, namely representational, organisational, and strategic agency as speech acts, and directional agency as a physical act. These types consisted of different natures and purposes and are presented as a framework. The information-gap task supported strategic agency and an opinion-sharing task supported personalisation and identity construction or representational agency.
Automatic semantic integration during L2 sentential reading
Authors: AHN SUNYOUNG , JIANG NAN
Published: May 2017

Research has shown that L1 speakers can routinely generate mental imagery corresponding to sentence meaning in reading comprehension. This may reflect an efficient process of semantic integration in which information from the input combines with an individual's linguistic and real world knowledge to form a semantic representation of a sentence. Semantic integration in L2 reading has received limited attention. The present study attempted to examine the activation of mental imagery in reading among L2 speakers and thus to assess the efficiency of semantic integration during L2 reading. L2 Korean learners were tested on a sentence-based picture recognition task in which they were asked to respond to a picture immediately after reading a sentence related to the picture. Results showed that L2 Korean learners resembled native Korean speakers in their ability to generate mental imageries that reflected subtle semantic differences in sentence input.
Easier Living – mir zuliebe
Authors: Buchkremer Ulrike , Haberthür Annina , Soyka Michael , Storch Maja
Published: May 2017

Mit dem eigens kreierten, neuartigen Gruppentherapieprogramm „Easier Living - mir zuliebe“ rücken die erfahrenen Autoren die langfristige gesundheitsbezogene Ressourcenförderung ins Zentrum der Behandlung psychiatrischer Patienten. Das auf dem Zürcher Ressourcen Modells (ZRM®) basierende Programm bietet (teil-)stationär und ambulant behandelten Patienten die Möglichkeit, sich mit einem „gesundheitsschädigenden“ Verhaltensmuster achtsam und ressourcenorientiert auseinanderzusetzen. Übergeordnete Ziele der Gruppentherapie sind der Aufbau von Selbstmanagement- Kompetenz und die Entwicklung zunehmender Selbstfürsorge. Der Fokus liegt sowohl auf der psychischen wie auf der physischen Gesundheit - dementsprechend weisen die gesundheitsbezogenen Themen eine große Spannbreite auf: Abgrenzung, Work-Life-Balance, Motivationsschwierigkeiten, fehlende Bewegung sowie der Umgang mit Pseudoressourcen wie Essen, Alkohol, Tabak und anderen Konsummitteln. Der Theorieteil liefert aktuelle Befunde zu den Themen Gesundheitsförderung bei psychiatrischen Patienten, Ressourcenaktivierung, Embodiment und Selbstfürsorge, zudem werden die Grundlagen des ZRM® ausführlich beschrieben. Der Trainingsteil bietet ein ausgearbeitetes Manual für die Durchführung des Gruppentherapieprogrammes „Easier Living - mir zuliebe“. Das Vorgehen wird Schritt für Schritt beschrieben, sodass auch Berufseinsteiger mit wenig Erfahrung eine sichere Grundlage für die Durchführung erhalten.
Survey of Attitudes Toward Aviation Safety Management System (SMS)	Training
Authors: Kearns Suzanne K. , Aitken Schermer Julie
Published: May 2017

Abstract. With a growing volume of traffic, the aviation industry is moving to fully embrace a predictive approach to safety management, which requires the implementation of safety management system (SMS) training on an international scale. An online survey was distributed through an International Civil Aviation Organization (ICAO) State Letter to solicit perceptions of SMS training from a variety of international aviation professionals. The survey collected 1,103 complete responses. The results identified robust differences in how SMS training is perceived by men and women and by professionals from different geographic regions. Female respondents had more negative attitudes toward training than did males. Regarding regional differences, Middle Eastern participants had the most positive attitudes while Europeans reported the most negative attitudes toward SMS training. The data suggest caution is warranted before global distribution of SMS training and illustrate the importance of a learner analysis, as individual differences among learners may impact the effectiveness and adoption of SMSs.
Perceptions Toward the Federal Flight Deck Officer Program and Willingness to Fly
Authors: Winter Scott R. , Rice Stephen , Friedenreich Kasey , Mehta Rian , Kaiser Bryan
Published: May 2017

Abstract. In the aftermath of the September 11 terrorist attacks against the United States, numerous changes were implemented to aviation security. One of those programs was the arming of commercial airline pilots with handguns while they were on duty in a flight capacity. Since its inception, the Federal Flight Deck Officer (FFDO) program has been controversial in nature. The purpose of this study was to examine participant perceptions and their willingness to fly based on whether or not the pilot of their hypothetical flight was armed and participating in the FFDO program. A sample of 812 participants was selected from both India and the United States using Amazon’s Mechanical Turk® (MTurk). In general, the findings indicate that participants were more willing to fly when their pilot was armed; however, American females indicated no significant difference between the two conditions. Affect measures were also collected from participants and suggest that the relationship between the condition and the participants’ willingness to fly was mediated by emotions. The findings of the study provide information on participants’ view of the arming of pilots and suggest that, for the most part, participants in this study seem supportive of FFDO and the arming of pilots of commercial airliners. This finding is limited to participants who take part in online human intelligence tasks through services such as MTurk, who may or may not have been a commercial flight passenger.
Automation Surprise
Authors: de Boer Robert J. , Hurts Karel
Published: May 2017

Abstract. Automation surprise (AS) has often been associated with aviation safety incidents. Although numerous laboratory studies have been conducted, few data are available from routine flight operations. A survey among a representative sample of 200 Dutch airline pilots was used to determine the prevalence of AS and the severity of its consequences, and to test some of the factors leading to AS. Results show that AS is a relatively widespread phenomenon that occurs three times per year per pilot on average but rarely has serious consequences. In less than 10% of the AS cases that were reviewed, an undesired aircraft state was induced. Reportable occurrences are estimated to occur only once every 1–3 years per pilot. Factors leading to a higher prevalence of AS include less flying experience, increasing complexity of the flight control mode, and flight duty periods of over 8 hr. It is concluded that AS is a manifestation of system and interface complexity rather than cognitive errors.
In silico analysis of pathways activation landscape in oral squamous cell carcinoma and oral leukoplakia
Authors: Makarev Eugene , Schubert Adrian D , Kanherkar Riya R , London Nyall , Teka Mahder , Ozerov Ivan , Lezhnina Ksenia , Bedi Atul , Ravi Rajani , Mehra Rannee , Hoque Mohammad O , Sloma Ido , Gaykalova Daria A , Csoka Antonei B , Sidransky David , Zhavoronkov Alex , Izumchenko Evgeny
Published: May 2017

A subset of patients with oral squamous cell carcinoma (OSCC), the most common subtype of head and neck squamous cell carcinoma (HNSCC), harbor dysplastic lesions (often visually identified as leukoplakia) prior to cancer diagnosis. Although evidence suggest that leukoplakia represents an initial step in the progression to cancer, signaling networks driving this progression are poorly understood. Here, we applied in silico Pathway Activation Network Decomposition Analysis (iPANDA), a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in OSCC and pre-neoplastic oral lesions. In tumor samples, our analysis detected major conserved mitogenic and survival signaling pathways strongly associated with HNSCC, suggesting that some of the pathways identified by our algorithm, but not yet validated as HNSCC related, may be attractive targets for future research. While pathways activation landscape in the majority of leukoplakias was different from that seen in OSCC, a subset of pre-neoplastic lesions has demonstrated some degree of similarity to the signaling profile seen in tumors, including dysregulation of the cancer-driving pathways related to survival and apoptosis. These results suggest that dysregulation of these signaling networks may be the driving force behind the early stages of OSCC tumorigenesis. While future studies with larger leukoplakia data sets are warranted to further estimate the values of this approach for capturing signaling features that characterize relevant lesions that actually progress to cancers, our platform proposes a promising new approach for detecting cancer-promoting pathways and tailoring the right therapy to prevent tumorigenesis.
An immunogenic phenotype in paternal antigen‐specific CD8+ T cells at embryo implantation elicits later fetal loss in mice
Authors: Moldenhauer Lachlan M , Diener Kerrilyn R , Hayball John D , Robertson Sarah A
Published: May 2017

Central to pregnancy success is a state of T cell tolerance to paternal antigens, which is initiated at conception. The role and regulation of specific phenotypes of CD8+ T cells in mediating pregnancy tolerance is not clear. This study aimed to investigate the impact on pregnancy outcome of altering the cytokine environment during maternal CD8+ T cell priming in early pregnancy. Transgenic Act‐mOVA male mice were mated to C57BL/6 (B6) females to generate fetuses expressing ovalbumin (OVA) as a model paternal antigen. OVA‐reactive CD8+ OT‐I T cells were activated in vitro with OVA in the presence of either transforming growth factor‐β1 (TGFB1) plus interleukin‐10 (IL10), or IL2, to mimic normal or dysregulated uterine conditions, respectively, and transferred into pregnant mice on gestational day 3.5. OT‐I T cells activated with TGFB1 and IL10, like naive OT‐I T cells, did not alter embryo implantation or fetal viability. In contrast, OT‐I T cells activated with IL2 caused extensive fetal loss manifesting in mid‐gestation. IL2‐activated OT‐I T cells expressed less FOXP3 and higher interferon‐γ (IFNG) than cells activated with TGFB1 and IL10. Fetal loss did not occur in females mated with B6 males, demonstrating the antigen specificity of fetal loss, and was not abrogated by maternal genetic C1q deficiency indicating a mechanism independent of antibody‐mediated cytotoxicity. These data indicate that alternative phenotypes generated in maternal CD8+ T cells at the time of priming with paternal antigens can impact pregnancy outcome, such that inappropriate activation of CD8+ T cells before implantation is capable of causing antigen‐specific fetal loss later in pregnancy.
Exploiting biased reptation for continuous flow preparative DNA fractionation in a versatile microfluidic platform
Authors: Gumuscu Burcu , Bomer Johan G. , de Boer Hans L. , van den Berg Albert , Eijkel Jan C. T.
Published: May 2017

A new approach is presented for preparative, continuous flow fractionation of sub-10-kbp DNA fragments, which exploits the variation in the field-dependent mobility of the DNA molecules based on their length. Orthogonally pulsed electric fields of significantly different magnitudes are applied to a microchip filled with a sieving matrix of 1.2% agarose gel. Using this method, we demonstrate a high-resolution separation of 0.5, 1, 2, 5, and 10 kbp DNA fragments within 2 min. During the separation, DNA fragments are also purified from other ionic species. Preparative fractionation of sub-10-kbp DNA molecules plays an important role in second-generation sequencing. The presented device performs rapid high-resolution fractionation and it can be reliably manufactured with simple microfabrication procedures.
Toward point-of-care management of chronic respiratory conditions: Electrochemical sensing of nitrite content in exhaled breath condensate using reduced graphene oxide
Authors: Gholizadeh Azam , Voiry Damien , Weisel Clifford , Gow Andrew , Laumbach Robert , Kipen Howard , Chhowalla Manish , Javanmard Mehdi
Published: May 2017

We present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate (EBC). We discuss the fabrication and characterization of a miniaturized electrochemical sensor for detecting nitrite content in EBC using reduced graphene oxide. The nitrite content in EBC has been demonstrated to be a promising biomarker of inflammation in the respiratory tract, particularly in asthma. We utilized the unique properties of reduced graphene oxide (rGO); specifically, the material is resilient to corrosion while exhibiting rapid electron transfer with electrolytes, thus allowing for highly sensitive electrochemical detection with minimal fouling. Our rGO sensor was housed in an electrochemical cell fabricated from polydimethyl siloxane (PDMS), which was necessary to analyze small EBC sample volumes. The sensor is capable of detecting nitrite at a low over-potential of 0.7 V with respect to an Ag/AgCl reference electrode. We characterized the performance of the sensors using standard nitrite/buffer solutions, nitrite spiked into EBC, and clinical EBC samples. The sensor demonstrated a sensitivity of 0.21 μA μM−1 cm−2 in the range of 20–100 μM and of 0.1 μA μM−1 cm−2 in the range of 100–1000 μM nitrite concentration and exhibited a low detection limit of 830 nM in the EBC matrix. To benchmark our platform, we tested our sensors using seven pre-characterized clinical EBC samples with concentrations ranging between 0.14 and 6.5 μM. This enzyme-free and label-free method of detecting biomarkers in EBC can pave the way for the development of portable breath analyzers for diagnosing and managing changes in respiratory inflammation and disease.
Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy
Authors: Kondo Taisuke , Morita Rimpei , Okuzono Yuumi , Nakatsukasa Hiroko , Sekiya Takashi , Chikuma Shunsuke , Shichita Takashi , Kanamori Mitsuhiro , Kubo Masato , Koga Keiko , Miyazaki Takahiro , Kassai Yoshiaki , Yoshimura Akihiko
Published: May 2017

Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8+ TSCM cells can be generated in vitro from naive CD8+ T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4+ and CD8+ T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iTSCM cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.
Controlling for the species-area effect supports constrained long-term Mesozoic terrestrial vertebrate diversification
Authors: Close Roger A. , Benson Roger B.J. , Upchurch Paul , Butler Richard J.
Published: May 2017

Variation in the geographic spread of fossil localities strongly biases inferences about the evolution of biodiversity, due to the ubiquitous scaling of species richness with area. This obscures answers to key questions, such as how tetrapods attained their tremendous extant diversity. Here, we address this problem by applying sampling standardization methods to spatial regions of equal size, within a global Mesozoic-early Palaeogene data set of non-flying terrestrial tetrapods. We recover no significant increase in species richness between the Late Triassic and the Cretaceous/Palaeogene (K/Pg) boundary, strongly supporting bounded diversification in Mesozoic tetrapods. An abrupt tripling of richness in the earliest Palaeogene suggests that this diversity equilibrium was reset following the K/Pg extinction. Spatial heterogeneity in sampling is among the most important biases of fossil data, but has often been overlooked. Our results indicate that controlling for variance in geographic spread in the fossil record significantly impacts inferred patterns of diversity through time.
TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis
Authors: Sidler Daniel , Wu Ping , Herro Rana , Claus Meike , Wolf Dennis , Kawakami Yuko , Kawakami Toshiaki , Burkly Linda , Croft Michael
Published: May 2017

Atopic dermatitis (AD) and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. Here we show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of AD-specific T helper type 2 (Th2) and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in AD, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17. Furthermore, subcutaneous injection of recombinant TWEAK into naive mice induces cutaneous inflammation with histological and molecular signs of both diseases. TWEAK is therefore a critical contributor to skin inflammation and a possible therapeutic target in AD and psoriasis.
Single-molecule detection of dihydroazulene photo-thermal reaction using break junction technique
Authors: Huang Cancan , Jevric Martyn , Borges Anders , Olsen Stine T. , Hamill Joseph M. , Zheng Jue-Ting , Yang Yang , Rudnev Alexander , Baghernejad Masoud , Broekmann Peter , Petersen Anne Ugleholdt , Wandlowski Thomas , Mikkelsen Kurt V. , Solomon Gemma C. , Brøndsted Nielsen Mogens , Hong Wenjing
Published: May 2017

Charge transport by tunnelling is one of the most ubiquitous elementary processes in nature. Small structural changes in a molecular junction can lead to significant difference in the single-molecule electronic properties, offering a tremendous opportunity to examine a reaction on the single-molecule scale by monitoring the conductance changes. Here, we explore the potential of the single-molecule break junction technique in the detection of photo-thermal reaction processes of a photochromic dihydroazulene/vinylheptafulvene system. Statistical analysis of the break junction experiments provides a quantitative approach for probing the reaction kinetics and reversibility, including the occurrence of isomerization during the reaction. The product ratios observed when switching the system in the junction does not follow those observed in solution studies (both experiment and theory), suggesting that the junction environment was perturbing the process significantly. This study opens the possibility of using nano-structured environments like molecular junctions to tailor product ratios in chemical reactions.
TRPV4 plays a role in breast cancer cell migration via Ca2+-dependent activation of AKT and downregulation of E-cadherin cell cortex protein
Authors: Lee W H , Choong L Y , Jin T H , Mon N N , Chong S , Liew C S , Putti T , Lu S Y , Harteneck C , Lim Y P
Published: May 2017

TRPV4 belongs to the ‘Transient Receptor Potential’ (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation and inflammation. Unlike other TRP superfamily channels, its role in cancers are unknown until recently when we reported TRPV4 to be required for cancer cell softness that may promote breast cancer cell extravasation and metastasis. Here, we elucidated the molecular mechanisms mediated by TRPV4 in the metastatic breast cancer cells. TRPV4-mediated signaling was demonstrated to involve Ca2+-dependent activation of AKT and downregulation of E-cadherin expression, which was abolished upon TRPV4 silencing. Functionally, TRPV4-enhanced breast caner cell transendothelial migration requires AKT activity while a combination of transcriptional and post-translational regulation contributed to the TRPV4-mediated E-cadherin downregulation. Finally, mass spectrometry analysis revealed that TRPV4 is required for the expression of a network of secreted proteins involved in extracellular matrix remodeling. In conclusion, TRPV4 may regulate breast cancer metastasis by regulating cell softness through the Ca2+-dependent AKT-E-cadherin signaling axis and regulation of the expression of extracellular proteins.
AKT is indispensable for coordinating Par-4/JNK cross talk in p21 downmodulation during ER stress
Authors: Rasool R U , Nayak D , Chakraborty S , Faheem M M , Rah B , Mahajan P , Gopinath V , Katoch A , Iqra Z , Yousuf S K , Mukherjee D , Kumar L D , Nargotra A , Goswami A
Published: May 2017

The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT. The molecular dynamics studies identified important interactions, which may be responsible for the AKT inhibition and efficacy of 3-AWA towards AKT binding pocket. Interestingly, the p21 deceleration was rescued by incubating the cells with 3-AWA in the presence of an ER stress inhibitor, Salubrinal. Furthermore, we demonstrated that p21 expression decreases solitarily in Par-4+/+ MEFs; albeit, ER stress-induced JNK activation was observed in both Par-4+/+ and Par-4−/− MEFs. Par-4 knockdown or overexpression studies established that ectopic Par-4 along with ER stress are not sufficient to downregulate p21 in PC-3 cells but are adequate for DU-145 cells and that the ER stress inflicted activation of JNK, inhibition of AKT and Par-4 induction are all crucial to p21 downmodulation by 3-AWA. By using isogenic cell lines, such as HCT-116 p53+/+ and HCT-116 p53−/−, we found that deceleration in p21 expression due to ER stress is p53 independent. Moreover, in orthotopic carcinogen-induced rat colorectal carcinoma model, we found that 3-AWA inhibits colorectal tumor growth and formation of colorectal polyps at a tolerable dose, similar to the first-line drug for colorectal cancer-5-fluorouracil.
Chaos as an intermittently forced linear system
Authors: Brunton Steven L. , Brunton Bingni W. , Proctor Joshua L. , Kaiser Eurika , Kutz J. Nathan
Published: May 2017

Understanding the interplay of order and disorder in chaos is a central challenge in modern quantitative science. Approximate linear representations of nonlinear dynamics have long been sought, driving considerable interest in Koopman theory. We present a universal, data-driven decomposition of chaos as an intermittently forced linear system. This work combines delay embedding and Koopman theory to decompose chaotic dynamics into a linear model in the leading delay coordinates with forcing by low-energy delay coordinates; this is called the Hankel alternative view of Koopman (HAVOK) analysis. This analysis is applied to the Lorenz system and real-world examples including Earth’s magnetic field reversal and measles outbreaks. In each case, forcing statistics are non-Gaussian, with long tails corresponding to rare intermittent forcing that precedes switching and bursting phenomena. The forcing activity demarcates coherent phase space regions where the dynamics are approximately linear from those that are strongly nonlinear.
Palliative care for Parkinson’s disease: suggestions from a council of patient and carepartners
Authors: Hall Kirk , Sumrall Malenna , Thelen Gil , Kluger Benzi M. ,   on behalf of the 2015 Parkinson’s Disease Foundation sponsored “Palliative Care and Parkinson’s Disease” Patient Advisory Council
Published: May 2017

In 2015, the Parkinson’s Disease Foundation sponsored the first international meeting on Palliative Care and Parkinson’s disease and the Patient Centered Outcomes Research Institute funded the first comparative effectiveness trial of palliative care for Parkinson’s disease. A council of Parkinson’s disease patients and carepartners was engaged to assist with both projects. This council wrote the following manuscript as an opinion piece addressed to the clinical and research community on how palliative care could be applied to people living with Parkinson’s disease and their families. The council endorses palliative care as an approach to the care of Parkinson’s disease patients and their families that seeks to reduce suffering through spiritual, psychosocial, and medical support. This approach should start at the time of diagnosis, as this is a very challenging time for patients and carepartners; includes better emotional support, educational resources, and closer follow-up than is currently standard; and continue through end-of-life care and bereavement.
Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry
Authors: Au Sam H. , Edd Jon , Stoddard Amy E. , Wong Keith H. K. , Fachin Fabio , Maheswaran Shyamala , Haber Daniel A. , Stott Shannon L. , Kapur Ravi , Toner Mehmet
Published: May 2017

Circulating tumor cell clusters (CTC clusters) are potent initiators of metastasis and potentially useful clinical markers for patients with cancer. Although there are numerous devices developed to isolate individual circulating tumor cells from blood, these devices are ineffective at capturing CTC clusters, incapable of separating clusters from single cells and/or cause cluster damage or dissociation during processing. The only device currently able to specifically isolate CTC clusters from single CTCs and blood cells relies on the batch immobilization of clusters onto micropillars which necessitates long residence times and causes damage to clusters during release. Here, we present a two-stage continuous microfluidic chip that isolates and recovers viable CTC clusters from blood. This approach uses deterministic lateral displacement to sort clusters by capitalizing on two geometric properties: size and asymmetry. Cultured breast cancer CTC clusters containing between 2–100 + cells were recovered from whole blood using this integrated two-stage device with minimal cluster dissociation, 99% recovery of large clusters, cell viabilities over 87% and greater than five-log depletion of red blood cells. This continuous-flow cluster chip will enable further studies examining CTC clusters in research and clinical applications.
Multiple viral infections in Agaricus bisporus - Characterisation of 18 unique RNA viruses and 8 ORFans identified by deep sequencing
Authors: Deakin Gregory , Dobbs Edward , Bennett Julie M. , Jones Ian M. , Grogan Helen M. , Burton Kerry S.
Published: May 2017

Thirty unique non-host RNAs were sequenced in the cultivated fungus, Agaricus bisporus, comprising 18 viruses each encoding an RdRp domain with an additional 8 ORFans (non-host RNAs with no similarity to known sequences). Two viruses were multipartite with component RNAs showing correlative abundances and common 3′ motifs. The viruses, all positive sense single-stranded, were classified into diverse orders/families. Multiple infections of Agaricus may represent a diverse, dynamic and interactive viral ecosystem with sequence variability ranging over 2 orders of magnitude and evidence of recombination, horizontal gene transfer and variable fragment numbers. Large numbers of viral RNAs were detected in multiple Agaricus samples; up to 24 in samples symptomatic for disease and 8–17 in asymptomatic samples, suggesting adaptive strategies for co-existence. The viral composition of growing cultures was dynamic, with evidence of gains and losses depending on the environment and included new hypothetical viruses when compared with the current transcriptome and EST databases. As the non-cellular transmission of mycoviruses is rare, the founding infections may be ancient, preserved in wild Agaricus populations, which act as reservoirs for subsequent cell-to-cell infection when host populations are expanded massively through fungiculture.
Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective
Authors: Hahn Soojung , Nam Myeong-Ok , Noh Jung Hyun , Lee Dong Hyeon , Han Hyun Wook , Kim Duk Hwan , Hahm Ki Baik , Hong Sung Pyo , Yoo Jun-Hwan , Yoo Jongman
Published: May 2017

The current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organoid-based epithelial to mesenchymal transition (OEMT) model, which could be used as a novel intestinal fibrosis model. Intestinal epithelial organoids (IEOs) were isolated and cultured from the small intestines of normal mice. IEOs were treated with transforming growth factor- β1 (TGF-β1) or Tumor necrosis factor-α (TNF-α) to evaluate their phenotypic change. Raw 264.7 cells (macrophage) stimulated with lipopolysaccharide were co-cultured with IEOs in growth media with or without TGF-β1. TGF-β1 alone slightly induced epithelial to mesenchymal transition (EMT) in the IEOs but mainly disrupted them. Macrophage released cytokines synergistically induced mesenchymal phenotypic changes in TGF-β1 stimulated intestinal organoids. TNF-α and TGF-β1 synergistically induced proliferation of mesenchymal cells as well as EMT in the IEOs. We generated a novel OEMT model based on our finding that TNF-α and TGF-β synergistically induce type 2 EMT in IEOs. This 3D EMT model with in vivo physiology could be used to study EMT associated intestinal fibrosis.
Up-regulation of long non-coding RNA XLOC_010235 regulates epithelial-to-mesenchymal transition to promote metastasis by associating with Snail1 in gastric cancer
Authors: Liu Yu-yi , Chen Ze-hong , Peng Jian-jun , Wu Jia-lin , Yuan Yu-jie , Zhai Er-tao , Cai Shi-rong , He Yu-long , Song Wu
Published: May 2017

We previously performed long non-coding RNA (lncRNA) expression microarray analyses to identify novel indicators for gastric cancer (GC) metastasis and prognosis in which we identified lncRNA XLOC_010235 (XLOC) as a candidate RNA. However, XLOC_010235 molecular mechanism of action remains unclear. Gain and loss of function approaches were used to investigate the biological role of XLOC in vitro. The effects of XLOC on cell viability were assessed by CCK-8 proliferation assays. Real-time PCR, western-blot and immunofluorescence were used to evaluate the mRNA and protein expression of Snail and multiple EMT related molecules. The positive XLOC/Snail1 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. Ectopic expression of XLOC facilitate cell viability, migration and invasion, leading to the acceleration of metastasis, while depletion of XLOC expression hindered cell migration and invasion. Moreover, over-expression of XLOC was found to play a important role in epithelial-to-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression, in which transcriptional factor Snail1 was involved. These results advance our understanding of the role of lncRNA XLOC_010235 as a active regulator of EMT by associating with Snail1, which may help in the development of new therapeutics.