bluuebunny/crossref_metadata_2025 huggingface dataset:
CHICKEN OR EGG? RETHINKING THE RELATIONSHIP BETWEEN THE SILVER AND TINNED CERAMIC VESSEL ASSEMBLAGES
Authors: Aulsebrook S.
Published: February 2018

Since the 1960s, when the existence of tinned ceramic vessels in the Late Bronze Age Aegean was first recognised, our knowledge of this phenomenon and the catalogue of known examples have expanded significantly. Even before the nature of these objects was fully understood, scholars had suggested that their primary purpose was to imitate metal, particularly silver, vessels. Several silver vessel assemblages, including one from the tholos at Kokla, have been singled out for their perceived special relationship with tinned ceramics. However, closer analysis of tinned vessels has suggested that they were less similar to silver vessels than previously thought, especially in terms of their range of forms, details of shape and even colour. Recent scholarship has also emphasised that the concept of imitation is very complex and its investigation requires a more nuanced approach. Yet references to tinned vessels as straightforward imitations of, or even substitutes for, silver vessels remain common. In 2014, an opportunity arose to examine the Kokla silver vessels in greater detail. A strong connection between the Kokla group and tinned vessels is evident, although this does not mean that the latter depended upon assemblages such as the former for inspiration. The unique features of the Kokla group suggest it may have been a local innovation to emulate the usage of tinned vessels while simultaneously stressing the higher social status of its users. This paper concludes that situating tinned vessels within the ceramic tradition and thus regarding them as an enhanced form of ceramic, rather than an inferior form of metal vessel, better explains the nature of this phenomenon.
Introduction & overview
Authors: Stamatopoulou Maria
Published: February 2018

Over the past year, Greek archaeology has seen a remarkable number of new publications, both fieldwork data reports (ADelt vols 65–68 for 2010–2013 in ten fascicules, AEMTh 25 and AEThSE 4, among others) and conference proceedings, exhibition catalogues, monographs and Festschriften that include much new and unpublished material. Regular updates continue to appear in AGOnline, but it has been impossible to process all this material in the space of a few months for publication in this year's Archaeology in Greece. Some of the new exciting discoveries are, however, presented in the ‘Newsround’ section, and we hope to provide further updates in next year's AG.
Archaeological textiles excavated in Greece
Authors: Spantidaki Stella , Margariti Christina
Published: February 2018

This paper offers an account of the archaeological textiles excavated in Greece, consideration of the challenges one has to deal with when studying such materials and a discussion of ways to overcome them. A complete list of archaeological textiles excavated in Greece is not within the scope of this paper, since such comprehensive studies have been published previously (Spantidaki and Moulhérat 2012; Moulhérat and Spantidaki 2016) and, of course, the corpus of such textiles is continuously expanding.

The study of textiles is an emerging and fast-growing field of Greek archaeology (Gleba 2011). The number of archaeologists and conservators working with and studying archaeological textiles is steadily increasing, thus raising the general awareness of textiles and expanding the corpus of known ancient fabrics. In recent years, several research projects have investigated ancient Greek textiles, such as those conducted by the Centre for Textile Research at the University of Copenhagen (for example Textile Economies in the Mediterranean Area), several funded by Marie Skłodowska Curie Action grants and some by European Research Council grants (for example Production and Consumption: Textile Economy and Urbanisation in Mediterranean Europe 1000–500 BCE hosted by Cambridge University).
Stone quarrying in Greece: ten years of research
Authors: Russell Ben
Published: February 2018

It has been ten years since the publication of Lorenzo Lazzarini's monumental volume on the quarrying, use and properties of the coloured marbles of Greece: Poikiloi Lithoi, Versiculores Maculae: I Marmi Colorati della Grecia Antica (Lazzarini 2007). The first study since Angelina Dworakowska's Quarries in Ancient Greece (Dworakowska 1975) to attempt a large-scale examination of quarrying across Greece, Lazzarini's approach is fundamentally an archaeometric one. Analysis of the evidence for quarrying in different regions is set alongside minero-petrographic and geochemical analyses of the materials extracted. Lazzarini focuses on 12 lithotypes: marmor lacedaemonium from Laconia, variously referred to as serpentino and porfido verde antico; three stone types from the Mani peninsula: rosso antico tenario, nero antico tenario and cipollino tenario; from Chios, the famous marmor chium or portasanta, breccia di Aleppo and nero antico chiota; the breccia di settebasi and semesanto of Skyros; the intensively exploited marmor carystium or cipollino verde, as well as the marmor chalcidicum or fior di pesco from Euboea; and from central and northern Greece, marmor thessalicum or verde antico and the breccia policroma della Vittoria. For each of these lithotypes, Lazzarini considers the evidence for their use and distribution, illustrated with a distribution map in each case, and provides a thorough overview of what is known about their quarries. Archaeological and geological approaches are here combined, and this is a hallmark of much recent work on the question of quarrying and stone use through Greek history.
Temporal patterns in principal Salmonella serotypes in the USA; 1996–2014
Authors: Powell M. R. , Crim S. M. , Hoekstra R. M. , Williams M. S. , Gu W.
Published: February 2018

Analysing temporal patterns in foodborne illness is important to designing and implementing effective food safety measures. The reported incidence of illness due to Salmonella in the USA. Foodborne Diseases Active Surveillance Network (FoodNet) sites has exhibited no declining trend since 1996; however, there have been significant annual trends among principal Salmonella serotypes, which may exhibit complex seasonal patterns. Data from the original FoodNet sites and penalised cubic B-spline regression are used to estimate temporal patterns in the reported incidence of illness for the top three Salmonella serotypes during 1996–2014. Our results include 95% confidence bands around the estimated annual and monthly curves for each serotype. The results show that Salmonella serotype Typhimurium exhibits a statistically significant declining annual trend and seasonality (P < 0.001) marked by peaks in late summer and early winter. Serotype Enteritidis exhibits a significant annual trend with a higher incidence in later years and seasonality (P < 0.001) marked by a peak in late summer. Serotype Newport exhibits no significant annual trend with significant seasonality (P < 0.001) marked by a peak in late summer.
Chickenpox outbreak in a tribal and industrial zone from the Union Territory of Dadra and Nagar Haveli, India
Authors: Vaidya S. R. , Tilavat S. M. , Kumbhar N. S. , Kamble M. B.
Published: February 2018

During 9thDecember 2016 and 12thFebruary 2017, 149-chickenpox cases were reported in a tribal and industrial zone of Rakholi (n= 80) and Surangi (n= 69) villages from Union Territory of India. An epidemiological investigation was performed to assess the characteristics and determinants of the chickenpox outbreak. Overall, the attack rate per 100 population in Rakholi village (n= 1757) was 4.5% and 19.1% in Surangi village (n= 360). Ages of the cases were ranged from 6 months to 55 years and there were 53 females and 96 males. For the laboratory investigations, 25 serum samples, three urine specimens, three throat swabs and six blister/skin swabs were collected from 37-suspected chickenpox cases. Altogether, 30-suspected cases were laboratory confirmed by either IgM EIA or varicella zoster virus (VZV) DNA PCR. Both VZV-specific IgM and IgG antibodies were detected in 19-suspected cases. Two suspected cases showed the presence of VZV-specific IgG antibodies but not IgM antibodies. On the contrary, three suspected cases showed VZV-specific IgM but not IgG antibodies. Overall, 31 of 37-suspected cases (including one equivocal case) were laboratory confirmed. The partial sequencing of ORF-28 gene of VZV revealed circulation of clade-1 viruses. In conclusion, this investigation provides detail information about the chickenpox outbreak in the tribal and industrial setting from India. Furthermore, the study emphasises the need to investigate more chickenpox outbreaks in different parts of India.
Is Distance to the Nearest Registered Public Automated Defibrillator Associated with the Probability of Bystander Shock for Victims of Out-of-Hospital Cardiac Arrest?
Authors: Neves Briard Joel , de Montigny Luc , Ross Dave , de Champlain François , Segal Eli
Published: February 2018

Introduction

Rapid access to defibrillation is a key element in the management of out-of-hospital cardiac arrests (OHCAs). Public automated external defibrillators (PAEDs) are becoming increasingly available, but little information exists regarding the relation between the proximity to the arrest and their usage in urban areas.

Methods

This study is a retrospective, observational, cross-sectional analysis of non-traumatic OHCA during a 24-month period in the greater Montreal area (Quebec, Canada). Using logistic regression, bystander shock odds are described with regards to distance from the OHCA scene to the nearest PAED, adjusted for prehospital care arrival delay and time of day, and stratifying for type of location.

Results

Out of a total of 2,443 OHCA victims identified, 77 (3%) received bystander PAED shock, 622 (26%) occurred out-of-home, and 743 (30%) occurred during business hours. When controlling for time (business hours versus other hours) and minimum response delay for prehospital care arrival, a marginal negative association was found between bystander shock and distance to the nearest PAED in logged meters (aOR=0.80; CI, 0.64-0.99) for out-of-home cardiac arrests. No significant association was found between distance and bystander shock for at-home arrests. Out-of-home victims had significantly higher odds of receiving bystander shock up to 175 meters of distance to a PAED inclusively (aOR=2.52; CI, 1.07-5.89).

Conclusion

For out-of-home cardiac arrests, proximity to a PAED was associated with bystander shock in the greater Montreal area. Strategies aiming to increase accessibility and use of these life-saving devices could further expand this advantage by assisting bystanders in rapidly locating nearby PAEDs.

Neves BriardJ, de MontignyL, RossD, de ChamplainF, SegalE. Is distance to the nearest registered public automated defibrillator associated with the probability of bystander shock for victims of out-of-hospital cardiac arrest?Prehosp Disaster Med. 2018;33(2):153–159.
A Review of State Public Health Emergency Declarations in Peru: 2014-2016
Authors: Bambarén Celso , Alatrista Maria del Socorro
Published: February 2018

Peru has different legal mechanisms of emergency, one of which is the Public Health Emergency that is applicable when: there is high-risk for, or the existence of an outbreak, epidemic, or pandemic; the occurrence of cases of a disease classified as eliminated or eradicated; the occurrence of emerging or re-emerging infectious diseases with high epidemic potential; the occurrence of rapid disseminated epidemics that simultaneously affect more than one department; as well as the existence of an event that affects the continuity of health services.

From July 2014 to December 2016, 23 Public Health Emergencies were declared, out of which 57% were in the high-risk or existence of epidemics, 30% were due to some natural or anthropic events that generate a sudden decrease in the operative capacity of health services, and 13% were due to the existence of a rapid spreading epidemic that could affect more than one department in the country. The risk or occurrence of epidemiological outbreaks, mainly of Dengue, was the main cause of emergency declaration. One-hundred and forty million US dollars were allocated to implement the action plans that were part of the declaration, of which 72% was used to keep the operational capacity of health services and 28% to vector and epidemiological control measures.

BambarénC, AlatristaMdS. A review of state public health emergency declarations in Peru: 2014-2016. Prehosp Disaster Med. 2018;33(2):197–200.
The demand for air quality: evidence from the housing market in Bogotá, Colombia
Authors: Carriazo Fernando , Gomez-Mahecha John Alexander
Published: February 2018

Identifying a demand function for air quality is a key input to calculate welfare measurements of pollution abatement policies. We defined intra-urban housing submarkets to apply a Second Stage hedonic pricing model that allowed us to identify an inverse demand function for PM10 reductions in Bogotá. The monthly benefits of compliance with the U.S. Environmental Protection Agency standard (50 μg/m3– annual average), and the far more stringent World Health Organization standard (20 μg/m3– annual average) are valued at US$12.16 and US$189.64 per household, respectively. These values, in turn, represent about 1.35 per cent and 21.04 per cent of the average household income. The hedonic model applied hereby shows that intra-urban housing submarkets are suitable for the identification of a demand function to be used by policy makers interested in evaluating non-marginal benefits (costs) from air quality improvements (deterioration).
FINANCIAL SECTOR INTERCONNECTEDNESS AND MONETARY POLICY TRANSMISSION
Authors: Barattieri Alessandro , Eden Maya , Stevanovic Dalibor
Published: February 2018

We present a stylized model that illustrates how interbank trading can reduce the sensitivity of lending to entrepreneurs' net worth, thus affecting the transmission mechanism of monetary policy through the credit channel. We build a model-consistent measure of interconnectedness and document that, in the United States, this measure has increased substantially during the period 1952–2016. Finally, interacting the measure of interconnectedness in a structural vector autoregression and a factor-augmented vector autoregression for the US economy, we find that the impulse responses of several real and financial variables to monetary policy shocks are dampened as interconnectedness increases. We confirm the same result using data from 10 Euro area countries for the period 1999–2016.
Phonological priming and the role of phonology in nonnative word recognition
Authors: GOR KIRA
Published: February 2018

Research on nonnative auditory word recognition makes use of a lexical decision task with phonological priming to explore the role of phonological form in nonnative lexical access. In a medium-lag lexical decision task with phonological priming, nonnative speakers treat minimal pairs of words differentiated by a difficult phonological contrast as a repetition of the same word. While native speakers show facilitation in medium-lag priming only for identical word pairs, nonnative speakers also show facilitation for minimal pairs. In short-lag phonological priming, when the prime and the target have phonologically overlapping onsets, nonnative speakers show facilitation, while native speakers show inhibition. This review discusses two possible reasons for facilitation in nonnative phonological priming: reduced sensitivity to nonnative phonological contrasts, and reduced lexical competition of nonnative words with underdifferentiated, or fuzzy phonolexical representations. Nonnative words may be processed sublexically, which leads to sublexical facilitation instead of the inhibition resulting from lexical competition.
Knowledge of nutrition and physical activity in apparently healthy Indian adults
Authors: Pandit-Agrawal Deepa , Khadilkar Anuradha , Chiplonkar Shashi , Khadilkar Vaman
Published: February 2018

Objective

To assess knowledge of nutrition and physical activity; examine associations of knowledge with sociodemographic and anthropometric parameters; and evaluate the relationship between knowledge and practice in adults.

Design

In a cross-sectional design, 720 adults were selected using random sampling. Data on anthropometry, body fat, diet, physical activity, and nutrition and physical activity knowledge were collected using standardized questionnaires. Tertiles were used to categorize nutrition knowledge (NK) and physical activity knowledge (PK).

Settings

Subjects selected through routine health checks from hospitals, housing societies and residential areas.

Subjects

A total of 720 adults (361 men) aged 35–50 years participated.

Results

Mean age was 42·7 (sd 9·4) years and mean BMI was 25·8 (sd 5·0) kg/m2. Mean energy intake was 64 %, protein was 68 % and fat was 144 % of the RDA. Mean NK and PK scores were 10·2 (sd 2·9) and 6·5 (sd 1·7), respectively, and were similar across genders (P>0·05). Individuals with higher education exhibited significantly higher NK and PK. Individuals with high fat had significantly higher NK and PK (P<0·05) than participants with normal fat percentage. Overweight and obese individuals had significantly higher PK (P<0·05). Multivariate regression modelling indicated that NK was positively associated with dietary intakes of leafy vegetables, salads and sprouts but negatively associated with fruit intake. BMI, television and reading time were positively associated with PK, even after adjusting for sociodemographic status.

Conclusions

There is a need for increased efforts towards developing health education programmes focusing on transforming nutrition and physical activity knowledge into practice and adherence to guidelines.
Early, regular breast-milk pumping may lead to early breast-milk feeding cessation
Authors: Yourkavitch Jennifer , Rasmussen Kathleen M , Pence Brian W , Aiello Allison , Ennett Susan , Bengtson Angela M , Chetwynd Ellen , Robinson Whitney
Published: February 2018

Objective

To estimate the effect of early, regular breast-milk pumping on time to breast-milk feeding (BMF) and exclusive BMF cessation, for working and non-working women.

Design

Using the Infant Feeding Practices Survey II (IFPS II), we estimated weighted hazard ratios (HR) for the effect of regular pumping (participant defined) compared with non-regular/not pumping, reported at month 2, on both time to BMF cessation (to 12 months) and time to exclusive BMF cessation (to 6 months), using inverse probability weights to control confounding.

Setting

USA, 2005–2007.

Subjects

BMF (n 1624) and exclusively BMF (n 971) IFPS II participants at month 2.

Results

The weighted HR for time to BMF cessation was 1·62 (95 % CI 1·47, 1·78) and for time to exclusive BMF cessation was 1·14 (95 % CI 1·03, 1·25). Among non-working women, the weighted HR for time to BMF cessation was 2·05 (95 % CI 1·84, 2·28) and for time to exclusive BMF cessation was 1·10 (95 % CI 0·98, 1·22). Among working women, the weighted HR for time to BMF cessation was 0·90 (95 % CI 0·75, 1·07) and for time to exclusive BMF cessation was 1·14 (95 % CI 0·96, 1·36).

Conclusions

Overall, regular pumpers were more likely to stop BMF and exclusive BMF than non-regular/non-pumpers. Non-working regular pumpers were more likely than non-regular/non-pumpers to stop BMF. There was no effect among working women. Early, regular pumpers may need specialized support to maintain BMF.
When the Present Became Future: The Ambiguity behind the Consent in the Marriage Rite of the 1662Book of Common Prayer
Authors: Spinks Bryan
Published: February 2018

In a preparatory essay for the International Anglican Liturgical Consultation 2011, on the topic of marriage, Thomas Cooper questioned the long-held view that the question of consent in the Prayer Book tradition was derived from the older betrothal vow. Arguing from the Latin of the Sarum Use, ‘Volo’, he argued that ‘Will you ..?’ and ‘I will’ reflects the Old English present tense and is part of the marriage vow. This article questions Cooper’s argument, and instead argues that the use of ‘will’ as a future tense already in Middle English and used in betrothals pre-dates the Latin text. As a result, the separation of the consent (understood as an immediate future intention) from the qvow as in the 1979 AmericanBook of Common Prayerand the Church of EnglandCommon Worship 2000is entirely justified.
Climate change mitigation beyond agriculture: a review of food system opportunities and implications
Authors: Niles Meredith T. , Ahuja Richie , Barker Todd , Esquivel Jimena , Gutterman Sophie , Heller Martin C. , Mango Nelson , Portner Diana , Raimond Rex , Tirado Cristina , Vermeulen Sonja
Published: February 2018

A large body of research has explored opportunities to mitigate climate change in agricultural systems; however, less research has explored opportunities across the food system. Here we expand the existing research with a review of potential mitigation opportunities across the entire food system, including in pre-production, production, processing, transport, consumption and loss and waste. We detail and synthesize recent research on the topic, and explore the applicability of different climate mitigation strategies in varying country contexts with different economic and agricultural systems. Further, we highlight some potential adaptation co-benefits of food system mitigation strategies and explore the potential implications of such strategies on food systems as a whole. We suggest that a food systems research approach is greatly needed to capture such potential synergies, and highlight key areas of additional research including a greater focus on low- and middle-income countries in particular. We conclude by discussing the policy and finance opportunities needed to advance mitigation strategies in food systems.
Economic impact of organic agriculture hotspots in the United States
Authors: Marasteanu I. Julia , Jaenicke Edward C.
Published: February 2018

In this paper, we assess whether or not organic agriculture has a positive impact on local economies. We first identify organic agriculture hotspots (clusters of counties with positively correlated high numbers of organic operations) using spatial statistics. Then, we estimate a treatment effects model that classifies a county's membership in an organic hotspot as an endogenous treatment variable. By modeling what a hotspot county's economic indicators would have been had the county not been part of a hotspot, this model captures the effect of being in a hotspot on a county's economic indicators. We perform the same analysis for general agricultural farm hotspots to confirm that the benefits associated with organic production hotspots are, in fact, due to the organic component. Our results show that organic hotspot membership leads to a lower county-level poverty rate and a higher median household income. A similar result is not found when investigating the impact of general agriculture hotspots. On the other hand, our result is robust to alternative hotspot definitions based on type of organic operations to alternative methods of estimating average treatment effects on the treated. These results provide strong motivation for considering hotspots of organic handling operations, which refers to middlemen such as processors, wholesalers and brokers, and hotspots of organic production to be local economic development tools, and may be of interest to policymakers whose objective is to promote rural development. Our results may incentivize policymakers to specifically focus on organic development, rather than the more general development of agriculture, as a means to promote economic growth in rural areas, and may further point them in the direction of not only encouraging the presence of organic operations, but of fostering the development of clusters or hotspots of these operations.
Chronic neutrophilic leukemia: new science and new diagnostic criteria
Authors: Szuber Natasha , Tefferi Ayalew
Published: February 2018

Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm defined by persistent, predominantly mature neutrophil proliferation, marrow granulocyte hyperplasia, and frequent splenomegaly. The seminal discovery of oncogenic driver mutations in CSF3R in the majority of patients with CNL in 2013 generated a new scientific framework for this disease as it deepened our understanding of its molecular pathogenesis, provided a biomarker for diagnosis, and rationalized management using novel targeted therapies. Consequently, in 2016, the World Health Organization (WHO) revised the diagnostic criteria for CNL to reflect such changes in its genomic landscape, now including the presence of disease-defining activating CSF3R mutations as a key diagnostic component of CNL. In this communication, we provide a background on the history of CNL, its clinical and hemopathologic features, and its molecular anatomy, including relevant additional genetic lesions and their significance. We also outline the recently updated WHO diagnostic criteria for CNL. Further, the natural history of the disease is reviewed as well as potential prognostic variables. Finally, we summarize and discuss current treatment options as well as prospective novel therapeutic targets in hopes that they will yield meaningful improvements in patient management and outcomes.
The small GTPase RhoU lays downstream of JAK/STAT signaling and mediates cell migration in multiple myeloma
Authors: Canovas Nunes Sara , Manzoni Martina , Pizzi Marco , Mandato Elisa , Carrino Marilena , Quotti Tubi Laura , Zambello Renato , Adami Fausto , Visentin Andrea , Barilà Gregorio , Trentin Livio , Manni Sabrina , Neri Antonino , Semenzato Gianpietro , Piazza Francesco
Published: February 2018

Multiple myeloma is a post-germinal center B-cell neoplasm, characterized by the proliferation of malignant bone marrow plasma cells, whose survival and proliferation is sustained by growth factors and cytokines present in the bone marrow microenvironment. Among them, IL-6 triggers the signal downstream of its receptor, leading to the activation of the JAK/STAT pathway. The atypical GTPase RhoU lays downstream of STAT3 transcription factor and could be responsible for mediating its effects on cytoskeleton dynamics. Here we demonstrate that RHOU is heterogeneously expressed in primary multiple myeloma cells and significantly modulated with disease progression. At the mRNA level, RHOU expression in myeloma patients correlated with the expression of STAT3 and its targets MIR21 and SOCS3. Also, IL-6 stimulation of human myeloma cell lines up-regulated RHOU through STAT3 activation. On the other hand, RhoU silencing led to a decrease in cell migration with the accumulation of actin stress fibers, together with a decrease in cyclin D2 expression and in cell cycle progression. Furthermore, we found that even though lenalidomide positively regulated RhoU expression leading to higher cell migration rates, it actually led to cell cycle arrest probably through a p21 dependent mechanism. Lenalidomide treatment in combination with RhoU silencing determined a loss of cytoskeletal organization inhibiting cell migration, and a further increase in the percentage of cells in a resting phase. These results unravel a role for RhoU not only in regulating the migratory features of malignant plasma cells, but also in controlling cell cycle progression.
Inhibition of KRAS-dependent lung cancer cell growth by deltarasin: blockage of autophagy increases its cytotoxicity
Authors: Leung Elaine Lai Han , Luo Lian Xiang , Liu Zhong Qiu , Wong Vincent Kam Wai , Lu Lin Lin , Xie Ying , Zhang Ni , Qu Yuan Qing , Fan Xing Xing , Li Ying , Huang Min , Xiao Dai Kai , Huang Jun , Zhou Yan Ling , He Jian Xing , Ding Jian , Yao Xiao Jun , Ward David C. , Liu Liang
Published: February 2018

Deltarasin is a recently identified small molecule that can inhibit KRAS–PDEδ interactions by binding to a hydrophobic pocket on PDEδ, resulting in the impairment of cell growth, KRAS activity, and RAS/RAF signaling in human pancreatic ductal adenocarcinoma cell lines. Since KRAS mutations are the most common oncogene mutations in lung adenocarcinomas, implicated in over 30% of all lung cancer cases, we examined the ability of deltarasin to inhibit KRAS-dependent lung cancer cell growth. Here, for the first time, we document that deltarasin produces both apoptosis and autophagy in KRAS-dependent lung cancer cells in vitro and inhibits lung tumor growth in vivo. Deltarasin induces apoptosis by inhibiting the interaction of with PDEδ and its downstream signaling pathways, while it induces autophagy through the AMPK-mTOR signaling pathway. Importantly, the autophagy inhibitor, 3-methyl adenine (3-MA) markedly enhances deltarasin-induced apoptosis via elevation of reactive oxygen species (ROS). In contrast, inhibition of ROS by N-acetylcysteine (NAC) significantly attenuated deltarasin-induced cell death. Collectively, these observations suggest that the anti-cancer cell activity of deltarasin can be enhanced by simultaneously blocking “tumor protective” autophagy, but inhibited if combined with an anti-oxidant.
KRAS induces lung tumorigenesis through microRNAs modulation
Authors: Shi Lei , Middleton Justin , Jeon Young-Jun , Magee Peter , Veneziano Dario , Laganà Alessandro , Leong Hui-Sun , Sahoo Sudhakar , Fassan Matteo , Booton Richard , Shah Rajesh , Crosbie Philip A. J. , Garofalo Michela
Published: February 2018

Oncogenic KRAS induces tumor onset and development by modulating gene expression via different molecular mechanisms. MicroRNAs (miRNAs) are small non-coding RNAs that have been established as main players in tumorigenesis. By overexpressing wild type or mutant KRAS (KRASG12D) and using inducible human and mouse cell lines, we analyzed KRAS-regulated microRNAs in non-small-cell lung cancer (NSCLC). We show that miR-30c and miR-21 are significantly upregulated by both KRAS isoforms and induce drug resistance and enhance cell migration/invasion via inhibiting crucial tumor suppressor genes, such as NF1, RASA1, BID, and RASSF8. MiR-30c and miR-21 levels were significantly elevated in tumors from patients that underwent surgical resection of early stages NSCLC compared to normal lung and in plasma from the same patients. Systemic delivery of LNA-anti-miR-21 in combination with cisplatin in vivo completely suppressed the development of lung tumors in a mouse model of lung cancer. Mechanistically, we demonstrated that ELK1 is responsible for miR-30c and miR-21 transcriptional activation by direct binding to the miRNA proximal promoter regions. In summary, our study defines that miR-30c and miR-21 may be valid biomarkers for early NSCLC detection and their silencing could be beneficial for therapeutic applications.
Generalized leaky integrate-and-fire models classify multiple neuron types
Authors: Teeter Corinne , Iyer Ramakrishnan , Menon Vilas , Gouwens Nathan , Feng David , Berg Jim , Szafer Aaron , Cain Nicholas , Zeng Hongkui , Hawrylycz Michael , Koch Christof , Mihalas Stefan
Published: February 2018

There is a high diversity of neuronal types in the mammalian neocortex. To facilitate construction of system models with multiple cell types, we generate a database of point models associated with the Allen Cell Types Database. We construct a set of generalized leaky integrate-and-fire (GLIF) models of increasing complexity to reproduce the spiking behaviors of 645 recorded neurons from 16 transgenic lines. The more complex models have an increased capacity to predict spiking behavior of hold-out stimuli. We use unsupervised methods to classify cell types, and find that high level GLIF model parameters are able to differentiate transgenic lines comparable to electrophysiological features. The more complex model parameters also have an increased ability to differentiate between transgenic lines. Thus, creating simple models is an effective dimensionality reduction technique that enables the differentiation of cell types from electrophysiological responses without the need for a priori-defined features. This database will provide a set of simplified models of multiple cell types for the community to use in network models.
Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
Authors: Corbin Laura J. , Tan Vanessa Y. , Hughes David A. , Wade Kaitlin H. , Paul Dirk S. , Tansey Katherine E. , Butcher Frances , Dudbridge Frank , Howson Joanna M. , Jallow Momodou W. , John Catherine , Kingston Nathalie , Lindgren Cecilia M. , O’Donavan Michael , O’Rahilly Stephen , Owen Michael J. , Palmer Colin N. A. , Pearson Ewan R. , Scott Robert A. , van Heel David A. , Whittaker John , Frayling Tim , Tobin Martin D. , Wain Louise V. , Smith George Davey , Evans David M. , Karpe Fredrik , McCarthy Mark I. , Danesh John , Franks Paul W. , Timpson Nicholas J.
Published: February 2018

Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner.
Can civil lawsuits stem the tide of direct-to-consumer marketing of unproven stem cell interventions
Authors: Horner Claire , Tenenbaum Evelyn , Sipp Douglas , Master Zubin
Published: February 2018

The sale of unproven stem cell interventions (SCIs) by commercial entities has proliferated in highly developed countries, most notably in the USA. Yet, there have been few criminal prosecutions and regulatory enforcement actions against providers who have violated laws and best practice standards due to the lack of resources and legal ambiguity. While the stem cell research community has invested much in protecting patients and preventing the growth of this industry, some patients are seeking remedies under civil law to hold stem cell clinics responsible for fraudulent practices. Several patients have filed lawsuits against providers demanding compensation for physical injuries caused by unproven treatments and financial losses due to fraud and false advertising. Lawsuits can be used as a tool not only to compensate plaintiffs but also to achieve positive public health and policy outcomes. In this paper, we explore the value of a public health litigation strategy as a countermeasure against the exploitative practices of the unproven SCI industry by analyzing stem cell lawsuits and comparing them with other major public health litigation efforts. We argue that stem cell lawsuits complement other approaches to reining in unsafe practices. In particular, stem cell lawsuits could intensify publicity and raise awareness of the harms of unproven treatments, set legal precedent, reshape the media narrative from one focused on the right to try or practice to one highlighting the need for adequate safety and efficacy standards, and encourage authorities to turn their attention to policy reform and enforcement.
New insights into the cellular responses to iron nanoparticles in Capsicum annuum
Authors: Yuan Junxia , Chen Yu , Li Huasheng , Lu Jinying , Zhao Hui , Liu Min , Nechitaylo Galina S. , Glushchenko Natalia N.
Published: February 2018

In this study, the anatomical and ultrastructural responses of Capsicum annuum to iron nanoparticles (Fe NPs) were determined. The results showed that the bio-effects of Fe NPs on plants could be positive or negative, depending on the additive concentrations. Low concentrations of Fe NPs were found to promote plant growth. Light and electron microscope analyses showed that the Fe NPs promoted plant growth by altering the leaf organization, and increasing the chloroplast number and grana stacking, as well as regulating the development of vascular bundles. Meanwhile, it was found that the Fe NPs could be absorbed in the roots, and then transported to the central cylinder in bio-available forms, where they were translocated and utilized by the leaves and stems. In contrast, high concentrations of Fe NPs appeared to be harmful to the plants, and the majority of Fe NPs were aggregated into cell walls and transported via the apoplastic pathway in the roots, which may potentially block the transfer of iron nutrients. Taken together, the aforementioned data showed that the rational use of Fe NPs could alleviate iron deficiency, and Fe NPs could be an ideal supply for Fe2+ ions fertilizers in agriculture.
Global Peak in Atmospheric Radiocarbon Provides a Potential Definition for the Onset of the Anthropocene Epoch in 1965
Authors: Turney Chris S. M. , Palmer Jonathan , Maslin Mark A. , Hogg Alan , Fogwill Christopher J. , Southon John , Fenwick Pavla , Helle Gerhard , Wilmshurst Janet M. , McGlone Matt , Bronk Ramsey Christopher , Thomas Zoë , Lipson Mathew , Beaven Brent , Jones Richard T. , Andrews Oliver , Hua Quan
Published: February 2018

Anthropogenic activity is now recognised as having profoundly and permanently altered the Earth system, suggesting we have entered a human-dominated geological epoch, the ‘Anthropocene’. To formally define the onset of the Anthropocene, a synchronous global signature within geological-forming materials is required. Here we report a series of precisely-dated tree-ring records from Campbell Island (Southern Ocean) that capture peak atmospheric radiocarbon (14C) resulting from Northern Hemisphere-dominated thermonuclear bomb tests during the 1950s and 1960s. The only alien tree on the island, a Sitka spruce (Picea sitchensis), allows us to seasonally-resolve Southern Hemisphere atmospheric 14C, demonstrating the ‘bomb peak’ in this remote and pristine location occurred in the last-quarter of 1965 (October-December), coincident with the broader changes associated with the post-World War II ‘Great Acceleration’ in industrial capacity and consumption. Our findings provide a precisely-resolved potential Global Stratotype Section and Point (GSSP) or ‘golden spike’, marking the onset of the Anthropocene Epoch.
Joint Effect of Non-invasive Central Systolic Blood Pressure and Peripheral Systolic Blood Pressure on Incident Hypertension in a Chinese Community-based Population
Authors: Wang Shixuan , Zhou Zechen , Fan Fangfang , Qi Litong , Jia Jia , Sun Pengfei , Jiang Yimeng , Kou Minghao , Chen Dafang , Zhang Yan , Huo Yong
Published: February 2018

Central blood pressure level is not always consistent with peripheral blood pressure level, and especially their joint effect on incident hypertension is not well established. A total of 1607 non-hypertensive subjects from an atherosclerosis cohort in Beijing, China were included. Central systolic blood pressure (cSBP) was obtained using Omron HEM-9000AI machine and peripheral systolic blood pressure (pSBP) was measured using Omron HEM-7117 electronic sphygmomanometer, separately. Hypertension was defined as BP ≥ 140/90 mmHg or self-reported hypertension or taking any antihypertension drugs at the follow-up survey. After a median follow-up of 2.3 years, incident hypertension was 13.1%. Every 1 standard deviation increase of cSBP and pSBP was associated with 1.98 (95%CI: 1.69–2.33) and 2.84 (95%CI: 2.30–3.52) times of incident hypertension after adjustment for confounders. Moreover, hypertension risk in single pSBP ≥ 120 mmHg group, single cSBP ≥ 120 mmHg group, and both pSBP and cSBP ≥ 120 mmHg group was 2.83 (95%CI: 0.98–8.16), 3.28 (95%CI: 1.24–8.70), and 11.47 (95%CI: 4.97–26.46) times higher than both pSBP and cSBP < 120 mmHg group, respectively. The joint effect of cSBP and pSBP is superior to either cSBP or pSBP to predict incident hypertension in a Chinese community-based population. Screening of central blood pressure should be considered in non-hypertensive population for the purpose of primary intervention, especially for subjects with pSBP ≥ 120 mmHg.
Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations
Authors: Lempens Pauline , Meehan Conor J. , Vandelannoote Koen , Fissette Kristina , de Rijk Pim , Van Deun Armand , Rigouts Leen , de Jong Bouke C.
Published: February 2018

The majority of Mycobacterium tuberculosis isolates resistant to isoniazid harbour a mutation in katG. Since these mutations cause a wide range of minimum inhibitory concentrations (MICs), largely below the serum level reached with higher dosing (15 mg/L upon 15–20 mg/kg), the drug might still remain partly active in presence of a katG mutation. We therefore investigated which genetic mutations predict the level of phenotypic isoniazid resistance in clinical M. tuberculosis isolates. To this end, the association between known and unknown isoniazid resistance-conferring mutations in whole genome sequences, and the isoniazid MICs of 176 isolates was examined. We found mostly moderate-level resistance characterized by a mode of 6.4 mg/L for the very common katG Ser315Thr mutation, and always very high MICs (≥19.2 mg/L) for the combination of katG Ser315Thr and inhA c-15t. Contrary to common belief, isolates harbouring inhA c-15t alone, partly also showed moderate-level resistance, particularly when combined with inhA Ser94Ala. No overt association between low-confidence or unknown mutations, except in katG, and isoniazid resistance (level) was found. Except for the rare katG deletion, line probe assay is thus not sufficiently accurate to predict the level of isoniazid resistance for a single mutation in katG or inhA.
Simultaneous Strength-Ductility Enhancement of a Nano-Lamellar AlCoCrFeNi2.1 Eutectic High Entropy Alloy by Cryo-Rolling and Annealing
Authors: Bhattacharjee T. , Wani I. S. , Sheikh S. , Clark I. T. , Okawa T. , Guo S. , Bhattacharjee P. P. , Tsuji N.
Published: February 2018

Nano-lamellar (L12 + B2) AlCoCrFeNi2.1 eutectic high entropy alloy (EHEA) was processed by cryo-rolling and annealing. The EHEA developed a novel hierarchical microstructure featured by fine lamellar regions consisting of FCC lamellae filled with ultrafine FCC grains (average size ~200–250 nm) and B2 lamellae, and coarse non-lamellar regions consisting of ultrafine FCC (average size ~200–250 nm), few coarse recrystallized FCC grains and rather coarse unrecrystallized B2 phase (~2.5 µm). This complex and hierarchical microstructure originated from differences in strain-partitioning amongst the constituent phases, affecting the driving force for recrystallization. The hierarchical microstructure of the cryo-rolled and annealed material resulted in simultaneous enhancement in strength (Yield Strength/YS: 1437 ± 26 MPa, Ultimate Tensile Strength/UTS: 1562 ± 33 MPa) and ductility (elongation to failure/ef ~ 14 ± 1%) as compared to the as-cast as well as cold-rolled and annealed materials. The present study for the first time demonstrated that cryo-deformation and annealing could be a novel microstructural design strategy for overcoming strength-ductility trade off in multiphase high entropy alloys.
Ceramic Microbial Fuel Cells Stack: power generation in standard and supercapacitive mode
Authors: Santoro Carlo , Flores-Cadengo Cristina , Soavi Francesca , Kodali Mounika , Merino-Jimenez Irene , Gajda Iwona , Greenman John , Ieropoulos Ioannis , Atanassov Plamen
Published: February 2018

In this work, a microbial fuel cell (MFC) stack containing 28 ceramic MFCs was tested in both standard and supercapacitive modes. The MFCs consisted of carbon veil anodes wrapped around the ceramic separator and air-breathing cathodes based on activated carbon catalyst pressed on a stainless steel mesh. The anodes and cathodes were connected in parallel. The electrolytes utilized had different solution conductivities ranging from 2.0 mScm−1 to 40.1 mScm−1, simulating diverse wastewaters. Polarization curves of MFCs showed a general enhancement in performance with the increase of the electrolyte solution conductivity. The maximum stationary power density was 3.2 mW (3.2 Wm−3) at 2.0 mScm−1 that increased to 10.6 mW (10.6 Wm−3) at the highest solution conductivity (40.1 mScm−1). For the first time, MFCs stack with 1 L operating volume was also tested in supercapacitive mode, where full galvanostatic discharges are presented. Also in the latter case, performance once again improved with the increase in solution conductivity. Particularly, the increase in solution conductivity decreased dramatically the ohmic resistance and therefore the time for complete discharge was elongated, with a resultant increase in power. Maximum power achieved varied between 7.6 mW (7.6 Wm−3) at 2.0 mScm−1 and 27.4 mW (27.4 Wm−3) at 40.1 mScm−1.
Consequences of SPAK inactivation on Hyperkalemic Hypertension caused by WNK1 mutations: evidence for differential roles of WNK1 and WNK4
Authors: Rafael Chloé , Soukaseum Christelle , Baudrie Véronique , Frère Perrine , Hadchouel Juliette
Published: February 2018

Mutations of the gene encoding WNK1 [With No lysine (K) kinase 1] or WNK4 cause Familial Hyperkalemic Hypertension (FHHt). Previous studies have shown that the activation of SPAK (Ste20-related Proline/Alanine-rich Kinase) plays a dominant role in the development of FHHt caused by WNK4 mutations. The implication of SPAK in FHHt caused by WNK1 mutation has never been investigated. To clarify this issue, we crossed WNK1+/FHHt mice with SPAK knock-in mice in which the T-loop Thr243 residue was mutated to alanine to prevent activation by WNK kinases. We show that WNK1+/FHHT:SPAK
243A/243A
mice display an intermediate phenotype, between that of control and SPAK
243A/243A
mice, with normal blood pressure but hypochloremic metabolic alkalosis. NCC abundance and phosphorylation levels also decrease below the wild-type level in the double-mutant mice but remain higher than in SPAK
243A/243A
mice. This is different from what was observed in WNK4-FHHt mice in which SPAK inactivation completely restored the phenotype and NCC expression to wild-type levels. Although these results confirm that FHHt caused by WNK1 mutations is dependent on the activation of SPAK, they suggest that WNK1 and WNK4 play different roles in the distal nephron.
Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7
Authors: Liu Haolin , Wang Chao , Lee Schuyler , Ning Fangkun , Wang Yang , Zhang Qianqian , Chen Zhongzhou , Zang Jianye , Nix Jay , Dai Shaodong , Marrack Philippa , Hagman James , Kappler John , Zhang Gongyi
Published: February 2018

We have reported that JMJD5 and JMJD7 (JMJD5/7) are responsible for the clipping of arginine methylated histone tails to generate “tailless nucleosomes”, which could release the pausing RNA polymerase II (Pol II) into productive transcription elongation. JMJD5/7 function as endopeptidases that cleave histone tails specifically adjacent to methylated arginine residues and continue to degrade N-terminal residues of histones via their aminopeptidase activity. Here, we report structural and biochemical studies on JMJD5/7 to understand the basis of substrate recognition and catalysis mechanism by this JmjC subfamily. Recognition between these enzymes and histone substrates is specific, which is reflected by the binding data between enzymes and substrates. High structural similarity between JMJD5 and JMJD7 is reflected by the shared common substrates and high binding affinity. However, JMJD5 does not bind to arginine methylated histone tails with additional lysine acetylation while JMJD7 does not bind to arginine methylated histone tails with additional lysine methylation. Furthermore, the complex structures of JMJD5 and arginine derivatives revealed a Tudor domain-like binding pocket to accommodate the methylated sidechain of arginine, but not lysine. There also exists a glutamine close to the catalytic center, which may suggest a unique imidic acid mediated catalytic mechanism for proteolysis by JMJD5/7.