bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery
Authors: Tripodi Andrea Angelo Pierluigi , Ranđelović Ivan , Biri-Kovács Beáta , Szeder Bálint , Mező Gábor , Tóvári József
Published: December 2019

Among various homing devices, peptides containing the NGR tripeptide sequence represent a promising approach to selectively recognize CD13 receptor isoforms on the surface of tumor cells. They have been successfully used for the delivery of various chemotherapeutic drugs to tumor vessels. Here, we report on the murine plasma stability, in vitro andin vivoantitumor activity of our recently described bioconjugates containing daunorubicin as payload. Furthermore, CD13 expression of KS Kaposi’s Sarcoma cell line and HT-29 human colon carcinoma cell line was investigated. Flow cytometry studies confirm the fast cellular uptake resulting in the rapid delivery of the active metabolite Dau = Aoa-Gly-OH to tumor cells. The increased in vitro antitumor effect might be explained by the faster rearrangement from NGR toisoDGR in case of conjugate2(Dau = Aoa-GFLGK(c[NleNGRE]-GG)-NH2) in comparison with conjugate1(Dau = Aoa-GFLGK(c[KNGRE]-GG)-NH2). Nevertheless, results indicated that both conjugates showed significant effect on inhibition of proliferation in the primary tumor and also on blood vessel formation making them a potential candidate for targeting angiogenesis processes in tumors where CD13 and integrins are involved.
Effect of Smartphone-Based Telemonitored Exercise Rehabilitation among Patients with Coronary Heart Disease
Authors: Song Yanxin , Ren Chuan , Liu Ping , Tao Liyuan , Zhao Wei , Gao Wei
Published: December 2019

The aim of this study was to investigate the effects of telemonitored exercise rehabilitation on patients with coronary heart disease (CHD) in China. Ninety-six patients with stable CHD were included and analyzed (48 in telemonitored group and 48 in control group). All patients received routine follow-up, and patients in telemonitored group participated in smartphone-based telemonitored cardiac rehabilitation. Patients’ demographic information, medical history, diagnosis and treatment of CHD, and laboratory results were collected. The difference of cardiopulmonary exercise testing (CPET), blood test, and echocardiographic parameters; exercise habits; control rate of blood lipid and blood glucose; and incidence of adverse events between the two groups during 6 months of follow-up was analyzed. After intervention, the subjects in the telemonitored group performed significantly better in VO2peak, exercise compliance, and some other parameters than those in the control group. Telemonitored exercise rehabilitation is an effective rehabilitation mode for CHD patients in China.
Geothermal sources and utilization practice in six countries along the southern part of the Pannonian basin
Authors: Rman Nina , Bălan Lidia-Lenuța , Bobovečki Ivana , Gál Nóra , Jolović Boban , Lapanje Andrej , Marković Tamara , Milenić Dejan , Skopljak Ferid , Rotár-Szalkai Ágnes , Samardžić Natalija , Szőcs Teodóra , Šolaja Dragana , Toholj Nenad , Vijdea Anca-Marina , Vranješ Ana
Published: December 2019

Data on thermal water sources with outflow temperature of 30 °C and above were analyzed from the N-ern parts of Bosnia and Herzegovina, Serbia and Croatia, S-ern parts of Hungary, W-ern parts of Romania, and NE-ern parts of Slovenia, altogether from an area of 99,347 km2. The overview identified 771 geothermal sources; only 7 were thermal springs. The average well depth is about 1.2 km. About 13% of wells are younger than 10 years, additional 17% below 30 years; while 26% are older than 50 years. Average thermal water outflow temperature is 54 °C being the highest, 170 °C, in Croatia. Most thermal water is produced from basin fill sediments—Lower and Upper Pannonian (Mio-Pliocene) loose sandstones which are tapped by 86% of wells. The rest appertains to basement rocks—fissured, fractured and karstified Paleozoic, Mesozoic and Middle Miocene metamorphic, carbonate and siliciclastic rocks. In total, 72% sources hold water rights, 6% mining rights, 2% geothermal rights and 1% has no rights. The permits allow much higher water abstraction as currently listed. Usage for bathing and balneology encompasses 24% of all active sources (155), some of these also with heating (23). 104 objects (16%) are used for heating, also district heating (13) and individual space heating (3). An additional 10% (70) are used in agriculture, mainly greenhouse heating. There are 41 reinjection wells (5%). It is primarily in Hungary that drinking water (17%), industrial usage (5%) and monitoring wells (2%) are also common.
The utility of failure: a taxonomy for research and scholarship
Authors: Young Meredith
Published: December 2019

Introduction Health professions education (HPE) research and scholarship utilizes a range of methodologies, traditions, and disciplines. Many conducting scholarship in HPE may not have had the opportunity to consider the value of a well-designed but failed scholarly project, benefitted from role-modelling of the value of failure, nor have engaged with the common nature of failure in research and scholarship.

Methods Drawing on key concepts from philosophy of science, this piece describes the necessity and benefit of failure in research and scholarship, presents a taxonomy of failure relevant to HPE research, and applies this taxonomy to works published in the Perspectives on Medical Education failures/surprises series.

Results I propose three forms of failure relevant to HPE scholarship: innovation-driven, discovery-oriented, and serendipitous failure. Innovation-driven failure was the most commonly represented type of failure in the failures/surprises section, and discovery-oriented the least common.

Conclusions Considering failure in research and scholarship, four conclusions are drawn. First, failure is integral to research and scholarship—it is how theories are refined, discoveries are made, and innovations are developed. Second, we must purposefully engage with the opportunities that failure provide—understanding why a particular well-designed project failed is an opportunity for further insight. Third, we must engage publicly with failure in order to better communicate and role model the complexities of executing scholarship or innovating in HPE. Fourth, in order to make failure truly an opportunity for growth, we must, as a community, humanize and normalize failure as part of a productive scholarly approach.
The multi-scale nature of the solar wind
Authors: Verscharen Daniel , Klein Kristopher G. , Maruca Bennett A.
Published: December 2019

The solar wind is a magnetized plasma and as such exhibits collective plasma behavior associated with its characteristic spatial and temporal scales. The characteristic length scales include the size of the heliosphere, the collisional mean free paths of all species, their inertial lengths, their gyration radii, and their Debye lengths. The characteristic timescales include the expansion time, the collision times, and the periods associated with gyration, waves, and oscillations. We review the past and present research into the multi-scale nature of the solar wind based on in-situ spacecraft measurements and plasma theory. We emphasize that couplings of processes across scales are important for the global dynamics and thermodynamics of the solar wind. We describe methods to measure in-situ properties of particles and fields. We then discuss the role of expansion effects, non-equilibrium distribution functions, collisions, waves, turbulence, and kinetic microinstabilities for the multi-scale plasma evolution.
Odd bedfellows: how choice architecture can enhance autonomy and mitigate inequality
Authors: TULLY KENDRA
Published: December 2019

The concept and use of choice architecture in public policy arouses warranted suspicion among scholars and the general public. Liberal scholars fear that without limitations, the contemporary wave of nudge theory and policies threaten individual autonomy. In this paper, I argue that the use of choice architecture in particular policy areas can not only enhance individual autonomy, but also work to mitigate larger social inequalities. Research demonstrates that too much choice leads to ‘choice paralysis’, especially in instances where knowledge is low and stakes are high. By limiting and nudging choices in these contexts, individuals are likely to feel less overwhelmed and more in control. A stronger sense of control and additional resources elevates the experience of autonomy felt by vulnerable populations (those with low knowledge and resources). This paper offers a theoretically robust defense of choice architecture by examining the relationship between choice architecture and autonomy.
How Individuals Constitute Group Agents
Authors: Harris Keith
Published: December 2019

Several social metaphysicians have argued that groups are constituted by, but not identical to, their members. While the constitution view is promising, there are significant difficulties with existing versions of that view. Fortunately, lessons may be extracted from more traditional metaphysics and applied to the case of group agents. Drawing on such lessons, I present a novel account of the constitution relation holding between individuals and group agents. According to the resulting structural-constitution view, when individuals constitute a group of a certain kind, they do so in virtue of exhibiting the structure characteristic of groups of that kind.
Exploring sample size limits of AMS gas Ion Source 14C analysis at Cologneams
Authors: Melchert Jan Olaf , Stolz Alexander , Dewald Alfred , Gierga Merle , Wischhöfer Philipp , Rethemeyer Janet
Published: December 2019

Increasing demands for small-scale radiocarbon (14C) analyses required the installation of a “SO-110 B” type ion source (HVE Europa B.V.) at our 6 MV Tandetron AMS (HVE) dedicated for the direct injection of CO2 using either the gas injection system (GIS) from Ionplus AG or a EuroVector EA 3000 elemental analyzer (EA). We tested both systems with multiple series of 14C-free and modern standards (2.5–50 µg C) combusted in quartz ampoules or EA containers and were able to quantify exogenous C introduced. In EA-GIS-AMS analysis exogenous C is mainly derived from the EA sample containers. Blank values for 50 µg C combusted in solvent-cleaned tin (Sn) vessels were 0.0127 ± 0.0012 F14C (boats) and 0.0090 ± 0.0010 F14C (capsules), while they were much higher for thermally cleaned silver (Ag) capsules. The processing of gas samples for GIS-AMS yields similar blank values corresponding to 0.30 ± 0.08 µg exogenous C with 0.93 ± 0.23 F14C consisting of 0.28 µg C modern and 0.02 µg C fossil C. The combustion of larger amounts of blank material (1 mg C) in a single quartz tube split into aliquots gives lower blanks (0.0064 ± 0.0008 F14C; 50 µg C). Thus, 14C analysis of small, gaseous samples is now possible at CologneAMS.
The characteristics of glucose homoeostasis in grass carp and Chinese longsnout catfish after oral starch administration: a comparative study between herbivorous and carnivorous species of fish
Authors: Su Jingzhi , Gong Yulong , Mei Lingyu , Xi Longwei , Chi Shuyan , Yang Yunxia , Jin Junyan , Liu Haokun , Zhu Xiaoming , Xie Shouqi , Han Dong
Published: December 2019

An oral starch administration trial was used to evaluate glucose homoeostasis in grass carp (Ctenopharyngodon idella) and Chinese longsnout catfish (Leiocassis longirostrisGünther). Fish were administered with 3 g of a water and starch mixture (with 3:2 ratio) per 100 g body weight after fasting for 48 h. Fish were sampled at 0, 1, 3, 6, 12, 24 and 48 h after oral starch administration. In grass carp, plasma levels of glucose peaked at 3 h but returned to baseline at 6 h. However, in Chinese longsnout catfish, plasma glucose levels peaked at 6 h and returned to baseline at 48 h. The activity of intestinal amylase was increased in grass carp at 1 and 3 h, but no significant change in Chinese longsnout catfish was observed. The activity of hepatic glucose-6-phosphatase fell significantly in grass carp but change was not evident in Chinese longsnout catfish. The expression levels and enzymic activity of hepatic pyruvate kinase increased in grass carp, but no significant changes were observed in the Chinese longsnout catfish. Glycogen synthase (gys) and glycogen phosphorylase (gp) were induced in grass carp. However, there was no significant change ingysand a clear down-regulation ofgpin Chinese longsnout catfish. In brief, compared with Chinese longsnout catfish, grass carp exhibited a rapid increase and faster clearance rate of plasma glucose. This effect was closely related to significantly enhanced levels of digestion, glycolysis, glycogen metabolism and glucose-induced lipogenesis in grass carp, as well as the inhibition of gluconeogenesis.
A simple molecular identification method of theThrips tabaci(Thysanoptera: Thripidae) cryptic species complex
Authors: Farkas Péter , György Zsuzsanna , Tóth Annamária , Sojnóczki Annamária , Fail József
Published: December 2019

The onion thrips (Thrips tabaciLindeman, 1889) is a key pest of a wide range of crops because of its ecological attributes such as polyphagy, high reproduction rate, ability to transmit tospoviruses and resistance to insecticides. Recent studies revealed thatT. tabaciis a cryptic species complex and it has three lineages (leek-associated arrhenotokous L1-biotype, leek-associated thelytokous L2-biotype and tobacco-associated arrhenotokous T-biotype), however, the adults remain indistinguishable.T. tabaciindividuals were collected from different locations of Hungary to create laboratory colonies from each biotypes. Mitochondrial COI (mtCOI) region was sequenced from morphologically identified individuals. After sequence analysis SNPs were identified and used for CAPS marker development, which were suitable for distinguishing the threeT. tabacilineages. Genetic analysis of theT. tabacispecies complex based on mtCOI gene confirmed the three well-known biotypes (L1, L2, T) and a new biotype because the new molecular evidence presented in this study suggests T-biotype ofT. tabaciforming two distinct (sub)clades (T1 and T2). This genetic finding indicates that the genetic variability ofT. tabacipopulations is still not fully mapped. We validated our developed marker on thrips individuals from our thrips colonies. The results demonstrated that the new marker effectively identifies the differentT. tabacibiotypes. We believe that our reliable genotyping method will be useful in further studies focusing onT. tabacibiotypes and in pest management by scanning the composition of sympatricT. tabacipopulations.
Previous herbivory alerts conspecific gravid sawflies to avoid unsuitable host plants
Authors: Valladares G. A. , Coll-Aráoz M. V. , Alderete M. , Vera M. T. , Fernández P. C.
Published: December 2019

The willow sawfly,Nematus oligospilus(Förster), is a pest inSalixcommercial forests and has been reported worldwide. Female adults must recognize a suitable host plant to oviposit, since her offspring lack the ability to move to another host. We evaluated the effect of conspecific herbivory on the oviposition choices ofN. oligospilusfemales by providing damaged (DP) and undamaged (UP) plants ofSalix humboldtiana, a native willow from South America, as oviposition substrates. Local and systemic effects were studied. For the local treatment, a twig from the DP with damaged leaves was contrasted to a twig from a UP in dual choice experiments. For systemic treatment, a twig from the DP with intact leaves was contrasted to a twig from a UP. We estimated the use of olfactory and contact cues by comparing volatile emission of DP and UP, and by analysing the behaviour of the females during host recognition after landing on the leaf surface. In the context of the preference–performance hypothesis (PPH), we also tested if oviposition site selection maximizes offspring fitness by evaluating neonate hatching, larval performance and survival of larvae that were born and bred on either DP or UP. Our results demonstrate that previous conspecific herbivory onS. humboldtianahas a dramatic impact on female oviposition choices and offspring performance of the sawflyN. oligospilus.Females showed a marked preference for laying eggs on UP ofS. humboldtiana.This preference was found for both local and systemic treatments. Volatile emission was quantitatively changed after conspecific damage suggesting that it could be related toN. oligospilusavoidance. In the dual choice preference experiments, the analysis of the behaviour of the females once landing on the leaf surface suggested the use of contact cues triggering egg laying on leaves from UP and avoidance of leaves from DP. Furthermore, 48 h of previous conspecific feeding was sufficient to dramatically impair neonate hatching, as well as larval development and survival, suggesting a rapid and effective reaction of the induced resistance mechanisms of the tree. In agreement with the PPH, these results support the idea that decisions made by colonizing females may result in optimal outcomes for their offspring in a barely studied insect model, and also opens the opportunity for studying tree-induced defences in the unexplored South American willowS. humboldtiana.
Potassium rates on the cationic balance of an Oxisol and soybean nutritional status after 8 years of K deprivation
Authors: Firmano Ruan Francisco , de Oliveira Adilson , de Castro Cesar , Alleoni Luís Reynaldo Ferracciú
Published: December 2019

Highly weathered soils from humid tropics naturally have low contents of available potassium (K) to plants. Under these conditions, the K deprivation can change the equilibrium among cations in the soil and the nutritional status of some crops as soybean (Glycine max (L.) Merrill). A field experiment related to K fertilisation, spring soybean and diverse species of fall/winter crops, such as wheat (Triticum aestivum L.), corn (Zea mays L.), sunflower (Helianthus annuus L.) or oat (Avena strigosa L.), has been carried out in Southern Brazil since 1983. The K deprivation for 8 years reduced soybean grain yield and the K contents in soil and plant tissues. K extractants, such as Mehlich-1 and ion exchange resins, had diverse sensitivities with the variation in the K exchangeable contents induced by K rates. The increased soil K content after K fertilisation reduced calcium (Ca) and magnesium (Mg) contents in index leaves and altered its contents in the soil extracted by 1 mol L−1 KCl and ion exchange resins. Among the micronutrients, only B contents changed due to increased K rates, and had significant correlations with K and Ca contents in index leaves. The calculated Diagnosis and Recommendation Integrated System (DRIS) indices were compatible with soybean yield and K contents in soybean index leaves.
The inhibitory action mode of nitrocompounds on in vitro rumen methanogenesis: a comparison of nitroethane, 2-nitroethanol and 2-nitro-1-propanol
Authors: Zhang Z. W. , Wang Y. L. , Wang W. K. , Li Y. H , Cao Z. J. , Li S. L. , Yang H. J.
Published: December 2019

Nitroethane (NE), 2-nitroethanol (NEOH) and 2-nitro-1-propanol (NPOH) were investigated in order to determine their inhibitory effects on in vitro ruminal fermentation and methane (CH4) production of a hay-rich substrate (alfalfa hay: maize meal = 4:1, w/w). The rumen liquor collected from cannulated Holstein dairy cows was incubated at 39 °C for 72 h. The addition of NE, NEOH and NPOH slowed down the fermentation process and notably decreased molar CH4 proportion by 96.8, 96.4 and 35.0%, respectively. The abundance of total methanogen and methanogens from the order Methanobacteriales were all decreased with NE, NEOH and NPOH supplementation. Meanwhile, the nitrocompound addition reduced mcrA gene expression, coenzyme F420 and F430 contents. The correlation analysis showed that CH4 production was correlated positively with the population abundance of total methanogens, Methanobacteriales, mcrA gene expression, coenzyme contents of F420 and F430. The nitrocompound addition decreased acetate concentration and increased propionate and butyrate concentrations in the culture fluid. In summary, both NE and NEOH addition presented nearly the same inhibitory effectiveness on in vitro CH4 production; they were more effective than NPOH. The results of the current study provide evidence that NE, NEOH and NPOH can dramatically decrease methanogen population, mcrA gene expression and the coenzyme content of F420 and F430 in ruminal methanogenesis.
“Shakespeare for All Times and Peoples”: Shakespeare at Spelman College and the Atlanta University Center
Authors: MAXWELL LYNN
Published: December 2019

In this paper I explore what it means to require Shakespeare at a historically black college by looking at Adrienne Herndon's 1906 essay “Shakespeare at Atlanta University” and W. E. B. Du Bois's Souls of Black Folk. Despite the frequent association of Shakespeare requirements with a conservative agenda, both Herndon and Du Bois imagine possibilities for powerful politics in the performance and study of Shakespeare. Reading these two texts together suggests that teaching, studying, and performing Shakespeare might still be powerful politics at black institutions.
Corporate Leverage and the Dynamics of Its Components
Authors: Hovakimian Armen , Hovakimian Gayané
Published: December 2019

We investigate the dynamics of observed and target leverage ratios and deviations from the targets. The cross-sectional persistence in leverage ratios is driven by persistent targets, whereas time-series variation is driven by transitory deviations from targets. Consistent with dynamic trade-off theories, persistence is higher when the costs of deviating from targets are lower and when the adjustment costs are higher. Deviations are less persistent for firms that are over-levered and firms that are smaller, younger, or more focused or that have lower credit ratings. In recessions, excess leverage is less persistent for larger firms and is more persistent for smaller firms.
Distribution and assessment of the conservation status ofErioderma pedicellatumin Asia
Authors: TAGIRDZHANOVA Gulnara , STEPANCHIKOVA Irina S. , HIMELBRANT Dmitry E. , VYATKINA Marina P. , DYOMINA Aleksandra V. , DIRKSEN Veronika G. , SCHEIDEGGER Christoph
Published: December 2019

The first detailed survey is presented of a recently discovered population ofErioderma pedicellatum, a globally rare lichen, in the primeval spruce forests of the Kamchatka Peninsula, Russia. Three subpopulations are described, located in the Levaya Schapina River basin, in the Kimitina River basin, and on the slopes of the extinct volcano, Nikolka. In total, we observed 1894 thalli on 167 Yezo spruce trunks. In Kamchatka,E. pedicellatumoccurs exclusively on bark-covered spruce twigs of mainly young and dwarf-stressed older trees. We discovered a high number of juvenile thalli, which suggests that this population is reproducing. However, its habitat is declining because spruce forests in the region are the target of industrial clear-cutting and there is a high incidence of forest fires. Over the next 60 years, which corresponds to three generations ofE. pedicellatum, we infer that continued habitat loss will induce a 48% decline in these lichen populations. As a result of our analyses, the Asian population is classified as ‘Vulnerable’, based on IUCN Red List criteria.
GraphisandAllographa(lichenized Ascomycota:Graphidaceae) in Sri Lanka, with six new species and a biogeographical comparison investigating a potential signature of the ‘biotic ferry’ species interchange
Authors: WEERAKOON Gothamie , APTROOT André , LÜCKING Robert , ARACHCHIGE Omal , WIJESUNDARA Siril
Published: December 2019

We provide an updated survey for Sri Lanka of species ofGraphis sensuStaiger, recently divided intoGraphiss. str. andAllographa, including brief descriptions and a key to all 124 species currently known. Six new species are described:Allographa bambusicolaWeerakoon, Lücking & Aptroot, a bambusicolousAllographawith entire labia, a laterally carbonized excipulum, 80–100 × 15–17 µm large, muriform ascospores and a rather thick, irregularly verrucose lateral thalline margin of the lirellae;A. weerasooriyanaWeerakoon, Arachchige & Lücking, a corticolousAllographaresemblingA. rusticaKremp. in overall anatomy and chemistry, but with a verrucose thalline margin of the lirellae and labia not distinctly raised above the thalline margin;Graphis flosculiferaWeerakoon, Lücking & Aptroot, a corticolousGraphisresemblingG. insulanabut differing in the unique disposition of the lirellae and the slightly more elongate ascospores;G. rajapakshanaWeerakoon, Lücking & Aptroot, a corticolousGraphisresemblingG. desquamescens, including in ascospore size, but with lirellae with a distinct lateral thalline margin;G. rimosothallinaWeerakoon, Lücking & Aptroot, a corticolousGraphiswith a thick, uneven, rimose thallus andFissurina-like lirellae, a completely carbonized excipulum and transversely 7-septate ascospores, 32–37 × 8–10 µm; andG. thunsinhalayensisWeerakoon, Arachchige & Lücking, a corticolousGraphisresemblingG. subalbostriatabut with smaller ascospores and lacking white lines between the striae of the labia. We also validate the nameG. verrucoserpensLücking. A total of 106 species are reported here for the first time from Sri Lanka. A biogeographical comparison with two other well-sampled countries (Costa Rica and Thailand) revealed a significantly higher similarity in species composition with Costa Rica than between Thailand and Costa Rica, suggesting a potential signature of the ‘biotic ferry’ hypothesis, that is the migration of lineages from Gondwana (partly corresponding to the modern Neotropics) via the north-eastwards drifting Indian subcontinent and subsequent interchange with Laurasia (partly corresponding to the modern eastern Paleotropics). However, the evolutionary timeline of the clades involved does not support this hypothesis and suggests an alternative explanation of geologically more recent mid- to long-distance dispersal.
New species and first records of Eremothecella (Arthoniales) from the Andaman and Nicobar Islands, India
Authors: JAGADEESH RAM T. A. M. , SINHA G. P.
Published: December 2019

Five species of Eremothecella are recorded from the Andaman Islands, two of which are described as new: Eremothecella ajaysinghii Jagad. Ram & G. P. Sinha and E. nicobarica Jagad. Ram & G. P. Sinha. Eremothecella ajaysinghii has whitish grey, pruinose ascomata and 8–10(–11)-septate ascospores, while E. nicobarica has non-pruinose ascomata and (14–)15–17-septate ascospores. Eremothecella calamicola Syd., E. macrosperma (Zahlbr.) Sérus. and E. variratae (Aptroot & Sipman) Sérus. are reported as new records for India. An updated worldwide key to species of the genus is presented.
Staurothele nemorumsp. nov. (Ascomycota:Verrucariaceae), with a revised key to North AmericanStaurotheles. lat.
Authors: MORSE Caleb A. , LADD Douglas
Published: December 2019

Staurothele nemorumis described as new to science from the southern Great Plains of central North America. The species is characterized by a thin, areolate, epilithic thallus, sessile perithecia, globose to oblong hymenial algal cells and 8-spored asci.Staurothele hymenogoniais restored to the North American flora, based on material from the south-western Great Plains. An updated key to North American members ofStaurotheles. lat. is provided.
Strongholds of Ostrea edulis populations in estuaries in Essex, SE England and their association with traditional oyster aquaculture: evidence to support a MPA designation
Authors: Allison Sarah , Hardy Malcolm , Hayward Kate , Cameron Tom C. , Underwood Graham J. C.
Published: December 2019

The flat oyster Ostrea edulis has declined significantly in European waters since the 1850s as a result of anthropogenic activity. Ostrea edulis was designated a UK Biodiversity Action Plan Species and Habitat in 1995, and as a Feature of Conservation Importance (FOCI) within the UK Marine & Coastal Access Act 2009. To promote the recovery of oyster beds, a greater understanding of its abundance and distribution is required. Distribution of O. edulis across the proposed Blackwater, Crouch, Roach and Colne MCZ in Essex was determined between 2008 and 2012. Ostrea edulis were present in four estuary zones; with highest sample abundance in the Blackwater and Ray Sand zones. Size structure of populations varied, with the Ray Sand and Colne zones showing a significant lack of individuals with shell height <39 mm. Ostrea edulis occurred in highest number on shell substratum, followed by silty sediments. There were no significant associations between O. edulis abundance or size structure with water column Chl a, suspended solids, oxygen, nitrate or ammonium concentrations, temperature or pH. Highest abundance and most equitable population shell-size distribution for O. edulis were located within, or adjacent to, actively managed aquaculture zones. This suggests that traditional seabed management contributed to the maintenance or recovery of the species of conservation concern. Demonstration that the Essex estuaries were a stronghold for Ostrea edulis in the southern North sea area led to the designation of the Blackwater, Crouch, Roach and Colne estuaries Marine Conservation Zone in 2013.
Living with dementia: the felt worth of support workers
Authors: Hale Leigh Anne , Jenkins Matthew Lee , Mayland Beth , Buttery Yvette , Norris Pauline , Butler Mary , Holland Michelle , Ngocha-Chaderopa Esther , McKenzie-Green Barbara , Czuba Karol , Sezier Ann , Kayes Nicola
Published: December 2019

Considering the important role that paid support workers play in care of older people with dementia, it is vital that researchers and relevant organisations understand the factors that lead to them feeling valued for the work that they do, and the consequences of such valuing (or lack thereof). The current study employed semi-structured interviews to understand the individual experiences of 15 support workers based both in residential care homes and private homes. The General Inductive Approach was used to analyse the interview transcriptions and to develop a conceptual model that describes the conditions that lead to support workers feeling valued for the work that they do. This model consists of organisational or individual strategies, the context in which support work takes place, and various interactions, actions and intervening conditions that facilitate or prevent support workers feeling valued. A significant finding in this research was the role of interpersonal relationships and interactions which underlie all other aspects of the conceptual model developed here. By understanding the importance of how employers, families of older adults with dementia and peers interact with support workers, we may promote not only the quality of work that support workers deliver, but also the wellbeing of the support workers themselves.
Conservation status of the threatened and endemic Rufous-throated DipperCinclus schulziin Argentina
Authors: POLITI NATALIA , MARTINUZZI SEBASTIÁN , ARAGÓN PATRICIA SARDINA , MIRANDA VERÓNICA , ALBANESI SEBASTIÁN , PUECHAGUT PATRICIA , RADELOFF VOLKER C. , PIDGEON ANNA , RIVERA LUIS
Published: December 2019

The Rufous-throated DipperCinclus schulziis endemic to the Southern Yungas of north-western Argentina and southern Bolivia. The species is categorised as ‘Vulnerable’ on the IUCN Red List on the basis of small population size and restricted range. The purpose of our study was to determine the distribution of potentially suitable habitat for the Rufous-throated Dipper, estimate its population size, and assess potential distribution within strict protected areas, in north-western Argentina. We surveyed 44 rivers in the Southern Yungas of Argentina from 2010 to 2013 to determine dipper density (i.e. the number of individuals detected per km surveyed). The dipper’s potential distribution was assessed using a maximum entropy modeling approach based on 31 occurrence points and eight bioclimatic and two topographic variables as predictors. The species is dependent on mountain forest rivers, so the potential distribution was restricted to rivers. We estimated dipper population size by multiplying density by the potential distribution along rivers. Finally, we calculated the extent of suitable habitat contained within the boundaries of Argentina´s National Parks. Dipper density was 0.94 ± 1.55 individuals/km. We estimate that within north-west Argentina there are ~2,815 km of river that are potential habitat, with an area of occupancy of 141 km2and a population size of 2,657 ± 4,355 dippers. However, of this river extent, less than 5% is within National Parks. Our results highlight the need to create new and to enlarge existing National Parks that protect the potentially suitable habitat of the species. Although more information is needed for Bolivia, the country-level area of occupancy and population size of the dipper found in Argentina provides strong evidence that the IUCN Red List classification of this species as ‘Vulnerable’ is warranted.
X‐ray Signatures of Lightning‐Induced Electron Precipitation
Authors: Marshall R. A. , Xu W. , Sousa A. , McCarthy M. , Millan R.
Published: December 2019

We present detailed numerical modeling to predict expected X‐ray signatures from lightning‐induced electron precipitation (LEP) events. Simulations include the transionospheric propagation of the lightning electromagnetic pulse; ray tracing through the magnetosphere, including Landau damping; wave‐particle interactions resulting in loss cone fluxes; and Monte Carlo simulation of the electron precipitation process, including bremsstrahlung photon production and propagation to a balloon observing platform. Modeling is included to show that our simulated events are consistent with subionospheric very low frequency observations of LEP. Simulations show that these events should be observable from balloon‐based platforms. The modeled LEP event signatures, including X‐ray flux, spectrum, and pulse shape, are then compared with observations of energetic X‐ray pulses from the Balloon Array for Radiation‐belt Relativistic Electron Losses 1U balloon taken in January 2013 and are shown to be highly consistent with the observations. The pulses were observed near
, while the balloon was off the coast of Antarctica at about 70°S, 5–20°W. Correlations with GOES imagery and global lightning data, together with analysis of the temporal and spectral signatures of these pulses, led to the initial suggestion that these events could be signatures of LEP. However, for only a fraction of these events could a causative lightning discharge be identified in global lightning data sets. This poor correlation may be partially attributed to causative strokes being missed by the global lightning networks; nonetheless, we discuss other possible explanations for these events.
Contribution of Anisotropic Electron Current to the Magnetotail Current Sheet as a Function of Location and Plasma Conditions
Authors: Artemyev A. V. , Angelopoulos V. , Vasko I. Y. , Petrukovich A. A. , Runov A. , Saito Y. , Avanov L. A. , Giles B. L. , Russell C. T. , Strangeway R. J.
Published: December 2019

The magnetotail current sheet carries the current responsible for the largest fraction of the energy storage in the magnetotail, the magnetic energy in the lobes. It is thus inextricably linked with the dynamics and evolution of many magnetospheric phenomena, such as substorms. The magnetotail current sheet structure and stability depend mostly on the kinetic properties of the plasma populating the magnetotail. One of the most underinvestigated properties of this plasma is electron temperature anisotropy, which may contribute a large fraction of the total current. Using observations from five missions in the magnetotail, we examine the electron temperature anisotropy, Te‖/Te⊥, and its potential contribution to the current density, quantified by the firehose parameter (βe‖−βe⊥)/2, across y∈[−20,20]RE and x∈[−100,−10]RE. We find that a significant fraction (>30%) of all current sheets have an anisotropic electron current density >10% of the total current. These current sheets form two distinct groups: (1) near‐Earth (<30 RE) accompanied by weak plasma flows (<100 km/s) and enhanced equatorial magnetic field (>3 nT) and (2) middle tail (>40 RE) accompanied by fast plasma flows (>300 km/s) and small equatorial magnetic field (≤1 nT). For a significant number of near‐Earth current sheets, the anisotropic electron current can be >25% of the total current density. Our findings suggest that electron temperature anisotropy should be included in current sheet models describing realistic magnetotail structure and dynamics.
Bach2 deficiency leads autoreactive B cells to produce IgG autoantibodies and induce lupus through a T cell-dependent extrafollicular pathway
Authors: Jang Eunkyeong , Kim Un Kyo , Jang Kiseok , Song Young Soo , Cha Ji-Young , Yi Hansol , Youn Jeehee
Published: December 2019

Class-switched IgG autoantibodies but not unswitched IgM autoantibodies play a crucial role in the development of systemic lupus erythematosus (SLE). Bach2 is known to be essential for class switch recombination of Ig genes, but recent genomic and clinical studies have suggested an association of Bach2 deficiency with SLE. This study was undertaken to examine the mechanism by which Bach2 regulates the development of SLE. Despite defects in Ig class switch recombination and germinal center formation when actively immunized,Bach2−/−mice spontaneously accumulated IgG autoantibody-secreting cells without germinal center reactions in a regulatory T cell-independent manner, and this phenomenon was accompanied by manifestations akin to SLE. Transcriptome analyses revealed that Bach2 regulated the expression of genes related to germinal center formation and SLE pathogenesis in B cells. B cell-specific deletion of Bach2 was sufficient to impair the development of germinal center B cells but insufficient to promote the production of IgG autoantibodies. Bach2 deficiency caused CD4+T cells to overexpress Icos and differentiate into extrafollicular helper T cells in a cell-autonomous manner. These findings suggest that Bach2-deficient autoreactive B cells preferentially react at extrafollicular sites to give rise to IgG class-switched pathogenic plasma cells and that this effect requires the help of Bach2-Icoshihelper T cells. Thus, the cell-autonomous roles of Bach2 in B cells and in their cognate CD4+T cells are required to maintain self-tolerance against SLE.
Sandwich-structure transferable free-form OLEDs for wearable and disposable skin wound photomedicine
Authors: Jeon Yongmin , Choi Hye-Ryung , Kwon Jeong Hyun , Choi Seungyeop , Nam Kyung Mi , Park Kyoung-Chan , Choi Kyung Cheol
Published: December 2019

Free-form optoelectronic devices can provide hyper-connectivity over space and time. However, most conformable optoelectronic devices can only be fabricated on flat polymeric materials using low-temperature processes, limiting their application and forms. This paper presents free-form optoelectronic devices that are not dependent on the shape or material. For medical applications, the transferable OLED (10 μm) is formed in a sandwich structure with an ultra-thin transferable barrier (4.8 μm). The results showed that the fabricated sandwich-structure transferable OLED (STOLED) exhibit the same high-efficiency performance on cylindrical-shaped materials and on materials such as textile and paper. Because the neutral axis is freely adjustable using the sandwich structure, the textile-based OLED achieved both folding reliability and washing reliability, as well as a long operating life (>150 h). When keratinocytes were irradiated with red STOLED light, cell proliferation and cell migration increased by 26 and 32%, respectively. In the skin equivalent model, the epidermis thickness was increased by 39%; additionally, in organ culture, not only was the skin area increased by 14%, but also, re-epithelialization was highly induced. Based on the results, the STOLED is expected to be applicable in various wearable and disposable photomedical devices.
Cancer-educated mesenchymal stem cells promote the survival of cancer cells at primary and distant metastatic sites via the expansion of bone marrow-derived-PMN-MDSCs
Authors: Sai Buqing , Dai Yafei , Fan Songqing , Wang Fan , Wang Lujuan , Li Zheng , Tang Jingqun , Wang Li , Zhang Xina , Zheng Leliang , Chen Fei , Li Guiyuan , Xiang Juanjuan
Published: December 2019

Bone marrow mesenchymal stem cells (BMSCs) are multipotent stromal cells that can differentiate into a variety of cell types. BMSCs are chemotactically guided towards the cancer cells and contribute to the formation of a cancer microenvironment. The homing of BMSCs was affected by various factors. Disseminated tumour cells (DTCs) in distant organs, especially in the bone marrow, are the source of cancer metastasis and cancer relapse. DTC survival is also determined by the microenvironment. Here we aim to elucidate how cancer-educated BMSCs promote the survival of cancer cells at primary tumour sites and distant sites. We highlight the dynamic change by identifying different gene expression signatures in intratumoral BMSCs and in BMSCs that move back in the bone marrow. Intratumoral BMSCs acquire high mobility and displayed immunosuppressive effects. Intratumoral BMSCs that ultimately home to the bone marrow exhibit a strong immunosuppressive function. Cancer-educated BMSCs promote the survival of lung cancer cells via expansion of MDSCs in bone marrow, primary tumour sites and metastatic sites. These Ly6G+ MDSCs suppress proliferation of T cells. CXCL5, nitric oxide and GM-CSF produced by cancer-educated BMSCs contribute to the formation of malignant microenvironments. Treatment with CXCL5 antibody, the iNOS inhibitor 1400w and GM-CSF antibody reduced MDSC expansion in the bone marrow, primary tumour sites and metastatic sites, and promoted the efficiency of PD-L1 antibody. Our study reveals that cancer-educated BMSCs are the component of the niche for primary lung cancer cells and DTCs, and that they can be the target for immunotherapy.
Mitochondria ubiquitin ligase, MARCH5 resolves hepatitis B virus X protein aggregates in the liver pathogenesis
Authors: Yoo Young-Suk , Park Yeon-Ji , Lee Ho-Soo , Oanh Nguyen Thi Kim , Cho Mi-Young , Heo June , Lee Eun-Seo , Cho Hyeseon , Park Yong-Yea , Cho Hyeseong
Published: December 2019

Infection of hepatitis B virus (HBV) increase the incidence of chronic liver disease and hepatocellular carcinoma (HCC). The hepatitis B viral x (HBx) protein encoded by the HBV genome contributes to the pathogenesis of HCC and thus, negative regulation of HBx is beneficial for the alleviation of the disease pathogenesis. MARCH5 is a mitochondrial E3 ubiquitin ligase and here, we show that high MARCH5 expression levels are correlated with improved survival in HCC patients. MARCH5 interacts with HBx protein mainly accumulated in mitochondria and targets it for degradation. The N-terminal RING domain of MARCH5 was required for the interaction with HBx, and MARCH5H43W lacking E3 ligase activity failed to reduce HBx protein levels. High expression of HBx results in the formation of protein aggregates in semi-denaturing detergent agarose gels and MARCH5 mediates the elimination of protein aggregates through the proteasome pathway. HBx-induced ROS production, mitophagy, and cyclooxygenase-2 gene expression were suppressed in the presence of high MARCH5 expression. These results suggest MARCH5 as a target for alleviating HBV-mediated liver disease.
Permeability of membranes in the liquid ordered and liquid disordered phases
Authors: Ghysels An , Krämer Andreas , Venable Richard M. , Teague Walter E. , Lyman Edward , Gawrisch Klaus , Pastor Richard W.
Published: December 2019

The functional significance of ordered nanodomains (or rafts) in cholesterol rich eukaryotic cell membranes has only begun to be explored. This study exploits the correspondence of cellular rafts and liquid ordered (Lo) phases of three-component lipid bilayers to examine permeability. Molecular dynamics simulations of Lo phase dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol show that oxygen and water transit a leaflet through the DOPC and cholesterol rich boundaries of hexagonally packed DPPC microdomains, freely diffuse along the bilayer midplane, and escape the membrane along the boundary regions. Electron paramagnetic resonance experiments provide critical validation: the measured ratio of oxygen concentrations near the midplanes of liquid disordered (Ld) and Lo bilayers of DPPC/DOPC/cholesterol is 1.75 ± 0.35, in very good agreement with 1.3 ± 0.3 obtained from simulation. The results show how cellular rafts can be structurally rigid signaling platforms while remaining nearly as permeable to small molecules as the Ld phase.
Reanalysing genomic data by normalized coverage values uncovers CNVs in bone marrow failure gene panels
Authors: Lauhasurayotin Supanun , Cuvelier Geoff D. , Klaassen Robert J. , Fernandez Conrad V. , Pastore Yves D. , Abish Sharon , Rayar Meera , Steele MacGregor , Jardine Lawrence , Breakey Vicky R. , Brossard Josee , Sinha Roona , Silva Mariana , Goodyear Lisa , Lipton Jeffrey H. , Michon Bruno , Corriveau-Bourque Catherine , Sung Lillian , Shabanova Iren , Li Hongbing , Zlateska Bozana , Dhanraj Santhosh , Cada Michaela , Scherer Stephen W. , Dror Yigal
Published: December 2019

Inherited bone marrow failure syndromes (IBMFSs) are genetically heterogeneous disorders with cytopenia. Many IBMFSs also feature physical malformations and an increased risk of cancer. Point mutations can be identified in about half of patients. Copy number variation (CNVs) have been reported; however, the frequency and spectrum of CNVs are unknown. Unfortunately, current genome-wide methods have major limitations since they may miss small CNVs or may have low sensitivity due to low read depths. Herein, we aimed to determine whether reanalysis of NGS panel data by normalized coverage value could identify CNVs and characterize them. To address this aim, DNA from IBMFS patients was analyzed by a NGS panel assay of known IBMFS genes. After analysis for point mutations, heterozygous and homozygous CNVs were searched by normalized read coverage ratios and specific thresholds. Of the 258 tested patients, 91 were found to have pathogenic point variants. NGS sample data from 165 patients without pathogenic point mutations were re-analyzed for CNVs; 10 patients were found to have deletions. Diamond Blackfan anemia genes most commonly exhibited heterozygous deletions, and included RPS19, RPL11, and RPL5. A diagnosis of GATA2-related disorder was made in a patient with myelodysplastic syndrome who was found to have a heterozygous GATA2 deletion. Importantly, homozygous FANCA deletion were detected in a patient who could not be previously assigned a specific syndromic diagnosis. Lastly, we identified compound heterozygousity for deletions and pathogenic point variants in RBM8A and PARN genes. All deletions were validated by orthogonal methods. We conclude that careful analysis of normalized coverage values can detect CNVs in NGS panels and should be considered as a standard practice prior to do further investigations.
Publisher Correction: Sex-dependent dominance maintains migration supergene in rainbow trout
Authors: Pearse Devon E. , Barson Nicola J. , Nome Torfinn , Gao Guangtu , Campbell Matthew A. , Abadía-Cardoso Alicia , Anderson Eric C. , Rundio David E. , Williams Thomas H. , Naish Kerry A. , Moen Thomas , Liu Sixin , Kent Matthew , Moser Michel , Minkley David R. , Rondeau Eric B. , Brieuc Marine S. O. , Sandve Simen Rød , Miller Michael R. , Cedillo Lucydalila , Baruch Kobi , Hernandez Alvaro G. , Ben-Zvi Gil , Shem-Tov Doron , Barad Omer , Kuzishchin Kirill , Garza John Carlos , Lindley Steven T. , Koop Ben F. , Thorgaard Gary H. , Palti Yniv , Lien Sigbjørn
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.