bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preferential binding of a stable G3BP ribonucleoprotein complex to intron‐retaining transcripts in mouse brain and modulation of their expression in the cerebellum
Authors: Martin Sophie , Bellora Nicolas , González‐Vallinas Juan , Irimia Manuel , Chebli Karim , de Toledo Marion , Raabe Monika , Eyras Eduardo , Urlaub Henning , Blencowe Ben J. , Tazi Jamal 
Published: August 2016

AbstractNeuronal granules play an important role in the localization and transport of translationally silenced messenger ribonucleoproteins in neurons. Among the factors associated with these granules, the RNA‐binding protein G3BP1 (stress‐granules assembly factor) is involved in neuronal plasticity and is induced in Alzheimer's disease. We immunopurified a stable complex containing G3BP1 from mouse brain and performed high‐throughput sequencing and cross‐linking immunoprecipitation to identify the associated RNAs. The G3BP‐complex contained the deubiquitinating protease USP10, CtBP1 and the RNA‐binding proteins Caprin‐1, G3BP2a and splicing factor proline and glutamine rich, or PSF. The G3BP‐complex binds preferentially to transcripts that retain introns, and to non‐coding sequences like 3’‐untranslated region and long non‐coding RNAs. Specific transcripts with retained introns appear to be enriched in the cerebellum compared to the rest of the brain and G3BP1 depletion decreased this intron retention in the cerebellum of G3BP1 knockout mice. Among the enriched transcripts, we found an overrepresentation of genes involved in synaptic transmission, especially glutamate‐related neuronal transmission. Notably, G3BP1 seems to repress the expression of the mature Grm5 (metabotropic glutamate receptor 5) transcript, by promoting the retention of an intron in the immature transcript in the cerebellum. Our results suggest that G3BP is involved in a new functional mechanism to regulate non‐coding RNAs including intron‐retaining transcripts, and thus have broad implications for neuronal gene regulation, where intron retention is widespread.
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Gait in children and adolescents with Charcot‐Marie‐Tooth disease: a systematic review
Authors: Kennedy Rachel A. , Carroll Kate , McGinley Jennifer L. 
Published: August 2016

AbstractSymptoms of Charcot‐Marie‐Tooth (CMT) disease typically arise in childhood or adolescence with gait difficulty most common. A systematic review was conducted to synthesise, review, and characterise gait in paediatric CMT. Health‐related electronic databases were reviewed with search terms related to CMT and gait. Of 454 articles, 10 articles describing seven studies met eligibility criteria; samples ranged from 1 to 81, included mixed CMT sub‐types and had a participant mean age of 13 years. Assessments included a variety of methods to examine only barefoot gait. Heterogeneity of gait patterns was noted. Children and adolescents with CMT walked slower, most likely due to shorter stride length. Common kinematic and kinetic abnormalities included significant foot drop during swing, reduced calf muscle power, and proximal compensatory mechanisms in the lower limb. Little data were found to inform typical functional gait characteristics or change over time. Of note, barefoot assessment does not reflect function in everyday life where footwear is commonly worn. With limited existing literature, future studies of gait in paediatric CMT need to evaluate the influence of diagnostic sub‐types and disease progression; the effect of factors such as footwear and the environment; and to explore changes in gait and function throughout childhood and adolescence.
Media Plurality: Private versus Mixed Duopolies
Authors: PIRES ARMANDO JOSÉ GARCIA 
Published: August 2016

AbstractIn this paper, we analyze the level of media plurality in a market with two private news firms (private duopoly) and in a market with a private news firm and a public news firm (mixed duopoly). In the private duopoly news firms maximize profits. In the mixed duopoly, the private news firm maximizes profits, while the public news firm maximizes social welfare. We show that, in spite of the public news firm maximizing social welfare, neither media plurality nor social welfare needs to be higher under the mixed duopoly compared with the private duopoly. This will depend on the relation between the costs of adapting news to readers' political preferences, the intensity of the readers' political preferences, and the size of the advertising market.
Melatonin prevents radiation‐induced oxidative stress and periodontal tissue breakdown in irradiated rats with experimental periodontitis
Authors: Köse O. , Arabaci T. , Kizildag A. , Erdemci B. , Özkal Eminoğlu D. , Gedikli S. , Özkanlar S. , Zihni M. , Albayrak M. , Kara A. , Kermen E. 
Published: August 2016

Background and ObjectiveThe aim of this study was to analyze the biochemical and histochemical effects of radiation therapy and protective melatonin administration on periodontal tissues in rats with experimental periodontitis.Material and MethodsSixty male Sprague Dawley rats were divided into six groups, as follows: control; experimental periodontitis (Ped); radiotherapy administration (Rt); experimental periodontitis and exposure to irradiation (Ped‐Rt); radiotherapy and protective melatonin administration (Rt‐Mel); and periodontitis, radiation therapy and protective melatonin administration (Ped‐Rt‐Mel). The rats were killed at the end of the experimental procedure, and the oxidative stress level and periodontal destruction were compared among the groups.ResultsThe oxidative stress index and the levels of 8‐hydroxy‐2′‐deoxyguanosine, malondialdehyde and C‐terminal telopeptide of type I collagen were found to be significantly higher in the Ped‐Rt group compared with the Ped group (p < 0.05), and the levels were lower in the Ped‐Rt‐Mel group than in the Ped‐Rt group (p < 0.05). Alveolar bone destruction and attachment level were also significantly lower in the Ped‐Rt‐Mel group than in the Ped‐Rt group (p < 0.05).ConclusionIt was found that radiotherapy increased oxidative stress, the periodontal attachment level and alveolar bone loss, and protective melatonin administration significantly reduced the oxidative parameters and prevented periodontal damage in irradiated rats with experimental periodontitis. Further research is needed regarding the use of systemic melatonin administration before radiation therapy.
Fish and tetrapod communities across a marine to brackish salinity gradient in the Pennsylvanian (early Moscovian) Minto Formation of New Brunswick, Canada, and their palaeoecological and palaeogeographical implications
Authors: Ó Gogáin Aodhán , Falcon‐Lang Howard J. , Carpenter David K. , Miller Randall F. , Benton Michael J. , Pufahl Peir K. , Ruta Marcello , Davies Thomas G. , Hinds Steven J. , Stimson Matthew R. 
Published: August 2016

AbstractEuryhaline adaptations in Pennsylvanian vertebrates allowed them to inhabit the marine to freshwater spectrum. This is illustrated by new assemblages of fish and tetrapods from the early Moscovian Minto Formation of New Brunswick, Canada. Fish include chondrichthyans (xenacanthids and the enigmaticAgeleodus), acanthodians (gyracanthids and acanthodiforms), sarcopterygians (rhizodontids, megalichthyids and dipnoans), and actinopterygians (eurynotiforms). Tetrapods include small‐ to medium‐sized, and largely aquatic, stem tetrapods (colosteids) and anthracosaurs (embolomeres). A key finding is that the parautochthonous fossil assemblages are preserved across a salinity gradient, with diversity (measured by the Simpson Index) declining from open marine environments, through brackish embayments, and reaching a nadir in tidal estuaries. Chondrichthyans dominate the entire salinity spectrum (65% of fossils), a distribution that demonstrates a euryhaline mode of life, and one large predatory chondrichthyan,Orthacanthus, may have practised filial cannibalism in coastal nurseries because its heteropolar coprolites contain juvenile xenacanthid teeth. In contrast, other fish communities were more common in open marine settings while tetrapods were more common in coastal brackish waters. While all these faunas were also likely to have been euryhaline, their osmoregulation was, perhaps, less versatile. The demonstration of widespread euryhalinity among fish and aquatic tetrapods explains why Pennsylvanian faunas generally show a cosmopolitan biogeography because taxa were able to disperse via seaways. It also resolves the paradox of enriched strontium isotopic signatures observed in these faunas because organisms would have been, at times, exposed to continental water bodies as well. Therefore, our new findings contribute to the long‐running debate about the ecology of Pennsylvanian fishes and tetrapods.
An Agrobacterium‐delivered CRISPR/Cas9 system for high‐frequency targeted mutagenesis in maize
Authors: Char Si Nian , Neelakandan Anjanasree K. , Nahampun Hartinio , Frame Bronwyn , Main Marcy , Spalding Martin H. , Becraft Philip W. , Meyers Blake C. , Walbot Virginia , Wang Kan , Yang Bing 
Published: August 2016

SummaryCRISPR/Cas9 is a powerful genome editing tool in many organisms, including a number of monocots and dicots. Although the design and application of CRISPR/Cas9 is simpler compared to other nuclease‐based genome editing tools, optimization requires the consideration of the DNA delivery and tissue regeneration methods for a particular species to achieve accuracy and efficiency. Here, we describe a public sector system, ISU Maize CRISPR, utilizing Agrobacterium‐delivered CRISPR/Cas9 for high‐frequency targeted mutagenesis in maize. This system consists of an Escherichia coli cloning vector and an Agrobacterium binary vector. It can be used to clone up to four guide RNAs for single or multiplex gene targeting. We evaluated this system for its mutagenesis frequency and heritability using four maize genes in two duplicated pairs: Argonaute 18 (ZmAgo18a and ZmAgo18b) and dihydroflavonol 4‐reductase or anthocyaninless genes (a1 and a4). T0 transgenic events carrying mono‐ or diallelic mutations of one locus and various combinations of allelic mutations of two loci occurred at rates over 70% mutants per transgenic events in both Hi‐II and B104 genotypes. Through genetic segregation, null segregants carrying only the desired mutant alleles without the CRISPR transgene could be generated in T1 progeny. Inheritance of an active CRISPR/Cas9 transgene leads to additional target‐specific mutations in subsequent generations. Duplex infection of immature embryos by mixing two individual Agrobacterium strains harbouring different Cas9/gRNA modules can be performed for improved cost efficiency. Together, the findings demonstrate that the ISU Maize CRISPR platform is an effective and robust tool to targeted mutagenesis in maize.
Improved methods for evaluating pre‐clinical and histological effects of subcutaneous fat reduction using high‐intensity focused ultrasound in a porcine model
Authors: Kwon T.‐R. , Im S. , Jang Y.‐J. , Oh C. T. , Choi E. J. , Jung S. J. , Hong H. , Choi Y. S. , Choi S. Y. , Kim Y. S. , Kim B. J. 
Published: August 2016

BackgroundNon‐invasive body sculpting procedures are becoming increasingly popular. High‐intensity focused ultrasound (HIFU) treatment is a non‐surgical fat reduction procedure that permanently destroys unwanted abdominal fat. Despite its increasing popularity, evaluation methods for the procedure have not yet been fully developed.AimsThe objective of this study was to develop evaluation methods for HIFU for non‐surgical, permanent fat reduction in the anterior abdomen using a porcine model.MethodsThe abdomens of female pigs (Sus scrofa, n = 7) were treated with a HIFU device (SCIZER™, Classys Inc, Seoul, Korea). We examined treatment effects using photography, ultrasound, gross and microscopic pathology, and serum lipid and liver function level analysis, carbon tracer test, and histological examination in order to determine the mechanism of action, efficacy, and safety of the procedure.ResultsHIFU treatment effectively reduced abdominal fat in a porcine model; it accurately treated the target subcutaneous fat layer and the subcutaneous fat was reduced effectively via ultrasonic measurement after HIFU treatment. On histological staining (H&E, toluidine blue, oil red O and immunohistochemistry), we found that subcutaneous fat reduction occurred effectively via accurate treatment of the targeted subcutaneous fat layer. On hematological assay, there were changes within normal range, and values remained stable after 48 h. Via carbon tracer test, the migration of activated macrophages was identified within the axillary lymph node (LN). PPAR‐delta, a protein defined by immunohistochemistry staining, was overexpressed in the early stage on days 1 and 7, but a gradual decreasing pattern was confirmed.ConclusionWe successfully used a HIFU device for body contouring and fat reduction in a pre‐clinical study. These results provide that the essential clues toward the effective evaluation, guiding selection of the appropriate diagnostic investigations.
THEOLOGY, SCIENCE, AND CLOUD OF THE IMPOSSIBLE
Authors: Keller Catherine 
Published: August 2016

AbstractAs a work of constructive theology attentive to the deconstructive edge of theology itself, Cloud of the Impossible offers a contemplative space for fresh transdisciplinary encounters. The ancient apophatic practice (of “unsaying,” docta ignorantia) here fosters a knowledge tuned to its own currently indeterminate edges. The present conversation surfaces issues of religion in relation to both science and ethics. It effects a multilateral advance in thinking the “apophatic entanglement” by which a relational ontology, with its attention to the materiality of our fragile planetary interdependence, is intensified through a theology of disciplined uncertainty.
PETER HARRISON, LUDWIG WITTGENSTEIN, AND THE PROBLEM OF PRE‐MODERN RELIGION
Authors: Ristuccia Nathan J. 
Published: August 2016

AbstractPeter Harrison's Gifford Lectures demonstrate that the modern concepts of “religion” and “science” do not correspond to any fixed sphere of life in the pre‐modern world. Because these terms are incommensurate and ideological, they misconstrue the past. I examine the influence and affinities of Ludwig Wittgenstein's philosophy on Harrison's study in order to argue that Harrison's project approaches Wittgenstein's. Harrison's book is a therapeutic history, untying a knot in scholarly language. I encourage Harrison, however, to clarify how future scholars can progress in their study of phenomena once termed “scientific” or “religious” without succumbing to these same mistakes.
THE MODERN INVENTION OF “SCIENCE‐AND‐RELIGION”: WHAT FOLLOWS?
Authors: Harrison Peter 
Published: August 2016

AbstractI am grateful to the four reviewers of The Territories of Science and Religion for their careful and insightful readings of the book, and their kind words about it. They all got the central arguments pretty much right, and thus any critical comments are not the result of fundamental misunderstandings. While there are some common themes in the assessments, each reviewer, happily, has offered a distinct perspective on the book. For this reason I will deal with their comments in turn, but with a focus throughout on a generally expressed concern about the broader implications of the book's historical analysis, and what positive or concrete proposals might follow from it.
Ca2+ transport and signalling in enamel cells
Authors: Nurbaeva Meerim K. , Eckstein Miriam , Feske Stefan , Lacruz Rodrigo S. 
Published: August 2016

AbstractDental enamel is one of the most remarkable examples of matrix‐mediated biomineralization. Enamel crystals form de novo in a rich extracellular environment in a stage‐dependent manner producing complex microstructural patterns that are visually stunning. This process is orchestrated by specialized epithelial cells known as ameloblasts which themselves undergo striking morphological changes, switching function from a secretory role to a cell primarily engaged in ionic transport. Ameloblasts are supported by a host of cell types which combined represent the enamel organ. Fully mineralized enamel is the hardest tissue found in vertebrates owing its properties partly to the unique mixture of ionic species represented and their highly organized assembly in the crystal lattice. Among the main elements found in enamel, Ca2+ is the most abundant ion, yet how ameloblasts modulate Ca2+ dynamics remains poorly known. This review describes previously proposed models for passive and active Ca2+ transport, the intracellular Ca2+ buffering systems expressed in ameloblasts and provides an up‐dated view of current models concerning Ca2+ influx and extrusion mechanisms, where most of the recent advances have been made. We also advance a new model for Ca2+ transport by the enamel organ.
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Novel Acylguanidine-Based Inhibitor of HIV-1
Authors: Mwimanzi Philip , Tietjen Ian , Miller Scott C. , Shahid Aniqa , Cobarrubias Kyle , Kinloch Natalie N. , Baraki Bemuluyigza , Richard Jonathan , Finzi Andrés , Fedida David , Brumme Zabrina L. , Brockman Mark A. 
Published: August 2016

ABSTRACT

The emergence of transmissible HIV-1 strains with resistance to antiretroviral drugs highlights a continual need for new therapies. Here we describe a novel acylguanidine-containing compound, 1-(2-(azepan-1-yl)nicotinoyl)guanidine (or SM111), that inhibits
in vitro
replication of HIV-1, including strains resistant to licensed protease, reverse transcriptase, and integrase inhibitors, without major cellular toxicity. At inhibitory concentrations, intracellular p24
Gag
production was unaffected, but virion release (measured as extracellular p24
Gag
) was reduced and virion infectivity was substantially impaired, suggesting that SM111 acts at a late stage of viral replication. SM111-mediated inhibition of HIV-1 was partially overcome by a Vpu I17R mutation alone or a Vpu W22* truncation in combination with Env N136Y. These mutations enhanced virion infectivity and Env expression on the surface of infected cells in the absence and presence of SM111 but also impaired Vpu's ability to downregulate CD4 and BST2/tetherin. Taken together, our results support acylguanidines as a class of HIV-1 inhibitors with a distinct mechanism of action compared to that of licensed antiretrovirals. Further research on SM111 and similar compounds may help to elucidate knowledge gaps related to Vpu's role in promoting viral egress and infectivity.

IMPORTANCE
New inhibitors of HIV-1 replication may be useful as therapeutics to counteract drug resistance and as reagents to perform more detailed studies of viral pathogenesis. SM111 is a small molecule that blocks the replication of wild-type and drug-resistant HIV-1 strains by impairing viral release and substantially reducing virion infectivity, most likely through its ability to prevent Env expression at the infected cell surface. Partial resistance to SM111 is mediated by mutations in Vpu and/or Env, suggesting that the compound affects host/viral protein interactions that are important during viral egress. Further characterization of SM111 and similar compounds may allow more detailed pharmacological studies of HIV-1 egress and provide opportunities to develop new treatments for HIV-1.
In Vitro
Studies Show that Sequence Variability Contributes to Marked Variation in Hepatitis B Virus Replication, Protein Expression, and Function Observed across Genotypes
Authors: Sozzi Vitina , Walsh Renae , Littlejohn Margaret , Colledge Danni , Jackson Kathy , Warner Nadia , Yuen Lilly , Locarnini Stephen A. , Revill Peter A. 
Published: August 2016

ABSTRACT
The hepatitis B virus (HBV) exists as 9 major genotypes (A to I), one minor strain (designated J) and multiple subtypes. Marked differences in HBV natural history, disease progression and treatment response are exhibited by many of these genotypes and subtypes. For example, HBV genotype C is associated with later hepatitis B e antigen (HBeAg) seroconversion and high rates of liver cancer compared to other HBV genotypes, whereas genotype A2 is rarely associated with HBeAg-negative disease or liver cancer. The reasons for these and other differences in HBV natural history are yet to be determined but could in part be due to sequence differences in the HBV genome that alter replicative capacity and/or gene expression. Direct comparative studies on HBV replication and protein expression have been limited to date due largely to the absence of infectious HBV cDNA clones for each of the HBV genotypes present in the same genetic arrangement. We have produced replication-competent infectious cDNA clones of the most common subtypes of genotypes A to D, namely, A2, B2, C2, D3, and the minor strain J, and compared their HBV replication phenotype using transient-transfection models. We identified striking differences in HBV replicative capacity as well as HBeAg and surface (HBsAg) protein expression across genotypes, which may in part be due to sequence variability in regulatory regions of the HBV genome. Functional analysis showed that sequence differences in the major upstream regulatory region across genotypes impacted promoter activity.

IMPORTANCE
There have been very few studies directly comparing the replication phenotype of different HBV genotypes, for which there are marked differences in natural history and disease progression worldwide. We have generated replication-competent 1.3-mer cDNA clones of the major genotypes A2, B2, C2, and D3, as well as a recently identified strain J, and identified striking differences in replicative capacity and protein expression that may contribute to some of the observed differences in HBV natural history observed globally.
Evaluation of a minor eye conditions scheme delivered by community optometrists
Authors: Konstantakopoulou E , Edgar D F , Harper R A , Baker H , Sutton M , Janikoun S , Larkin G , Lawrenson J G 
Published: August 2016

BackgroundThe establishment of minor eye conditions schemes (MECS) within community optometric practices provides a mechanism for the timely assessment of patients presenting with a range of acute eye conditions. This has the potential to reduce waiting times and avoid unnecessary referrals to hospital eye services (HES).ObjectiveTo evaluate the clinical effectiveness, impact on hospital attendances and patient satisfaction with a minor eye service provided by community optometrists.MethodsActivity and outcome data were collected for 12 months in the Lambeth and Lewisham MECS. A patient satisfaction questionnaire was given to patients at the end of their MECS appointment. A retrospective difference-in-differences analysis of hospital activity compared changes in the volume of referrals by general practitioners (GPs) from a period before (April 2011–March 2013) to after (April 2013–March 2015) the introduction of the scheme in Lambeth and Lewisham relative to a neighbouring area (Southwark) where the scheme had not been commissioned. Appropriateness of case management was assessed by consensus using clinical members of the research team.ResultsA total of 2123 patients accessed the scheme. Approximately two-thirds of patients (67.5%) were referred by their GP. The commonest reasons for patients attending for a MECS assessment were ‘red eye’ (36.7% of patients), ‘painful white eye’ (11.1%) and ‘flashes and floaters’ (10.2%). A total of 64.1% of patients were managed in optometric practice and 18.9% were referred to the HES; of these, 89.2% had been appropriately referred. First attendances to HES referred by GPs reduced by 26.8% (95% CI −40.5% to −13.1%) in Lambeth and Lewisham compared to Southwark.ConclusionsThe Lambeth and Lewisham MECS demonstrates clinical effectiveness, reduction in hospital attendances and high patient satisfaction and represents a successful collaboration between commissioners, local HES units and primary healthcare providers.