bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNAseq analysis reveals the role of secondary metabolism in the response of URS 21, a race‐nonspecific resistant cultivar, to crown rust
Authors: Figueiró A. de A. , Gonzalez‐Hernandez J. L. , Pacheco M. T. , Reese R. N. , de Morais G. L. , Guzman F. , Swaminathan P. , Delatorre C. A. 
Published: September 2016

Crown rust (Puccinia coronata f. sp. avenae) can devastate oats (Avena sativa). Plants possessing durable resistance are desirable and they may contain mechanisms that differ from those underlying genes with specific effects. Gathering information about the molecular mechanisms involved, especially those not associated with the hypersensitive reaction, and combining those acting at different infection stages may increase the ability to defeat the pathogen. The cultivar URS 21 has strongly reduced the intensity and growth of crown rust for the last 14 years, demonstrating durable race‐nonspecific resistance expressed at adult and seedling stages. The main objective of this study was to identify, by deep sequencing, oat transcripts induced by P. coronata in the URS 21 cultivar inoculated at seedling stage. Two important reactions to inoculation, secondary metabolism and the oxidative response, were studied further. The expression of specific genes associated with biosynthesis of secondary metabolites was evaluated in adult plants by RT‐PCR, as well as the accumulation of saponins and avenanthramides, found to be important in other pathosystems, and comparisons were made with the susceptible cultivar URS 22. The URS 21 resistance mechanism probably involves several components including the biosynthesis of avenanthramides and steroid saponins; also, several genes related to antioxidative stress were down‐regulated. A large number of oat sequences were generated by RNA‐seq analysis in this study, which will help in the search for genes involved in the race‐nonspecific resistance; they may also be useful in the development of markers to search for QTLs associated with race‐nonspecific resistance.
Neutrophil Receptor Response to Bacterial N‐formyl Peptides is Similar in Term Newborn Infants and Adults in Contrast to IL‐8
Authors: Stålhammar M. E. , Sindelar R. , Douhan Håkansson L. 
Published: September 2016

AbstractWe have previously observed that neutrophils from neonates exhibit different migratory responses to intermediate and end‐target chemoattractants compared to adults. The aim of this study was to investigate the effect of the chemoattractants IL‐8 (intermediate) and formyl‐methionyl‐leucyl‐phenylalanine (fMLP; end‐target) on cell surface receptor expression involved in adhesion, migration and granule release of neutrophils from term newborn infants and adults. Heparinized cord blood from 16 healthy term newborn infants delivered by caesarean section and peripheral blood from 17 healthy adults were incubated with 1 μm IL‐8 or 0.1 μm fMLP, previously defined as optimal inducers of neutrophil migration. The leukocytes were labelled with antibodies to cell surface receptors (CD11b, CD15S, CD18, CD35, CD44, CD64, CD65, CD88, CD162, CD181 and CD182). Receptor expression was quantified by flow cytometry analysis. Upregulation of CD11b and downregulation of CD88 and CD182 after stimulation with IL‐8 were more pronounced in adults than in neonates (P < 0.05, P < 0.05 and P ≤ 0.001, respectively), whereas fMLP induced changes in receptor expression that were of the same magnitude in neutrophils from neonates as from adults. We observed similar expression of receptors that mediate adhesion, migration, granule activation and phagocytosis induced by fMLP in neutrophils from neonates and adults. In contrast, differences between neonates and adults, induced by IL‐8, suggest that the neutrophil response to intermediate chemoattractants might lead to a compromised infectious response in newborn infants.
Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll‐like Receptor Stimulation in Peripheral Monocytes
Authors: Orhan F. , Bhat M. , Sandberg K. , Ståhl S. , Piehl F. ,   Karolinska Schizophrenia Project (KaSP) consortium, Svensson C. , Erhardt S. , Schwieler L. 
Published: September 2016

AbstractTryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll‐like receptors (TLRs), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid (KYNA), quinolinic acid (QUIN) and tryptophan. Stimulation of TLR‐2, TLR‐3, TLR‐4, TLR‐7/8 and TLR‐9 was found to induce the production of kynurenine, but only stimulation of TLR‐3 increased levels of further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR‐1, TLR‐5 and TLR‐6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLRs can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders.
Alternative splicing provides a proactive mechanism for the diurnal CONSTANS dynamics in Arabidopsis photoperiodic flowering
Authors: Gil Kyung‐Eun , Park Mi‐Jeong , Lee Hyo‐Jun , Park Young‐Joon , Han Shin‐Hee , Kwon Young‐Ju , Seo Pil Joon , Jung Jae‐Hoon , Park Chung‐Mo 
Published: September 2016

SummaryThe circadian clock control of CONSTANS (CO) transcription and the light‐mediated stabilization of its encoded protein coordinately adjust photoperiodic flowering by triggering rhythmic expression of the floral integrator flowering locus T (FT). Diurnal accumulation of CO is modulated sequentially by distinct E3 ubiquitin ligases, allowing peak CO to occur in the late afternoon under long days. Here we show that CO abundance is not simply targeted by E3 enzymes but is also actively self‐adjusted through dynamic interactions between two CO isoforms. Alternative splicing of CO produces two protein variants, the full‐size COα and the truncated COβ lacking DNA‐binding affinity. Notably, COβ, which is resistant to E3 enzymes, induces the interaction of COα with CO‐destabilizing E3 enzymes but inhibits the association of COα with CO‐stabilizing E3 ligase. These observations demonstrate that CO plays an active role in sustaining its diurnal accumulation dynamics during Arabidopsis photoperiodic flowering.
In Vitro Evaluation of the Aberdeen Knot for Continuous Suture Patterns with Large Gauge Suture
Authors: Gillen Alex M. , Munsterman Amelia S. , Farag Ramsis , Coleridge Matthew O. D. , Reid Hanson R. 
Published: September 2016

ObjectiveTo evaluate the strength, size, and holding capacity of the Aberdeen knot compared to surgeon's and square knots using large gauge suture.Study DesignIn vitro mechanical study.Study PopulationKnotted suture.MethodsAberdeen, surgeon's, and square knots were tested using 2 and 3 USP polyglactin 910 and 2 USP polydioxanone under linear tension on a universal testing machine. Mode of failure and knot holding capacity (KHC) were recorded and relative knot security (RKS) was calculated as a percentage of KHC. Knot volume and weight were quantified by a digital micrometer and balance, respectively. Strength between number of throws, suture, suture size, and knot type were compared by ANOVA and post hoc testing. P≤.05 was considered significant.ResultsAberdeen knots had higher KHC and RKS than surgeon's or square knots for all suture types and number of throws (P<.001). For all suture materials, none of the Aberdeen knots unraveled, but a portion of square and surgeon's knots with <7 throws did unravel (P=.101). Aberdeen knots had a smaller volume and weight than both surgeon's and square knots with equal numbers of throws (P<.001). The knot with the combined highest RKS and smallest size and weight was an Aberdeen knot with 4 throws using 3 USP polyglactin 910.ConclusionThe Aberdeen knots were stronger, more secure, and smaller than surgeon's and square knots for ending a continuous suture pattern. Clinically, the Aberdeen knot may be a useful alternative for completion of continuous patterns using large gauge suture, without sacrificing knot integrity.
A pencil beam dose calculation model for CyberKnife system
Authors: Liang Bin , Li Yongbao , Liu Bo , Zhou Fugen , Xu Shouping , Wu Qiuwen 
Published: September 2016

PurposeCyberKnife system is initially equipped with fixed circular cones for stereotactic radiosurgery. Two dose calculation algorithms, Ray‐Tracing and Monte Carlo, are available in the supplied treatment planning system. A multileaf collimator system was recently introduced in the latest generation of system, capable of arbitrarily shaped treatment field. The purpose of this study is to develop a model based dose calculation algorithm to better handle the lateral scatter in an irregularly shaped small field for the CyberKnife system.MethodsA pencil beam dose calculation algorithm widely used in linac based treatment planning system was modified. The kernel parameters and intensity profile were systematically determined by fitting to the commissioning data. The model was tuned using only a subset of measured data (4 out of 12 cones) and applied to all fixed circular cones for evaluation. The root mean square (RMS) of the difference between the measured and calculated tissue‐phantom‐ratios (TPRs) and off‐center‐ratio (OCR) was compared. Three cone size correction techniques were developed to better fit the OCRs at the penumbra region, which are further evaluated by the output factors (OFs). The pencil beam model was further validated against measurement data on the variable dodecagon‐shaped Iris collimators and a half‐beam blocked field. Comparison with Ray‐Tracing and Monte Carlo methods was also performed on a lung SBRT case.ResultsThe RMS between the measured and calculated TPRs is 0.7% averaged for all cones, with the descending region at 0.5%. The RMSs of OCR at infield and outfield regions are both at 0.5%. The distance to agreement (DTA) at the OCR penumbra region is 0.2 mm. All three cone size correction models achieve the same improvement in OCR agreement, with the effective source shift model (SSM) preferred, due to their ability to predict more accurately the OF variations with the source to axis distance (SAD). In noncircular field validation, the pencil beam calculated results agreed well with the film measurement of both Iris collimators and the half‐beam blocked field, fared much better than the Ray‐Tracing calculation.ConclusionsThe authors have developed a pencil beam dose calculation model for the CyberKnife system. The dose calculation accuracy is better than the standard linac based system because the model parameters were specifically tuned to the CyberKnife system and geometry correction factors. The model handles better the lateral scatter and has the potential to be used for the irregularly shaped fields. Comprehensive validations on MLC equipped system are necessary for its clinical implementation. It is reasonably fast enough to be used during plan optimization.
Identification of Essential Genes in the Salmonella Phage SPN3US Reveals Novel Insights into Giant Phage Head Structure and Assembly
Authors: Thomas Julie A. , Benítez Quintana Andrea Denisse , Bosch Martine A. , Coll De Peña Adriana , Aguilera Elizabeth , Coulibaly Assitan , Wu Weimin , Osier Michael V. , Hudson André O. , Weintraub Susan T. , Black Lindsay W. 
Published: September 2016

ABSTRACT

Giant tailed bacterial viruses, or phages, such as
Pseudomonas aeruginosa
phage ϕKZ, have long genomes packaged into large, atypical virions. Many aspects of ϕKZ and related phage biology are poorly understood, mostly due to the fact that the functions of the majority of their proteins are unknown. We hypothesized that the
Salmonella enterica
phage SPN3US could be a useful model phage to address this gap in knowledge. The 240-kb SPN3US genome shares a core set of 91 genes with ϕKZ and related phages, ∼61 of which are virion genes, consistent with the expectation that virion complexity is an ancient, conserved feature. Nucleotide sequencing of 18 mutants enabled assignment of 13 genes as essential, information which could not have been determined by sequence-based searches for 11 genes. Proteome analyses of two SPN3US virion protein mutants with knockouts in
64
and
241
provided new insight into the composition and assembly of giant phage heads. The
64
mutant analyses revealed all the genetic determinants required for assembly of the SPN3US head and a likely head-tail joining role for gp64, and its homologs in related phages, due to the tailless-particle phenotype produced. Analyses of the mutation in
241
, which encodes an RNA polymerase β subunit, revealed that without this subunit, no other subunits are assembled into the head, and enabled identification of a “missing” β′ subunit domain. These findings support SPN3US as an excellent model for giant phage research, laying the groundwork for future analyses of their highly unusual virions, host interactions, and evolution.

IMPORTANCE
In recent years, there has been a paradigm shift in virology with the realization that extremely large viruses infecting prokaryotes (giant phages) can be found in many environments. A group of phages related to the prototype giant phage ϕKZ are of great interest due to their virions being among the most complex of prokaryotic viruses and their potential for biocontrol and phage therapy applications. Our understanding of the biology of these phages is limited, as a large proportion of their proteins have not been characterized and/or have been deemed putative without any experimental verification. In this study, we analyzed
Salmonella
phage SPN3US using a combination of genomics, genetics, and proteomics and in doing so revealed new information regarding giant phage head structure and assembly and virion RNA polymerase composition. Our findings demonstrate the suitability of SPN3US as a model phage for the growing group of phages related to ϕKZ.
Visualising linked health data to explore health events around preventable hospitalisations in NSW Australia
Authors: Falster Michael O , Jorm Louisa R , Leyland Alastair H 
Published: September 2016

ObjectiveTo explore patterns of health service use in the lead-up to, and following, admission for a ‘preventable’ hospitalisation.Setting266 950 participants in the 45 and Up Study, New South Wales (NSW) AustraliaMethodsLinked data on hospital admissions, general practitioner (GP) visits and other health events were used to create visual representations of health service use. For each participant, health events were plotted against time, with different events juxtaposed using different markers and panels of data. Various visualisations were explored by patient characteristics, and compared with a cohort of non-admitted participants matched on sociodemographic and health characteristics. Health events were displayed over calendar year and in the 90 days surrounding first preventable hospitalisation.ResultsThe visualisations revealed patterns of clustering of GP consultations in the lead-up to, and following, preventable hospitalisation, with 14% of patients having a consultation on the day of admission and 27% in the prior week. There was a clustering of deaths and other hospitalisations following discharge, particularly for patients with a long length of stay, suggesting patients may have been in a state of health deterioration. Specialist consultations were primarily clustered during the period of hospitalisation. Rates of all health events were higher in patients admitted for a preventable hospitalisation than the matched non-admitted cohort.ConclusionsWe did not find evidence of limited use of primary care services in the lead-up to a preventable hospitalisation, rather people with preventable hospitalisations tended to have high levels of engagement with multiple elements of the healthcare system. As such, preventable hospitalisations might be better used as a tool for identifying sicker patients for managed care programmes. Visualising longitudinal health data was found to be a powerful strategy for uncovering patterns of health service use, and such visualisations have potential to be more widely adopted in health services research.
Isoflurane, sevoflurane and desflurane use in cane toads (Rhinella marina)
Authors: Morrison Kaleigh E. , Strahl‐Heldreth Danielle , Clark‐Price Stuart C. 
Published: September 2016

Anaesthetic chamber concentrations of isoflurane, sevoflurane and desflurane that resulted in loss of righting reflex within 15 minutes in 50 per cent of toads (Rhinella marina) exposed (ED50‐LRR<15MIN) were identified. The median and range ED50‐LRR<15MIN was 1.4 (0.9–1.4) per cent for isoflurane, 1.75 (1.1–1.9) per cent for sevoflurane and 4.4 (4.3–5.5) per cent for desflurane. Subsequently, toads were exposed to 1.5 times the ED50‐LRR<15MIN and times to loss and return of righting reflex were identified. All toads for all anaesthetics lost righting reflex. The median and range loss of righting reflex was 4:00 (3:00–5:30) minutes for isoflurane, 4:45 (3:30–7:00) minutes for sevoflurane, and 4:15 (4:00–5:30) minutes for desflurane and was not different between anaesthetics. Time to return of righting reflex was 175 (123–211) minutes for isoflurane, 192 (116–383) minutes for sevoflurane and 74 (52–220) minutes for desflurane. Time to return of righting reflex was significantly shorter for desflurane compared with isoflurane or sevoflurane. The use of isoflurane, sevoflurane or desflurane can be used to provide immobilisation to cane toads and potentially other anurans. Induction times are likely similar when using an anaesthetic chamber to provide anaesthesia. However recovery time may take twice as long when utilising isoflurane or sevoflurane over desflurane.
The last glaciation in Caithness, Scotland: revised till stratigraphy and ice-flow paths indicate multiple ice flow phases
Authors: Hall Adrian M. , Riding James B. 
Published: September 2016

This paper reviews existing information on the last glaciation of Caithness and presents new evidence for additional till units and for long distance ice-flow paths based on till palynomorphs, indicator erratics and striae. Early, radial expansion of Northern Highland ice probably occurred at 31 – 29 ka. After ice withdrawal from the north coast, Moray Firth ice returned before a second withdrawal. Thereafter Moray Firth ice advanced to limits close to the Atlantic shelf edge between 21 and 18 ka. Deglaciation of hill summits was completed by 18.4 – 17.8 ka but the low ground south of Wick only became ice free after 16.5 ka.
Recognition of these multiple ice-flow events is consistent with the dynamic behaviour of the last ice sheet exhibited in mathematical simulations. The event sequence differs, however, from nineteenth century and recent two-stage flow set reconstructions as each main flow set is shown to represent multiple events following similar paths but under different ice sheet configurations. Various configurations allow ice to flow northwards across Caithness and so remove any requirement for the Fennoscandian Ice Sheet to directly block and divert the outflow of ice from the Moray Firth during the last glaciation.
Whole exome sequencing analysis reveals TRPV3 as a risk factor for cardioembolic stroke/subtitle
Authors: Carrera Caty , Jiménez-Conde Jordi , Derdak Sophia , Rabionet Kelly , Vives-Bauzá Cristofol , Soriano-Tárrega Carolina , Giralt-Steinhauer Eva , Mola-Caminal Marina , Diaz-Navarro Rosa M. , Tur Silvia , Muiño Elena , Gallego-Fabrega Cristina , Beltran Sergi , Roquer Jaume , Ruiz Agustin , Sotolongo-Grau Oscar , Krupinski Jurek , Lee Jin-Moo , Cruchaga Carlos , Delgado Pilar , Malik Rainer , Worrall Brad B. , Seshadri Sudha , Montaner Joan , Fernández-Cadenas Israel ,   the Metastroke Consortium, ISGC Consortium and Genestroke Consortium
Published: September 2016

SummaryGenetic studies suggest that hundreds of genes associated with stroke remain unidentified. Exome sequencing proves useful for finding new genes associated with stroke. We aimed to find new genetic risk factors for cardioembolic stroke by analysing exome sequence data using new strategies. For discovery, we analysed 42 cardioembolic stroke cases and controls with extreme phenotypes (cohort 1), and for replication, 32 cardioembolic stroke cases and controls (cohort 2) using the SeqCapExome capture kit. We then analysed the replicated genes in two new cohorts that comprised 834 cardioembolic strokes and controls (cohort 3) and 64,373 cardioembolic strokes and controls (cohort 4). Transcriptomic in-silico functional analyses were also performed. We found 26 coding regions with a higher frequency of mutations in cardioembolic strokes after correcting for the number of mutations found in the whole exome of every patient. The TRPV3 gene was associated with cardioembolic stroke after replication of exome sequencing analysis (p-value-discovery: 0.018, p-value-replication: 0.014). The analysis of the TRPV3 gene using polymorphisms in cohort 3 and 4 revealed two polymorphisms associated with cardioembolic stroke in both cohorts, the most significant polymorphism being rs151091899 (p-value: 3.1 × 10−05; odds ratio: 5.4) in cohort 3. The genotype of one polymorphism of TRPV3 was associated with a differential expression of genes linked to cardiac malformations. In conclusion, new strategies using exome sequence data have revealed TRPV3 as a new gene associated with cardioembolic stroke. This strategy among others might be useful in finding new genes associated with complex genetic diseases.
Generation and in vitro characterisation of inhibitory nanobodies towards plasminogen activator inhibitor 1
Authors: Zhou Xiaohua , Hendrickx Maarten L. V. , Hassanzadeh-Ghassabeh Gholamreza , Muyldermans Serge , Declerck Paul J. 
Published: September 2016

SummaryPlasminogen activator inhibitor 1 (PAI-1) is the principal physiological inhibitor of tissue-type plasminogen activator (t-PA) and has been identified as a risk factor in cardiovascular diseases. In order to generate nanobodies against PAI-1 to interfere with its functional properties, we constructed three nanobody libraries upon immunisation of three alpacas with three different PAI-1 variants. Three panels of nanobodies were selected against these PAI-1 variants. Evaluation of the amino acid sequence identity of the complementarity determining region-3 (CDR3) reveals 34 clusters in total. Five nanobodies (VHH-s-a98, VHH-2w-64, VHH-s-a27, VHH-s-a93 and VHH-2g-42) representing five clusters exhibit inhibition towards PAI-1 activity. VHH-s-a98 and VHH-2w-64 inhibit both glycosylated and non-glycosylated PAI-1 variants through a substrate-inducing mechanism, and bind to two different regions close to αhC and the hinge region of αhF; the profibrinolytic effect of both nanobodies was confirmed using an in vitro clot lysis assay. VHH-s-a93 may inhibit PAI-1 activity by preventing the formation of the initial PAI-1•t-PA complex formation and binds to the hinge region of the reactive centre loop. Epitopes of VHH-s-a27 and VHH-2g-42 could not be deduced yet. These five nanobodies interfere with PAI-1 activity through different mechanisms and merit further evaluation for the development of future profibrinolytic therapeutics.