bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camptotheca acuminata 10‐hydroxycamptothecin O‐methyltransferase: an alkaloid biosynthetic enzyme co‐opted from flavonoid metabolism
Authors: Salim Vonny , Jones A. Daniel , DellaPenna Dean 
Published: April 2018

SummaryThe medicinal plant Camptotheca acuminata accumulates camptothecin, 10‐hydroxycamptothecin, and 10‐methoxycamptothecin as its major bioactive monoterpene indole alkaloids. Here, we describe identification and functional characterization of 10‐hydroxycamptothecin O‐methyltransferase (Ca10OMT), a member of the Diverse subclade of class II OMTs. Ca10OMT is highly active toward both its alkaloid substrate and a wide range of flavonoids in vitro and in this way contrasts with other alkaloid OMTs in the subclade that only utilize alkaloid substrates. Ca10OMT shows a strong preference for the A‐ring 7‐OH of flavonoids, which is structurally equivalent to the 10‐OH of 10‐hydroxycamptothecin. The substrates of other alkaloid OMTs in the subclade bear little similarity to flavonoids, but the 3‐D positioning of the 7‐OH, A‐ and C‐rings of flavonoids is nearly identical to the 10‐OH, A‐ and B‐rings of 10‐hydroxycamptothecin. This structural similarity likely explains the retention of flavonoid OMT activity by Ca10OMT and also why kaempferol and quercetin aglycones are potent inhibitors of its 10‐hydroxycamptothecin activity. The catalytic promiscuity and strong inhibition of Ca10OMT by flavonoid aglycones in vitro prompted us to investigate the potential physiological roles of the enzyme in vivo. Based on its regioselectivity, kinetic parameters and absence of 7‐OMT flavonoids in vivo, we conclude that the major and likely only substrate of Ca10OMTin vivo is 10‐hydroxycamptothecin. This is likely accomplished by Ca10OMT being kept spatially separated at the tissue levels from potentially inhibitory flavonoid aglycones, and flavonoid aglycones being rapidly glycosylated to non‐inhibitory flavonoid glycosides.
EARLY STARVATION1 specifically affects the phosphorylation action of starch‐related dikinases
Authors: Malinova Irina , Mahto Harendra , Brandt Felix , AL‐Rawi Shadha , Qasim Hadeel , Brust Henrike , Hejazi Mahdi , Fettke Joerg 
Published: April 2018

SummaryStarch phosphorylation by starch‐related dikinases glucan, water dikinase (GWD) and phosphoglucan, water dikinase (PWD) is a key step in starch degradation. Little information is known about the precise structure of the glucan substrate utilized by the dikinases and about the mechanisms by which these structures may be influenced. A 50‐kDa starch‐binding protein named EARLY STARVATION1 (ESV1) was analyzed regarding its impact on starch phosphorylation. In various in vitro assays, the influences of the recombinant protein ESV1 on the actions of GWD and PWD on the surfaces of native starch granules were analyzed. In addition, we included starches from various sources as well as truncated forms of GWD. ESV1 preferentially binds to highly ordered, α‐glucans, such as starch and crystalline maltodextrins. Furthermore, ESV1 specifically influences the action of GWD and PWD at the starch granule surface. Starch phosphorylation by GWD is decreased in the presence of ESV1, whereas the action of PWD increases in the presence of ESV1. The unique alterations observed in starch phosphorylation by the two dikinases are discussed in regard to altered glucan structures at the starch granule surface.
Identification and characterisation of a previously unknown drought tolerance‐associated microRNA in barley
Authors: Zhou Hui , Hussain Syed S. , Hackenberg Michael , Bazanova Natalia , Eini Omid , Li Jie , Gustafson Perry , Shi Bujun 
Published: April 2018

SummaryDrought is the most serious abiotic stress, and causes crop losses on a worldwide scale. The present study identified a previously unknown microRNA (designated as hvu‐miRX) of 21 nucleotides (nt) in length in barley. Its precursor (designated pre‐miRX) and primary transcript (designated pri‐miRX) were also identified, with lengths of 73 and 559 nt, respectively. The identified upstream sequence of pri‐miRX contained both the TATA box and the CAAT box, which are both required for initiation of transcription. Transient promoter activation assays showed that the core promoter region of pri‐miRX ranged 500 nt from the transcription start site. In transgenic barley overexpression of the wheat DREB3 transcription factor (TaDREB3) caused hvu‐miRX to be highly expressed as compared with the same miRNA in non‐transgenic barley. However, the high expression was not directly associated with TaDREB3. Genomic analysis revealed that the hvu‐miRX gene was a single copy located on the short arm of chromosome 2 and appeared to be only conserved in Triticeae, but not in other plant species. Notably, transgenic barley that overexpressed hvu‐miRX showed drought tolerance. Degradome library analysis and other tests showed that hvu‐miRX targeted various genes including transcription factors via the cleavage mode. Our data provides an excellent opportunity to develop drought stress tolerant cereals using hvu‐miRX.
A cytological approach to studying meiotic recombination and chromosome dynamics in Arabidopsis thaliana male meiocytes in three dimensions
Authors: Hurel Aurélie , Phillips Dylan , Vrielynck Nathalie , Mézard Christine , Grelon Mathilde , Christophorou Nicolas 
Published: April 2018

SummaryDuring meiotic prophase I chromosomes undergo dramatic conformational changes that accompany chromosome condensation, pairing and recombination between homologs. These changes include the anchoring of telomeres to the nuclear envelope and their clustering to form a bouquet. In plants, these events have been studied and illustrated in intact meiocytes of species with large genomes. Arabidopsis thaliana is an excellent genetic model in which major molecular pathways that control synapsis and recombination between homologs have been uncovered. Yet the study of chromosome dynamics is hampered by current cytological methods that disrupt the three‐dimensional (3D) architecture of the nucleus. Here we set up a protocol to preserve the 3D configuration of A. thaliana meiocytes. We showed that this technique is compatible with the use of a variety of antibodies that label structural and recombination proteins and were able to highlight the presence of clustered synapsis initiation centers at the nuclear periphery. By using fluorescence in situ hybridization we also studied the behavior of chromosomes during pre‐meiotic G2 and prophase I, revealing the existence of a telomere bouquet during A. thaliana male meiosis. In addition we showed that the number of telomeres in a bouquet and its volume vary greatly, thus revealing the complexity of telomere behavior during meiotic prophase I. Finally, by using probes that label subtelomeric regions of individual chromosomes, we revealed differential localization behaviors of chromosome ends. Our protocol opens new areas of research for investigating chromosome dynamics in A. thaliana meiocytes.
Chromosome‐scale pseudomolecules refined by optical, physical and genetic maps in flax
Authors: You Frank M. , Xiao Jin , Li Pingchuan , Yao Zhen , Jia Gaofeng , He Liqiang , Zhu Tingting , Luo Ming‐Cheng , Wang Xiue , Deyholos Michael K. , Cloutier Sylvie 
Published: April 2018

SummaryGenomes of varying sizes have been sequenced with next‐generation sequencing platforms. However, most reference sequences include draft unordered scaffolds containing chimeras caused by mis‐scaffolding. A BioNano genome (BNG) optical map was constructed to improve the previously sequenced flax genome (Linum usitatissimum L., 2n = 30, about 373 Mb), which consisted of 3852 scaffolds larger than 1 kb and totalling 300.6 Mb. The high‐resolution BNG map of cv. CDC Bethune totalled 317 Mb and consisted of 251 BNG contigs with an N50 of 2.15 Mb. A total of 622 scaffolds (286.6 Mb, 94.9%) aligned to 211 BNG contigs (298.6 Mb, 94.2%). Of those, 99 scaffolds, diagnosed to contain assembly errors, were refined into 225 new scaffolds. Using the newly refined scaffold sequences and the validated bacterial artificial chromosome‐based physical map of CDC Bethune, the 211 BNG contigs were scaffolded into 94 super‐BNG contigs (N50 of 6.64 Mb) that were further assigned to the 15 flax chromosomes using the genetic map. The pseudomolecules total about 316 Mb, with individual chromosomes of 15.6 to 29.4 Mb, and cover 97% of the annotated genes. Evidence from the chromosome‐scale pseudomolecules suggests that flax has undergone palaeopolyploidization and mesopolyploidization events, followed by rearrangements and deletions or fusion of chromosome arms from an ancient progenitor with a haploid chromosome number of eight.
LBD18 uses a dual mode of a positive feedback loop to regulate ARF expression and transcriptional activity in Arabidopsis
Authors: Pandey Shashank K. , Lee Han Woo , Kim Min‐Jung , Cho Chuloh , Oh Eunkyoo , Kim Jungmook 
Published: April 2018

SummaryA hierarchy of transcriptional regulators controlling lateral root formation in Arabidopsis thaliana has been identified, including the AUXIN RESPONSE FACTOR 7 (ARF7)/ARF19‐LATERAL ORGAN BOUNDARIES DOMAIN 16 (LBD16)/LBD18 transcriptional network; however, their feedback regulation mechanisms are not known. Here we show that LBD18 controls ARF activity using the dual mode of a positive feedback loop. We showed that ARF7 and ARF19 directly bind AuxRE in the LBD18 promoter. A variety of molecular and biochemical experiments demonstrated that LBD18 binds a specific DNA motif in the ARF19 promoter to regulate its expression in vivo as well as in vitro. LBD18 interacts with ARFs including ARF7 and ARF19 via the Phox and Bem1 domain of ARF to enhance the transcriptional activity of ARF7 on AuxRE, and competes with auxin/indole‐3‐acetic acid (IAA) repressors for ARF binding, overriding the negative feedback loop exerted by Aux/IAA repressors. Taken together, these results show that LBD18 and ARFs form a double positive feedback loop, and that LBD18 uses the dual mode of a positive feedback loop by binding directly to the ARF19 promoter and through the protein–protein interactions with ARF7 and ARF19. This novel mechanism of feedback loops may constitute a robust feedback mechanism that ensures continued lateral root growth in response to auxin in Arabidopsis.
Direct Activation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by PF-06409577 Inhibits Flavivirus Infection through Modification of Host Cell Lipid Metabolism
Authors: Jiménez de Oya Nereida , Blázquez Ana-Belén , Casas Josefina , Saiz Juan-Carlos , Martín-Acebes Miguel A. 
Published: April 2018

ABSTRACTMosquito-borne flaviviruses are a group of RNA viruses that constitute global threats for human and animal health. Replication of these pathogens is strictly dependent on cellular lipid metabolism. We have evaluated the effect of the pharmacological activation of AMP-activated protein kinase (AMPK), a master regulator of lipid metabolism, on the infection of three medically relevant flaviviruses, namely, West Nile virus (WNV), Zika virus (ZIKV), and dengue virus (DENV). WNV is responsible for recurrent outbreaks of meningitis and encephalitis, affecting humans and horses worldwide. ZIKV has caused a recent pandemic associated with birth defects (microcephaly), reproductive disorders, and severe neurological complications (Guillain-Barré syndrome). DENV is the etiological agent of the most prevalent mosquito-borne viral disease, which can induce a potentially lethal complication called severe dengue. Our results showed, for the first time, that activation of AMPK using the specific small molecule activator PF-06409577 reduced WNV, ZIKV, and DENV infection. This antiviral effect was associated with an impairment of viral replication due to the modulation of host cell lipid metabolism exerted by the compound. These results support that the pharmacological activation of AMPK, which currently constitutes an important pharmacological target for human diseases, could also provide a feasible approach for broad-spectrum host-directed antiviral discovery.
Activities of Combinations of Antistaphylococcal Antibiotics with Fusidic Acid against Staphylococcal Biofilms in
In Vitro
Static and Dynamic Models
Authors: Siala Wafi , Rodriguez-Villalobos Hector , Fernandes Prabhavathi , Tulkens Paul M. , Van Bambeke Françoise 
Published: April 2018

ABSTRACT

Staphylococcal biofilms are a major cause of therapeutic failure, especially when caused by multiresistant strains. Oral fusidic acid is currently being redeveloped in the United States for skin, skin structure, and orthopedic infections, in which biofilms play a major role. The aim of this study was to examine the activity of fusidic acid alone or combined with other antistaphylococcal drugs against biofilms made by a reference strain and five clinical isolates of
Staphylococcus aureus
or
Staphylococcus epidermidis
in
in vitro
static and dynamic models (microtiter plates and a CDC reactor) exposed to clinically relevant concentrations. In microtiter plates, antibiotics alone were poorly active, with marked differences among strains. At concentrations mimicking the free-drug human maximum concentration of drug in serum (
C
max
), the combination of fusidic acid with linezolid, daptomycin, or vancomycin resulted in increased activity against 4 to 5 strains, while the combination with doxycycline, rifampin, or moxifloxacin increased activity against 1 to 3 strains only. In the CDC reactor, biofilms were grown under constant flow and antibiotic concentrations decreased over time according to human elimination rates. A bactericidal effect was obtained when fusidic acid was combined with daptomycin or linezolid, but not with vancomycin. The higher tolerance of biofilms to antibiotics in the CDC reactor is probably attributable to the more complex architecture they adopt when growing under constant flow. Because biofilms grown in the CDC reactor are considered more similar to those developing
in vivo
, the data support further testing of combinations of fusidic acid with daptomycin or linezolid in models pertinent to chronic skin, skin structure, or orthopedic infections.
Controlled cohort evaluation of theLiveLightermass media campaign’s impact on adults’ reported consumption of sugar-sweetened beverages
Authors: Morley Belinda C , Niven Philippa H , Dixon Helen G , Swanson Maurice G , McAleese Alison B , Wakefield Melanie A 
Published: April 2018

ObjectiveTo evaluate theLiveLighter‘Sugary Drinks’ campaign impact on awareness, knowledge and sugar-sweetened beverage (SSB) consumption.DesignCohort study with population surveys undertaken in intervention and comparison states at baseline (n=900 each), with 78% retention at follow-up (intervention: n=673; comparison: n=730). Analyses tested interactions by state (intervention, comparison) and time (baseline, follow-up).Setting and participantsAdults aged 25–49 years residing in the Australian states of Victoria and South Australia.InterventionThe 6-week mass media campaign ran in Victoria in October/November 2015. It focused on the contribution of SSBs to the development of visceral ‘toxic fat’, graphically depicted around vital organs, and ultimately serious disease. Paid television advertising was complemented by radio, cinema, online and social media advertising, and stakeholder and community engagement.Primary outcome measureSelf-reported consumption of SSBs, artificially sweetened drinks and water.Secondary outcome measuresCampaign recall and recognition; knowledge of the health effects of overweight and SSB consumption; perceived impact of SSB consumption on body weight and of reduced consumption on health.ResultsA significant reduction in frequent SSB consumption was observed in the intervention state (intervention: 31% compared with 22%, comparison: 30% compared with 29%; interaction p<0.01). This was accompanied by evidence of increased water consumption (intervention: 66% compared with 73%; comparison: 68% compared with 67%; interaction p=0.09) among overweight/obese SSB consumers. This group also showed increased knowledge of the health effects of SSB consumption (intervention: 60% compared with 71%, comparison: 63% compared with 59%; interaction p<0.05) and some evidence of increased prevalence of self-referent thoughts about SSB’s relationship to weight gain (intervention: 39% compared with 45%, comparison: 43% compared with 38%; interaction p=0.06).ConclusionsThe findings provide evidence of reduced SSB consumption among adults in the target age range following theLiveLightercampaign. This is notable in a context where public health campaigns occur against a backdrop of heavy commercial product advertising promoting increased SSB consumption.
Influence of playing rugby on long-term brain health following retirement: a systematic review and narrative synthesis
Authors: Cunningham Joice , Broglio Steven , Wilson Fiona 
Published: April 2018

ObjectivesThe aim of this review was to systematically investigate long-term brain health in retired rugby players.MethodsSix databases were systematically searched from inception to January 2018 using Medical Subject Headings and keywords. Two reviewers independently screened studies for inclusion. Cross-sectional studies of living retired male or female rugby players in which at least one cognitive test was used as an outcome measure were included. Data extraction was performed using Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Methodological quality was assessed independently by two reviewers using the Downs and Black methodological quality tool.ResultsThis review yielded six studies with an overall methodological quality of ‘moderate’. A total of 672 male retired rugby players (mean ages of 38–52 years) were included in this review. Three studies investigated neuropsychological functioning in retired rugby players in comparison with controls, with no significant evidence of decreased performance in the majority of tests when compared with controls. Five out of the six studies explored self-reported measures of cognition. Three studies compared retired rugby players to controls, one of which found significantly increased subjective cognitive complaints among retired rugby players. The other two studies found that persistent postconcussion symptoms were associated with a higher number of self-reported concussions. Two studies reported decreased fine motor control in retired rugby players in comparison with controls. Neurometabolites and electrophysiological changes were explored by two studies, with minimal and non-significant findings.ConclusionsOverall findings are mixed. Methodological biases reduce the overall study quality and limited the conclusions that can be drawn. Findings of decreased fine motor control in retired athletes may be influenced by lack of controlling for evidence of upper limb musculoskeletal injuries. While some studies show evidence of reduced cognitive function among former athletes, the results are not significantly lower than population norms. Cognitive findings from this review are inconsistent within and across study cohorts and are biased towards positive findings when self-report methods were selected. Current evidence suggests that large gaps remain in the understanding of the cause-and-effect relationships between playing rugby and long-term brain health in retired players.
Low scale composite Higgs model and 1.8 ∼2 TeV diboson excess
Authors: Bian Ligong , Liu Da , Shu Jing 
Published: April 2018

We consider a simple solution to explain the recent diboson excess observed by ATLAS and CMS Collaborations in models with custodial symmetry [Formula: see text]. The [Formula: see text] triplet vector boson [Formula: see text] with mass range of [Formula: see text] TeV would be produced through the Drell–Yan process with sizable diboson decay branching to account for the excess. The other [Formula: see text] bidoublet axial vector boson [Formula: see text] would cancel all deviations of electroweak obervables induced by [Formula: see text] even if the SM fermions mix with some heavy vector-like (composite) fermions which couple to [Formula: see text] (“nonuniversally partially composite”), therefore allows arbitrary couplings between each SM fermion and [Formula: see text]. We present our model in the “General Composite Higgs” framework with [Formula: see text] breaking at scale [Formula: see text] and demand the first Weinberg sum rule and positive gauge boson form factors as the theoretical constraints. We find that our model can fit the diboson excess very well if the left-handed SM light quarks, charged leptons and tops have zero, zero/moderately small and moderate/large composite components for reasonable values of [Formula: see text] and [Formula: see text]. The correlation between tree level [Formula: see text] parameter and the [Formula: see text] suggest a large [Formula: see text] contribution to [Formula: see text] and it is indeed a [Formula: see text] effect in our parameter space which provides a strong hint for our scenario if this diboson excess is confirmed by the [Formula: see text] TeV LHC Run II.
Beam dynamics pre-design with KONUS principle for the DTL of SPPC p-Linac
Authors: Liu Jing , Li Haipeng , Lu Yuanrong , Su Jiancang , Liu Xiaolong , Fu Qi 
Published: April 2018

As the Higgs bosons were observed on the LHC in 2012, a two-stage particle collider program named CEPC-SPPC is proposed for precise measurement of Higgs properties and exploring the new physics models. In order to deliver a 2.1-TeV proton beam into the Super Proton–Proton Collider (SPPC), the injector chain will use a 1.2-GeV proton linac (p-Linac) and three synchrotrons of p-RCS, MSS and SS. This paper focuses on the preliminary conceptual design of the DTL within the p-Linac and mainly concerns about the beam dynamics studies. Taking advantages of the KONUS principle and LORASR code, a 325 MHz, 50.65 MeV DTL design which is composed of three tanks in 15.6 m will be presented. The whole DTL contains 129 gaps for beam acceleration, one quadruple doublet which is behind the buncher and eight quadruple triplets of which three are located after each tank, respectively. The aims of this pre-study are to optimize the acceleration electric field distribution together with the focusing magnetic field parameters, enhance the beam transmission quality of beam envelopes, particle distribution and energy spread, then improve the DTL performance in terms of transmission efficiency and so on. The results of the analyses show that the DTL pre-design achieves 16.8 times high energy gain and meets all the p-Linac requirements well.
First write like you speak, then write like you write
Authors: Yaffe Philip 
Published: April 2018

Each "Communication Corner" essay is self-contained; however, they build on each other. For best results, before reading this essay and doing the exercise, go to the first essay "How an Ugly Duckling Became a Swan," then read each succeeding essay.
In this installment, Philip Yaffe introduces a two-step plan to create well-written text that will not only impress the reader, but also engage the reader to digest and comprehend new ideas or concepts with ease.