bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling the mode of action of plant proteases
Authors: van der Hoorn Renier A. L. , Rivas Susana 
Published: April 2018

This article is a Commentary on Schaller et al. (pp. 901–915), Liu & Moschou (pp. 916–922), James et al. (pp. 923–928), Dissmeyer et al. (pp. 929–935), Demir et al. (pp. 936–943), Zhang et al. (pp. 1106–1126), Radchuk et al. (pp. 1127–1142), Cai et al. (pp. 1143–1155), Lema Asqui et al. (pp. 1156–1166), Beloshistov et al. (pp. 1167–1178) and Klemenčič & Funk (pp. 1179–1191), all of which are published in this issue.
Randomized, double‐blind comparison of aripiprazole/sertraline combination and placebo/sertraline combination in patients with major depressive disorder
Authors: Kamijima Kunitoshi , Kimura Mahito , Kuwahara Kazuo , Kitayama Yuri , Tadori Yoshihiro 
Published: April 2018

AimThis study compared the efficacy and safety of aripiprazole/sertraline combination (ASC) and placebo/sertraline combination (PSC) in patients with major depressive disorder (MDD) who showed an inadequate response to sertraline 100 mg/day.MethodsThe study comprised a screening period, an 8‐week prospective treatment (single‐blind sertraline 25–100 mg/day) period, and a 6‐week double‐blind treatment period. Patients with DSM‐5‐defined MDD were enrolled. Following the prospective treatment, non‐responders were randomly assigned to the ASC group (aripiprazole 3–12 mg/day/sertraline 100 mg/day) or the PSC group (sertraline 100 mg/day). The primary efficacy end‐point was the mean change in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score from baseline to 6 weeks.ResultsA total of 412 patients were randomly assigned to either the ASC group (n = 209) or the PSC group (n = 203). Mean change in MADRS total score was significantly greater in patients with ASC than PSC (−9.2 vs −7.2; P = 0.0070). Treatment‐emergent adverse events (TEAE) that occurred in ≥10% of patients with ASC versus PSC were nasopharyngitis (13.4% vs 11.3%) and akathisia (12.9% vs 3.4%). All TEAE reported in the ASC group were mild or moderate in severity. Rates of discontinuations due to TEAE were low in both the ASC (1.9%) and PSC (1.5%) groups. There were no notable issues in safety assessments in the ASC group compared with the PSC group.ConclusionIn patients with MDD who showed an inadequate response to treatment with sertraline 100 mg/day, ASC was efficacious and well tolerated.
Depth camera indoor mapping for 3D virtual radio play
Authors: Virtanen Juho‐Pekka , Kurkela Matti , Turppa Tuomas , Vaaja Matti T. , Julin Arttu , Kukko Antero , Hyyppä Juha , Ahlavuo Marika , von Numers Jessica Edén , Haggrén Henrik , Hyyppä Hannu 
Published: April 2018

AbstractBy combining game engines with indoor mapping, it is possible to create interactive virtual environments that represent the real world. In this paper a virtual version of an audio installation in a historic building is produced, where the user freely explores the building and experiences a set of audio clips, creating a virtual radio play. A depth camera indoor mapping system, Matterport, captured a set of staged interiors. The aim was to evaluate the quality and usability of the indoor models and to demonstrate applying them in 3D application development. The quality of the models was evaluated by comparison with laser scanning, revealing limitations with Matterport: increasing the size of the measured area lowered the level of detail and accuracy of volumetric models. The quality of textures was not affected by this limitation, maintaining the appearance of models. To obtain optimised models for mobile 3D applications, a manual revision process was applied.
Disparities in out‐of‐pocket inpatient expenditures in rural Shaanxi Province, western China from 2011 to 2014: a time series analysis
Authors: Yang Caijun , Cai Wenfang , Li Zongjie , Fang Yu 
Published: April 2018

AbstractObjectiveTo investigate the long‐term trend of disparity of monthly average out‐of‐pocket inpatient expenditures (OOP) between areas with different developing levels since the new healthcare reform.MethodsTime series regression was used to assess the trend of disparities of OOP and monthly average inpatient expenditures (AIE) between areas with different developing levels in rural Shaanxi Province, western China. The data of OOP and AIE in primary health institutions, secondary hospitals, tertiary hospitals and also all levels of the hospital were analysed separately covering the period 2011 through to 2014.ResultsThe disparity of AIE at all levels of hospitals was increasing (coefficient = 0.003, P = 0.029), and only the disparity of AIE in secondary hospitals was statistical significant (coefficient = 0.003, P = 0.012) when separately considering different levels of the hospital. The disparity of OOP in all levels of the hospital was increasing (coefficient = 0.007, P = 0.001), and the OOP in primary hospitals contributed most of the disparity (coefficient = 0.019, P = 0.000), followed by OOP in secondary (coefficient = 0.008, P = 0.003) and tertiary hospitals (coefficient = 0.004, P = 0.091).ConclusionsA statistically significant absolute increase in the trend of disparities of OOP and AIE at all levels of hospital was detected after the new healthcare reform in Shaanxi Province, western China. The increase rate of disparity of OOP was bigger than that of AIE. A modified health insurance plan should be proposed to guarantee equity in the future.
A critical role for Arabidopsis MILDEW RESISTANCE LOCUS O2 in systemic acquired resistance
Authors: Gruner Katrin , Zeier Tatyana , Aretz Christina , Zeier Jürgen 
Published: April 2018

SummaryMembers of the MILDEW RESISTANCE LOCUS O (MLO) gene family confer susceptibility to powdery mildews in different plant species, and their existence therefore seems to be disadvantageous for the plant. We recognized that expression of the Arabidopsis MLO2 gene is induced after inoculation with the bacterial pathogen Pseudomonas syringae, promoted by salicylic acid (SA) signaling, and systemically enhanced in the foliage of plants exhibiting systemic acquired resistance (SAR). Importantly, distinct mlo2 mutant lines were unable to systemically increase resistance to bacterial infection after inoculation with P. syringae, indicating that the function of MLO2 is necessary for biologically induced SAR in Arabidopsis. Our data also suggest that the close homolog MLO6 has a supportive but less critical role in SAR. In contrast to SAR, basal resistance to bacterial infection was not affected in mlo2. Remarkably, SAR‐defective mlo2 mutants were still competent in systemically increasing the levels of the SAR‐activating metabolites pipecolic acid (Pip) and SA after inoculation, and to enhance SAR‐related gene expression in distal plant parts. Furthermore, although MLO2 was not required for SA‐ or Pip‐inducible defense gene expression, it was essential for the proper induction of disease resistance by both SAR signals. We conclude that MLO2 acts as a critical downstream component in the execution of SAR to bacterial infection, being required for the translation of elevated defense responses into disease resistance. Moreover, our data suggest a function for MLO2 in the activation of plant defense priming during challenge by P. syringae.
Glutathione transferases catalyze recycling of auto‐toxic cyanogenic glucosides in sorghum
Authors: Bjarnholt Nanna , Neilson Elizabeth H. J. , Crocoll Christoph , Jørgensen Kirsten , Motawia Mohammed Saddik , Olsen Carl Erik , Dixon David P. , Edwards Robert , Møller Birger Lindberg 
Published: April 2018

SummaryCyanogenic glucosides are nitrogen‐containing specialized metabolites that provide chemical defense against herbivores and pathogens via the release of toxic hydrogen cyanide. It has been suggested that cyanogenic glucosides are also a store of nitrogen that can be remobilized for general metabolism via a previously unknown pathway. Here we reveal a recycling pathway for the cyanogenic glucoside dhurrin in sorghum (Sorghum bicolor) that avoids hydrogen cyanide formation. As demonstrated in vitro, the pathway proceeds via spontaneous formation of a dhurrin‐derived glutathione conjugate, which undergoes reductive cleavage by glutathione transferases of the plant‐specific lambda class (GSTLs) to produce p‐hydroxyphenyl acetonitrile. This is further metabolized to p‐hydroxyphenylacetic acid and free ammonia by nitrilases, and then glucosylated to form p‐glucosyloxyphenylacetic acid. Two of the four GSTLs in sorghum exhibited high stereospecific catalytic activity towards the glutathione conjugate, and form a subclade in a phylogenetic tree of GSTLs in higher plants. The expression of the corresponding two GSTLs co‐localized with expression of the genes encoding the p‐hydroxyphenyl acetonitrile‐metabolizing nitrilases at the cellular level. The elucidation of this pathway places GSTs as key players in a remarkable scheme for metabolic plasticity allowing plants to reverse the resource flow between general and specialized metabolism in actively growing tissue.
BEL1‐LIKE HOMEODOMAIN 11 regulates chloroplast development and chlorophyll synthesis in tomato fruit
Authors: Meng Lanhuan , Fan Zhongqi , Zhang Qiang , Wang Cuicui , Gao Ying , Deng Yikang , Zhu Benzhong , Zhu Hongliang , Chen Jianye , Shan Wei , Yin Xueren , Zhong Silin , Grierson Donald , Jiang Cai‐Zhong , Luo Yunbo , Fu Da‐Qi 
Published: April 2018

SummaryChloroplast development and chlorophyll(Chl)metabolism in unripe tomato contribute to the growth and quality of the fruit, however these mechanisms are poorly understood. In this study, we initially investigated seven homeobox‐containing transcription factors (TFs) with specific ripening‐associated expression patterns using virus‐induced gene silencing (VIGS) technology and found that inhibiting the expression of one of these TFs, BEL1‐LIKE HOMEODOMAIN11 (SlBEL11), significantly increased Chl levels in unripe tomato fruit. This enhanced Chl accumulation was further validated by generating stable RNA interference (RNAi) transgenic lines. RNA sequencing (RNA‐seq) of RNAi‐SlBEL11 fruit at the mature green (MG) stage showed that 48 genes involved in Chl biosynthesis, photosynthesis and chloroplast development were significantly upregulated compared with the wild type (WT) fruit. Genomic global scanning for Homeobox TF binding sites combined with RNA‐seq differential gene expression analysis showed that 22 of these 48 genes were potential target genes of SlBEL11 protein. These genes included Chl biosynthesis‐related genes encoding for protochlorophyllide reductase (POR), magnesium chelatase H subunit (CHLH) and chlorophyllide a oxygenase (CAO), and chloroplast development‐related genes encoding for chlorophyll a/b binding protein (CAB), homeobox protein knotted 2 (TKN2) and ARABIDOPSIS PSEUDO RESPONSE REGULATOR 2‐LIKE (APRR2‐like). Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation quantitative polymerase chain reaction (PCR) (ChIP‐qPCR) assays were employed to verify that SlBEL11 protein could bind to the promoters for TKN2, CAB and POR. Taken together, our findings demonstrated that SlBEL11 plays an important role in chloroplast development and Chl synthesis in tomato fruit.
Genome‐wide Hi‐C analysis reveals extensive hierarchical chromatin interactions in rice
Authors: Dong Qianli , Li Ning , Li Xiaochong , Yuan Zan , Xie Dejian , Wang Xiaofei , Li Jianing , Yu Yanan , Wang Jinbin , Ding Baoxu , Zhang Zhibin , Li Changping , Bian Yao , Zhang Ai , Wu Ying , Liu Bao , Gong Lei 
Published: April 2018

SummaryThe non‐random spatial packing of chromosomes in the nucleus plays a critical role in orchestrating gene expression and genome function. Here, we present a Hi‐C analysis of the chromatin interaction patterns in rice (Oryza sativa L.) at hierarchical architectural levels. We confirm that rice chromosomes occupy their own territories with certain preferential inter‐chromosomal associations. Moderate compartment delimitation and extensive TADs (Topologically Associated Domains) were determined to be associated with heterogeneous genomic compositions and epigenetic marks in the rice genome. We found subtle features including chromatin loops, gene loops, and off‐/near‐diagonal intensive interaction regions. Gene chromatin loops associated with H3K27me3 could be positively involved in gene expression. In addition to insulated enhancing effects for neighbor gene expression, the identified rice gene loops could bi‐directionally (+/−) affect the expression of looped genes themselves. Finally, web‐interleaved off‐diagonal IHIs/KEEs (Interactive Heterochromatic Islands or KNOT ENGAGED ELEMENTs) could trap transposable elements (TEs) via the enrichment of silencing epigenetic marks. In parallel, the near‐diagonal FIREs (Frequently Interacting Regions) could positively affect the expression of involved genes. Our results suggest that the chromatin packing pattern in rice is generally similar to that in Arabidopsis thaliana but with clear differences at specific structural levels. We conclude that genomic composition, epigenetic modification, and transcriptional activity could act in combination to shape global and local chromatin packing in rice. Our results confirm recent observations in rice and A. thaliana but also provide additional insights into the patterns and features of chromatin organization in higher plants.
GNA11 differentially mediates fibroblast growth factor 2‐ and vascular endothelial growth factor A‐induced cellular responses in human fetoplacental endothelial cells
Authors: Zou Qing‐yun , Zhao Ying‐jie , Li Hua , Wang Xiang‐zhen , Liu Ai‐xia , Zhong Xin‐qi , Yan Qin , Li Yan , Zhou Chi , Zheng Jing 
Published: April 2018

Key points
Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function.
It is not known whether GNA11 mediates FGF2‐ and VEGFA‐induced endothelial cell responses under physiological chronic low O2.
In the present study, we show that knockdown of GNA11 significantly decreases FGF2‐ and VEGFA‐induced fetoplacental endothelial cell migration but not proliferation and permeability.
Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C‐β3.
The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2‐ and VEGFA‐induced fetoplacental endothelial function.
AbstractDuring pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gαq/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2‐ and VEGFA‐induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O2 (3% O2), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P < 0.05) FGF2‐ and VEGFA‐stimulated fetoplacental endothelial migration (by ∼36% and ∼50%, respectively) but not proliferation and permeability. GNA11 siRNA also elevated (P < 0.05) FGF2‐ and VEGFA‐induced phosphorylation of phospholipase C‐β3 (PLCβ3) at S537 in a time‐dependent fashion but not mitogen‐activated protein kinase 3/1 (ERK1/2) and v‐akt murine thymoma viral oncogene homologue 1 (AKT1). These data suggest that GNA11 mediates FGF2‐ and VEGFA‐stimulated fetoplacental endothelial cell migration partially via altering the activation of PLCβ3.
Pathogenic Effects of IFIT2 and Interferon-β during Fatal Systemic Candida albicans Infection
Authors: Stawowczyk Marcin , Naseem Shamoon , Montoya Valeria , Baker Darren P. , Konopka James , Reich Nancy C. 
Published: April 2018

ABSTRACTA balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminatedCandida albicans. Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, andC. albicansis a common culprit that leads to high rates of mortality. When IFIT2 knockout mice were infected systemically withC. albicans, they were found to have improved survival and reduced fungal burden compared to wild-type mice. One of the mechanisms by which IFIT2 increases the pathological effects of invasiveC. albicansappears to be suppression of NADPH oxidase activation. Loss of IFIT2 increases production of reactive oxygen species by leukocytes, and we demonstrate that IFIT2 is a binding partner of a critical regulatory subunit of NADPH oxidase, p67phox. Since the administration of IFN has been used therapeutically to combat viral infections, cancer, and multiple sclerosis, we evaluated administration of IFN-β to mice prior toC. albicansinfection. IFN-β treatment promoted pathology and death fromC. albicansinfection. We provide evidence that IFIT2 increases the pathological effects of invasiveC. albicansand that administration of IFN-β has deleterious effects during infection.IMPORTANCEThe attributable mortality associated with systemicC. albicansinfections in health care settings is significant, with estimates greater than 40%. This life-threatening disease is common in patients with weakened immune systems, either due to disease or as a result of therapies. Type I interferons (IFN) are cytokines of the innate defense response that are used as immune modulators in the treatment of specific cancers, viral infections, and multiple sclerosis. In this study, we show using a murine model that the loss of a specific IFN-stimulated gene coding for IFIT2 improves survival following systemicC. albicansinfection. This result infers a harmful effect of IFN duringC. albicansinfection and is supported by our finding that administration of IFN-β prior to invasive infection promotes fatal pathology. The findings contribute to our understanding of the innate immune response toC. albicans, and they suggest that IFN therapies present a risk factor for disseminated candidiasis.
Viable-but-Nonculturable Listeria monocytogenes and Salmonella enterica Serovar Thompson Induced by Chlorine Stress Remain Infectious
Authors: Highmore Callum J. , Warner Jennifer C. , Rothwell Steve D. , Wilks Sandra A. , Keevil C. William 
Published: April 2018

ABSTRACT

The microbiological safety of fresh produce is monitored almost exclusively by culture-based detection methods. However, bacterial food-borne pathogens are known to enter a viable-but-nonculturable (VBNC) state in response to environmental stresses such as chlorine, which is commonly used for fresh produce decontamination. Here, complete VBNC induction of green fluorescent protein-tagged
Listeria monocytogenes
and
Salmonella enterica
serovar Thompson was achieved by exposure to 12 and 3 ppm chlorine, respectively. The pathogens were subjected to chlorine washing following incubation on spinach leaves. Culture data revealed that total viable
L. monocytogenes
and
Salmonella
Thompson populations became VBNC by 50 and 100 ppm chlorine, respectively, while enumeration by direct viable counting found that chlorine caused a <1-log reduction in viability. The pathogenicity of chlorine-induced VBNC
L. monocytogenes
and
Salmonella
Thompson was assessed by using
Caenorhabditis elegans
. Ingestion of VBNC pathogens by
C. elegans
resulted in a significant life span reduction (
P
= 0.0064 and
P
< 0.0001), and no significant difference between the life span reductions caused by the VBNC and culturable
L. monocytogenes
treatments was observed.
L. monocytogenes
was visualized beyond the nematode intestinal lumen, indicating resuscitation and cell invasion. These data emphasize the risk that VBNC food-borne pathogens could pose to public health should they continue to go undetected.

IMPORTANCE
Many bacteria are known to enter a viable-but-nonculturable (VBNC) state in response to environmental stresses. VBNC cells cannot be detected by standard laboratory culture techniques, presenting a problem for the food industry, which uses these techniques to detect pathogen contaminants. This study found that chlorine, a sanitizer commonly used for fresh produce, induces a VBNC state in the food-borne pathogens
Listeria monocytogenes
and
Salmonella enterica
. It was also found that chlorine is ineffective at killing total populations of the pathogens. A life span reduction was observed in
Caenorhabditis elegans
that ingested these VBNC pathogens, with VBNC
L. monocytogenes
as infectious as its culturable counterpart. These data show that VBNC food-borne pathogens can both be generated and avoid detection by industrial practices while potentially retaining the ability to cause disease.
The Blast Fungus Decoded: Genomes in Flux
Authors: Langner Thorsten , Białas Aleksandra , Kamoun Sophien 
Published: April 2018

ABSTRACT

Plant disease outbreaks caused by fungi are a chronic threat to global food security. A prime case is blast disease, which is caused by the ascomycete fungus
Magnaporthe oryzae
(syn.
Pyricularia oryzae
), which is infamous as the most destructive disease of the staple crop rice. However, despite its Linnaean binomial name,
M. oryzae
is a multihost pathogen that infects more than 50 species of grasses. A timely study by P. Gladieux and colleagues (mBio 9:e01219-17, 2018,
https://doi.org/10.1128/mBio.01219-17
) reports the most extensive population genomic analysis of the blast fungus thus far.
M. oryzae
consists of an assemblage of differentiated lineages that tend to be associated with particular host genera. Nonetheless, there is clear evidence of gene flow between lineages consistent with maintaining
M. oryzae
as a single species. Here, we discuss these findings with an emphasis on the ecologic and genetic mechanisms underpinning gene flow. This work also bears practical implications for diagnostics, surveillance, and management of blast diseases.