bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rank-Based Procedures in Factorial Designs: Hypotheses About Non-Parametric Treatment Effects
Authors: Brunner Edgar , Konietschke Frank , Pauly Markus , Puri Madan L. 
Published: December 2016

Summary
Existing tests for factorial designs in the non-parametric case are based on hypotheses formulated in terms of distribution functions. Typical null hypotheses, however, are formulated in terms of some parameters or effect measures, particularly in heteroscedastic settings. Here this idea is extended to non-parametric models by introducing a novel non-parametric analysis-of-variance type of statistic based on ranks or pseudoranks which is suitable for testing hypotheses formulated in meaningful non-parametric treatment effects in general factorial designs. This is achieved by a careful detailed study of the common distribution of rank-based estimators for the treatment effects. Since the statistic is asymptotically not a pivotal quantity we propose three different approximation techniques, discuss their theoretic properties and compare them in extensive simulations together with two additional Wald-type tests. An extension of the presented idea to general repeated measures designs is briefly outlined. The rank- and pseudorank-based procedures proposed maintain the preassigned type I error rate quite accurately, also in unbalanced and heteroscedastic models.
Association Between TNF‐α Promoter −308 A/G Polymorphism and Systemic Lupus Erythematosus Susceptibility: A Case–Control Study and Meta‐Analysis
Authors: Yang Z.‐C. , Xu F. , Tang M. , Xiong X. 
Published: December 2016

AbstractThe tumour necrosis factor‐α (TNF‐α) promoter −308 A/G polymorphism plays an important role in the aetiology of systemic lupus erythematosus (SLE). Several studies have estimated the association between TNF‐α −308 A/G and SLE risk. However, results were inconsistent. A case–control study was carried out to explore the association between TNF‐α −308 A/G and the SLE risk in a Chinese Han population. Meta‐analysis combining present with previous studies was conducted to further explore the association. Our case–control study included 556 patients with SLE along with 570 matched healthy controls. TNF‐α −308 A allele was significantly increased in patients with SLE compared with controls (OR = 2.184, 95% CI: 1.718–2.778, P < 0.001). Genotypes AA and AG were associated with the susceptibility to SLE as compared with the GG genotype, as well as the dominant model (AA+AG versus GG), respectively. The meta‐analysis included 41 comparative studies involving 4799 patients and 6635 controls. An association between SLE and allele A was found in the overall populations (OR = 1.70, 95% CI: 1.46–1.98, P < 0.001). In addition, we discussed the correlation between this polymorphism and lupus nephritis (LN) risk, showing that allele A was significantly related to LN in the overall populations (OR = 1.80, 95% CI: 1.21–2.68, P = 0.004). The results from our case–control study and the meta‐analysis indicate that the TNF‐α −308 A allele is significantly associated with an increased risk of SLE/LN.
M2000 (β‐D‐Mannuronic Acid) as a Novel Antagonist for Blocking the TLR2 and TLR4 Downstream Signalling Pathway
Authors: Aletaha S. , Haddad L. , Roozbehkia M. , Bigdeli R. , Asgary V. , Mahmoudi M. , Mirshafiey A. 
Published: December 2016

AbstractTo date, selective blockade of Toll‐like receptor (TLR) signalling has been developed as a new approach for treatment for many inflammatory diseases. As β‐D‐mannuronic acid (M2000) has been known as an anti‐inflammatory molecule in several experimental models, we investigated the antagonistic effects of M2000 on TLR2 and TLR4 downstream signalling transduction pathway in human embryonic kidney (HEK) 293 cell lines overexpressing TLR2/CD14 and the TLR4/MD2/CD14 complex, respectively. M2000 effectively inhibited mRNA expression of MyD88 and p65, major subunit of nuclear factor‐κB, in HEK293 cells stimulated by lipoteichoic acid (LTA, a TLR2 agonist) and lipopolysaccharide (LPS, a TLR4 agonist) with no evidence of cytotoxicity. In addition, M2000 also suppressed LTA and LPS‐induced production of TNF‐α and IL‐6 inflammatory cytokines in these cells. Furthermore, the results revealed that M2000 had no significant effect on Tollip mRNA expression as a negative regulator of TLR signalling in aforesaid cells. Overall, these data point to M2000 inhibitory effect on Toll‐like receptor (TLR) 2, 4 signalling in HEK293 cells. This information might provide new insights into the possible roles of this small drug in order to introduce it as a TLR signalling pathway inhibitor. However, more studies are needed to confirm β‐D‐mannuronic acid antagonistic effects including the effects of M2000 on peritoneal isolated macrophages and also on blood cells in patients with inflammatory diseases such as ankylosing spondylitis.
Invasive fungal infection after heart transplantation: A 7‐year, single‐center experience
Authors: Echenique Ignacio A. , Angarone Michael P. , Gordon Robert A. , Rich Jonathan , Anderson Allen S. , McGee Edwin C. , Abicht Travis O. , Kang Joseph , Stosor Valentina 
Published: December 2016

AbstractBackgroundInvasive fungal infections (IFIs) are an infrequent but major complication of heart transplantation (HT). We sought to describe the epidemiology at our institution.MethodsA prospective cohort study of 159 heart transplant recipients was performed from June 2005 to December 2012. IFIs were defined by European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria.ResultsBy univariate analysis, Hispanic ethnicity was associated with IFI (P=.01, odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7‐27.9). Subsequently, a multivariate logistic regression was performed adjusting for Hispanic ethnicity, age, and gender. Seventeen IFIs were identified, occurring at a median 110 days post HT (interquartile range: 32‐411 days). Five IFIs (29% of IFIs and 3.1% of all HT) occurred during the HT hospitalization, with 13 IFIs during the first year (incidence 8.2%).ConclusionsThe cumulative incidence was 10.7%. IFIs were associated with pre‐ and post‐HT vancomycin‐resistant Enterococcus colonization and/or infection, post‐HT renal replacement therapy, anti‐thymocyte globulin induction, and antibody‐mediated rejection. There were no associations with diabetes mellitus, desensitization, 2R/3R cellular rejection, treatments for rejection, re‐operation, neutropenia, or cytomegalovirus infection. IFIs were associated with death (P=.02, OR 3.9, 95% CI 1.3‐12.1) and 1‐year mortality (P<.001, OR 9.0, 95% CI 2.3‐35.7), but not 3‐year mortality. Associations with Hispanic ethnicity must be validated. Optimal strategies for risk reduction and prophylaxis remain undefined.
Color Processing in Synesthesia: What Synesthesia Can and Cannot Tell Us About Mechanisms of Color Processing
Authors: Janik McErlean Agnieszka B. , Banissy Michael J. 
Published: December 2016

AbstractSynesthetic experiences of color have been traditionally conceptualized as a perceptual phenomenon. However, recent evidence suggests a role of higher order cognition in the formation of synesthetic experiences. Here, we discuss how synesthetic experiences of color differ from and influence veridical color processing, and how non‐perceptual processes such as imagery and color memory might play a role in eliciting synesthetic color experience.
Microscale magnetic microparticle‐based immunopurification of cytokinins from Arabidopsis root apex
Authors: Plačková Lenka , Oklestkova Jana , Pospíšková Kristýna , Poláková Kateřina , Buček Jan , Stýskala Jakub , Zatloukal Marek , Šafařík Ivo , Zbořil Radek , Strnad Miroslav , Doležal Karel , Novák Ondřej 
Published: December 2016

SummaryCytokinins (CKs) are pivotal plant hormones that have crucial roles in plant growth and development. However, their isolation and quantification are usually challenging because of their extremely low levels in plant tissues (pmol g−1 fresh weight). We have developed a simple microscale magnetic immunoaffinity‐based method for selective one‐step isolation of CKs from very small amounts of plant tissue (less than 0.1 mg fresh weight). The capacity of the immunosorbent and the effect of the complex plant matrix on the yield of the rapid one‐step purification were tested using a wide range of CK concentrations. The total recovery range of the new microscale isolation procedure was found to be 30–80% depending on individual CKs. Immunoaffinity extraction using group‐specific monoclonal CK antibodies immobilized onto magnetic microparticles was combined with a highly sensitive ultrafast mass spectrometry‐based method with a detection limit close to one attomole. This combined approach allowed metabolic profiling of a wide range of naturally occurring CKs (bases, ribosides and N9‐glucosides) in 1.0‐mm sections of the Arabidopsis thaliana root meristematic zone. The magnetic immunoaffinity separation method was shown to be a simple and extremely fast procedure requiring minimal amounts of plant tissue.
The impact of Arabidopsis thaliana SNF1‐related‐kinase 1 (SnRK1)‐activating kinase 1 (SnAK1) and SnAK2 on SnRK1 phosphorylation status: characterization of a SnAK double mutant
Authors: Glab Nathalie , Oury Céline , Guérinier Thomas , Domenichini Séverine , Crozet Pierre , Thomas Martine , Vidal Jean , Hodges Michael 
Published: December 2016

SummaryArabidopsis thaliana SNF1‐related‐kinase 1 (SnRK1)‐activating kinase 1 (AtSnAK1) and AtSnAK2 have been shown to phosphorylate in vitro and activate the energy signalling integrator, SnRK1. To clarify this signalling cascade in planta, a genetic‐ and molecular‐based approach was developed. Homozygous single AtSnAK1 and AtSnAK2 T‐DNA insertional mutants did not display an apparent phenotype. Crossing of the single mutants did not allow the isolation of double‐mutant plants, whereas self‐pollinating the S1−/− S2+/− sesquimutant specifically gave approximatively 22% individuals in their offspring that, when rescued on sugar‐supplemented media in vitro, were shown to be AtSnAK1 AtSnAK2 double mutants. Interestingly, this was not obtained in the case of the other sesquimutant, S1+/− S2−/−. Although reduced in size, the double mutant had the capacity to produce flowers, but not seeds. Immunological characterization established the T‐loop of the SnRK1 catalytic subunit to be non‐phosphorylated in the absence of both SnAKs. When the double mutant was complemented with a DNA construct containing an AtSnAK2 open reading frame driven by its own promoter, a normal phenotype was restored. Therefore, wild‐type plant growth and development is dependent on the presence of SnAK in vivo, and this is correlated with SnRK1 phosphorylation. These data show that both SnAKs are kinases phosphorylating SnRK1, and thereby they contribute to energy signalling in planta.
Identification of core subunits of photosystem II as action sites of HSP21, which is activated by the GUN5‐mediated retrograde pathway in Arabidopsis
Authors: Chen Si‐Ting , He Ning‐Yu , Chen Juan‐Hua , Guo Fang‐Qing 
Published: December 2016

SummaryPhotosystem II (PSII) is the most thermolabile photosynthetic complex. Physiological evidence suggests that the small chloroplast heat‐shock protein 21 (HSP21) is involved in plant thermotolerance, but the molecular mechanism of its action remains largely unknown. Here, we have provided genetic and biochemical evidence that HSP21 is activated by the GUN5‐dependent retrograde signaling pathway, and stabilizes PSII by directly binding to its core subunits such as D1 and D2 proteins under heat stress. We further demonstrate that the constitutive expression of HSP21 sufficiently rescues the thermosensitive stability of PSII and survival defects of the gun5 mutant with dramatically improving granal stacking under heat stress, indicating that HSP21 is a key chaperone protein in maintaining the integrity of the thylakoid membrane system under heat stress. In line with our interpretation based on several lines of in vitro and in vivo protein‐interaction evidence that HSP21 interacts with core subunits of PSII, the kinetics of HSP21 binding to the D1 and D2 proteins was determined by performing an analysis of microscale thermophoresis. Considering the major role of HSP21 in protecting the core subunits of PSII from thermal damage, its heat‐responsive activation via the heat‐shock transcription factor HsfA2 is critical for the survival of plants under heat stress. Our findings reveal an auto‐adaptation loop pathway that plant cells optimize particular needs of chloroplasts in stabilizing photosynthetic complexes by relaying the GUN5‐dependent plastid signal(s) to activate the heat‐responsive expression of HSP21 in the nucleus during adaptation to heat stress in plants.
A bacterial artificial chromosome (BAC) genomic approach reveals partial clustering of the furanocoumarin pathway genes in parsnip
Authors: Roselli Sandro , Olry Alexandre , Vautrin Sonia , Coriton Olivier , Ritchie Dave , Galati Gianni , Navrot Nicolas , Krieger Célia , Vialart Guilhem , Bergès Hélène , Bourgaud Frédéric , Hehn Alain 
Published: December 2016

SummaryFuranocoumarins are specialized metabolites that are involved in the defense of plants against phytophagous insects. The molecular and functional characterization of the genes involved in their biosynthetic pathway is only partially complete. Many recent reports have described gene clusters responsible for the biosynthesis of specialized metabolites in plants. To investigate possible co‐localization of the genes involved in the furanocoumarin pathway, we sequenced parsnip BAC clones spanning two different gene loci. We found that two genes previously identified in this pathway, CYP71AJ3 and CYP71AJ4, were located on the same BAC, whereas a third gene, PsPT1, belonged to a different BAC clone. Chromosome mapping using fluorescence in situ hybridization (FISH) indicated that PsPT1 and the CYP71AJ3‐CYP71AJ4 clusters are located on two different chromosomes. Sequencing the BAC clone harboring PsPT1 led to the identification of a gene encoding an Fe(II) α‐ketoglutarate‐dependent dioxygenase (PsDIOX) situated in the neighborhood of PsPT1 and confirmed the occurrence of a second gene cluster involved in the furanocoumarin pathway. This enzyme metabolizes p‐coumaroyl CoA, leading exclusively to the synthesis of umbelliferone, an important intermediate compound in furanocoumarin synthesis. This work provides an insight into the genomic organization of genes from the furanocoumarin biosynthesis pathway organized in more than one gene cluster. It also confirms that the screening of a genomic library and the sequencing of BAC clones represent a valuable tool to identify genes involved in biosynthetic pathways dedicated to specialized metabolite synthesis.
Influences of pH and Iron Concentration on the Salivary Microbiome in Individual Humans with and without Caries
Authors: Zhou Jianye , Jiang Nan , Wang Zhenzhen , Li Longqing , Zhang Jumei , Ma Rui , Nie Hongbing , Li Zhiqiang 
Published: December 2016

ABSTRACT
This study aimed to identify the differences in the oral microbial communities in saliva from patients with and without caries by performing sequencing with the Illumina MiSeq platform, as well as to further assess their relationships with environmental factors (salivary pH and iron concentration). Forty-three volunteers were selected, including 21 subjects with and 22 without caries, from one village in Gansu, China. Based on 966,255 trimmed sequences and clustering at the 97% similarity level, 1,303 species-level operational taxonomic units were generated. The sequencing data for the two groups revealed that (i) particular distribution patterns (synergistic effects or competition) existed in the subjects with and without caries at both the genus and species levels and (ii) both the salivary pH and iron concentration had significant influences on the microbial community structure.

IMPORTANCE
The significant influences of the oral environment observed in this study increase the current understanding of the salivary microbiome in caries. These results will be useful for expanding research directions and for improving disease diagnosis, prognosis, and therapy.
Contribution of Pentose Catabolism to Molecular Hydrogen Formation by Targeted Disruption of Arabinose Isomerase (
araA
) in the Hyperthermophilic Bacterium Thermotoga maritima
Authors: White Derrick , Singh Raghuveer , Rudrappa Deepak , Mateo Jackie , Kramer Levi , Freese Laura , Blum Paul 
Published: December 2016

ABSTRACT

Thermotoga maritima
ferments a broad range of sugars to form acetate, carbon dioxide, traces of lactate, and near theoretic yields of molecular hydrogen (H
2
). In this organism, the catabolism of pentose sugars such as arabinose depends on the interaction of the pentose phosphate pathway with the Embden-Myerhoff and Entner-Doudoroff pathways. Although the values for H
2
yield have been determined using pentose-supplemented complex medium and predicted by metabolic pathway reconstruction, the actual effect of pathway elimination on hydrogen production has not been reported due to the lack of a genetic method for the creation of targeted mutations. Here, a spontaneous and genetically stable
pyrE
deletion mutant was isolated and used as a recipient to refine transformation methods for its repair by homologous recombination. To verify the occurrence of recombination and to assess the frequency of crossover events flanking the deleted region, a synthetic
pyrE
allele, encoding synonymous nucleotide substitutions, was used. Targeted inactivation of
araA
(encoding arabinose isomerase) in the
pyrE
mutant was accomplished using a divergent, codon-optimized
Thermosipho africanus pyrE
allele fused to the
T. maritima groES
promoter as a genetic marker. Mutants lacking
araA
were unable to catabolize arabinose in a defined medium. The
araA
mutation was then repaired using targeted recombination. Levels of synthesis of H
2
using arabinose-supplemented complex medium by wild-type and
araA
mutant cell lines were compared. The difference between strains provided a direct measurement of H
2
production that was dependent on arabinose consumption. Development of a targeted recombination system for genetic manipulation of
T. maritima
provides a new strategy to explore H
2
formation and life at an extremely high temperature in the bacterial domain.

IMPORTANCE
We describe here the development of a genetic system for manipulation of
Thermotoga maritima
.
T. maritima
is a hyperthermophilic anaerobic bacterium that is well known for its efficient synthesis of molecular hydrogen (H
2
) from the fermentation of sugars. Despite considerable efforts to advance compatible genetic methods, chromosome manipulation has remained elusive and hindered use of
T. maritima
or its close relatives as model hyperthermophiles. Lack of a genetic method also prevented efforts to manipulate specific metabolic pathways to measure their contributions to H
2
yield. To overcome this barrier, a homologous chromosomal recombination method was developed and used to characterize the contribution of arabinose catabolism to H
2
formation. We report here a stable genetic method for a hyperthermophilic bacterium that will advance studies on the basic and synthetic biology of
Thermotogales
.
Arsenic Detoxification by Geobacter Species
Authors: Dang Yan , Walker David J. F. , Vautour Kaitlin E. , Dixon Steven , Holmes Dawn E. 
Published: December 2016

ABSTRACT

Insight into the mechanisms for arsenic detoxification by
Geobacter
species is expected to improve the understanding of global cycling of arsenic in iron-rich subsurface sedimentary environments. Analysis of 14 different
Geobacter
genomes showed that all of these species have genes coding for an arsenic detoxification system (
ars
operon), and several have genes required for arsenic respiration (
arr
operon) and methylation (
arsM
). Genes encoding four arsenic repressor-like proteins were detected in the genome of
G. sulfurreducens
; however, only one (ArsR1) regulated transcription of the
ars
operon. Elimination of
arsR1
from the
G. sulfurreducens
chromosome resulted in enhanced transcription of genes coding for the arsenic efflux pump (Acr3) and arsenate reductase (ArsC). When the gene coding for Acr3 was deleted, cells were not able to grow in the presence of either the oxidized or reduced form of arsenic, while
arsC
deletion mutants could grow in the presence of arsenite but not arsenate. These studies shed light on how
Geobacter
influences arsenic mobility in anoxic sediments and may help us develop methods to remediate arsenic contamination in the subsurface.

IMPORTANCE
This study examines arsenic transformation mechanisms utilized by
Geobacter
, a genus of iron-reducing bacteria that are predominant in many anoxic iron-rich subsurface environments.
Geobacter
species play a major role in microbially mediated arsenic release from metal hydroxides in the subsurface. This release raises arsenic concentrations in drinking water to levels that are high enough to cause major health problems. Therefore, information obtained from studies of
Geobacter
should shed light on arsenic cycling in iron-rich subsurface sedimentary environments, which may help reduce arsenic-associated illnesses. These studies should also help in the development of biosensors that can be used to detect arsenic contaminants in anoxic subsurface environments. We examined 14 different
Geobacter
genomes and found that all of these species possess genes coding for an arsenic detoxification system (
ars
operon), and some also have genes required for arsenic respiration (
arr
operon) and arsenic methylation (
arsM
).
Insecticidal Specificity of Cry1Ah to Helicoverpa armigera Is Determined by Binding of APN1 via Domain II Loops 2 and 3
Authors: Zhou Zishan , Liu Yuxiao , Liang Gemei , Huang Yongping , Bravo Alejandra , Soberón Mario , Song Fuping , Zhou Xueping , Zhang Jie 
Published: December 2016

ABSTRACT

Bacillus thuringiensis
Cry1Ah protein is highly toxic against
Helicoverpa armigera
but shows no toxicity against
Bombyx mori
larvae. In contrast, the closely related Cry1Ai toxin showed the opposite phenotype: high activity against
B. mori
but no toxicity against
H. armigera.
Analysis of binding of Cry1Ah to brush border membrane vesicle (BBMV) proteins from
H. armigera
and
B. mori
by surface plasmon resonance revealed association of toxin binding with insect specificity. Pulldown experiments identified aminopeptidase N1 (APN1) as a Cry1Ah binding protein that was not observed in the assays using
B. mori
BBMV proteins. The APN1 Cry1Ah binding region was narrowed to the region from
A
548 to
S
798 (fragment H3) by expressing four different APN1 fragments in
Escherichia coli
and analyzing Cry1Ah binding by ligand blot. Binding competition experiments of Cry1Ah to APN1 fragment H3 using synthetic peptides corresponding to four predicted domain II loop regions showed that loop 2 and loop 3 have additive effects on binding to APN1 fragment H3. Moreover, switching of loop 2 and loop 3 regions from Cry1Ah to Cry1Ai toxins showed that loop 2 and loop 3 are both involved in specificity and toxicity against
H. armigera
.

IMPORTANCE
Domain II loop regions have been shown to be involved in binding to larval gut proteins mediating insect specificity. The modification of loop regions is a direct and effective method to construct new Cry toxin variants to increase toxicity or modify specificity. Our results show that the exchange of loop regions from one toxin into another is a successful scheme for modification of
B. thuringiensis
Cry toxin specificity.