bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmune hepatitis: From current knowledge and clinical practice to future research agenda
Authors: Sebode Marcial , Hartl Johannes , Vergani Diego , Lohse Ansgar W. ,   the International Autoimmune Hepatitis Group (IAIHG)
Published: April 2017

AbstractAutoimmune hepatitis is a chronic inflammatory liver disease. Unknown triggers lead to a mainly T cell‐mediated immune response targeting the liver, the main auto‐antigen of which has not been identified yet. The diagnosis of autoimmune hepatitis is based on the elevation of immunoglobulin G/hypergammaglobulinemia, detection of characteristic autoantibodies as well as a typical pattern on liver histology. Exclusion of other causes of hepatitis and response to immunosuppressive treatment support the diagnosis of autoimmune hepatitis. The mainstay of autoimmune hepatitis treatment has, from its first description to the current time, consisted of predniso(lo)ne to induce remission, in combination with azathioprine, which is used to maintain it. Nonetheless, side effects and non‐response with ongoing inflammation despite standard therapy demand treatment alternatives. Only through a better understanding of the pathogenesis of autoimmune hepatitis can a more selective and effective treatment be offered to patients in the future. Until this goal is reached, improvement of diagnostic approaches and optimization of current therapy rank highest on the research agenda for autoimmune hepatitis.
Cirrhosis is a risk factor for atrial fibrillation: A nationwide, population‐based study
Authors: Lee HyunJung , Choi Eue‐Keun , Rhee Tae‐Min , Lee So‐Ryoung , Lim Woo‐Hyun , Kang Si‐Hyuck , Han Kyung‐Do , Cha Myung‐Jin , Oh Seil 
Published: April 2017

AbstractBackground & AimsInformation is lacking regarding whether cirrhosis is associated with atrial fibrillation development. We aimed to investigate the incidence and clinical significance of atrial fibrillation in cirrhotic patients.MethodsCirrhotic patients (n=3596; mean age, 54.7±12.3 years; male, 72.5%) without previous atrial fibrillation were selected from the Korean National Health Insurance Service National Sample Cohort database between 2004 and 2008. Age‐ and sex‐matched controls (n=17 980) were randomly sampled in a 5:1 ratio from non‐cirrhotic individuals. Both cohorts were followed up for incident atrial fibrillation and death until 2013.ResultsDuring 9 years of follow‐up, atrial fibrillation was newly detected in 113 (3.1%) cirrhosis patients and 385 (2.1%) controls (incidence: 3.48 and 2.16 per 1000 person‐years respectively). Cirrhotic patients were at higher risk for atrial fibrillation development compared to controls (hazard ratio, 1.46; 95% confidence interval, 1.18‐1.80) after multivariate adjustment. On subgroup analysis, cirrhosis increased the risk for atrial fibrillation, especially in younger (age younger than 65 years) men without comorbidities (CHA2DS2‐VASc score, 0). Cirrhotic patients showed increased overall mortality compared to controls (hazard ratio, 4.80; 95% confidence interval, 4.47‐5.15) as well as increased cardiovascular mortality (hazard ratio, 1.37; 95% confidence interval, 1.07‐1.75). However, there was no significant association between development of atrial fibrillation and increased mortality in cirrhosis patients (P=.188 and .260).ConclusionsCirrhosis was an independent risk factor for atrial fibrillation development, especially in younger, otherwise healthy men, stressing the importance of cardiac assessment in cirrhotic patients. Meanwhile, atrial fibrillation development in cirrhosis patients was not associated with increased mortality.
The fate of recently fixed carbon after drought release: towards unravelling C storage regulation in Tilia platyphyllos and Pinus sylvestris
Authors: Galiano Lucía , Timofeeva Galina , Saurer Matthias , Siegwolf Rolf , Martínez‐Vilalta Jordi , Hommel Robert , Gessler Arthur 
Published: April 2017

AbstractCarbon reserves are important for maintaining tree function during and after stress. Increasing tree mortality driven by drought globally has renewed the interest in how plants regulate allocation of recently fixed C to reserve formation. Three‐year‐old seedlings of two species (Tilia platyphyllos and Pinus sylvestris) were exposed to two intensities of experimental drought during ~10 weeks, and 13C pulse labelling was subsequently applied with rewetting. Tracking the 13C label across different organs and C compounds (soluble sugars, starch, myo‐inositol, lipids and cellulose), together with the monitoring of gas exchange and C mass balances over time, allowed for the identification of variations in C allocation priorities and tree C balances that are associated with drought effects and subsequent drought release. The results demonstrate that soluble sugars accumulated in P. sylvestris under drought conditions independently of growth trends; thus, non‐structural carbohydrates (NSC) formation cannot be simply considered a passive overflow process in this species. Once drought ceased, C allocation to storage was still prioritized at the expense of growth, which suggested the presence of ‘drought memory effects’, possibly to ensure future growth and survival. On the contrary, NSC and growth dynamics in T. platyphyllos were consistent with a passive (overflow) view of NSC formation.
Cellular and humoral immunity after vaccination or natural mumps infection
Authors: Terada Kihei , Hagihara Kimiko , Oishi Tomohiro , Miyata Ippei , Akaike Hiroto , Ogita Satoko , Ohno Naoki , Ouchi Kazunobu 
Published: April 2017

AbstractBackgroundThis study measured cell‐mediated immunity (CMI) and serum antibody to clarify the basis of breakthrough after vaccination and reinfection after mumps.MethodsFrom a pool of 54 college students, 17 seronegative subjects and 14 subjects with intermediate level of antibodies against mumps were vaccinated with a monovalent mumps vaccine, and CMI was assessed using interferon‐γ release assay.ResultsCMI positivity according to pre‐existing antibody level, defined as titer <2.0 index units, negative; 2.0–3.9 index units, intermediate; and ≥4.0 index units, positive, was 8/17 (47.1%), 9/14 (64.3%) and 19/23 (82.6%) before vaccination, respectively. Of the 17 seronegative subjects, seven (41.2%) had a history of vaccination and/or natural infection, four (57.1%) of whom were CMI positive or intermediate. Ten (71%) of 14 subjects with intermediate antibody level had a history of vaccination or natural infection, eight (80%) of whom were CMI positive or intermediate. After vaccination the interferon (IFN)‐γ and antibody titers increased significantly, but seven (41.2%) of the 17 seronegative subjects and 13 (92.9%) of the 14 intermediate‐level subjects tested positive for both antibody and CMI. In a comparison of the natural infection group (confirmed as IgG seropositive and/or CMI positive without vaccination) versus the vaccination group, IgG antibody titer (mean ± SD) was 14.4 ± 8.0 versus 3.6 ± 2.4 index units (P < 0.01) and IFN‐γ was 122.7 ± 90.0 pg/mL versus 59.5 ± 37.8 pg/mL (P > 0.05), respectively.ConclusionVaccination or even natural mumps infection did not always induce both cellular and humoral immunity.
Human galectin‐9 on the porcine cells affects the cytotoxic activity of M1‐differentiated THP‐1 cells through inducing a shift in M2‐differentiated THP‐1 cells
Authors: Jung Sung Han , Hwang Jeong Ho , Kim Sang Eun , Kim Young Kyu , Park Hyo Chang , Lee Hoon Taek 
Published: April 2017

AbstractBackgroundIn xenotransplantation, immune rejection by macrophages occurs rapidly and remains a major obstacle. Studies to control immune rejection in macrophages have been continuing to date. Recent studies have reported that human galectin‐9 (hGal‐9) can regulate the function of regulatory T cells (Treg), as well as cytotoxicity T cells (CTL) and natural killer cells (NK). Although the effect of hGal‐9 on lymphocytes has been well studied, the relationship between hGal‐9 and myeloid cells has been scarcely studied.MethodsTo confirm the decreased cytotoxic activity effect by hGal‐9 in M1‐differentiated THP‐1 cells, we established the hGal‐9 expressing transgenic porcine cell line. hGal‐9 siRNA was transfected to transgenic cells and recombinant hGal‐9 (rhGal‐9) was treated to co‐culturing condition, and then, flow cytometry assay was conducted for analyzing the cytotoxic activity of M1‐differentiated THP‐1 cells. Related inflammatory cytokines (IL‐1β, IL‐10, TNF‐α, IL‐6, IL‐12, IL‐23, and TGF‐β) and related enzymes (iNOS and Arginase 1) were analyzed by qPCR and Western blot assay. To identify the shift in M1/M2‐differentiated THP‐1 cells, expression levels of CCR7, CD163, iNOS, and Arginase 1 and population of M2 marker positive cells were analyzed.ResultsThe expression levels of pro‐inflammatory cytokines in M1‐differentiated THP‐1 cells co‐cultured with hGal‐9‐expressing porcine kidney epithelial cells were decreased, but not in co‐cultured THP‐1 cells. However, the expression levels of anti‐inflammatory cytokines were also increased in co‐cultured M1‐differentiated THP‐1 cells. The cytotoxicity effect of M1‐differentiated THP‐1 cells on transgenic cells was decreased while the expression levels of anti‐inflammatory cytokines and M2 macrophages‐related molecules were increased. M2 differentiation program was turned on while M1 program was turned down by enhancing the phosphorylation levels of Akt and PI3K and the expression level of PPAR‐γ. Due to these changes, differentiation of M2 program was enhanced in cells co‐cultured with hGal‐9.ConclusionsThese data suggested that hGal‐9 has a reduction in M1‐differentiated THP‐1 cell cytotoxic activity‐related acute immune rejection in pig‐to‐human xenotransplantation in addition to its role in lymphoid lineage immune cell regulation.
Interaction between 2,4-Diacetylphloroglucinol- and Hydrogen Cyanide-Producing Pseudomonas brassicacearum LBUM300 and Clavibacter michiganensis subsp. michiganensis in the Tomato Rhizosphere
Authors: Paulin Mélanie M. , Novinscak Amy , Lanteigne Carine , Gadkar Vijay J. , Filion Martin 
Published: April 2017

ABSTRACT

We have previously demonstrated that inoculation of tomato plants with 2,4-diacetylphloroglucinol (DAPG)- and hydrogen cyanide (HCN)-producing
Pseudomonas brassicacearum
LBUM300 could significantly reduce bacterial canker symptoms caused by
Clavibacter michiganensis
subsp.
michiganensis
. In this study, in order to better characterize the population dynamics of LBUM300 in the rhizosphere of tomato plants, we characterized the role played by DAPG and HCN production by LBUM300 on rhizosphere colonization of healthy and
C. michiganensis
subsp.
michiganensis
-infected tomato plants. The impact of
C. michiganensis
subsp.
michiganensis
presence on the expression of DAPG and HCN biosynthetic genes in the rhizosphere was also examined.
In planta
assays were performed using combinations of
C. michiganensis
subsp.
michiganensis
and wild-type LBUM300 or DAPG (LBUM300Δ
phlD
) or HCN (LBUM300Δ
hcnC
) isogenic mutant strains. Populations of LBUM300 and
phlD
and
hcnC
gene expression levels were quantified in rhizosphere soil at several time points up to 264 h postinoculation using culture-independent quantitative PCR (qPCR) and reverse transcriptase quantitative PCR (RT-qPCR) TaqMan assays, respectively. The presence of
C. michiganensis
subsp.
michiganensis
significantly increased rhizospheric populations of LBUM300. In
C. michiganensis
subsp.
michiganensis
-infected tomato rhizospheres, the populations of wild-type LBUM300 and strain LBUM300Δ
hcnC
, both producing DAPG, were significantly higher than the population of strain LBUM300Δ
phlD
. A significant upregulation of
phlD
expression was observed in the presence of
C. michiganensis
subsp.
michiganensis
, while
hcnC
expression was only slightly increased in the mutant strain LBUM300Δ
phlD
when
C. michiganensis
subsp.
michiganensis
was present. Additionally, biofilm production was found to be significantly reduced in strain LBUM300Δ
phlD
compared to the wild-type and LBUM300Δ
hcnC
strains.

IMPORTANCE
The results of this study suggest that
C. michiganensis
subsp.
michiganensis
infection of tomato plants contributes to increasing rhizospheric populations of LBUM300, a biocontrol agent, as well as the overexpression of the DAPG biosynthetic operon in this bacterium. The increasing rhizospheric populations of LBUM300 represent one of the key factors in controlling
C. michiganensis
subsp.
michiganensis
in tomato plants, as DAPG-producing bacteria have shown the ability to decrease bacterial canker symptoms in tomato plants.
Inhibitory Effect of Coumarin on Syntrophic Fatty Acid-Oxidizing and Methanogenic Cultures and Biogas Reactor Microbiomes
Authors: Popp Denny , Plugge Caroline M. , Kleinsteuber Sabine , Harms Hauke , Sträuber Heike 
Published: April 2017

ABSTRACT

Coumarins are widely found in plants as natural constituents having antimicrobial activity. When considering plants that are rich in coumarins for biogas production, adverse effects on microorganisms driving the anaerobic digestion process are expected. Furthermore, coumarin derivatives, like warfarin, which are used as anticoagulating medicines, are found in wastewater, affecting its treatment. Coumarin, the structure common to all coumarins, inhibits the anaerobic digestion process. However, the details of this inhibition are still elusive. Here, we studied the impact of coumarin on acetogenesis and methanogenesis. First, coumarin was applied at four concentrations between 0.25 and 1 g · liter
−1
to pure cultures of the methanogens
Methanosarcina barkeri
and
Methanospirillum hungatei
, which resulted in up to 25% less methane production. Acetate production of syntrophic propionate- and butyrate-degrading cultures of
Syntrophobacter fumaroxidans
and
Syntrophomonas wolfei
was inhibited by 72% at a coumarin concentration of 1 g · liter
−1
. Coumarin also inhibited acetogenesis and acetoclastic methanogenesis in a complex biogas reactor microbiome. When a coumarin-adapted microbiome was used, acetogenesis and methanogenesis were not inhibited. According to amplicon sequencing of bacterial 16S rRNA genes and
mcrA
genes, the communities of the two microbiomes were similar, although
Methanoculleus
was more abundant and
Methanobacterium
less abundant in the coumarin-adapted than in the nonadapted microbiome. Our results suggest that well-dosed feeding with coumarin-rich feedstocks to full-scale biogas reactors while keeping the coumarin concentrations below 0.5 g · liter
−1
will allow adaptation to coumarins by structural and functional community reorganization and coumarin degradation.

IMPORTANCE
Coumarins from natural and anthropogenic sources have an inhibitory impact on the anaerobic digestion process. Here, we studied in detail the adverse effects of the model compound coumarin on acetogenesis and methanogenesis, which are two important steps of the anaerobic digestion process. Coumarin concentrations lower than 0.5 g · liter
−1
had only a minor impact. Even though similar inhibitory effects can be assumed for coumarin derivatives, little effects on the anaerobic treatment of wastewater are expected where concentrations of coumarin derivatives are lower than 0.5 g · liter
−1
. However, when full-scale reactors are fed with coumarin-rich feedstocks, the biogas processes might be inhibited. Hence, these feedstocks should be utilized in a well-dosed manner or after adaptation of the microbial community.
Polio and Measles Down the Drain: Environmental Enterovirus Surveillance in the Netherlands, 2005 to 2015
Authors: Benschop Kimberley S. M. , van der Avoort Harrie G. , Jusic Edin , Vennema Harry , van Binnendijk Rob , Duizer Erwin 
Published: April 2017

ABSTRACT

Polioviruses (PVs) are members of the genus
Enterovirus
. In the Netherlands, the exclusion of PV circulation is based on clinical enterovirus (EV) surveillance (CEVS) of EV-positive cases and routine environmental EV surveillance (EEVS) conducted on sewage samples collected in the region of the Netherlands where vaccination coverage is low due to religious reasons. We compared the EEVS data to those of the CEVS to gain insight into the relevance of EEVS for poliovirus and nonpolio enterovirus surveillance. Following the polio outbreak in Syria, EEVS was performed at the primary refugee center in Ter Apel in the Netherlands, and data were compared to those of CEVS and EEVS. Furthermore, we assessed the feasibility of poliovirus detection by EEVS using measles virus detection in sewage during a measles outbreak as a proxy. Two Sabin-like PVs were found in routine EEVS, 11 Sabin-like PVs were detected in the CEVS, and one Sabin-like PV was found in the Ter Apel sewage. We observed significant differences between the three programs regarding which EVs were found. In 6 sewage samples collected during the measles outbreak in 2013, measles virus RNA was detected in regions where measles cases were identified. In conclusion, we detected PVs, nonpolio EVs, and measles virus in sewage and showed that environmental surveillance is useful for poliovirus detection in the Netherlands, where live oral poliovirus vaccine is not used and communities with lower vaccination coverage exist. EEVS led to the detection of EV types not seen in the CEVS, showing that EEVS is complementary to CEVS.

IMPORTANCE
We show that environmental enterovirus surveillance complements clinical enterovirus surveillance for poliovirus detection, or exclusion, and for nonpolio enterovirus surveillance. Even in the presence of adequate surveillance, only a very limited number of Sabin-like poliovirus strains were detected in a 10-year period, and no signs of transmission of oral polio vaccine (OPV) strains were found in a country using exclusively inactivated polio vaccine (IPV). Measles viruses can be detected during an outbreak in sewage samples collected and concentrated following procedures used for environmental enterovirus surveillance.
Genome-Wide Investigation of Biofilm Formation in Bacillus cereus
Authors: Yan Fang , Yu Yiyang , Gozzi Kevin , Chen Yun , Guo Jian-hua , Chai Yunrong 
Published: April 2017

ABSTRACT

Bacillus cereus
is a soil-dwelling Gram-positive bacterium capable of forming structured multicellular communities, or biofilms. However, the regulatory pathways controlling biofilm formation are less well understood in
B. cereus
. In this work, we developed a method to study
B. cereus
biofilms formed at the air-liquid interface. We applied two genome-wide approaches, random transposon insertion mutagenesis to identify genes that are potentially important for biofilm formation, and transcriptome analyses by RNA sequencing (RNA-seq) to characterize genes that are differentially expressed in
B. cereus
when cells were grown in a biofilm-inducing medium. For the first approach, we identified 23 genes whose disruption by transposon insertion led to altered biofilm phenotypes. Based on the predicted function, they included genes involved in processes such as nucleotide biosynthesis, iron salvage, and antibiotic production, as well as genes encoding an ATP-dependent protease and transcription regulators. Transcriptome analyses identified about 500 genes that were differentially expressed in cells grown under biofilm-inducing conditions. One particular set of those genes may contribute to major metabolic shifts, leading to elevated production of small volatile molecules. Selected volatile molecules were shown to stimulate robust biofilm formation in
B. cereus
. Our studies represent a genome-wide investigation of
B. cereus
biofilm formation.

IMPORTANCE
In this work, we established a robust method for
B. cereus
biofilm studies and applied two genome-wide approaches, transposon insertion mutagenesis and transcriptome analyses by RNA-seq, to identify genes and pathways that are potentially important for biofilm formation in
B. cereus
. We discovered dozens of genes and two major metabolic shifts that seem to be important for biofilm formation in
B. cereus
. Our study represents a genome-wide investigation on
B. cereus
biofilm formation.
Two Distinct α-
l
-Arabinofuranosidases in Caldicellulosiruptor Species Drive Degradation of Arabinose-Based Polysaccharides
Authors: Saleh Mohammad Abu , Han Wen-Jie , Lu Ming , Wang Bing , Li Huayue , Kelly Robert M. , Li Fu-Li 
Published: April 2017

ABSTRACT

Species in the extremely thermophilic genus
Caldicellulosiruptor
can degrade unpretreated plant biomass through the action of multimodular glycoside hydrolases. To date, most focus with these bacteria has been on hydrolysis of glucans and xylans, while the biodegradation mechanism for arabinose-based polysaccharides remains unclear. Here, putative α-
l
-arabinofuranosidases (AbFs) were identified in
Caldicellulosiruptor
species by homology to less-thermophilic versions of these enzymes. From this screen, an extracellular XynF was determined to be a key factor in hydrolyzing α-1,2-, α-1,3-, and α-1,5-
l
-arabinofuranosyl residues of arabinose-based polysaccharides. Combined with a GH11 xylanase (XynA), XynF increased arabinoxylan hydrolysis more than 6-fold compared to the level seen with XynA alone, likely the result of XynF removing arabinofuranosyl side chains to generate linear xylans that were readily degraded. A second AbF, the intracellular AbF51, preferentially cleaved the α-1,5-
l
-arabinofuranosyl glycoside bonds within sugar beet arabinan. β-Xylosidases, such as GH39 Xyl39B, facilitated the hydrolysis of arabinofuranosyl residues at the nonreducing terminus of the arabinose-branched xylo-oligosaccharides by AbF51. These results demonstrate the separate but complementary contributions of extracellular XynF and cytosolic AbF51 in processing the bioconversion of arabinose-containing oligosaccharides to fermentable monosaccharides.

IMPORTANCE
Degradation of hemicellulose, due to its complex chemical structure, presents a major challenge during bioconversion of lignocellulosic biomass to biobased fuels and chemicals. Degradation of arabinose-containing polysaccharides, in particular, can be a key bottleneck in this process. Among
Caldicellulosiruptor
species, the multimodular arabinofuranosidase XynF is present in only selected members of this genus. This enzyme exhibited high hydrolysis activity, broad specificity, and strong synergism with other hemicellulases acting on arabino-polysaccharides. An intracellular arabinofuranosidase, AbF51, occurs in all
Caldicellulosiruptor
species and, in conjunction with xylosidases, processes the bioconversion of arabinose-branched oligosaccharides to fermentable monosaccharides. Taken together, the data suggest that plant biomass degradation in
Caldicellulosiruptor
species involves extracellular XynF that acts synergistically with other hemicellulases to digest arabino-polysaccharides that are subsequently transported and degraded further by intracellular AbF51 to produce short-chain arabino sugars.