bluuebunny/crossref_metadata_2025_split huggingface dataset:
The N‐acetylglucosamine catabolic gene cluster in Trichoderma reesei is controlled by the Ndt80‐like transcription factor RON1
Authors: Kappel Lisa , Gaderer Romana , Flipphi Michel , Seidl‐Seiboth Verena 
Published: October 2015

SummaryChitin is an important structural constituent of fungal cell walls composed of N‐acetylglucosamine (GlcNAc) monosaccharides, but catabolism of GlcNAc has not been studied in filamentous fungi so far. In the yeast Candida albicans, the genes encoding the three enzymes responsible for stepwise conversion of GlcNAc to fructose‐6‐phosphate are clustered. In this work, we analysed GlcNAc catabolism in ascomycete filamentous fungi and found that the respective genes are also clustered in these fungi. In contrast to C. albicans, the cluster often contains a gene for an Ndt80‐like transcription factor, which we named RON1 (regulator of N‐acetylglucosamine catabolism 1). Further, a gene for a glycoside hydrolase 3 protein related to bacterial N‐acetylglucosaminidases can be found in the GlcNAc gene cluster in filamentous fungi. Functional analysis in Trichoderma reesei showed that the transcription factor RON1 is a key activator of the GlcNAc gene cluster and essential for GlcNAc catabolism. Furthermore, we present an evolutionary analysis of Ndt80‐like proteins in Ascomycota. All GlcNAc cluster genes, as well as the GlcNAc transporter gene ngt1, and an additional transcriptional regulator gene, csp2, encoding the homolog of Neurospora crassa CSP2/GRHL, were functionally characterised by gene expression analysis and phenotypic characterisation of knockout strains in T. reesei.
Use of telbivudine in kidney transplant recipients with chronic hepatitis B virus infection: A preliminary experience
Authors: Yap Desmond Y. H. , Chan Tak Mao 
Published: October 2015

AbstractTelbivudine is a relatively novel oral nucleoside analogue with favourable efficacy and tolerability in treatment‐naïve chronic hepatitis B virus (HBV) infection, but its data in kidney transplant recipients (KTRs) was lacking. The efficacy and tolerability of telbivudine in four treatment‐naïve HBsAg‐positive KTRs were reviewed (treatment duration 54 (36–72) months) HBV DNA declined from 2.6 × 105(7.8 × 103–1.5 × 107) copies/mL at baseline to 170 (0.0–3.2 × 104) copies/mL at 12 months, and became undetectable at 24 and 36 months (P = 0.060, 0.118 and 0.005 compared with baseline). Alanine aminotransferase levels dropped from 46.5 (30–48) IU/mL at baseline to 28 (13–45) IU/mL, 34.5 (15–71) IU/mL and 26 (12–41) IU/mL at 12, 24 and 36 months, respectively (P = 0.109, 0.715 and 0.068 compared with baseline). Serum creatinine level and estimated glomerular filtration rate (eGFR) remained stable after 36 months of treatment (P all > 0.05 compared with baseline). No virological breakthrough, cirrhosis or hepatocellular carcinoma occurred. Our pilot data suggests that telbivudine has favourable efficacy and renal safety profiles in HBsAg‐positive KTRs.
Domestication footprints anchor genomic regions of agronomic importance in soybeans
Authors: Han Yingpeng , Zhao Xue , Liu Dongyuan , Li Yinghui , Lightfoot David A. , Yang Zhijiang , Zhao Lin , Zhou Gang , Wang Zhikun , Huang Long , Zhang Zhiwu , Qiu Lijuan , Zheng Hongkun , Li Wenbin 
Published: October 2015

Summary

Present‐day soybeans consist of elite cultivars and landraces (Glycine max, fully domesticated (FD)), annual wild type (Glycine soja, nondomesticated (ND)), and semi‐wild type (semi‐domesticated (SD)). FD soybean originated in China, although the details of its domestication history remain obscure.

More than 500 diverse soybean accessions were sequenced using specific‐locus amplified fragment sequencing (SLAF‐seq) to address fundamental questions regarding soybean domestication.

In total, 64 141 single nucleotide polymorphisms (SNPs) with minor allele frequencies (MAFs) > 0.05 were found among the 512 tested accessions. The results indicated that the SD group is not a hybrid between the FD and ND groups. The initial domestication region was pinpointed to central China (demarcated by the Great Wall to the north and the Qinling Mountains to the south). A total of 800 highly differentiated genetic regions and > 140 selective sweeps were identified, and these were three‐ and twofold more likely, respectively, to encompass a known quantitative trait locus (QTL) than the rest of the soybean genome. Forty‐three potential quantitative trait nucleotides (QTNs; including 15 distinct traits) were identified by genome‐wide association mapping.

The results of the present study should be beneficial for soybean improvement and provide insight into the genetic architecture of traits of agronomic importance.
The Science of Public Administration: Problems, Presumptions, Progress, and Possibilities
Authors: Wright Bradley E. 
Published: October 2015

AbstractNearly 70 years ago, Dahl noted the difficulty of constructing a science of public administration that was plagued by three interrelated problems: values, behavior, and culture. Underlying all three problems was the presumption that public administration could establish a set of universal principles independent of moral or political ends, individual human differences, or social influences. In discussing these three broad and easily accessible themes, Dahl did more than identify and critique the field's problems and presumptions. He also provided a road map to move the field forward and establish a science of public administration. Drawing on the framework provided by Dahl, this article argues that the field has made considerable progress in recognizing, if not addressing, each problem raised by Dahl. Even so, several current presumptions or omissions are also identified that, if challenged, can provide additional possibilities to advance the science of public administration.
Effect of Different Media and Protein Source on Equine Gametes: Potential Impact During In Vitro Fertilization
Authors: González‐Fernández L , Macedo S , Lopes JS , Rocha A , Macías‐García B 
Published: October 2015

ContentsEquine in vitro fertilization (IVF) is still inconsistent. In the present work, we studied how modified Whitten's (MW) medium and Tissue Culture Medium 199 (TCM) added with Foetal Bovine Serum (FBS; 10% v/v) or Bovine Serum Albumin (BSA; 7 mg/ml) affected equine gametes to subsequently run IVF trials. Compact (Cp) and expanded (Ex) cumuli equine oocytes were matured and placed in TCM or MW supplemented with BSA or FBS for 18–20 h (no sperm added). In Ex oocytes, TCM‐199 added with FBS or BSA resulted in higher metaphase II (MII) rates (75.7% and 62.7%, respectively) than MW added with BSA (54%) or FBS (52.2%; p < 0.05); this was not observed for Cp oocytes. Equine sperm were capacitated in the same media at 10 × 106 sperm/ml for 4 h at 37°C; total motility and protein tyrosine phosphorylation (PY) were evaluated. While motility remained unchanged, TCM or MW added with FBS enhanced the number of sperm showing PY‐stained tails (25 ± 4.8% and 31 ± 6.6%; mean ± SEM, respectively) over BSA supplemented media (3 ± 1.2% and 11.7 ± 1.1%) for TCM and MW (p < 0.05). In view of the previous results, sperm were capacitated in TCM + FBS and MW + BSA (control); IVF trials were run in the same media supplemented with 200 ng/ml of progesterone, but no fertilization occurred. Our results show that TCM + FBS enhances Ex equine oocyte's meiotic competence over MW + BSA and TCM or MW added with FBS successfully induce equine PY over media supplemented with BSA.
The A1 Subunit of Shiga Toxin 2 Has Higher Affinity for Ribosomes and Higher Catalytic Activity than the A1 Subunit of Shiga Toxin 1
Authors: Basu Debaleena , Li Xiao-Ping , Kahn Jennifer N. , May Kerrie L. , Kahn Peter C. , Tumer Nilgun E. 
Published: October 2015

ABSTRACT

Shiga toxin (Stx)-producing
Escherichia coli
(STEC) infections can lead to life-threatening complications, including hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS), which is the most common cause of acute renal failure in children in the United States. Stx1 and Stx2 are AB5 toxins consisting of an enzymatically active A subunit associated with a pentamer of receptor binding B subunits. Epidemiological evidence suggests that Stx2-producing
E. coli
strains are more frequently associated with HUS than Stx1-producing strains. Several studies suggest that the B subunit plays a role in mediating toxicity. However, the role of the A subunits in the increased potency of Stx2 has not been fully investigated. Here, using purified A1 subunits, we show that Stx2A1 has a higher affinity for yeast and mammalian ribosomes than Stx1A1. Biacore analysis indicated that Stx2A1 has faster association and dissociation with ribosomes than Stx1A1. Analysis of ribosome depurination kinetics demonstrated that Stx2A1 depurinates yeast and mammalian ribosomes and an RNA stem-loop mimic of the sarcin/ricin loop (SRL) at a higher catalytic rate and is a more efficient enzyme than Stx1A1. Stx2A1 depurinated ribosomes at a higher level
in vivo
and was more cytotoxic than Stx1A1 in
Saccharomyces cerevisiae
. Stx2A1 depurinated ribosomes and inhibited translation at a significantly higher level than Stx1A1 in human cells. These results provide the first direct evidence that the higher affinity for ribosomes in combination with higher catalytic activity toward the SRL allows Stx2A1 to depurinate ribosomes, inhibit translation, and exhibit cytotoxicity at a significantly higher level than Stx1A1.
Lysine
11
-Linked Polyubiquitination of the AnkB F-Box Effector of Legionella pneumophila
Authors: Bruckert William M. , Abu Kwaik Yousef 
Published: October 2015

ABSTRACT

The fate of the polyubiquitinated protein is determined by the lysine linkages involved in the polymerization of the ubiquitin monomers, which has seven lysine residues (K
6
, K
11
, K
27
, K
29
, K
33
, K
48
, and K
63
). The translocated AnkB effector of the intravacuolar pathogen
Legionella pneumophila
is a bona fide F-box protein, which is localized to the cytosolic side of the
Legionella
-containing vacuole (LCV) and is essential for intravacuolar proliferation within macrophages and amoebae. The F-box domain of AnkB interacts with the host SCF1 E3 ubiquitin ligase that triggers the decoration of the LCV with K
48
-linked polyubiquitinated proteins that are targeted for proteasomal degradation. Here we report that AnkB becomes rapidly polyubiquitinated within the host cell, and this modification is independent of the F-box domain of AnkB, indicating host-mediated polyubiquitination. We show that the AnkB effector interacts specifically with the host E3 ubiquitin ligase Trim21. Mass spectrometry analyses have shown that AnkB is modified by K
11
-linked polyubiquitination, which has no effect on its stability. This work shows the first example of K
11
-linked polyubiquitination of a bacterial effector and its interaction with the host Trim21 ubiquitin ligase.
Treatment with Interleukin-7 Restores Host Defense against Pneumocystis in CD4+T-Lymphocyte-Depleted Mice
Authors: Ruan S. , Samuelson D. R. , Assouline B. , Morre M. , Shellito J. E. 
Published: October 2015

ABSTRACTPneumocystispneumonia (PCP) is a major cause of morbidity and mortality in patients with HIV infection. CD4+T lymphocytes are critical for host defense against this infection, but in the absence of CD4+T lymphocytes, CD8+T lymphocytes may provide limited host defense. The cytokine interleukin-7 (IL-7) functions to enhance lymphocyte proliferation, survival, and recruitment of immune cells to sites of infection. However, there is little known about the role of IL-7 in PCP or its potential use as an immunotherapeutic agent. We hypothesized that treatment with recombinant human IL-7 (rhIL-7) would augment host defense againstPneumocystisand accelerate pathogen clearance in CD4-depleted mice. Control and CD4-depleted mice were infected withPneumocystis, and rhIL-7 was administered via intraperitoneal injection. Our studies indicate that endogenous murine IL-7 is part of the normal host response toPneumocystis murinaand that administration of rhIL-7 markedly enhanced clearance ofPneumocystisin CD4-depleted mice. Additionally, we observed increased recruitment of CD8+T lymphocytes to the lungs and decreased apoptosis of pulmonary CD8+T lymphocytes in rhIL-7-treated animals compared to those in untreated mice. The antiapoptotic effect of rhIL-7 was associated with increased levels of Bcl-2 protein in T lymphocytes. rhIL-7 immunotherapy in CD4-depleted mice also increased the number of gamma interferon (IFN-γ)-positive CD8+central memory T lymphocytes in the lungs. We conclude that rhIL-7 has a potent therapeutic effect in the treatment of murinePneumocystispneumonia in CD4-depleted mice. This therapeutic effect is mediated through enhanced recruitment of CD8+T cells and decreased apoptosis of lung T lymphocytes, with a preferential action on central memory CD8+T lymphocytes.
Water and Small-Molecule Permeation of Dormant Bacillus subtilis Spores
Authors: Knudsen Scott M. , Cermak Nathan , Feijó Delgado Francisco , Setlow Barbara , Setlow Peter , Manalis Scott R. 
Published: October 2015

ABSTRACT

We use a suspended microchannel resonator to characterize the water and small-molecule permeability of
Bacillus subtilis
spores based on spores' buoyant mass in different solutions. Consistent with previous results, we found that the spore coat is not a significant barrier to small molecules, and the extent to which small molecules may enter the spore is size dependent. We have developed a method to directly observe the exchange kinetics of intraspore water with deuterium oxide, and we applied this method to wild-type spores and a panel of congenic mutants with deficiencies in the assembly or structure of the coat. Compared to wild-type spores, which exchange in approximately 1 s, several coat mutant spores were found to have relatively high water permeability with exchange times below the ∼200-ms temporal resolution of our assay. In addition, we found that the water permeability of the spore correlates with the ability of spores to germinate with dodecylamine and with the ability of TbCl
3
to inhibit germination with
l
-valine. These results suggest that the structure of the coat may be necessary for maintaining low water permeability.

IMPORTANCE
Spores of
Bacillus
species cause food spoilage and disease and are extremely resistant to standard decontamination methods. This hardiness is partly due to spores' extremely low permeability to chemicals, including water. We present a method to directly monitor the uptake of molecules into
B. subtilis
spores by weighing spores in fluid. The results demonstrate the exchange of core water with subsecond resolution and show a correlation between water permeability and the rate at which small molecules can initiate or inhibit germination in coat-damaged spores. The ability to directly measure the uptake of molecules in the context of spores with known structural or genetic deficiencies is expected to provide insight into the determinants of spores' extreme resistance.
Decision analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer
Authors: Boyd Kathleen A , Jones Rob J , Paul Jim , Birrell Fiona , Briggs Andrew H , Leung Hing Y 
Published: October 2015

ObjectiveTo determine the cost-effectiveness of salvage cryotherapy (SC) in men with radiation recurrent prostate cancer (RRPC).DesignCost-utility analysis using decision analytic modelling by a Markov model.Setting and methodsCompared SC and androgen deprivation therapy (ADT) in a cohort of patients with RRPC (biopsy proven local recurrence, no evidence of metastatic disease). A literature review captured published data to inform the decision model, and resource use data were from the Scottish Prostate Cryotherapy Service. The model was run in monthly cycles for RRPC men, mean age of 70 years. The model was run over the patient lifetime, to assess changes in patient health states and the associated quality of life, survival and cost impacts. Results are reported in terms of the discounted incremental costs and discounted incremental quality-adjusted life years (QALYs) gained between the 2 alternative interventions. Probabilistic sensitivity analysis used a 10 000 iteration Monte Carlo simulation.ResultsSC has a high upfront treatment cost, but delays the ongoing monthly cost of ADT. SC is the dominant strategy over the patient lifetime; it is more effective with an incremental 0.56 QALY gain (95% CI 0.28 to 0.87), and less costly with a reduced lifetime cost of £29 719 (€37 619) (95% CI −51 985 to −9243). For a ceiling ratio of £30 000, SC has a 100% probability to be cost-effective. The cost neutral point was at 3.5 years, when the upfront cost of SC (plus any subsequent cumulative cost of side effects and ADT) equates the cumulative cost in the ADT arm. Limitations of our model may arise from its insensitivity to parameter or structural uncertainty.ConclusionsThe platform for SC versus ADT cost-effective analysis can be employed to evaluate other treatment modalities or strategies in RRPC. SC is the dominant strategy, costing less over a patient's lifetime with improvements in QALYs.Trial registration numberThis economic analysis was undertaken as part of the CROP RCT study ISRCTN:72677390; it was a pre-trial economic model developed and analysed during the pre-results stage of the RCT.
Sympathetic autonomic dysfunction and impaired cardiovascular performance in higher risk surgical patients: implications for perioperative sympatholysis
Authors: Whittle John , Nelson Alexander , Otto James M , Stephens Robert C M , Martin Daniel S , Sneyd J Robert , Struthers Richard , Minto Gary , Ackland Gareth L 
Published: October 2015

ObjectiveRecent perioperative trials have highlighted the urgent need for a better understanding of why sympatholytic drugs intended to reduce myocardial injury are paradoxically associated with harm (stroke, myocardial infarction). We hypothesised that following a standardised autonomic challenge, a subset of patients may demonstrate excessive sympathetic activation which is associated with exercise-induced ischaemia and impaired cardiac output.MethodsHeart rate rise during unloaded pedalling (zero workload) prior to the onset of cardiopulmonary exercise testing (CPET) was measured in 2 observation cohorts of elective surgical patients. The primary outcome was exercise-evoked, ECG-defined ischaemia (>1 mm depression; lead II) associated with an exaggerated increase in heart rate (EHRR ≥12 bpm based on prognostic data for all-cause cardiac death in preceding epidemiological studies). Secondary outcomes included cardiopulmonary performance (oxygen pulse (surrogate for left ventricular stroke volume), peak oxygen consumption (VO2peak), anaerobic threshold (AT)) and perioperative heart rate.ResultsEHRR was present in 40.4–42.7% in both centres (n=232, n=586 patients). Patients with EHRR had higher heart rates perioperatively (p<0.05). Significant ST segment depression during CPET was more common in EHRR patients (relative risk 1.7 (95% CI 1.3 to 2.1); p<0.001). EHRR was associated with 11% (95%CI 7% to 15%) lower predicted oxygen pulse (p<0.0001), consistent with impaired left ventricular function.ConclusionsEHRR is common and associated with ECG-defined ischaemia and impaired cardiac performance. Perioperative sympatholysis may further detrimentally affect cardiac output in patients with this phenotype.
Particle Dark Matter in the galactic halo
Authors: Bernabei R. , Belli P. , d’Angelo S. , Di Marco A. , Montecchia F. , d’Angelo A. , Incicchitti A. , Cappella F. , Caracciolo V. , Cerulli R. , Dai C. J. , He H. L. , Kuang H. H. , Ma X. H. , Sheng X. D. , Wang R. G. , Ye Z. P. 
Published: October 2015

The DAMA/LIBRA–phase1 and the former DAMA/NaI data (cumulative exposure 1.33 ton [Formula: see text] yr, corresponding to 14 annual cycles) give evidence at 9.3[Formula: see text] C.L. for the presence of Dark Matter (DM) particles in the galactic halo, on the basis of the exploited model independent DM annual modulation signature by using highly radio-pure NaI(Tl) target. Results and comparisons will be shortly recalled. Recent analyses on possible diurnal effects and on the Earth shadowing effect (the latter holds only for some DM candidates) will be mentioned. The analysis of the time distribution of the low-energy single-hit events in DAMA/LIBRA–phase1 is reported for the first time. Finally, some perspectives of the presently running DAMA/LIBRA–phase2 will be mentioned.
The development of ground based gravitational wave astronomy and opportunities for Australia–China collaboration
Authors: Blair David , Ju Li , Zhao Chunnong , Wen Linqing , Chu Qi , Ma Yiqiu , Page Michael , Blair Carl , Fang Qi , Miao Haixing 
Published: October 2015

This paper begins by reviewing the development of gravitational wave astronomy from the first predictions of gravitational waves to development of technologies across the entire gravitational wave spectrum, and then focuses on the current status of ground based gravitational wave detectors. With substantial improvements already demonstrated in early commissioning it is emphasised that Advanced detectors are on track for first detection of gravitational waves. The importance of a worldwide array of detectors is emphasised, and recent results are shown that demonstrate the continued advantage of a southern hemisphere detector. Finally it is shown that a north–south pair of 8 km arm length detectors would give rise to a dramatic improvement in event rate, enabling a pair of detectors to encompass a 64-times larger volume of the universe, to conduct a census on all stellar mass black hole mergers to [Formula: see text] and to observe neutron star mergers to a distance of [Formula: see text][Formula: see text]800 Mpc.
CCL9 Induced by TGFβ Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Organ
Authors: Yan Hangyi H. , Jiang Jian , Pang Yanli , Achyut B.R. , Lizardo Michael , Liang Xinhua , Hunter Kent , Khanna Chand , Hollander Christine , Yang Li 
Published: October 2015

AbstractTumor cell survival in the hostile distant organ is a rate-limiting step in cancer metastasis. Bone marrow–derived myeloid cells can form a premetastatic niche and provide a tumor-promoting microenvironment. However, it is unclear whether these myeloid cells in the premetastatic site have any direct effect on tumor cell survival. Here, we report that chemokine CCL9 was highly induced in Gr-1+CD11b+ immature myeloid cells and in premetastatic lung in tumor-bearing mice. Knockdown of CCL9 in myeloid cells decreased tumor cell survival and metastasis. Importantly, CCL9 overexpression in myeloid cells lacking TGFβ signaling rescued the tumor metastasis defect observed in mice with myeloid-specific Tgfbr2 deletion. The expression level of CCL23, the human orthologue for CCL9, in peripheral blood mononuclear cells correlated with progression and survival of cancer patients. Our study demonstrates that CCL9 could serve as a good candidate for anti-metastasis treatment by targeting the rate-limiting step of cancer cell survival. In addition, targeting CCL9 may avoid the adverse effects of TGFβ-targeted therapy. Cancer Res; 75(24); 5283–98. ©2015 AACR.