bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of Arabidopsis UGT74 glucosyltransferases reveals a special role of UGT74C1 in glucosinolate biosynthesis
Authors: Grubb C. Douglas , Zipp Brandon J. , Kopycki Jakub , Schubert Melvin , Quint Marcel , Lim Eng‐Kiat , Bowles Dianna J. , Pedras M. Soledade C. , Abel Steffen 
Published: April 2014

SummaryThe study of glucosinolates and their regulation has provided a powerful framework for the exploration of fundamental questions about the function, evolution, and ecological significance of plant natural products, but uncertainties about their metabolism remain. Previous work has identified one thiohydroximate S‐glucosyltransferase, UGT74B1, with an important role in the core pathway, but also made clear that this enzyme functions redundantly and cannot be the sole UDP‐glucose dependent glucosyltransferase (UGT) in glucosinolate synthesis. Here, we present the results of a nearly comprehensive in vitro activity screen of recombinant Arabidopsis Family 1 UGTs, which implicate other members of the UGT74 clade as candidate glucosinolate biosynthetic enzymes. Systematic genetic analysis of this clade indicates that UGT74C1 plays a special role in the synthesis of aliphatic glucosinolates, a conclusion strongly supported by phylogenetic and gene expression analyses. Finally, the ability of UGT74C1 to complement phenotypes and chemotypes of the ugt74b1‐2 knockout mutant and to express thiohydroximate UGT activity in planta provides conclusive evidence for UGT74C1 being an accessory enzyme in glucosinolate biosynthesis with a potential function during plant adaptation to environmental challenge.
The chromatin landscape of the moss Physcomitrella patens and its dynamics during development and drought stress
Authors: Widiez Thomas , Symeonidi Aikaterini , Luo Chongyuan , Lam Eric , Lawton Michael , Rensing Stefan A. 
Published: April 2014

SummaryThe moss Physcomitrella patens is an important model organism for evo‐devo studies. Here, we determined the genome‐wide chromatin landscape of five important histone three (H3) modifications (H3K4me3, H3K27me3, H3K27Ac, H3K9Ac and H3K9me2) and describe the changes to these histone marks in two contrasted situations, developmental transition and abiotic (drought) stress. Integrative analysis of these histone H3 modifications revealed their preferential association into 15 chromatin states (CS) in genic regions of the P. patens genome. Synergistic relationships that influence expression levels were revealed for the three activating marks H3K4me3, H3K27Ac and H3K9Ac, while an antagonistic relationship was found between CS containing the H3K27me3 and H3K27Ac marks, suggesting that H3K27 is a key indexing residue regarding transcriptional output. Concerning the alteration of histone marks in response to developmental transition (juvenile to adult) and drought stress, the three activating marks H3K4me3, H3K27Ac and H3K9Ac show significant changes in both situations. However, changes to H3K27me3 are central only for genes differentially expressed during development. Interestingly, genes induced during drought stress show significant histone mark toggling during developmental transition. This situation suggests that drought induced adult (gametophore expressed) genes are primed to respond to this stress during the juvenile to adult transition.
The T2 Mycobacterium tuberculosis Genotype, Predominant in Kampala, Uganda, Shows Negative Correlation with Antituberculosis Drug Resistance
Authors: Lukoye Deus , Katabazi Fred A. , Musisi Kenneth , Kateete David P. , Asiimwe Benon B. , Okee Moses , Joloba Moses L. , Cobelens Frank G. J. 
Published: April 2014

ABSTRACT

Surveillance of the circulating
Mycobacterium tuberculosis
complex (MTC) strains in a given locality is important for understanding tuberculosis (TB) epidemiology. We performed molecular epidemiological studies on sputum smear-positive isolates that were collected for anti-TB drug resistance surveillance to establish the variability of MTC lineages with anti-TB drug resistance and HIV infection. Spoligotyping was performed to determine MTC phylogenetic lineages. We compared patients' MTC lineages with drug susceptibility testing (DST) patterns and HIV serostatus. Out of the 533 isolates, 497 (93.2%) had complete DST, PCR, and spoligotyping results while 484 (90.1%) participants had results for HIV testing. Overall, the frequency of any resistance was 75/497 (15.1%), highest among the LAM (34.4%; 95% confidence interval [CI], 18.5 to 53.2) and lowest among the T2 (11.5%; 95% CI, 7.6 to 16.3) family members. By multivariate analysis, LAM (adjusted odds ratio [OR
adj
], 5.0; 95% CI, 2.0 to 11.9;
P
< 0.001) and CAS (OR
adj
, 2.9; 95% CI, 1.4.0 to 6.3;
P
= 0.006) families were more likely to show any resistance than was T2. All other MTC lineages combined were more likely to be resistant to any of the anti-TB drugs than were the T2 strains (OR
adj
, 1.7; 95% CI, 1.0 to 2.9;
P
= 0.040). There were no significant associations between multidrug resistance and MTC lineages, but numbers of multidrug-resistant TB strains were small. No association was established between MTC lineages and HIV status. In conclusion, the T2 MTC lineage negatively correlates with anti-TB drug resistance, which might partly explain the reported low levels of anti-TB drug resistance in Kampala, Uganda. Patients' HIV status plays no role with respect to the MTC lineage distribution.
In Silico
Detection and Typing of Plasmids using PlasmidFinder and Plasmid Multilocus Sequence Typing
Authors: Carattoli Alessandra , Zankari Ea , García-Fernández Aurora , Voldby Larsen Mette , Lund Ole , Villa Laura , Møller Aarestrup Frank , Hasman Henrik 
Published: April 2014

ABSTRACT

In the work presented here, we designed and developed two easy-to-use Web tools for
in silico
detection and characterization of whole-genome sequence (WGS) and whole-plasmid sequence data from members of the family
Enterobacteriaceae
. These tools will facilitate bacterial typing based on draft genomes of multidrug-resistant
Enterobacteriaceae
species by the rapid detection of known plasmid types. Replicon sequences from 559 fully sequenced plasmids associated with the family
Enterobacteriaceae
in the NCBI nucleotide database were collected to build a consensus database for integration into a Web tool called PlasmidFinder that can be used for replicon sequence analysis of raw, contig group, or completely assembled and closed plasmid sequencing data. The PlasmidFinder database currently consists of 116 replicon sequences that match with at least at 80% nucleotide identity all replicon sequences identified in the 559 fully sequenced plasmids. For plasmid multilocus sequence typing (pMLST) analysis, a database that is updated weekly was generated from
www.pubmlst.org
and integrated into a Web tool called pMLST. Both databases were evaluated using draft genomes from a collection of
Salmonella enterica
serovar Typhimurium isolates. PlasmidFinder identified a total of 103 replicons and between zero and five different plasmid replicons within each of 49
S
. Typhimurium draft genomes tested. The pMLST Web tool was able to subtype genomic sequencing data of plasmids, revealing both known plasmid sequence types (STs) and new alleles and ST variants. In conclusion, testing of the two Web tools using both fully assembled plasmid sequences and WGS-generated draft genomes showed them to be able to detect a broad variety of plasmids that are often associated with antimicrobial resistance in clinically relevant bacterial pathogens.
In Vitro
Activity of AZD5847 against Geographically Diverse Clinical Isolates of Mycobacterium tuberculosis
Authors: Werngren Jim , Wijkander Maria , Perskvist Nasrin , Balasubramanian V. , Sambandamurthy Vasan K. , Rodrigues Camilla , Hoffner Sven 
Published: April 2014

ABSTRACT

The MIC of the novel antituberculosis (anti-TB) drug AZD5847 was determined against 146 clinical isolates from diverse geographical regions, including eastern Europe, North America, Africa, and Asia, using the automated Bactec Mycobacterial Growth Indicator Tube (MGIT) 960 system. These isolates originated from specimen sources such as sputum, bronchial alveolar lavage fluid, pleural fluid, abscess material, lung biopsies, and feces. The overall MIC
90
was 1.0 mg/liter (range, 0.125 to 4 mg/liter). The MICs of AZD5847 for isolates of
Mycobacterium tuberculosis
were similar among drug-sensitive strains, multidrug-resistant (MDR) strains, and extensively drug resistant (XDR) strains. The good
in vitro
activity of AZD5847 against
M. tuberculosis
and the lack of cross-resistance make this agent a promising anti-TB drug candidate.
Synergistic Effects of Clostridium perfringens Enterotoxin and Beta Toxin in Rabbit Small Intestinal Loops
Authors: Ma Menglin , Gurjar Abhijit , Theoret James R. , Garcia Jorge P. , Beingesser Juliann , Freedman John C. , Fisher Derek J. , McClane Bruce A. , Uzal Francisco A. 
Published: April 2014

ABSTRACT

The ability of
Clostridium perfringens
type C to cause human enteritis necroticans (EN) is attributed to beta toxin (CPB). However, many EN strains also express
C. perfringens
enterotoxin (CPE), suggesting that CPE could be another contributor to EN. Supporting this possibility, lysate supernatants from modified Duncan-Strong sporulation (MDS) medium cultures of three CPE-positive type C EN strains caused enteropathogenic effects in rabbit small intestinal loops, which is significant since CPE is produced only during sporulation and since
C. perfringens
can sporulate in the intestines. Consequently, CPE and CPB contributions to the enteropathogenic effects of MDS lysate supernatants of CPE-positive type C EN strain CN3758 were evaluated using isogenic
cpb
and
cpe
null mutants. While supernatants of wild-type CN3758 MDS lysates induced significant hemorrhagic lesions and luminal fluid accumulation, MDS lysate supernatants of the
cpb
and
cpe
mutants caused neither significant damage nor fluid accumulation. This attenuation was attributable to inactivating these toxin genes since complementing the
cpe
mutant or reversing the
cpb
mutation restored the enteropathogenic effects of MDS lysate supernatants. Confirming that both CPB and CPE are needed for the enteropathogenic effects of CN3758 MDS lysate supernatants, purified CPB and CPE at the same concentrations found in CN3758 MDS lysates also acted together synergistically in rabbit small intestinal loops; however, only higher doses of either purified toxin independently caused enteropathogenic effects. These findings provide the first evidence for potential synergistic toxin interactions during
C. perfringens
intestinal infections and support a possible role for CPE, as well as CPB, in some EN cases.
Palliative medicine specialists’ causal explanations for depression in the palliative care setting: a qualitative in-depth interview study
Authors: Ng Felicity , Crawford Gregory B , Chur-Hansen Anna 
Published: April 2014

ObjectiveMedical practitioners have different causal explanations for depression, and may have greater difficulty in explaining causality of depression in the palliative care setting. The objective of this study was to investigate and describe the causal explanations of depression in the palliative care setting, from the perspective of palliative medicine specialists.MethodsPalliative medicine specialists practising in Australia were recruited and purposively sampled. Individual semistructured, in-depth interviews were conducted to explore their explanatory models of depression, including a focus on causal explanations. Nine participants were interviewed to reach data saturation. Interview transcripts were analysed for themes.ResultsSix themes for causal explanations of depression were identified: (1) Depression is inexplicable; (2) Biological explanations—primarily neurotransmitter depletion; (3) Psychological explanations—including reaction to circumstances, inability to accept illness and dying, diminished self, and coping mechanisms; (4) Social explanations—including inadequate social support, and contribution from modern medicine and societal norms; (5) Interrelationships between causal factors—mainly multifactoriality; (6) Different explanation for de novo and pre-existing depressions. Participants also articulated a link between causal explanations and clinical interventions.ConclusionsPalliative medicine specialists hold causal explanations of depression that align with the biopsychosocial and vulnerability-stress models. They use multiple individual explanations with diverse theoretical underpinnings, and largely view depression as multifactorial in causality. Given that causal explanations are linked to clinical interventions, these findings have implications for clinical practice and medical education.
Elimination of IL-10–Inducing T-Helper Epitopes from an IGFBP-2 Vaccine Ensures Potent Antitumor Activity
Authors: Cecil Denise L. , Holt Gregory E. , Park Kyong Hwa , Gad Ekram , Rastetter Lauren , Childs Jennifer , Higgins Doreen , Disis Mary L. 
Published: April 2014

AbstractImmunization against self-tumor antigens can induce T-regulatory cells, which inhibit proliferation of type I CD4+ T-helper (TH1) and CD8+ cytotoxic T cells. Type I T cells are required for potent antitumor immunity. We questioned whether immunosuppressive epitopes could be identified and deleted from a cancer vaccine targeting insulin-like growth factor–binding protein (IGFBP-2) and enhance vaccine efficacy. Screening breast cancer patient lymphocytes with IFN-γ and interleukin (IL)-10 ELISPOT, we found epitopes in the N-terminus of IGFBP-2 that elicited predominantly TH1 whereas the C-terminus stimulated TH2 and mixed TH1/TH2 responses. Epitope-specific TH2 demonstrated a higher functional avidity for antigen than epitopes, which induced IFN-γ (P = 0.014). We immunized TgMMTV-neu mice with DNA constructs encoding IGFBP-2 N-and C-termini. T cell lines expanded from the C-terminus vaccinated animals secreted significantly more type II cytokines than those vaccinated with the N-terminus and could not control tumor growth when infused into tumor-bearing animals. In contrast, N-terminus epitope–specific T cells secreted TH1 cytokines and significantly inhibited tumor growth, as compared with naïve T cells, when adoptively transferred (P = 0.005). To determine whether removal of TH2-inducing epitopes had any effect on the vaccinated antitumor response, we immunized mice with the N-terminus, C-terminus, and a mix of equivalent concentrations of both vaccines. The N-terminus vaccine significantly inhibited tumor growth (P &lt; 0.001) as compared with the C-terminus vaccine, which had no antitumor effect. Mixing the C-terminus with the N-terminus vaccine abrogated the antitumor response of the N-terminus vaccine alone. The clinical efficacy of cancer vaccines targeting self-tumor antigens may be greatly improved by identification and removal of immunosuppressive epitopes. Cancer Res; 74(10); 2710–8. ©2014 AACR.
Releasing Pressure in Tumors: What Do We Know So Far and Where Do We Go from Here? A Review
Authors: Ariffin Arlizan B. , Forde Patrick F. , Jahangeer Saleem , Soden Declan M. , Hinchion John 
Published: April 2014

Abstract
Tumor interstitial pressure is a fundamental feature of cancer biology. Elevation in tumor pressure affects the efficacy of cancer treatment. It causes heterogenous intratumoral distribution of drugs and macromolecules. It also causes the development of hypoxia within tumor bulk, leading to reduced efficacy of therapeutic drugs and radiotherapy. Tumor pressure has been associated with increased metastatic potential and poor prognosis in some tumors. The formation of increased pressure in solid tumors is multifactorial. Factors known to affect tumor pressure include hyperpermeable tortuous tumor vasculatures, the lack of functional intratumoral lymphatic vessels, abnormal tumor microenvironment, and the solid stress exerted by proliferating tumor cells. Reducing this pressure is known to enhance the uptake and homogenous distribution of many therapies. Pharmacologic and biologic agents have been shown to reduce tumor pressure. These include antiangiogenic therapy, vasodilatory agents, antilymphogenic therapy, and proteolytic enzymes. Physical manipulation has been shown to cause reduction in tumor pressure. These include irradiation, hyperbaric oxygen therapy, hyper- or hypothermic therapy, and photodynamic therapy. This review explores the methods to reduce tumor pressure that may open up new avenues in cancer treatment. Cancer Res; 74(10); 2655–62. ©2014 AACR.
Healthy Lifestyle Change and Subclinical Atherosclerosis in Young Adults
Authors: Spring Bonnie , Moller Arlen C. , Colangelo Laura A. , Siddique Juned , Roehrig Megan , Daviglus Martha L. , Polak Joseph F. , Reis Jared P. , Sidney Stephen , Liu Kiang 
Published: April 2014

Background—
The benefits of healthy habits are well established, but it is unclear whether making health behavior changes as an adult can still alter coronary artery disease risk.

Methods and Results—

The Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study (n=3538) assessed 5 healthy lifestyle factors (HLFs) among young adults aged 18 to 30 years (year 0 baseline) and 20 years later (year 20): not overweight/obese, low alcohol intake, healthy diet, physically active, nonsmoker. We tested whether change from year 0 to 20 in a continuous composite HLF score (HLF change; range, −5 to +5) is associated with subclinical atherosclerosis (coronary artery calcification and carotid intima-media thickness) at year 20, after adjustment for demographics, medications, and baseline HLFs. By year 20, 25.3% of the sample improved (HLF change ≥+1); 40.4% deteriorated (had fewer HLFs); 34.4% stayed the same; and 19.2% had coronary artery calcification (>0). Each increase in HLFs was associated with reduced odds of detectable coronary artery calcification (odds ratio=0.85; 95% confidence interval, 0.74–0.98) and lower intima-media thickness (carotid bulb β=−0.024,
P
=0.001), and each decrease in HLFs was predictive to a similar degree of greater odds of coronary artery calcification (odds ratio=1.17; 95% confidence interval, 1.02–1.33) and greater intima-media thickness (β=+0.020,
P
<0.01).

Conclusions—
Healthy lifestyle changes during young adulthood are associated with decreased risk and unhealthy lifestyle changes are associated with increased risk for subclinical atherosclerosis in middle age.
An Analysis of Secular Change in Tides at Open-Ocean Sites in the Pacific
Authors: Zaron Edward D. , Jay David A. 
Published: April 2014

Abstract
Hourly sea level is examined at 25 open-ocean stations in the Pacific Ocean with records longer than 30 yr. A search for trends finds that the amplitude of the dominant semidiurnal tide M2 is increasing at 12 of the 13 sites where a statistically significant trend can be identified. It is also found that nontidal variance in the neighborhood of M2 is decreasing at all 12 of the sites where a significant increase in M2 tide is occurring. The trend in amplitude of the dominant diurnal tide K1 is significant at six stations, and it is both increasing (four stations) and decreasing (two stations). The trend in semidiurnal-band variance suggests the hypothesis that increases in M2 could be caused by improvements in time keeping or data processing that would reduce the apparent phase variability of the tide. This possibility is examined and found to be the likely explanation for tidal trends at four stations. Local changes are found to explain the trend at two stations, Johnston Island and Mokuoloe, as diagnosed from correlated changes in nonlinear overtides and site history. Changes in M2 at the equatorial station of Kanton are significant and unexplained by either timing errors or local morphodynamics; although, strong nonlinear overtides are present. Changing tides at five stations in the western Pacific, Malakal, Yap, Saipan, Kapingamarangi, and Pohnpei cannot be explained by the above and suggest a region where a connection between climate and tides may yet be identified.
The European Court legitimates access of Italian couples to assisted reproductive techniques and to pre-implantation genetic diagnosis
Authors: Turillazzi Emanuela , Frati Paola , Busardò Francesco Paolo , Gulino Matteo , Fineschi Vittorio 
Published: April 2014

On 28 August 2012, the European Court of Human Rights (ECHR) issued a judgment regarding the requirements for the legitimate access of couples to assisted reproductive techniques (ART) and to pre-implantation genetic diagnosis (PGD). This judgment concerns the case of an Italian couple who found out after their first child was born with cystic fibrosis that they were healthy carriers of the disease. When the woman became pregnant again in 2010 and underwent fetal screening, it was found that the unborn child also had cystic fibrosis, whereupon she had the pregnancy terminated on medical grounds. In order to have the embryo genetically screened prior to implantation under the procedure of PGD, the couple sought to use in vitro fertilisation to have another child. Since article 1 of the Italian law strictly limits access to ART to sterile/infertile couples or those in which the man has a sexually transmissible disease, the couple appealed to the European court, raising the question of the violation of articles 8 and 14 of the European Convention on Human Rights. The applicants lodged a complaint that they were not allowed legitimate access to ART and to PGD to select an embryo not affected by the disease. The European Court affirmed that the prohibition imposed by Italian law violated article 8 of the European Convention on Human Rights. Focusing on important regulatory and legal differences among EU Nations in providing ART treatments and PGD, we derived some important similarities and differences.
Application of variable-speed ground-source heat pumps to displacement ventilation systems for use in sub-tropical regions
Authors: Lee CK , Lam HN 
Published: April 2014

The merit of applying variable-speed ground-source heat pumps (VSGSHPs) to displacement ventilation (DV) systems was investigated for use in offices in Hong Kong. To improve the dehumidification capacity of the DV systems, a sensible heat recovery wheel was added between the mixed and supply air streams with a heat recovery effectiveness of 0.4. By maintaining the peak fluid temperature leaving the ground heat exchanger borefield after one year to be the same, the required borehole depth and the total energy consumption of the modified DV system were reduced by 16.8% and 19.4%, respectively, as compared to a conventional mixing ventilation system which employed a constant-speed ground-source heat pump. This enhanced the economic feasibility of applying ground-source heat pumps to sub-tropical regions. Practical application: The high initial cost of ground-source heat pump systems is the main obstacle to their wide acceptance in actual practice, particularly for application to sub-tropical regions where the air-conditioning demand is cooling-dominated. The present study demonstrates a design strategy in which both the initial and running cost of the ground-source heat pump systems can be reduced, thus enhancing the economic feasibility of the systems.