bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of arabinokinase in arabinose toxicity in plants
Authors: Behmüller Robert , Kavkova Eva , Düh Stefanie , Huber Christian G. , Tenhaken Raimund 
Published: May 2016

SummaryPlant cell wall polymers are synthesized by glycosyltransferases using nucleotide sugars as substrates. Most UDP‐sugars are synthesized from UDP‐glucose via de novo pathways but salvage pathways work in parallel to recycle sugars, which have been released during cell wall polymer and glycoprotein turnover. Here we report on the cloning and biochemical analysis of two arabinokinases in Arabidopsis. Arabinokinase is a 100 kDa protein located in the cytosol with a putative N‐terminal glycosyltransferase domain and a C‐terminal sugar‐1‐kinase domain. This unique structure is highly conserved in the plant kingdom. Arabinokinase has a high affinity for l‐arabinose, which is the only sugar substrate of this GHMP (galactose; homoserine; mevalonate; phosphomevalonate) kinase. Plants that were knocked‐out for arabinokinase and the previously described ara1‐1 mutant were characterized. The ARA1‐1 mutant form of the enzyme carries a point mutation in an α‐helix. The mutation is close to the substrate binding site and changes the Km value for arabinose from 80 μm in the wild type to 17 000 μm in ARA1‐1. The previous arabinose toxicity explanation is challenged by knockout plants in arabinokinase that accumulate higher levels of arabinose but do not show signs of arabinose toxicity. Analysis of marker genes from sugar signalling pathways (SnRK1 and Tor) suggest that ara1‐1 misinterprets its carbon energy status. Although glucose is present in ara1‐1 similar to wild type levels, it constitutively changes gene expression as typically found in wild type plants only under starvation conditions. Furthermore, ara1‐1 shows increased expression of marker genes for programmed cell death as found in other lesion mimic mutants.
The walnut (Juglans regia) genome sequence reveals diversity in genes coding for the biosynthesis of non‐structural polyphenols
Authors: Martínez‐García Pedro J. , Crepeau Marc W. , Puiu Daniela , Gonzalez‐Ibeas Daniel , Whalen Jeanne , Stevens Kristian A. , Paul Robin , Butterfield Timothy S. , Britton Monica T. , Reagan Russell L. , Chakraborty Sandeep , Walawage Sriema L. , Vasquez‐Gross Hans A. , Cardeno Charis , Famula Randi A. , Pratt Kevin , Kuruganti Sowmya , Aradhya Mallikarjuna K. , Leslie Charles A. , Dandekar Abhaya M. , Salzberg Steven L. , Wegrzyn Jill L. , Langley Charles H. , Neale David B. 
Published: May 2016

SummaryThe Persian walnut (Juglans regia L.), a diploid species native to the mountainous regions of Central Asia, is the major walnut species cultivated for nut production and is one of the most widespread tree nut species in the world. The high nutritional value of J. regia nuts is associated with a rich array of polyphenolic compounds, whose complete biosynthetic pathways are still unknown. A J. regia genome sequence was obtained from the cultivar ‘Chandler’ to discover target genes and additional unknown genes. The 667‐Mbp genome was assembled using two different methods (SOAPdenovo2 and MaSuRCA), with an N50 scaffold size of 464 955 bp (based on a genome size of 606 Mbp), 221 640 contigs and a GC content of 37%. Annotation with MAKER‐P and other genomic resources yielded 32 498 gene models. Previous studies in walnut relying on tissue‐specific methods have only identified a single polyphenol oxidase (PPO) gene (JrPPO1). Enabled by the J. regia genome sequence, a second homolog of PPO (JrPPO2) was discovered. In addition, about 130 genes in the large gallate 1‐β‐glucosyltransferase (GGT) superfamily were detected. Specifically, two genes, JrGGT1 and JrGGT2, were significantly homologous to the GGT from Quercus robur (QrGGT), which is involved in the synthesis of 1‐O‐galloyl‐β‐d‐glucose, a precursor for the synthesis of hydrolysable tannins. The reference genome for J. regia provides meaningful insight into the complex pathways required for the synthesis of polyphenols. The walnut genome sequence provides important tools and methods to accelerate breeding and to facilitate the genetic dissection of complex traits.
An evaluation of overall effectiveness and treatment satisfaction with intravenous immunoglobulin among patients with immune thrombocytopenia
Authors: Sholapur Naushin S. , Hamilton Korinne , Butler Lianna , Heddle Nancy M. , Arnold Donald M. 
Published: May 2016

BACKGROUNDA global assessment of patient satisfaction that considers therapeutic effect, toxicities, and convenience is needed to evaluate the acceptability of intravenous immunoglobulin (IVIG) as a treatment for patients with immune thrombocytopenia (ITP).STUDY DESIGN AND METHODSWe performed a cross‐sectional pilot study to assess the feasibility and usefulness of a treatment satisfaction questionnaire for adult patients with ITP receiving IVIG in an academic hematology clinic. Treatment satisfaction was evaluated by administration of a validated survey‐based tool 7 days after IVIG administration. The tool assessed treatment satisfaction across four domains (effectiveness, toxicity, convenience, and global satisfaction); results were summarized with mean scores.RESULTSTwelve patients were enrolled (nine females; median age, 44 years; interquartile range, 35‐69 years). Mean platelet increment after infusion was 54.2 × 109/L (SD, 47.6 × 109/L). Treatment satisfaction scores were highest in the side effect burden domain (88.2/100; SD, 19.3; higher scores indicate a lower burden of side effects). Six participants reported IVIG‐associated toxicities; most were “slightly” or “not at all” dissatisfied by the impact of side effects. The domain with the lowest score was convenience (62.0/100; SD, 24.7).CONCLUSIONThe assessment of treatment satisfaction using a survey‐based assessment tool was feasible for patients receiving IVIG and provided meaningful results that discriminated between domains. Patients found IVIG treatment to be inconvenient, but were satisfied with its tolerability as an ITP treatment. Larger studies are needed to determine the precise impact on each domain and the reproducibility of study results. Patient satisfaction scores can be used to compare different ITP treatments.
Analyzing treatment aggressiveness and identifying high‐risk patients in diabetic foot ulcer return to care
Authors: Remington Austin C. , Hernandez‐Boussard Tina , Warstadt Nicholus M. , Finnegan Micaela A. , Shaffer Robyn , Kwong Jereen Z. , Curtin Catherine 
Published: May 2016

AbstractRates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all‐cause 30‐day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30‐day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011–2012. All‐cause 30‐day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high‐risk for readmission can improve counseling and treatment strategies for this fragile patient population.
Changes in Leisure-Time Physical Activity and Subsequent Sickness Absence Due to Any Cause, Musculoskeletal, and Mental Causes
Authors: Holstila Ansku , Rahkonen Ossi , Lahelma Eero , Lahti Jouni 
Published: May 2016

Background:The association between changes in physical activity and sickness absence is poorly understood. The aim of this study was to examine the association between changes in leisure-time physical activity and long-term sickness absence due to any cause and musculoskeletal and mental causes.Methods:We measured physical activity at baseline in 2000–2002 (response rate 67%) and at follow-up in 2007 (response rate 83%) among middle-aged employees of the City of Helsinki, Finland. The survey data were linked to the Finnish Social Insurance Institute’s register data on sickness benefit periods > 9 days, including diagnoses (ICD-10; International Statistical Classification of Diseases and Related Health Problems, 10th revision) (mean follow-up 2.3 years). We used a negative binomial model to calculate rate ratios. The analyses included 4010 respondents (81% women).Results:Those who were persistently vigorously active and those whose physical activity level changed from low to moderate or vigorous, from moderate to vigorous, or from vigorous to moderate were at lower risk for sickness absence than were the persistently low-activity group. For sickness absence due to musculoskeletal causes, vigorous activity showed stronger associations, whereas mental causes showed no such associations.Conclusions:To reduce sickness absence due to both musculoskeletal and mental causes, middle-aged and aging employees should be encouraged to engage in physical activity.
Alveolar Type II Epithelial Cells Contribute to the Anti-Influenza A Virus Response in the Lung by Integrating Pathogen- and Microenvironment-Derived Signals
Authors: Stegemann-Koniszewski S. , Jeron Andreas , Gereke Marcus , Geffers Robert , Kröger Andrea , Gunzer Matthias , Bruder Dunja 
Published: May 2016

ABSTRACT

Influenza A virus (IAV) periodically causes substantial morbidity and mortality in the human population. In the lower lung, the primary targets for IAV replication are type II alveolar epithelial cells (AECII), which are increasingly recognized for their immunological potential. So far, little is known about their reaction to IAV and their contribution to respiratory antiviral immunity
in vivo
. Therefore, we characterized the AECII response during early IAV infection by analyzing transcriptional regulation in cells sorted from the lungs of infected mice. We detected rapid and extensive regulation of gene expression in AECII following
in vivo
IAV infection. The comparison to transcriptional regulation in lung tissue revealed a strong contribution of AECII to the respiratory response. IAV infection triggered the expression of a plethora of antiviral factors and immune mediators in AECII with a high prevalence for interferon-stimulated genes. Functional pathway analyses revealed high activity in pathogen recognition, immune cell recruitment, and antigen presentation. Ultimately, our analyses of transcriptional regulation in AECII and lung tissue as well as interferon I/III levels and cell recruitment indicated AECII to integrate signals provided by direct pathogen recognition and surrounding cells.
Ex vivo
analysis of AECII proved a powerful tool to increase our understanding of their role in respiratory immune responses, and our results clearly show that AECII need to be considered a part of the surveillance and effector system of the lower respiratory tract.

IMPORTANCE
In order to confront the health hazard posed by IAV, we need to complete our understanding of its pathogenesis. AECII are primary targets for IAV replication in the lung, and while we are beginning to understand their importance for respiratory immunity, the
in vivo
AECII response during IAV infection has not been analyzed. In contrast to studies addressing the response of AECII infected with IAV
ex vivo
, we have performed detailed gene transcriptional profiling of AECII isolated from the lungs of infected mice. Thereby, we have identified an exceptionally rapid and versatile response to IAV infection that is shaped by pathogen-derived as well as microenvironment-derived signals and aims at the induction of antiviral measures and the recruitment and activation of immune cells. In conclusion, our study presents AECII as active players in antiviral defense
in vivo
that need to be considered part of the sentinel and effector immune system of the lung.
Genome-Wide Mapping of Binding Sites Reveals Multiple Biological Functions of the Transcription Factor Cst6p in Saccharomyces cerevisiae
Authors: Liu Guodong , Bergenholm David , Nielsen Jens 
Published: May 2016

ABSTRACT

In the model eukaryote
Saccharomyces cerevisiae
, the transcription factor Cst6p has been reported to play important roles in several biological processes. However, the genome-wide targets of Cst6p and its physiological functions remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. Cst6p binds to the promoter regions of 59 genes with various biological functions when cells are grown on ethanol but hardly binds to the promoter at any gene when cells are grown on glucose. The retarded growth of the
CST6
deletion mutant on ethanol is attributed to the markedly decreased expression of
NCE103
, encoding a carbonic anhydrase, which is a direct target of Cst6p. The target genes of Cst6p have a large overlap with those of stress-responsive transcription factors, such as Sko1p and Skn7p. In addition, a
CST6
deletion mutant growing on ethanol shows hypersensitivity to oxidative stress and ethanol stress, assigning Cst6p as a new member of the stress-responsive transcriptional regulatory network. These results show that mapping of genome-wide binding sites can provide new insights into the function of transcription factors and highlight the highly connected and condition-dependent nature of the transcriptional regulatory network in
S. cerevisiae
.

IMPORTANCE
Transcription factors regulate the activity of various biological processes through binding to specific DNA sequences. Therefore, the determination of binding positions is important for the understanding of the regulatory effects of transcription factors. In the model eukaryote
Saccharomyces cerevisiae
, the transcription factor Cst6p has been reported to regulate several biological processes, while its genome-wide targets remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. We show that the binding of Cst6p to its target promoters is condition dependent and explain the mechanism for the retarded growth of the
CST6
deletion mutant on ethanol. Furthermore, we demonstrate that Cst6p is a new member of a stress-responsive transcriptional regulatory network. These results provide deeper understanding of the function of the dynamic transcriptional regulatory network in
S. cerevisiae
.
The ABC of Ribosome-Related Antibiotic Resistance
Authors: Wilson Daniel N. 
Published: May 2016

ABSTRACT

The increase in multidrug-resistant pathogenic bacteria is limiting the utility of our current arsenal of antimicrobial agents. Mechanistically understanding how bacteria obtain antibiotic resistance is a critical first step to the development of improved inhibitors. One common mechanism for bacteria to obtain antibiotic resistance is by employing ATP-binding cassette (ABC) transporters to actively pump the drug from the cell. The ABC-F family includes proteins conferring resistance to a variety of clinically important ribosome-targeting antibiotics; however, controversy remains as to whether resistance is conferred via efflux like other ABC transporters or whether another mechanism, such as ribosome protection, is at play. A recent study by Sharkey and coworkers (L. K. Sharkey, T. A. Edwards, and A. J. O’Neill, mBio 7:e01975-15, 2016,
http://dx.doi.org/10.1128/mBio.01975-15
) provides strong evidence that ABC-F proteins conferring antibiotic resistance utilize ribosome protection mechanisms, namely, by interacting with the ribosome and displacing the drug from its binding site, thus revealing a novel role for ABC-F proteins in antibiotic resistance.
Socioeconomic disadvantage and its implications for population health planning of obesity and overweight, using cross-sectional data from general practices from a regional catchment in Australia
Authors: Ghosh Abhijeet , Charlton Karen E , Batterham Marijka J 
Published: May 2016

ObjectivesTo identify smaller geographic and region-specific evidence to inform population health planning for overweight and obesity.DesignCross-sectional secondary analysis of data.SettingPrimary healthcare—17 general practices located in the Illawarra-Shoalhaven region of New South Wales (NSW).ParticipantsA subset (n=36 674) of the Sentinel Practices Data Sourcing project adult persons data set (n=118 794) that included information on disease status of all adult patients who had height and weight measurements recorded in their electronic health records and had visited the included general practices within the Illawarra-Shoalhaven region of NSW between September 2011 and September 2013.Main outcome measuresAge-adjusted odds ratio (aOR) of overweight and obesity was determined for high and low levels of socioeconomic disadvantage based on Socio-Economic Indexes for Areas (SEIFA)—Index of Relative Socio-Economic Disadvantage (IRSD) scores of patients' residential statistical local area.ResultsIn men, overweight was lowest in areas of highest socioeconomic disadvantage (aOR=0.910; 95% CI 0.830 to 0.998; p<0.001); but no statistically significant association with socioeconomic score was found for women. Overall obesity was associated with high socioeconomic disadvantage (aOR=1.292; 95% CI 1.210 to 1.379; p<0.001).ConclusionsThis type of data analysis reveals multiple layers of evidence that should be assessed for population health approaches to curb the epidemic of obesity and overweight. It strongly highlights the need for preventive health initiatives to be specific to gender and socioeconomic attributes of the target population.
Leprosy in England and Wales 1953–2012: surveillance and challenges in low incidence countries
Authors: Fulton Nicholas , Anderson Laura F , Watson John M , Abubakar Ibrahim 
Published: May 2016

ObjectiveTo review all notified cases of leprosy in England and Wales between 1953 and 2012.DesignNational surveillance study of all reported cases.SettingEngland and Wales.OutcomeNumber and characteristics of reported cases.ResultsDuring this period, a total of 1449 leprosy cases were notified. The incidence fell from 356 new cases notified between 1953 and 1962 to 139 new cases between 2003 and 2012. Where data were available, leprosy was more common in men, 15–45 year olds and those from the Indian subcontinent. There was considerable undernotification in 2001–2012.ConclusionsThe high level of under-reporting indicates a need for improved surveillance in the UK. Public Health England, in collaboration with the UK Panel of Leprosy opinion, has revised the UK Memorandum on Leprosy in order to provide updated guidance on diagnostic procedures, treatment, case management, contact tracing and notification.
Modified international e-Delphi survey to define healthcare professional competencies for working with teenagers and young adults with cancer
Authors: Taylor Rachel M , Feltbower Richard G , Aslam Natasha , Raine Rosalind , Whelan Jeremy S , Gibson Faith 
Published: May 2016

ObjectivesTo provide international consensus on the competencies required by healthcare professionals in order to provide specialist care for teenagers and young adults (TYA) with cancer.DesignModified e-Delphi survey.SettingInternational, multicentre study.ParticipantsExperts were defined as professionals having worked in TYA cancer care for more than 12 months. They were identified through publications and professional organisations.MethodsRound 1, developed from a previous qualitative study, included 87 closed-ended questions with responses on a nine-point Likert scale and further open-ended responses to identify other skills, knowledge and attitudes. Round 2 contained only items with no consensus in round 1 and suggestions of additional items of competency. Consensus was defined as a median score ranging from 7 to 9 and strength of agreement using mean absolute deviation of the median.ResultsA total of 179 registered to be members of the expert panel; valid responses were available from 158 (88%) in round 1 and 136/158 (86%) in round 2. The majority of participants were nurses (35%) or doctors (39%) from Europe (55%) or North America (35%). All 87 items in round 1 reached consensus with an additional 15 items identified for round 2, which also reached consensus. The strength of agreement was mostly high for statements. The areas of competence rated most important were agreed to be: ‘Identify the impact of disease on young people's life’ (skill), ‘Know about side effects of treatment and how this might be different to those experienced by children or older adults’ (knowledge), ‘Honesty’ (attitude) and ‘Listen to young people's concerns’ (aspect of communication).ConclusionsGiven the high degree of consensus, this list of competencies should influence education curriculum, professional development and inform workforce planning. Variation in strength of agreement for some competencies between professional groups should be explored further in pursuit of effective multidisciplinary team working.