bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent surrogate variable analysis to deconvolve confounding factors in large-scale microarray profiling studies
Authors: Teschendorff Andrew E. , Zhuang Joanna , Widschwendter Martin 
Published: April 2011

Abstract
Motivation: A common difficulty in large-scale microarray studies is the presence of confounding factors, which may significantly skew estimates of statistical significance, cause unreliable feature selection and high false negative rates. To deal with these difficulties, an algorithmic framework known as Surrogate Variable Analysis (SVA) was recently proposed.
Results: Based on the notion that data can be viewed as an interference pattern, reflecting the superposition of independent effects and random noise, we present a modified SVA, called Independent Surrogate Variable Analysis (ISVA), to identify features correlating with a phenotype of interest in the presence of potential confounding factors. Using simulated data, we show that ISVA performs well in identifying confounders as well as outperforming methods which do not adjust for confounding. Using four large-scale Illumina Infinium DNA methylation datasets subject to low signal to noise ratios and substantial confounding by beadchip effects and variable bisulfite conversion efficiency, we show that ISVA improves the identifiability of confounders and that this enables a framework for feature selection that is more robust to model misspecification and heterogeneous phenotypes. Finally, we demonstrate similar improvements of ISVA across four mRNA expression datasets. Thus, ISVA should be useful as a feature selection tool in studies that are subject to confounding.
Availability: An R-package isva is available from www.cran.r-project.org.
Contact: a.teschendorff@ucl.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
ABI3 and PIL5 Collaboratively Activate the Expression ofSOMNUSby Directly Binding to Its Promoter in ImbibedArabidopsisSeeds
Authors: Park Jeongmoo , Lee Nayoung , Kim Woohyun , Lim Soohwan , Choi Giltsu 
Published: April 2011

AbstractA previous study showed that SOMNUS (SOM), which encodes a C3H-type zinc finger protein, is a key negative regulator of seed germination that acts downstream of PHYTOCHROME INTERACTING FACTOR3-LIKE5 (PIL5). However, it was not determined if PIL5 is the sole regulator of SOM expression. Public microarray data suggest that the expression of SOM mRNA is regulated also by ABSCISIC ACID INSENSITIVE3 (ABI3), another key regulator of seed germination. By analyzing abi3 mutants and ABI3 overexpression lines, we show here that ABI3 activates the expression of SOM mRNA collaboratively with PIL5 in imbibed seeds. Chromatin immunoprecipitation analysis coupled with electrophoretic mobility shift assay indicate that ABI3 activates the expression of SOM mRNA by directly binding to two RY motifs present in the SOM promoter in vivo, which is further supported by the greatly decreased expression of a reporter gene driven by a SOM promoter bearing mutated RY motifs. At the protein level, the ABI3 protein interacts with the PIL5 protein. The ABI3-PIL5 interaction, however, does not affect targeting of ABI3 and PIL5 to SOM promoters. Taken together, our results indicate that ABI3 and PIL5 collaboratively activate the expression of SOM mRNA by directly binding to and interacting with each other at the SOM promoter.
MATE2 Mediates Vacuolar Sequestration of Flavonoid Glycosides and Glycoside Malonates inMedicago truncatula
Authors: Zhao Jian , Huhman David , Shadle Gail , He Xian-Zhi , Sumner Lloyd W. , Tang Yuhong , Dixon Richard A. 
Published: April 2011

AbstractThe majority of flavonoids, such as anthocyanins, proanthocyanidins, and isoflavones, are stored in the central vacuole, but the molecular basis of flavonoid transport is still poorly understood. Here, we report the functional characterization of a multidrug and toxin extrusion transporter (MATE2), from Medicago truncatula. MATE 2 is expressed primarily in leaves and flowers. Despite its high similarity to the epicatechin 3′-O-glucoside transporter MATE1, MATE2 cannot efficiently transport proanthocyanidin precursors. In contrast, MATE2 shows higher transport capacity for anthocyanins and lower efficiency for other flavonoid glycosides. Three malonyltransferases that are coexpressed with MATE2 were identified. The malonylated flavonoid glucosides generated by these malonyltransferases are more efficiently taken up into MATE2-containing membrane vesicles than are the parent glycosides. Malonylation increases both the affinity and transport efficiency of flavonoid glucosides for uptake by MATE2. Genetic loss of MATE2 function leads to the disappearance of leaf anthocyanin pigmentation and pale flower color as a result of drastic decreases in the levels of various flavonoids. However, some flavonoid glycoside malonates accumulate to higher levels in MATE2 knockouts than in wild-type controls. Deletion of MATE2 increases seed proanthocyanidin biosynthesis, presumably via redirection of metabolic flux from anthocyanin storage.
Unlocking the Barley Genome by Chromosomal and Comparative Genomics
Authors: Mayer Klaus F.X. , Martis Mihaela , Hedley Pete E. , Šimková Hana , Liu Hui , Morris Jenny A. , Steuernagel Burkhard , Taudien Stefan , Roessner Stephan , Gundlach Heidrun , Kubaláková Marie , Suchánková Pavla , Murat Florent , Felder Marius , Nussbaumer Thomas , Graner Andreas , Salse Jerome , Endo Takashi , Sakai Hiroaki , Tanaka Tsuyoshi , Itoh Takeshi , Sato Kazuhiro , Platzer Matthias , Matsumoto Takashi , Scholz Uwe , Doležel Jaroslav , Waugh Robbie , Stein Nils 
Published: April 2011

AbstractWe used a novel approach that incorporated chromosome sorting, next-generation sequencing, array hybridization, and systematic exploitation of conserved synteny with model grasses to assign ~86% of the estimated ~32,000 barley (Hordeum vulgare) genes to individual chromosome arms. Using a series of bioinformatically constructed genome zippers that integrate gene indices of rice (Oryza sativa), sorghum (Sorghum bicolor), and Brachypodium distachyon in a conserved synteny model, we were able to assemble 21,766 barley genes in a putative linear order. We show that the barley (H) genome displays a mosaic of structural similarity to hexaploid bread wheat (Triticum aestivum) A, B, and D subgenomes and that orthologous genes in different grasses exhibit signatures of positive selection in different lineages. We present an ordered, information-rich scaffold of the barley genome that provides a valuable and robust framework for the development of novel strategies in cereal breeding.
A Sister Group Contrast Using Untargeted Global Metabolomic Analysis Delineates the Biochemical Regulation Underlying Desiccation Tolerance in Sporobolus stapfianus
Authors: Oliver Melvin J. , Guo Lining , Alexander Danny C. , Ryals John A. , Wone Bernard W.M. , Cushman John C. 
Published: April 2011

Abstract
Understanding how plants tolerate dehydration is a prerequisite for developing novel strategies for improving drought tolerance. The desiccation-tolerant (DT) Sporobolus stapfianus and the desiccation-sensitive (DS) Sporobolus pyramidalis formed a sister group contrast to reveal adaptive metabolic responses to dehydration using untargeted global metabolomic analysis. Young leaves from both grasses at full hydration or at 60% relative water content (RWC) and from S. stapfianus at lower RWCs were analyzed using liquid and gas chromatography linked to mass spectrometry or tandem mass spectrometry. Comparison of the two species in the fully hydrated state revealed intrinsic differences between the two metabolomes. S. stapfianus had higher concentrations of osmolytes, lower concentrations of metabolites associated with energy metabolism, and higher concentrations of nitrogen metabolites, suggesting that it is primed metabolically for dehydration stress. Further reduction of the leaf RWC to 60% instigated a metabolic shift in S. stapfianus toward the production of protective compounds, whereas S. pyramidalis responded differently. The metabolomes of S. stapfianus leaves below 40% RWC were strongly directed toward antioxidant production, nitrogen remobilization, ammonia detoxification, and soluble sugar production. Collectively, the metabolic profiles obtained uncovered a cascade of biochemical regulation strategies critical to the survival of S. stapfianus under desiccation.
Predicting small‐mammal responses to climatic warming: autecology, geographic range, and the Holocene fossil record
Authors: TERRY REBECCA C. , LI CHENG (LILY) , HADLY ELIZABETH A. 
Published: April 2011

AbstractForecasting how species will respond to climatic change requires knowledge of past community dynamics. Here we use time‐series data from the small‐mammal fossil records of two caves in the Great Basin of the American West to evaluate how contrasting and variable local paleoclimates have shaped small‐mammal abundance dynamics over the last ∼7500 years of climatic change. We then predict how species and communities will respond to future scenarios of increased warming and aridity coupled with continued spread of an invasive annual grass (Bromus tectorum). We find that most community‐level responses to climatic change occur in the mammalian abundance structure at both sites; the dominance of the community by individuals from species with a southern geographic affinity increases with climatic warming. This suggests that responses occurredin siturather than by the immigration of new taxa over this time interval. Despite predictability at the community‐scale, species‐level relationships between abundance and climate are variable and are not necessarily explained by a species' geographic affinity. Species present at both sites, however, exhibit remarkably similar responses to climate at each site, indicating that species autecology (specifically dietary functional group) is important in determining response to climatic warming. Regression‐tree analyses show remarkable concordance between the two cave faunas and highlight the importance of a granivorous dietary strategy in this desert ecosystem. Under projections of increased temperature and decreased precipitation over the next 50 years, our results indicate that granivores should thrive as communities become more dominated by individuals with a southern geographic affinity. Granivores, however, are negatively impacted by the invasion of cheatgrass. The last century of anthropogenic impacts has thus placed granivores at a greater risk of extinction than predicted under climate‐only scenarios.
TRANSPARENT TESTA1 interacts with R2R3‐MYB factors and affects early and late steps of flavonoid biosynthesis in the endothelium of Arabidopsis thaliana seeds
Authors: Appelhagen Ingo , Lu Gui‐Hua , Huep Gunnar , Schmelzer Elmon , Weisshaar Bernd , Sagasser Martin 
Published: April 2011

SummaryWild type seed coats of Arabidopsis thaliana are brown due to the accumulation of proanthocyanidin pigments (PAs). The pigmentation requires activation of phenylpropanoid biosynthesis genes and mutations in some of these genes cause a yellow appearance of seeds, termed transparent testa (tt) phenotype. The TT1 gene encodes a WIP‐type zinc finger protein and is expressed in the seed coat endothelium where most of the PAs accumulate in wild type plants. In this study we show that TT1 is not only required for correct expression of PA‐specific genes in the seed coat, but also affects CHS, encoding the first enzyme of flavonoid biosynthesis. Many steps of this pathway are controlled by complexes of MYB and BHLH proteins with the WD40 factor TTG1. We demonstrate that TT1 can interact with the R2R3 MYB protein TT2 and that ectopic expression of TT2 can partially restore the lack in PA production in tt1. Reduced seed coat pigmentation was obtained using a TT1 variant lacking nuclear localisation signals. Based on our results we propose that the TT2/TT8/TTG1 regulon may also comprise early genes like CHS and discuss steps to further unravel the regulatory network controlling flavonoid accumulation in endothelium cells during A. thaliana seed development.
Invasive bacterial and fungal infections among hospitalized HIV‐infected and HIV‐uninfected children and infants in northern Tanzania
Authors: Crump John A. , Ramadhani Habib O. , Morrissey Anne B. , Msuya Levina J. , Yang Lan‐Yan , Chow Shein‐Chung , Morpeth Susan C. , Reyburn Hugh , Njau Boniface N. , Shaw Andrea V. , Diefenthal Helmut C. , Bartlett John A. , Shao John F. , Schimana Werner , Cunningham Coleen K. , Kinabo Grace D. 
Published: April 2011

SummaryObjective  To describe the contribution of paediatric HIV and of HIV co‐infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods.Methods  During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV‐1 RNA PCR was performed on those aged <18 months. HIV‐infected patients also received serum cryptococcal antigen testing and had their CD4‐positive T‐lymphocyte count and percent determined.Results  A total of 467 patients were enrolled whose median age was 2 years (range 2 months–13 years); Of those patients, 57.2% were female and 12.2% were HIV‐infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV‐uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively.Conclusion  Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over‐diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co‐infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.
Causes of stillbirth, neonatal death and early childhood death in rural Zambia by verbal autopsy assessments
Authors: Turnbull Eleanor , Lembalemba Mwila K. , Brad Guffey M. , Bolton‐Moore Carolyn , Mubiana‐Mbewe Mwangelwa , Chintu Namwinga , Giganti Mark J. , Nalubamba‐Phiri Mutinta , Stringer Elizabeth M. , Stringer Jeffrey S. A. , Chi Benjamin H. 
Published: April 2011

SummaryObjectives  To describe specific causes of the high rates of stillbirth, neonatal death and early child childhood death in Zambia.Methods  We conducted a household‐based survey in rural Zambia. Socio‐demographic and delivery characteristics were recorded, alongside a maternal HIV test. Verbal autopsy questionnaires were administered to elicit mortality‐related information and independently reviewed by three experienced paediatricians who assigned a cause and contributing factor to death. For this secondary analysis, deaths were categorized into: stillbirths (foetal death ≥28 weeks of gestation), neonatal deaths (≤28 days) and early childhood deaths (>28 days to <2 years).Results  Among 1679 households, information was collected on 148 deaths: 34% stillbirths, 26% neonatal and 40% early childhood deaths. Leading identifiable causes of stillbirth were intrauterine infection (26%) and birth asphyxia (18%). Of 32 neonatal deaths, 38 (84%) occurred within the first week of life, primarily because of infections (37%) and prematurity (34%). The majority of early childhood deaths were caused by suspected bacterial infections (82%). HIV prevalence was significantly higher in mothers who reported an early childhood death (44%) than mothers who did not (17%; P < 0.01). Factors significantly associated with mortality were lower socio‐economic status (P < 0.01), inadequate water or sanitation facilities (P < 0.01), home delivery (P = 0.04) and absence of a trained delivery attendant (P < 0.01).Conclusion  We provide community‐level data about the causes of death among children under 2 years of age. Infectious etiologies for mortality ranked highest. At a public health level, such information may have an important role in guiding prevention and treatment strategies to address perinatal and early childhood mortality.
Fragile X‐associated tremor/ataxia phenotype in a male carrier of unmethylated full mutation in the FMR1 gene
Authors: Loesch D Z , Sherwell S , Kinsella G , Tassone F , Taylor A , Amor D , Sung S , Evans A 
Published: April 2011

Loesch DZ, Sherwell S, Kinsella G, Tassone F, Taylor A, Amor D, Sung S, Evans A. Fragile X‐associated tremor/ataxia phenotype in a male carrier of unmethylated full mutation in the FMR1 gene.The Fragile X syndrome is caused by a CGG repeat expansion >200 in the promoter of the Fragile X mental retardation 1 (FMR1) gene termed full mutation (FM). These alleles are silenced through methylation of the FMR1 promoter, leading to deficit of the FMR1 protein (FMRP), and neurodevelopmental changes. However, occasional FM individuals have a complete lack of methylation, and those typically have only minor deficit of FMRP levels compared with normal controls and their intelligence may be in the normal range. FM alleles are generated through expansion of the CGG repeat from the premutation (PM) range of 55–200 repeats, linked to the late onset Fragile X‐associated tremor/ataxia syndrome (FXTAS). This disorder has been attributed to a ‘toxicity’ of the FMR1 mRNA, which is significantly elevated in male carriers of PM alleles and of unmethylated FM alleles. This is the first report of a 65‐year‐old male with an unmethylated FM allele and history of alcohol abuse, who developed symptoms of FXTAS. We postulate that, although the elevation of FMR1 transcripts associated with unmethylated FM alleles have a potential to cause FXTAS, in some cases this disorder may occur through an additional effect of exposure to neurotoxicants including alcohol.
Improvement of gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric‐coated mycophenolate sodium in liver transplant patients
Authors: Toledo Alexander H. , Hendrix Laura , Buchholz Valorie , Fisher Erin , Newton Kimberly , Smith Courtney , Gerber David A. 
Published: April 2011

Toledo AH, Hendrix L, Buchholz V, Fisher E, Newton K, Smith C, Gerber DA. Improvement of gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric‐coated mycophenolate sodium in liver transplant patients.  Clin Transplant 2012: 26: 156–163.  © 2011 John Wiley & Sons A/S.Abstract:  As many as 50% of liver transplant patients suffer gastrointestinal (GI) disturbances post‐transplant. Conversion from mycophenolate mofetil (MMF) to mycophenolate sodium (EC‐MPS) alleviates GI symptom burden in renal transplant recipients. We employed a validated patient and physician‐reported assessment to evaluate the impact of conversion to EC‐MPS in liver transplant patients. This is a prospective, longitudinal, single‐center, open‐label pilot study. Thirty‐one MMF‐treated liver transplant patients with GI symptoms were converted to equimolar EC‐MPS. Gastrointestinal Symptom Rating Scale (GSRS), GI Quality of Life, SF‐12v2 and physician‐reported assessments were used to evaluate GI symptom burden and severity. A significant improvement in overall GSRS score was noted from baseline (2.57; 95% CI 2.12–3.10) to one month (1.90; 1.68–2.12; p = 0.0007) and three months (1.82; 1.60–2.04; p = 0.0002) post‐conversion with significant reductions in all subgroups except Reflux. The overall Gastrointestinal Quality of Life Index (GIQLI) score also showed significant increase in health‐related quality of life between one month (90.89; 84.04–97.75) and three months (100.04; 94.57–105.51; p = 0.0009), with all subgroups except social functioning (p = 0.0861) and medical treatment (p = 0.3156) demonstrating significant improvements. This pilot study demonstrates improvement in GI symptom burden when converting from equimolar doses of MMF to EC‐MPS. This benefit persisted for three months without evidence of rejection.
Child and adolescent injury report card: New Zealand 2009
Authors: Bland Victoria , Shepherd Mike , Ameratunga Shanthi , Carter Wayne , Chambers Julie , Hassall Ian , Kool Bridget , Richards Gay , Sapolu‐Reweti Pepe , Dalziel Stuart 
Published: April 2011

Aim:  Injury is the leading cause of death of children and adolescents. Among the Organisation for Economic Co‐operation and Development nations, New Zealand has the highest rate of child and adolescent injury death. This study aimed to evaluate the status of New Zealand's child and adolescent unintentional injury prevention.Methods:  The methodology of the European Child Safety Alliance Child Safety Report Card (completed for 24 countries in Europe, generating a standardised assessment of child and adolescent injury prevention) was applied to New Zealand's injury prevention position. New Zealand's position with regard to 102 questions (spanning 12 injury topics) was investigated. This information was systematically presented to a panel of child and adolescent injury experts, and agreed scores for each item were derived.Results:  New Zealand's overall score was 33/60. Deficiencies were identified across many injury prevention topics including passenger and driver safety, pedestrian safety, water safety, falls, poisoning, burns/scalds and choking/strangulation. New Zealand lacks a robust home visiting programme and injury prevention strategies with specific child and adolescent targets.Conclusions:  New Zealand has not implemented a number of evidence‐based injury prevention policies. The information from this study should be interpreted in conjunction with the epidemiology of child and adolescent injury in New Zealand. The Child Safety Report Card provides a useful methodology to guide a country's child and adolescent injury prevention policy direction.