bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capturing Drug Responses by Quantitative Promoter Activity Profiling
Authors: Kajiyama K , Okada‐Hatakeyama M , Hayashizaki Y , Kawaji H , Suzuki H 
Published: September 2013

Quantitative analysis of cellular responses to drugs is of major interest in pharmaceutical research. Microarray technologies have been widely used for monitoring genome‐wide expression changes. However, this approach has several limitations in terms of coverage of targeted RNAs, sensitivity, and quantitativeness, which are crucial for accurate monitoring of cellular responses. In this article, we report an application of genome‐wide and quantitative profiling of cellular responses to drugs. We monitored promoter activities in MCF‐7 cells by Cap Analysis of Gene Expression using a single‐molecule sequencer. We identified a distinct set of promoters affected even by subtle inhibition of the Ras‐ERK and phosphatidylinositol‐3‐kinase‐Akt signal‐transduction pathways. Furthermore, we succeeded in explaining the majority of promoter responses to inhibition of the upstream epidermal growth factor receptor kinase quantitatively based on the promoter profiles upon inhibition of the two individual downstream signaling pathways. Our results demonstrate unexplored utility of highly quantitative promoter activity profiling in drug research.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e77; doi:10.1038/psp.2013.53; published online 25 September 2013
Green Tea Extract Containing a Highly Absorbent Catechin Prevents Diet-Induced Lipid Metabolism Disorder
Authors: Suzuki Takashi , Kumazoe Motofumi , Kim Yoonhee , Yamashita Shuya , Nakahara Kanami , Tsukamoto Shuntaro , Sasaki Masako , Hagihara Takatoki , Tsurudome Yukari , Huang Yuhui , Maeda-Yamamoto Mari , Shinoda Yuki , Yamaguchi Wataru , Yamada Koji , Tachibana Hirofumi 
Published: September 2013

AbstractWe investigated the effects of extracts of Benifuuki (a tea cultivar that contains methylated catechins such as epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3”Me)) in mice fed a high-fat/high-sucrose (HF/HS) diet. This tea cultivar was then compared with an extract of Yabukita (a popular tea cultivar that lacks methylated catechins). For 6 weeks, C57BL/6J mice were fed either HF/HS diet with or without tea extracts from tea cultivars, which contained almost identical ingredients except for methylated catechins (i.e., Yabukita (0.2% and 1%) or Benifuuki (0.2% and 1%) extract powders). Supplementation with Benifuuki 0.2% markedly lowered plasma levels of TG and NEFAs compared with mice supplemented with Yabukita 0.2%. The diet containing Benifuuki 1% decreased adipose tissue weights, liver TG and expression of lipogenic genes in the liver. These results suggested that Benifuuki had much greater lipid-lowering effects than Yabukita. Taken together, these data suggest that methylated catechins direct the strong lipid-lowering activity of Benifuuki.
microRNA profiles in coeliac patients distinguish different clinical phenotypes and are modulated by gliadin peptides in primary duodenal fibroblasts
Authors: Vaira Valentina , Roncoroni Leda , Barisani Donatella , Gaudioso Gabriella , Bosari Silvano , Bulfamante Gaetano , Doneda Luisa , Conte Dario , Tomba Carolina , Bardella Maria Teresa , Ferrero Stefano , Locatelli Martina , Elli Luca 
Published: September 2013

CD (coeliac disease) is a frequent autoimmune disorder of the small bowel, which is characterized by an immunological reaction against gluten and transglutaminase in genetically predisposed subjects. However, the molecular determinants underpinning CD pathogenesis are yet to be fully elucidated and little data are available about the involvement of miRNAs (microRNAs) in CD. In the present study, the duodenal mucosa miRNA expression was profiled in adult untreated CD presenting with a classic phenotype or iron-deficiency anaemia, treated patients with or without duodenal normalization, and non-CD subjects as controls. Deregulation of seven miRNAs (miR-31-5p, miR-192-3p, miR-194-5p, miR-551a, miR-551b-5p, miR-638 and miR-1290) was determined in a larger series of CD patients with different clinical phenotypes compared with non-CD subjects. These seven microRNAs were then analysed in duodenal fibroblasts obtained from CD patients and incubated with gliadin peptides (13- and 33-mer). The miRNA cluster miR-192/194, involved in matrix remodelling, was deregulated in CD according to the different clinical presentations, and miR-192-3p levels were modulated by gliadin peptides in vitro. In conclusion, the analysis of miRNAs deserves further consideration for its potential use in the treatment and management of CD.
Irx3 and Pax6 establish differential competence for Shh-mediated induction of GABAergic and glutamatergic neurons of the thalamus
Authors: Robertshaw Ellen , Matsumoto Ken , Lumsden Andrew , Kiecker Clemens 
Published: September 2013

Significance
Classic embryological studies suggested that small groups of cells called organizers change the fate of neighboring tissues through inductive processes. In these studies it was also postulated that the receiving tissue has to be “competent” to respond to the inducer in a specific way. In the posterior forebrain, the signaling factor Sonic hedgehog is released from an organizer called the zona limitans intrathalamica and induces GABAergic and glutamatergic neurons of the thalamus. Here we demonstrate that the differential expression of two transcription factors, Irx3 and Pax6, spatially limits the area of competence for these inductions.
Relationship between dynamical entropy and energy dissipation far from thermodynamic equilibrium
Authors: Green Jason R. , Costa Anthony B. , Grzybowski Bartosz A. , Szleifer Igal 
Published: September 2013

Significance
The dissipation of energy occurs naturally in systems as diverse as those in biology and as common as those responsible for the weather. Systems that dissipate energy while self-assembling also show promise as a synthetic route to responsive nanoscale materials. Optimizing the energy efficiency of these syntheses requires reducing the theoretical description to only those variables that are essential to an accurate prediction of the energy lost as heat. Here, with computer simulations and a model of assembly, we establish a methodology for identifying those essential variables. With this minimal description of the system we also find a linear relationship between the dynamical entropy of the self-assembling system and the energy dissipated as heat during assembly.
Unraveling the role of protein dynamics in dihydrofolate reductase catalysis
Authors: Luk Louis Y. P. , Javier Ruiz-Pernía J. , Dawson William M. , Roca Maite , Loveridge E. Joel , Glowacki David R. , Harvey Jeremy N. , Mulholland Adrian J. , Tuñón Iñaki , Moliner Vicent , Allemann Rudolf K. 
Published: September 2013

SignificanceThe role of protein dynamics in enzyme catalysis remains a topic of considerable debate. Here, we use a combination of experimental and computational methods to identify the origins of the observed changes in reactivity on isotopic substitution of dihydrofolate reductase fromEscherichia coli. Isotopic substitution causes differences in environmental coupling to the hydride transfer step and protein dynamics have therefore a small but measurable effect on the chemical reaction rate.
Size homeostasis in adherent cells studied by synthetic phase microscopy
Authors: Sung Yongjin , Tzur Amit , Oh Seungeun , Choi Wonshik , Li Victor , Dasari Ramachandra R. , Yaqoob Zahid , Kirschner Marc W. 
Published: September 2013

Significance
Accurate measurement of cell size is critical in studies of cell growth. Optical methods based on interferometry are known to be suitable for attached cells, but the existing techniques were originally designed for thin samples and are not ideal for thick ones, such as mitotic cells. Synthetic phase microscopy (SPM), a new tomographic interferometric method, offers an elegant solution to this problem. This paper demonstrates the ability of SPM to measure the growth of mammalian cells accurately, and it demonstrates a clear requirement for feedback in the growth process.
Contemporary Fiction
Authors: Eaglestone Robert 
Published: September 2013

Abstract
Contemporary Fiction: A Very Short Introduction explores a wide and diverse field, now global in dimension, with an enormous range of novels and writers that continues to grow at a fantastic speed. This VSI provides an exploration of the major themes, patterns, and debates of contemporary fiction. From genre, form, and experimentalism to the legacies of modernism and postmodernism, the relationship between globalization and terrorism, and the impact of technology, it examines how works both reflect the world in which we live and the artistic concerns of writers and readers alike.
Methods and challenges in timing chromosomal abnormalities within cancer samples
Authors: Purdom Elizabeth , Ho Christine , Grasso Catherine S. , Quist Michael J. , Cho Raymond J. , Spellman Paul 
Published: September 2013

Abstract
Motivation: Tumors acquire many chromosomal amplifications, and those acquired early in the lifespan of the tumor may be not only important for tumor growth but also can be used for diagnostic purposes. Many methods infer the order of the accumulation of abnormalities based on their occurrence in a large cohort of patients. Recently, Durinck et al. (2011) and Greenman et al. (2012) developed methods to order a single tumor’s chromosomal amplifications based on the patterns of mutations accumulated within those regions. This method offers an unprecedented opportunity to assess the etiology of a single tumor sample, but has not been widely evaluated.
Results: We show that the model for timing chromosomal amplifications is limited in scope, particularly for regions with high levels of amplification. We also show that the estimation of the order of events can be sensitive for events that occur early in the progression of the tumor and that the partial maximum likelihood method of Greenman et al. (2012) can give biased estimates, particularly for moderate read coverage or normal contamination. We propose a maximum-likelihood estimation procedure that fully accounts for sequencing variability and show that it outperforms the partial maximum-likelihood estimation method. We also propose a Bayesian estimation procedure that stabilizes the estimates in certain settings. We implement these methods on a small number of ovarian tumors, and the results suggest possible differences in how the tumors acquired amplifications.
Availability and implementation: We provide implementation of these methods in an R package cancerTiming, which is available from the Comprehensive R Archive Network (CRAN) at http://CRAN.R-project.org/.
Contact: epurdom@stat.Berkeley.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
BioServices: a common Python package to access biological Web Services programmatically
Authors: Cokelaer Thomas , Pultz Dennis , Harder Lea M. , Serra-Musach Jordi , Saez-Rodriguez Julio 
Published: September 2013

Abstract
Motivation: Web interfaces provide access to numerous biological databases. Many can be accessed to in a programmatic way thanks to Web Services. Building applications that combine several of them would benefit from a single framework.
Results: BioServices is a comprehensive Python framework that provides programmatic access to major bioinformatics Web Services (e.g. KEGG, UniProt, BioModels, ChEMBLdb). Wrapping additional Web Services based either on Representational State Transfer or Simple Object Access Protocol/Web Services Description Language technologies is eased by the usage of object-oriented programming.
Availability and implementation: BioServices releases and documentation are available at http://pypi.python.org/pypi/bioservices under a GPL-v3 license.
Contact: cokelaer@ebi.ac.uk or bioservices@googlegroups.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Accurate prediction of bacterial type IV secreted effectors using amino acid composition and PSSM profiles
Authors: Zou Lingyun , Nan Chonghan , Hu Fuquan 
Published: September 2013

Abstract
Motivation: Various human pathogens secret effector proteins into hosts cells via the type IV secretion system (T4SS). These proteins play important roles in the interaction between bacteria and hosts. Computational methods for T4SS effector prediction have been developed for screening experimental targets in several isolated bacterial species; however, widely applicable prediction approaches are still unavailable
Results: In this work, four types of distinctive features, namely, amino acid composition, dipeptide composition, .position-specific scoring matrix composition and auto covariance transformation of position-specific scoring matrix, were calculated from primary sequences. A classifier, T4EffPred, was developed using the support vector machine with these features and their different combinations for effector prediction. Various theoretical tests were performed in a newly established dataset, and the results were measured with four indexes. We demonstrated that T4EffPred can discriminate IVA and IVB effectors in benchmark datasets with positive rates of 76.7% and 89.7%, respectively. The overall accuracy of 95.9% shows that the present method is accurate for distinguishing the T4SS effector in unidentified sequences. A classifier ensemble was designed to synthesize all single classifiers. Notable performance improvement was observed using this ensemble system in benchmark tests. To demonstrate the model’s application, a genome-scale prediction of effectors was performed in Bartonella henselae, an important zoonotic pathogen. A number of putative candidates were distinguished.
Availability: A web server implementing the prediction method and the source code are both available at http://bioinfo.tmmu.edu.cn/T4EffPred.
Contact: hoofuquan@yahoo.com.cn
Supplementary information: Supplementary data are available at Bioinformatics online.
Increasing the complexity: new genes and new types of albinism
Authors: Montoliu Lluís , Grønskov Karen , Wei Ai‐Hua , Martínez‐García Mónica , Fernández Almudena , Arveiler Benoît , Morice‐Picard Fanny , Riazuddin Saima , Suzuki Tamio , Ahmed Zubair M. , Rosenberg Thomas , Li Wei 
Published: September 2013

SummaryAlbinism is a rare genetic condition globally characterized by a number of specific deficits in the visual system, resulting in poor vision, in association with a variable hypopigmentation phenotype. This lack or reduction in pigment might affect the eyes, skin, and hair (oculocutaneous albinism, OCA), or only the eyes (ocular albinism, OA). In addition, there are several syndromic forms of albinism (e.g. Hermansky–Pudlak and Chediak–Higashi syndromes, HPS and CHS, respectively) in which the described hypopigmented and visual phenotypes coexist with more severe pathological alterations. Recently, a locus has been mapped to the 4q24 human chromosomal region and thus represents an additional genetic cause of OCA, termed OCA5, while the gene is eventually identified. In addition, two new genes have been identified as causing OCA when mutated: SLC24A5 and C10orf11, and hence designated as OCA6 and OCA7, respectively. This consensus review, involving all laboratories that have reported these new genes, aims to update and agree upon the current gene nomenclature and types of albinism, while providing additional insights from the function of these new genes in pigment cells.
Quality of Life and Mental Health Related to Timing, Frequency and Dose of Hemodialysis
Authors: Cohen Scott D. , Kimmel Paul L. 
Published: September 2013

AbstractThe perceived quality of life (QOL) and mental health of dialysis patients can have a significant impact on clinical outcomes in the end‐stage renal disease (ESRD) population. There is growing interest in increasing dialysis frequency, dose and duration to achieve more adequate dialysis clearance, particularly of middle molecules. Over the past decade, there has been an interest in earlier initiation of dialysis; however, the results of the IDEAL study call this practice into question, and showed no difference in QOL scores between the early‐start and later start dialysis patients. There are inconsistent results regarding the impact of increased dialysis frequency and dose on patients' perceived health‐related QOL (HRQOL). Some studies of daily nocturnal dialysis patients show a positive impact on QOL, while others show no significant difference. The disparate outcomes may be partly related to differences in the demographic characteristics of the study populations and the specific questionnaires used to measure HRQOL. Additional research is necessary to determine whether changes in dialysis frequency, timing, and dose can positively or negatively impact patients' perceptions of their QOL and mental health.
An Association Between Peptidoglycan Synthesis and Organization of the Streptococcus pyogenes ExPortal
Authors: Vega Luis Alberto , Port Gary C. , Caparon Michael G. 
Published: September 2013

ABSTRACT

The ExPortal of
Streptococcus pyogenes
is a focal microdomain of the cytoplasmic membrane that clusters the translocons of the general secretory pathway with accessory factors to facilitate the maturation of secreted polypeptides. While it is known that the ExPortal is enriched in anionic lipids, the mechanisms that organize the ExPortal are poorly understood. In the present study, we examined the role of the cell wall in organizing and maintaining the ExPortal. Removal of the cell wall resulted in a loss of ExPortal focal integrity accompanied by the circumferential redistribution of ExPortal lipid and protein components. A similar loss occurred upon treatment with gallidermin, a nonpermeabilizing lantibiotic that targets the lipid II precursor of peptidoglycan synthesis, and this treatment disrupted the secretion of several ExPortal substrates. Furthermore, several enzymes involved in the membrane-associated steps of lipid II synthesis, including MraY and MurN, were found to localize to a single discrete focus in the membrane that was coincident with the focal location of the secretory translocons and the anionic lipid microdomain. These data suggest that the ExPortal is associated with the site of peptidoglycan precursor synthesis and that peptidoglycan biogenesis influences ExPortal organization. These data add to an emerging literature indicating that cell wall biogenesis, cell division, and protein secretion are spatially coorganized processes.

IMPORTANCE
Since Gram-positive bacteria lack a periplasmic space, they lack a protected compartment to spatially coordinate interaction between newly secreted proteins and the factors required to process them. This represents a significant problem for pathogens that depend on the secretion of toxins and cell wall-associated adhesins to cause disease. Streptococci solve this dilemma by restricting secretion and processing factors to a defined region of the membrane. However, the mechanisms that promote restriction are not understood. In this study, we show that restriction of these factors in the pathogen
Streptococcus pyogenes
is intimately linked with the presence of the cell wall and its synthesis. Furthermore, several cell wall synthesis proteins are also restricted to the site of protein secretion. This study contributes to our understanding of how the Gram-positive cell is organized to coordinate protein secretion and biogenesis with cell wall synthesis and to the ongoing development of antibiotics that target these processes.
Basal Levels of (p)ppGpp in Enterococcus faecalis: the Magic beyond the Stringent Response
Authors: Gaca Anthony O. , Kajfasz Jessica K. , Miller James H. , Liu Kuanqing , Wang Jue D. , Abranches Jacqueline , Lemos José A. 
Published: September 2013

ABSTRACT

The stringent response (SR), mediated by the alarmone (p)ppGpp, is a conserved bacterial adaptation system controlling broad metabolic alterations necessary for survival under adverse conditions. In
Enterococcus faecalis
, production of (p)ppGpp is controlled by the bifunctional protein RSH (for “Rel SpoT homologue”; also known as RelA) and by the monofunctional synthetase RelQ. Previous characterization of
E. faecalis
strains lacking
rsh
,
relQ
, or both revealed that RSH is responsible for activation of the SR and that alterations in (p)ppGpp production negatively impact bacterial stress survival and virulence. Despite its well-characterized role as the effector of the SR, the significance of (p)ppGpp during balanced growth remains poorly understood. Microarrays of
E. faecalis
strains producing different basal amounts of (p)ppGpp identified several genes and pathways regulated by modest changes in (p)ppGpp. Notably, expression of numerous genes involved in energy generation were induced in the ∆
rsh
∆
relQ
[(p)ppGpp
0
] strain, suggesting that a lack of basal (p)ppGpp places the cell in a “transcriptionally relaxed” state. Alterations in the fermentation profile and increased production of H
2
O
2
in the (p)ppGpp
0
strain substantiate the observed transcriptional changes. We confirm that, similar to what is seen in
Bacillus subtilis
, (p)ppGpp directly inhibits the activity of enzymes involved in GTP biosynthesis, and complete loss of (p)ppGpp leads to dysregulation of GTP homeostasis. Finally, we show that the association of (p)ppGpp with antibiotic survival does not relate to the SR but rather relates to basal (p)ppGpp pools. Collectively, this study highlights the critical but still underappreciated role of basal (p)ppGpp pools under balanced growth conditions.

IMPORTANCE
Drug-resistant bacterial infections continue to pose a significant public health threat by limiting therapeutic options available to care providers. The stringent response (SR), mediated by the accumulation of two modified guanine nucleotides collectively known as (p)ppGpp, is a highly conserved stress response that broadly remodels bacterial physiology to a survival state. Given the strong correlation of the SR with the ability of bacteria to survive antibiotic treatment and the direct association of (p)ppGpp production with bacterial infectivity, understanding how bacteria produce and utilize (p)ppGpp may reveal potential targets for the development of new antimicrobial therapies. Using the multidrug-resistant pathogen
Enterococcus faecalis
as a model, we show that small alterations to (p)ppGpp levels, well below concentrations needed to trigger the SR, severely affected bacterial metabolism and antibiotic survival. Our findings highlight the often-underappreciated contribution of basal (p)ppGpp levels to metabolic balance and stress tolerance in bacteria.