bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart
Authors: Segar Jeffrey L. , Volk Ken A. , Lipman Michael H. B. , Scholz Thomas D. 
Published: October 2012

New Findings
What is the central question of this study?The importance of endogenous thyroid hormone in contributing to pathophysiological adaptive growth of the fetal heart is not known.
What is the main finding and its importance?The study identifies that thyroid hormone is required for adaptive fetal cardiac growth in response to pressure overload. Understanding the pathophysiological cardiac growth process may allow for improved clinical care and new therapeutic strategies for fetuses and infants with congenital heart disease.
Thyroid hormone exerts broad effects on the adult heart, but little is known regarding the role of thyroid hormone in the regulation of cardiac growth early in development and in response to pathophysiological conditions. To address this issue, we determined the effects of fetal thyroidectomy on cardiac growth and growth‐related gene expression in control and pulmonary‐artery‐banded fetal sheep. Fetal thyroidectomy (THX) and/or placement of a restrictive pulmonary artery band (PAB) were performed at 126 ± 1 days of gestation (term, 145 days). Four groups of animals [n= 5–6 in each group; (i) control; (ii) fetal THX; (iii) fetal PAB; and (iv) fetal PAB + THX] were monitored for 1 week prior to being killed. Fetal heart rate was significantly lower in the two THX groups compared with the non‐THX groups, while mean arterial blood pressure was similar among groups. Combined left and right ventricle free wall + septum weight, expressed per kilogram of fetal weight, was significantly increased in PAB (6.27 ± 0.85 g kg−1) compared with control animals (4.72 ± 0.12 g kg−1). Thyroidectomy significantly attenuated the increase in cardiac mass associated with PAB (4.94 ± 0.13 g kg−1), while THX alone had no detectable effect on heart mass (4.95 ± 0.27 g kg−1). The percentage of binucleated cardiomyocytes was significantly decreased in THX and PAB +THX groups (∼16%) compared with the non‐THX groups (∼27%). No differences in levels of activated Akt, extracellular signal‐regulated kinase or c‐Jun N‐terminal kinase were detected among the groups. Markers of cellular proliferation but not apoptosis or expression of growth‐related genes were lower in the THX and THX+ PAB groups relative to thyroid‐intact animals. These findings suggest that in the late‐gestation fetal heart, thyroid hormone has important cellular growth functions in both physiological and pathophysiological states. Specifically, thyroid hormone is required for adaptive fetal cardiac growth in response to pressure overload.
Cell Death of Streptococcus mutans Induced by a Quorum-Sensing Peptide Occurs via a Conserved Streptococcal Autolysin
Authors: Dufour Delphine , Lévesque Céline M. 
Published: October 2012

ABSTRACT

Streptococcus mutans
, a member of the human indigenous oral microbiome, produces a quorum-sensing peptide called the competence-stimulating peptide (CSP) pheromone. We previously demonstrated that
S. mutans
expresses its CSP pheromone under specific stresses and responds to high levels of CSP by inducing cell death in a fraction of the bacterial population. Streptococci lack the classical SOS response, and the induction of the SigX regulon has been proposed to act as a general stress response in Gram-positive bacteria. We show here that inactivation of SigX abolished the CSP-induced cell death phenotype. Among SigX-regulated genes, SMU.836 (now named

lytF
Sm

), encoding a conserved streptococcal protein, is a functional peptidoglycan hydrolase involved in CSP-induced cell lysis. We also demonstrated that LytF

Sm

is most likely a self-acting autolysin, since LytF

Sm

produced by attacker cells cannot trigger CSP-induced lysis of LytF

Sm

-deficient target cells present in the same environment. Electron microscopy revealed important morphological changes accompanying autolysis of CSP-induced wild-type cultures that were absent in the LytF

Sm

-deficient mutant. The LytF

Sm

promoter was activated in the physiological context of elevated concentrations of the CSP pheromone under stress conditions, such as exposure to heat, hydrogen peroxide, and acid. In a long-term survival assay, the viability of a mutant deficient in LytF

Sm

autolysin was significantly lower than that observed for the wild-type strain. The results of this study suggest that cell death of
S. mutans
induced by its quorum-sensing CSP pheromone may represent a kind of altruistic act that provides a way for the species to survive environmental stresses at the expense of some of its cells.
The σ
E
Pathway Is Involved in Biofilm Formation by Crohn's Disease-Associated Adherent-Invasive Escherichia coli
Authors: Chassaing Benoit , Darfeuille-Michaud Arlette 
Published: October 2012

ABSTRACT

Ileal lesions of patients with Crohn's disease are colonized by adherent-invasive
Escherichia coli
(AIEC) bacteria that are able to adhere to and invade intestinal epithelial cells (IEC), to replicate within macrophages, and to form biofilm. Clinical observations showed that bacterial biofilms were associated with the mucosa of inflammatory bowel disease patients. In the present study, we analyzed the relationship between AIEC colonization of the gut and the formation of biofilm, focusing on the involvement of the σ
E
pathway in the AIEC-IEC interaction. We observed that σ
E
pathway inhibition in AIEC reference strain LF82 led to an impaired ability to adhere to and invade IEC but also induced a large decrease in the abilities to colonize the intestinal mucosa and form biofilm. This indicates that targeting of the σ
E
pathway could be a very potent therapeutic strategy by which to interfere with the ability of AIEC to form biofilm on the gut mucosa of Crohn's disease patients.
A Single Missense Mutation in a Coiled-Coil Domain of Escherichia coli Ribosomal Protein S2 Confers a Thermosensitive Phenotype That Can Be Suppressed by Ribosomal Protein S1
Authors: Aseev Leonid V. , Chugunov Anton O. , Efremov Roman G. , Boni Irina V. 
Published: October 2012

ABSTRACT

Ribosomal protein S2 is an essential component of translation machinery, and its viable mutated variants conferring distinct phenotypes serve as a valuable tool in studying the role of S2 in translation regulation. One of a few available
rpsB
mutants,
rpsB1
, shows thermosensitivity and ensures enhanced expression of leaderless mRNAs. In this study, we identified the nature of the
rpsB1
mutation. Sequencing of the
rpsB1
allele revealed a G-to-A transition in the part of the
rpsB
gene which encodes a coiled-coil domain of S2. The resulting E132K substitution resides in a highly conserved site, TKKE, a so-called N-terminal capping box, at the beginning of the second alpha helix. The protruding coiled-coil domain of S2 is known to provide binding with 16S rRNA in the head of the 30S subunit and, in addition, to interact with a key mRNA binding protein, S1. Molecular dynamics simulations revealed a detrimental impact of the E132K mutation on the coiled-coil structure and thereby on the interactions between S2 and 16S rRNA, providing a clue for the thermosensitivity of the
rpsB1
mutant. Using a strain producing a leaderless
lacZ
transcript from the chromosomal
lac
promoter, we demonstrated that not only the
rpsB1
mutation generating S2/S1-deficient ribosomes but also the
rpsA
::IS
10
mutation leading to partial deficiency in S1 alone increased translation efficiency of the leaderless mRNA by about 10-fold. Moderate overexpression of S1 relieved all these effects and, moreover, suppressed the thermosensitive phenotype of
rpsB1
, indicating the role of S1 as an extragenic suppressor of the E132K mutation.
Transcriptional Regulation of Aggregatibacter actinomycetemcomitans lsrACDBFG and
lsrRK
Operons and Their Role in Biofilm Formation
Authors: Torres-Escobar Ascención , Juárez-Rodríguez María Dolores , Lamont Richard J. , Demuth Donald R. 
Published: October 2012

ABSTRACT

Autoinducer-2 (AI-2) is required for biofilm formation and virulence of the oral pathogen
Aggregatibacter actinomycetemcomitans
, and we previously showed that
lsrB
codes for a receptor for AI-2. The
lsrB
gene is expressed as part of the
lsrACDBFG
operon, which is divergently transcribed from an adjacent
lsrRK
operon. In
Escherichia coli
,
lsrRK
encodes a repressor and AI-2 kinase that function to regulate
lsrACDBFG
. To determine if
lsrRK
controls
lsrACDBFG
expression and influences biofilm growth of
A. actinomycetemcomitans
, we first defined the promoters for each operon. Transcriptional reporter plasmids containing the 255-bp
lsrACDBFG-lsrRK
intergenic region (IGR) fused to
lacZ
showed that essential elements of
lsrR
promoter reside 89 to 255 bp upstream from the
lsrR
start codon. Two inverted repeat sequences that represent potential binding sites for LsrR and two sequences resembling the consensus cyclic AMP receptor protein (CRP) binding site were identified in this region. Using electrophoretic mobility shift assay (EMSA), purified LsrR and CRP proteins were shown to bind probes containing these sequences. Surprisingly, the 255-bp IGR did not contain the
lsrA
promoter. Instead, a fragment encompassing nucleotides +1 to +159 of
lsrA
together with the 255-bp IGR was required to promote
lsrA
transcription. This suggests that a region within the
lsrA
coding sequence influences transcription, or alternatively that the start codon of
A. actinomycetemcomitans lsrA
has been incorrectly annotated. Transformation of Δ
lsrR
, Δ
lsrK
, Δ
lsrRK
, and Δ
crp
deletion mutants with
lacZ
reporters containing the
lsrA
or
lsrR
promoter showed that LsrR negatively regulates and CRP positively regulates both
lsrACDBFG
and
lsrRK
. However, in contrast to what occurs in
E. coli
, deletion of
lsrK
had no effect on the transcriptional activity of the
lsrA
or
lsrR
promoters, suggesting that another kinase may be capable of phosphorylating AI-2 in
A. actinomycetemcomitans
. Finally, biofilm formation of the Δ
lsrR
, Δ
lsrRK
, and Δ
crp
mutants was significantly reduced relative to that of the wild type, indicating that proper regulation of the
lsr
locus is required for optimal biofilm growth by
A. actinomycetemcomitans
.
Identification of Transport Proteins Involved in Free Fatty Acid Efflux in Escherichia coli
Authors: Lennen Rebecca M. , Politz Mark G. , Kruziki Max A. , Pfleger Brian F. 
Published: October 2012

ABSTRACT

Escherichia coli
has been used as a platform host for studying the production of free fatty acids (FFA) and other energy-dense compounds useful in biofuel applications. Most of the FFA produced by
E. coli
are found extracellularly. This finding suggests that a mechanism for transport across the cell envelope exists, yet knowledge of proteins that may be responsible for export remains incomplete. Production of FFA has been shown to cause cell lysis, induce stress responses, and impair basic physiological processes. These phenotypes could potentially be diminished if efflux rates were increased. Here, a total of 15 genes and operons were deleted and screened for their impact on cell viability and titer in FFA-producing
E. coli
. Deletions of
acrAB
and
rob
and, to a lower degree of statistical confidence,
emrAB
,
mdtEF
, and
mdtABCD
reduced multiple measures of viability, while deletion of
tolC
nearly abolished FFA production. An
acrAB emrAB
deletion strain exhibited greatly reduced FFA titers approaching the
tolC
deletion phenotype. Expression of efflux pumps on multicopy plasmids did not improve endogenous FFA production in an
acrAB
+
strain, but plasmid-based expression of
acrAB
,
mdtEF
, and an
mdtEF
-
tolC
artificial operon improved the MIC of exogenously added decanoate for an
acrAB
mutant strain. The findings suggest that AcrAB-TolC is responsible for most of the FFA efflux in
E. coli
, with residual activity provided by other resistance-nodulation-cell division superfamily-type efflux pumps, including EmrAB-TolC and MdtEF-TolC. While the expression of these proteins on multicopy plasmids did not improve production over the basal level, their identification enables future engineering efforts.
The Extracytoplasmic Function Sigma Factor EcfO Protects Bacteroides fragilis against Oxidative Stress
Authors: Ndamukong Ivan C. , Gee Jason , Smith C. Jeffrey 
Published: October 2012

ABSTRACT

The anaerobe
Bacteroides fragilis
is a highly aerotolerant, opportunistic pathogen that is an important component of the human intestinal microbiota. Aerotolerance has been linked to a robust oxidative stress response, which in turn is necessary for maximal virulence in a mouse intra-abdominal abscess model. During oxidative stress, there is a dynamic change in gene expression that encompasses a third of the genome, but there is a paucity of information on factors that control this response. A large number of transcription regulators, including about 14 extracytoplasmic function (ECF) sigma factors, are affected by oxidative stress, and one of these, EcfO, was used as a model of ECF sigma factor activity during stress. Genetic and biochemical experiments showed that EcfO was located in an operon with a structurally unique anti-sigma factor, Reo. Cells deleted for EcfO were impaired during exposure to oxygen or other forms of oxidative stress, whereas
reo
mutants were more resistant to stress. Protein-protein interaction experiments demonstrated that Reo directly interacts with and regulates the activity of EcfO. Expression microarray and chromatin affinity precipitation assays were used to identify target genes regulated by EcfO, and an EcfO recognition sequence was identified. The results revealed that EcfO controls a regulon of novel lipoproteins whose distribution in nature is restricted to members of the
Bacteroidetes
phylum.
Utilisation of a thoracic oncology database to capture radiological and pathological images for evaluation of response to chemotherapy in patients with malignant pleural mesothelioma
Authors: Carey George B , Kazantsev Stephanie , Surati Mosmi , Rolle Cleo E , Kanteti Archana , Sadiq Ahad , Bahroos Neil , Raumann Brigitte , Madduri Ravi , Dave Paul , Starkey Adam , Hensing Thomas , Husain Aliya N , Vokes Everett E , Vigneswaran Wickii , Armato Samuel G , Kindler Hedy L , Salgia Ravi 
Published: October 2012

ObjectiveAn area of need in cancer informatics is the ability to store images in a comprehensive database as part of translational cancer research. To meet this need, we have implemented a novel tandem database infrastructure that facilitates image storage and utilisation.BackgroundWe had previously implemented the Thoracic Oncology Program Database Project (TOPDP) database for our translational cancer research needs. While useful for many research endeavours, it is unable to store images, hence our need to implement an imaging database which could communicate easily with the TOPDP database.MethodsThe Thoracic Oncology Research Program (TORP) imaging database was designed using the Research Electronic Data Capture (REDCap) platform, which was developed by Vanderbilt University. To demonstrate proof of principle and evaluate utility, we performed a retrospective investigation into tumour response for malignant pleural mesothelioma (MPM) patients treated at the University of Chicago Medical Center with either of two analogous chemotherapy regimens and consented to at least one of two UCMC IRB protocols, 9571 and 13473A.ResultsA cohort of 22 MPM patients was identified using clinical data in the TOPDP database. After measurements were acquired, two representative CT images and 0–35 histological images per patient were successfully stored in the TORP database, along with clinical and demographic data.DiscussionWe implemented the TORP imaging database to be used in conjunction with our comprehensive TOPDP database. While it requires an additional effort to use two databases, our database infrastructure facilitates more comprehensive translational research.ConclusionsThe investigation described herein demonstrates the successful implementation of this novel tandem imaging database infrastructure, as well as the potential utility of investigations enabled by it. The data model presented here can be utilised as the basis for further development of other larger, more streamlined databases in the future.
THREE PROBLEMS ABOUT DYNAMIC CONVEX HULLS
Authors: CHAN TIMOTHY M. 
Published: October 2012

We present three results related to dynamic convex hulls: • A fully dynamic data structure for maintaining a set of n points in the plane so that we can find the edges of the convex hull intersecting a query line, with expected query and amortized update time O( log 1+εn) for an arbitrarily small constant ε > 0. This improves the previous bound of O( log 3/2n). • A fully dynamic data structure for maintaining a set of n points in the plane to support halfplane range reporting queries in O( log n+k) time with O( polylog n) expected amortized update time. A similar result holds for 3-dimensional orthogonal range reporting. For 3-dimensional halfspace range reporting, the query time increases to O( log 2n/ log log n + k). • A semi-online dynamic data structure for maintaining a set of n line segments in the plane, so that we can decide whether a query line segment lies completely above the lower envelope, with query time O( log n) and amortized update time O(nε). As a corollary, we can solve the following problem in O(n1+ε) time: given a triangulated terrain in 3-d of size n, identify all faces that are partially visible from a fixed viewpoint.
Impacts of Shallow Convection on MJO Simulation: A Moist Static Energy and Moisture Budget Analysis
Authors: Cai Qiongqiong , Zhang Guang J. , Zhou Tianjun 
Published: October 2012

Abstract
The role of shallow convection in Madden–Julian oscillation (MJO) simulation is examined in terms of the moist static energy (MSE) and moisture budgets. Two experiments are carried out using the NCAR Community Atmosphere Model, version 3.0 (CAM3.0): a “CTL” run and an “NSC” run that is the same as the CTL except with shallow convection disabled below 700 hPa between 20°S and 20°N. Although the major features in the mean state of outgoing longwave radiation, 850-hPa winds, and vertical structure of specific humidity are reasonably reproduced in both simulations, moisture and clouds are more confined to the planetary boundary layer in the NSC run. While the CTL run gives a better simulation of the MJO life cycle when compared with the reanalysis data, the NSC shows a substantially weaker MJO signal. Both the reanalysis data and simulations show a recharge–discharge mechanism in the MSE evolution that is dominated by the moisture anomalies. However, in the NSC the development of MSE and moisture anomalies is weaker and confined to a shallow layer at the developing phases, which may prevent further development of deep convection. By conducting the budget analysis on both the MSE and moisture, it is found that the major biases in the NSC run are largely attributed to the vertical and horizontal advection. Without shallow convection, the lack of gradual deepening of upward motion during the developing stage of MJO prevents the lower troposphere above the boundary layer from being preconditioned for deep convection.
An objective approach to evaluating an internet-delivered genetics education resource developed for nurses: using Google Analytics™ to monitor global visitor engagement
Authors: Kirk Maggie , Morgan Rhian , Tonkin Emma , McDonald Kevin , Skirton Heather 
Published: October 2012

The rapid increase in gene-disease discoveries offers real promise of clinical applications for people and families affected by genetic conditions but for which health professionals are not prepared because of lack of training. The availability of clinically relevant education resources is critical to enabling nurses to develop the appropriate genetics-genomics knowledge and skills to provide optimum care for individuals and families. The Internet is a core resource to support teaching and learning in nurse education. Evaluating such resources is important to maximise the education experience, particularly for subjects traditionally perceived by nurses as being difficult. Telling Stories, Understanding Real Life Genetics is a web-based educational resource. It uses real accounts from individuals and professionals to promote understanding of the impact of genetics-genomics on the lives of people and their families. Google Analytics™ Web analytics service provides time series data for analysing web usage to optimise website effectiveness. We present data of visitor activity and behaviour from 123 countries over three years from 2009–2011 and consider how the application of the web analytics informs approaches to enhancing visibility of the website, provides an indicator of engagement with genetics-genomics both nationally and globally, and informs future expansion of the site as a global resource for health professional education. Telling Stories is an accessible, broad-reaching resource that is of global relevance for health professionals, attracting over 33,500 visitors between 2009–2011, with steadily increasing numbers of returning visitors. The United Kingdom, United States, Canada and the Netherlands are the largest site users. Returning visitors spend significantly more time on site and view more pages than new visitors. Most referring sites are education establishments. More needs to be done now to enhance the site’s accessibility for people of other languages and cultures.
Coral: an integrated suite of visualizations for comparing clusterings
Authors: Filippova Darya , Gadani Aashish , Kingsford Carl 
Published: October 2012

AbstractBackgroundClustering has become a standard analysis for many types of biological data (e.g interaction networks, gene expression, metagenomic abundance). In practice, it is possible to obtain a large number of contradictory clusterings by varying which clustering algorithm is used, which data attributes are considered, how algorithmic parameters are set, and which near-optimal clusterings are chosen. It is a difficult task to sift though such a large collection of varied clusterings to determine which clustering features are affected by parameter settings or are artifacts of particular algorithms and which represent meaningful patterns. Knowing which items are often clustered together helps to improve our understanding of the underlying data and to increase our confidence about generated modules.ResultsWe present Coral, an application for interactive exploration of large ensembles of clusterings. Coral makes all-to-all clustering comparison easy, supports exploration of individual clusterings, allows tracking modules across clusterings, and supports identification of core and peripheral items in modules. We discuss how each visual component in Coral tackles a specific question related to clustering comparison and provide examples of their use. We also show how Coral could be used to visually and quantitatively compare clusterings with a ground truth clustering.ConclusionAs a case study, we compare clusterings of a recently published protein interaction network ofArabidopsis thaliana. We use several popular algorithms to generate the network’s clusterings. We find that the clusterings vary significantly and that few proteins are consistently co-clustered in all clusterings. This is evidence that several clusterings should typically be considered when evaluating modules of genes, proteins, or sequences, and Coral can be used to perform a comprehensive analysis of these clustering ensembles.