bluuebunny/crossref_metadata_2025 huggingface dataset:
Infections in Long‐Term Care Populations in the United States
Authors: Dwyer Lisa L. , Harris‐Kojetin Lauren D. , Valverde Roberto H. , Frazier Joyce M. , Simon Alan E. , Stone Nimalie D. , Thompson Nicola D.
Published: March 2013

Objectives

To estimate infection prevalence and explore associated risk factors in nursing home (NH) residents, individuals receiving home health care (HHC), and individuals receiving hospice care.

Design

Cross‐sectional.

Setting

Nationally representative samples of 1,174 U.S. NHs in the 2004 National Nursing Home Survey (NNHS) and 1,036 U.S. HHC and hospice agencies in the 2007 National Home and Hospice Care Survey (NHHCS).

Participants

A nationally representative sample of 12,270 NH residents, 4,394 individuals receiving HHC, and 4,410 individuals receiving hospice care.

Measurements

International Classification of Diseases, Ninth Revision, Clinical Modification, codes were used to identify the presence of infection, including community‐acquired infection and those acquired during earlier healthcare exposures.

Results

Unweighted response rates were 78% for the 2004 NHHS and 67% for the 2007 NHHCS. Approximately 12% of NH residents and 12% of individuals receiving HHC had an infection at the time of the survey interview, and more than 10% of individuals receiving hospice care had an infection when discharged from hospice care. The most common infections were urinary tract infection (3.0–5.2%), pneumonia (2.2–4.4%), and cellulitis (1.6–2.0%). Short length of care and recent inpatient stay in a healthcare facility were associated with infections in all three populations. Taking 10 or more medications and urinary catheter exposure were significant in two of these three long‐term care populations.

Conclusion

Infection prevalence in HHC, hospice, and NH populations is similar. Although these infections may be community acquired or acquired during earlier healthcare exposures, these findings fill an important gap in understanding the national infection burden and may help inform future research on infection epidemiology and prevention strategies in long‐term care populations.
Regulation of contact inhibition of locomotion by Eph–ephrin signalling
Authors: BATSON J. , ASTIN J.W. , NOBES C.D.
Published: March 2013

Contact inhibition of locomotion (CIL) occurs when a cell stops migrating in a particular direction upon contact with another cell. Many cancer cells show Contact inhibition of locomotion when contacting one another but display contact‐unimpeded migration following collision with noncancer cells. Here we review current understanding of Contact inhibition of locomotion, from Abercrombie's historical studies of cells in tissue culture to more recent analyses of Contact inhibition of locomotion in vivo. We discuss the cellular machinery required for CIL and the molecular signals that regulate it. We focus on our recent finding that in prostate cancer cells, Contact inhibition of locomotion is regulated by a balance between EphA and EphB receptor signalling. We show that, as recently described for chick heart fibroblasts, microtubule dynamics are required for Contact inhibition of locomotion in prostate cancer cells and we propose that stabilization of microtubules could account for defective Contact inhibition of locomotion between cancer cells and noncancer cells.
Qualitative microanalysis of calcium local structure in tooth layers by means of micro‐RRS
Authors: LEANI J.J. , SÁNCHEZ H.J. , VALENTINUZZI M.C. , PÉREZ C. , GRENÓN M.C.
Published: March 2013

The Resonant inelastic X‐ray scattering or resonant Raman scattering is an inelastic process of second order that becomes important when the energy of the excitation radiation is below but close to an absorption edge. In this process, the emitted photons have a continuous energy distribution with a high energy cut‐off limit. In the last few years, experiments of resonant Raman scattering has become a very powerful technique to investigate excitations of electrons in solids. A qualitative study of the calcium local structure in the different layers of teeth was carried out. In order to perform the analysis, several measurements of tooth samples were achieved using monochromatic synchrotron radiation at the XRF station of the D09B‐XRF beamline at the Brazilian synchrotron facility (LNLS, Campinas), below and close to the K absorption edge of Ca to inspect the resonant Raman scattering spectra. First of all, the spectra were analyzed with specific software to fit the experimental data. After that, the residuals were determined and a  fast Fourier transform smoothing procedure was applied, taking into account the instrument functions of the detecting system. These oscillations present patterns that depend of the tooth layer, i.e. of the calcium state.
Hypercoagulability as a contributor to thrombotic complications in the liver transplant recipient
Authors: Arshad Freeha , Lisman Ton , Porte Robert J.
Published: March 2013

Traditionally, perioperative bleeding complications were a major concern during orthotopic liver transplantation, but a tremendous decline in transfusion requirements has been reported over the last decade. In recent years, there has been an increasing awareness towards perioperative thrombotic complications, including liver vessel thrombosis, and systemic venous and arterial thromboembolic events. Whereas a number of these thrombotic complications were previously categorized as surgical complications, increasing clinical and laboratory evidence suggest a role for the haemostatic system in thrombotic complications occurring during and after transplantation. High levels of the platelet adhesive protein von Willebrand factor with low levels of its regulator ADAMTS13, an increased potential to generate thrombin, and temporary hypofibrinolysis are all indicative of increased haemostatic potential after transplantation. Clinical evidence for a role of the haemostatic system in post‐operative thromboses includes a higher thrombotic risk in patients with various acquired thrombotic risk factors. Although data on efficacy of anticoagulant therapy after liver transplantation are scarce, one study has shown a significant decrease in the risk for late hepatic artery thrombosis by antithrombotic therapy with aspirin. These findings suggest that antihaemostatic therapy in prevention or treatment of thromboembolic complications after liver transplantation may be relevant. Studies on efficacy and safety of these interventions are required as many of the thrombotic complications have a pronounced negative impact on graft and patient survival.
Lithium isotopes as indicators of meteorite parent body alteration
Authors: Sephton Mark A. , James Rachael H. , Fehr Manuela A. , Bland Philip A. , Gounelle Matthieu
Published: March 2013

Hydrothermal processing on planetesimals in the early solar system produced new mineral phases, including those generated by the transformation of anhydrous silicates into their hydrated counterparts. Carbonaceous chondrites represent tangible remnants of such alteration products. Lithium isotopes are known to be responsive to aqueous alteration, yet previously recognized variability within whole rock samples from the same meteorite appears to complicate the use of these isotopes as indicators of processing by water. We demonstrate a new way to use lithium isotopes that reflects aqueous alteration in carbonaceous chondrites. Temperature appears to exert a control on the production of acetic acid‐soluble phases, such as carbonates and poorly crystalline Fe‐oxyhydroxides. Temperature and degree of water‐rock interaction determines the amount of lithium isotope fractionation expressed as the difference between whole rock and acetic acid‐leachable fractions. Using these features, the type 1 chondrite Orgueil (δ7Li(whole rock) = 4.3‰; Δ7Li(acetic‐whole) = 1.2‰) can be distinguished from the type 2 chondrites Murchison (δ7Li(whole rock) = 3.8; Δ7Li(acetic‐whole) = 8.8‰) and carbonate‐poor Tagish Lake (δ7Li(whole rock) = 4.3; Δ7Li(acetic‐whole) = 9.4‰). This initial study suggests that lithium isotopes have the potential to reveal the role of liquid water in the early solar system.
Congruence between distribution modelling and phylogeographical analyses reveals Quaternary survival of a toadflax species (Linaria elegans) in oceanic climate areas of a mountain ring range
Authors: Fernández‐Mazuecos Mario , Vargas Pablo
Published: March 2013

The role of Quaternary climatic shifts in shaping the distribution of Linaria elegans, an Iberian annual plant, was investigated using species distribution modelling and molecular phylogeographical analyses. Three hypotheses are proposed to explain the Quaternary history of its mountain ring range.

The distribution of L. elegans was modelled using the maximum entropy method and projected to the last interglacial and to the last glacial maximum (LGM) using two different paleoclimatic models: the Community Climate System Model (CCSM) and the Model for Interdisciplinary Research on Climate (MIROC). Two nuclear and three plastid DNA regions were sequenced for 24 populations (119 individuals sampled). Bayesian phylogenetic, phylogeographical, dating and coalescent‐based population genetic analyses were conducted.

Molecular analyses indicated the existence of northern and southern glacial refugia and supported two routes of post‐glacial recolonization. These results were consistent with the LGM distribution as inferred under the CCSM paleoclimatic model (but not under the MIROC model). Isolation between two major refugia was dated back to the Riss or Mindel glaciations, > 100 kyr before present (bp).

The Atlantic distribution of inferred refugia suggests that the oceanic (buffered)–continental (harsh) gradient may have played a key and previously unrecognized role in determining Quaternary distribution shifts of Mediterranean plants.
The Economic Efficiency of Sampling Size: The Case of Beef Trim Revisited
Authors: Powell Mark R.
Published: March 2013

A recent paper by Ferrier and Buzby provides a framework for selecting the sample size when testing a lot of beef trim for Escherichia coli O157:H7 that equates the averted costs of recalls and health damages from contaminated meats sold to consumers with the increased costs of testing while allowing for uncertainty about the underlying prevalence of contamination. Ferrier and Buzby conclude that the optimal sample size is larger than the current sample size. However, Ferrier and Buzby's optimization model has a number of errors, and their simulations failed to consider available evidence about the likelihood of the scenarios explored under the model. After correctly modeling microbial prevalence as dependent on portion size and selecting model inputs based on available evidence, the model suggests that the optimal sample size is zero under most plausible scenarios. It does not follow, however, that sampling beef trim for E. coli O157:H7, or food safety sampling more generally, should be abandoned. Sampling is not generally cost effective as a direct consumer safety control measure due to the extremely large sample sizes required to provide a high degree of confidence of detecting very low acceptable defect levels. Food safety verification sampling creates economic incentives for food producing firms to develop, implement, and maintain effective control measures that limit the probability and degree of noncompliance with regulatory limits or private contract specifications.
Population of anatomically variable 4D XCAT adult phantoms for imaging research and optimization
Authors: Segars W. P. , Bond Jason , Frush Jack , Hon Sylvia , Eckersley Chris , Williams Cameron H. , Feng Jianqiao , Tward Daniel J. , Ratnanather J. T. , Miller M. I. , Frush D. , Samei E.
Published: March 2013

Purpose:

The authors previously developed the 4D extended cardiac‐torso (XCAT) phantom for multimodality imaging research. The XCAT consisted of highly detailed whole‐body models for the standard male and female adult, including the cardiac and respiratory motions. In this work, the authors extend the XCAT beyond these reference anatomies by developing a series of anatomically variable 4D XCAT adult phantoms for imaging research, the first library of 4D computational phantoms.

Methods:

The initial anatomy of each phantom was based on chest–abdomen–pelvis computed tomography data from normal patients obtained from the Duke University database. The major organs and structures for each phantom were segmented from the corresponding data and defined using nonuniform rational B‐spline surfaces. To complete the body, the authors manually added on the head, arms, and legs using the original XCAT adult male and female anatomies. The structures were scaled to best match the age and anatomy of the patient. A multichannel large deformation diffeomorphic metric mapping algorithm was then used to calculate the transform from the template XCAT phantom (male or female) to the target patient model. The transform was applied to the template XCAT to fill in any unsegmented structures within the target phantom and to implement the 4D cardiac and respiratory models in the new anatomy. Each new phantom was refined by checking for anatomical accuracy via inspection of the models.

Results:

Using these methods, the authors created a series of computerized phantoms with thousands of anatomical structures and modeling cardiac and respiratory motions. The database consists of 58 (35 male and 23 female) anatomically variable phantoms in total. Like the original XCAT, these phantoms can be combined with existing simulation packages to simulate realistic imaging data. Each new phantom contains parameterized models for the anatomy and the cardiac and respiratory motions and can, therefore, serve as a jumping point from which to create an unlimited number of 3D and 4D variations for imaging research.

Conclusions:

A population of phantoms that includes a range of anatomical variations representative of the public at large is needed to more closely mimic a clinical study or trial. The series of anatomically variable phantoms developed in this work provide a valuable resource for investigating 3D and 4D imaging devices and the effects of anatomy and motion in imaging. Combined with Monte Carlo simulation programs, the phantoms also provide a valuable tool to investigate patient‐specific dose and image quality, and optimization for adults undergoing imaging procedures.
Objected constrained registration and manifold learning: A new patient setup approach in image guided radiation therapy of thoracic cancer
Authors: Chen Ting , Jabbour Salma K. , Qin Songbing , Haffty Bruce G. , Yue Ning
Published: March 2013

Purpose:

The management of thoracic malignancies with radiation therapy is complicated by continuous target motion. In this study, a real time motion analysis approach is proposed to improve the accuracy of patient setup.

Methods:

For 11 lung cancer patients a long training fluoroscopy was acquired before the first treatment, and multiple short testing fluoroscopies were acquired weekly at the pretreatment patient setup of image guided radiotherapy (IGRT). The data analysis consisted of three steps: first a 4D target motion model was constructed from 4DCT and projected to the training fluoroscopy through deformable registration. Then the manifold learning method was used to construct a 2D subspace based on the target motion (kinetic) and location (static) information in the training fluoroscopy. Thereafter the respiratory phase in the testing fluoroscopy was determined by finding its location in the subspace. Finally, the phase determined testing fluoroscopy was registered to the corresponding 4DCT to derive the pretreatment patient position adjustment for the IGRT. The method was tested on clinical image sets and numerical phantoms.

Results:

The registration successfully reconstructed the 4D motion model with over 98% volume similarity in 4DCT, and over 95% area similarity in the training fluoroscopy. The machine learning method derived the phase values in over 98% and 93% test images of the phantom and patient images, respectively, with less than 3% phase error. The setup approach achieved an average accumulated setup error less than 1.7 mm in the cranial‐caudal direction and less than 1 mm in the transverse plane. All results were validated against the ground truth of manual delineations by an experienced radiation oncologist. The expected total time for the pretreatment setup analysis was less than 10 s.

Conclusions:

By combining the registration and machine learning, the proposed approach has the potential to improve the accuracy of pretreatment setup for patients with thoracic malignancy.
RT X‐Ray Physics Review.
Authors: Davros William
Published: March 2013

RT X‐Ray Physics Review., Huda and W. Greene‐Donnelly K., Medical Physics Publishing, Madison, WI, 2011. 460 pp. Price: $55. ISBN: 9781930524545 (softcover).
Minimum classification error-based weighted support vector machine kernels for speaker verification
Authors: Suh Youngjoo , Kim Hoirin
Published: March 2013

Support vector machines (SVMs) have been proved to be an effective approach to speaker verification. An appropriate selection of the kernel function is a key issue in SVM-based classification. In this letter, a new SVM-based speaker verification method utilizing weighted kernels in the Gaussian mixture model supervector space is proposed. The weighted kernels are derived by using the discriminative training approach, which minimizes speaker verification errors. Experiments performed on the NIST 2008 speaker recognition evaluation task showed that the proposed approach provides substantially improved performance over the baseline kernel-based method.
Relation between loudness in categorical units and loudness in phons and sones
Authors: Heeren Wiebke , Hohmann Volker , Appell Jens E. , Verhey Jesko L.
Published: March 2013

Data are presented on the relation between loudness measured in categorical units (CUs) using a standardized loudness scaling method (ISO 16832, 2006) and loudness expressed as the classical standardized measures phon and sone. Based on loudness scaling of narrowband noise signals by 31 normal-hearing subjects, sound pressure levels eliciting the same categorical loudness were derived for various center frequencies. The results were comparable to the standardized equal-loudness level contours. A comparison between the loudness function in CUs at 1000 Hz and the standardized loudness function in sones indicates a cubic relation between the two loudness measures.
Origin of Species in Geologic Time: Alternatives to the Eldredge-Gould Model
Authors: Harper Charles W.
Published: March 2013

Formal statements of the Eldredge-Gould model, which proposes that new species have originated almost wholly through evolution in small peripheral isolate populations, and the phyletic gradualism model, which proposes that new species have originated through phyletic evolution in large, widely distributed populations, clarify the relationship of these models as extremes in a spectrum of possibilities, and suggest alternative models incorporating elements of both.
Greenhouse Effect Due to Chlorofluorocarbons: Climatic Implications
Authors: Ramanathan V.
Published: March 2013

The infrared bands of chlorofluorocarbons and chlorocarbons enhance the atmospheric greenhouse effect. This enhancement may lead to an appreciable increase in the global surface temperature if the atmospheric concentrations of these compounds reach values of the order of 2 parts per billion.
Precambrian Eukaryotic Organisms: A Reassessment of the Evidence
Authors: Knoll Andrew H. , Barghoorn Elso S.
Published: March 2013

Comparison of partially degraded unialgal cultures of
Chroococcus turgidus
with coccoid microfossils from the Late Precambrian Bitter Springs formation, Australia, suggests that the Precambrian fossil record has been seriously misinterpreted. Use of degradational features as taxonomic characters has resulted in unrealistically high estimates of Precambrian algal diversity. There is at present no compelling evidence for the presence of eukaryotic microfossils in rocks from the Bitter Springs formation or any older sedimentary sequences.
Poor Children in Rich Countries
Authors: Smeeding Timothy M. , Torrey Barbara Boyld
Published: March 2013

Every wealthy, industrial country has children who are living in poverty. The United States, the wealthiest country of six studied, has a higher poverty rate among children than the other five countries. Each country reduces the poverty of its children with government programs, but substantial differences in the effectiveness of these programs exist among countries. Understanding such differences may be useful in considering how to reduce poverty among children in the United States.
Transcriptional Activation of a Cutinase Gene in Isolated Fungal Nuclei by Plant Cutin Monomers
Authors: Podila Gopi K. , Dickman Martin B. , Kolarrukudy P. E.
Published: March 2013

The molecular mechanism by which fungal spores that land on plants sense the contact and consequently trigger cutinase gene expression to gain entry into the plant was studied in isolated nuclei. Nuclear runoff experiments showed that the induction involved transcriptional activation. Monomers, unique to cutin, and a soluble protein factor from the fungal extract selectively activated cutinase gene transcription, probably by promoting initiation in nuclei isolated from uninduced
Fusarium solani pisi
. This in vitro transcriptional activation produced normal-sized cutinase messenger RNA. Alterations in the monomer structure diminished the transcriptional activation.
Role of the Phenylalanine-Hydroxylating System in Aromatic Substance Degradation and Lipid Metabolism in the Oleaginous Fungus Mortierella alpina
Authors: Wang Hongchao , Chen Haiqin , Hao Guangfei , Yang Bo , Feng Yun , Wang Yu , Feng Lu , Zhao Jianxin , Song Yuanda , Zhang Hao , Chen Yong Q. , Wang Lei , Chen Wei
Published: March 2013

Mortierella alpina
is a filamentous fungus commonly found in soil that is able to produce lipids in the form of triacylglycerols that account for up to 50% of its dry weight. Analysis of the
M. alpina
genome suggests that there is a phenylalanine-hydroxylating system for the catabolism of phenylalanine, which has never been found in fungi before. We characterized the phenylalanine-hydroxylating system in
M. alpina
to explore its role in phenylalanine metabolism and its relationship to lipid biosynthesis. Significant changes were found in the profile of fatty acids in
M. alpina
grown on medium containing an inhibitor of the phenylalanine-hydroxylating system compared to
M. alpina
grown on medium without inhibitor. Genes encoding enzymes involved in the phenylalanine-hydroxylating system (phenylalanine hydroxylase [PAH], pterin-4α-carbinolamine dehydratase, and dihydropteridine reductase) were expressed heterologously in
Escherichia coli
, and the resulting proteins were purified to homogeneity. Their enzymatic activity was investigated by high-performance liquid chromatography (HPLC) or visible (Vis)-UV spectroscopy. Two functional PAH enzymes were observed, encoded by distinct gene copies. A novel role for tetrahydrobiopterin in fungi as a cofactor for PAH, which is similar to its function in higher life forms, is suggested. This study establishes a novel scheme for the fungal degradation of an aromatic substance (phenylalanine) and suggests that the phenylalanine-hydroxylating system is functionally significant in lipid metabolism.
Carbohydrate-Binding Module–Cyclodextrin Glycosyltransferase Fusion Enables Efficient Synthesis of 2-
O
-
d
-Glucopyranosyl-
l
-Ascorbic Acid with Soluble Starch as the Glycosyl Donor
Authors: Han Ruizhi , Li Jianghua , Shin Hyun-Dong , Chen Rachel R. , Du Guocheng , Liu Long , Chen Jian
Published: March 2013

In this study, we achieved the efficient synthesis of 2-
O
-
d
-glucopyranosyl-
l
-ascorbic acid (AA-2G) from soluble starch by fusing a carbohydrate-binding module (CBM) from
Alkalimonas amylolytica
α-amylase (CBM
Amy
) to cyclodextrin glycosyltransferase (CGTase) from
Paenibacillus macerans
. One fusion enzyme, CGT-CBM
Amy
, was constructed by fusing the CBM
Amy
to the C-terminal region of CGTase, and the other fusion enzyme, CGTΔE-CBM
Amy
, was obtained by replacing the E domain of CGTase with CBM
Amy
. The two fusion enzymes were then used to synthesize AA-2G from soluble starch as a cheap and easily soluble glycosyl donor. Under the optimal conditions, the AA-2G yields produced using CGTΔE-CBM
Amy
and CGT-CBM
Amy
were 2.01 g/liter and 3.03 g/liter, respectively, which were 3.94- and 5.94-fold of the yield from the wild-type CGTase (0.51 g/liter). The reaction kinetics of the two fusion enzymes were analyzed and modeled to confirm the enhanced specificity toward soluble starch. It was also found that, compared to the wild-type CGTase, the two fusion enzymes had relatively high hydrolysis and disproportionation activities, factors that favor AA-2G synthesis. Finally, it was speculated that the enhancement of soluble starch specificity may be related to the changes of substrate binding ability and the substrate binding sites between the CBM and the starch granule.
Elucidation of the Role of the Methylene-Tetrahydromethanopterin Dehydrogenase MtdA in the Tetrahydromethanopterin-Dependent Oxidation Pathway in Methylobacterium extorquens AM1
Authors: Martinez-Gomez N. Cecilia , Nguyen Sandy , Lidstrom Mary E.
Published: March 2013

The methylotroph
Methylobacterium extorquens
AM1 oxidizes methanol and methylamine to formaldehyde and subsequently to formate, an intermediate that serves as the branch point between assimilation (formation of biomass) and dissimilation (oxidation to CO
2
). The oxidation of formaldehyde to formate is dephosphotetrahydromethanopterin (dH
4
MPT) dependent, while the assimilation of carbon into biomass is tetrahydrofolate (H
4
F) dependent. This bacterium contains two different enzymes, MtdA and MtdB, both of which are dehydrogenases able to use methylene-dH
4
MPT, an intermediate in the oxidation of formaldehyde to formate. Unique to MtdA is a second enzymatic activity with methylene-H
4
F. Since methylene-H
4
F is the entry point into the biomass pathways, MtdA plays a key role in assimilatory metabolism. However, its role in oxidative metabolism via the dH
4
MPT-dependent pathway and its apparent inability to replace MtdB
in vivo
on methanol growth are not understood. Here, we have shown that an
mtdB
mutant is able to grow on methylamine, providing a system to study the role of MtdA. We demonstrate that the absence of MtdB results in the accumulation of methenyl-dH
4
MPT. Methenyl-dH
4
MPT is shown to be a competitive inhibitor of the reduction of methenyl-H
4
F to methylene-H
4
F catalyzed by MtdA, with an estimated

K
i

of 10 μM. Thus, methenyl-dH
4
MPT accumulation inhibits H
4
F-dependent assimilation. Overexpression of
mch
in the
mtdB
mutant strain, predicted to reduce methenyl-dH
4
MPT accumulation, enhances growth on methylamine. Our model proposes that MtdA regulates carbon flux due to differences in its kinetic properties for methylene-dH
4
MPT and for methenyl-H
4
F during growth on single-carbon compounds.
Role of the PAS Sensor Domains in the Bacillus subtilis Sporulation Kinase KinA
Authors: Winnen Brit , Anderson Eric , Cole James L. , King Glenn F. , Rowland Susan L.
Published: March 2013

Histidine kinases are sophisticated molecular sensors that are used by bacteria to detect and respond to a multitude of environmental signals. KinA is the major histidine kinase required for initiation of sporulation upon nutrient deprivation in
Bacillus subtilis
. KinA has a large N-terminal region (residues 1 to 382) that is uniquely composed of three tandem Per-ARNT-Sim (PAS) domains that have been proposed to constitute a sensor module. To further enhance our understanding of this “sensor” region, we defined the boundaries that give rise to the minimal autonomously folded PAS domains and analyzed their homo- and heteroassociation properties using analytical ultracentrifugation, nuclear magnetic resonance (NMR) spectroscopy, and multiangle laser light scattering. We show that PAS
A
self-associates very weakly, while PAS
C
is primarily a monomer. In contrast, PAS
B
forms a stable dimer (

K
d

[dissociation constant] of <10 nM), and it appears to be the main N-terminal determinant of KinA dimerization. Analysis of KinA mutants deficient for one or more PAS domains revealed a critical role for PAS
B
, but not PAS
A
, in autophosphorylation of KinA. Our findings suggest that dimerization of PAS
B
is important for keeping the catalytic domain of KinA in a functional conformation. We use this information to propose a model for the structure of the N-terminal sensor module of KinA.
myo
-Inositol and
d
-Ribose Ligand Discrimination in an ABC Periplasmic Binding Protein
Authors: Herrou Julien , Crosson Sean
Published: March 2013

The periplasmic binding protein (PBP) IbpA mediates the uptake of
myo
-inositol by the IatP-IatA ATP-binding cassette transmembrane transporter. We report a crystal structure of
Caulobacter crescentus
IbpA bound to
myo
-inositol at 1.45 Å resolution. This constitutes the first structure of a PBP bound to inositol. IbpA adopts a type I PBP fold consisting of two α-β lobes that surround a central hinge. A pocket positioned between the lobes contains the
myo
-inositol ligand, which binds with submicromolar affinity (0.76 ± 0.08 μM). IbpA is homologous to ribose-binding proteins and binds
d
-ribose with low affinity (50.8 ± 3.4 μM). On the basis of IbpA and ribose-binding protein structures, we have designed variants of IbpA with inverted binding specificity for
myo
-inositol and
d
-ribose. Five mutations in the ligand-binding pocket are sufficient to increase the affinity of IbpA for
d
-ribose by 10-fold while completely abolishing binding to
myo
-inositol. Replacement of
ibpA
with these mutant alleles unable to bind
myo
-inositol abolishes
C. crescentus
growth in medium containing
myo
-inositol as the sole carbon source. Neither deletion of
ibpA
nor replacement of
ibpA
with the high-affinity ribose binding allele affected
C. crescentus
growth on
d
-ribose as a carbon source, providing evidence that the IatP-IatA transporter is specific for
myo
-inositol. This study outlines the evolutionary relationship between ribose- and inositol-binding proteins and provides insight into the molecular basis upon which these two related, but functionally distinct, classes of periplasmic proteins specifically bind carbohydrate ligands.
Bacillus subtilis Mutants with Knockouts of the Genes Encoding Ribonucleases RNase Y and RNase J1 Are Viable, with Major Defects in Cell Morphology, Sporulation, and Competence
Authors: Figaro Sabine , Durand Sylvain , Gilet Laetitia , Cayet Nadège , Sachse Martin , Condon Ciarán
Published: March 2013

The genes encoding the ribonucleases RNase J1 and RNase Y have long been considered essential for
Bacillus subtilis
cell viability, even before there was concrete knowledge of their function as two of the most important enzymes for RNA turnover in this organism. Here we show that this characterization is incorrect and that Δ
rnjA
and Δ
rny
mutants are both viable. As expected, both strains grow relatively slowly, with doubling times in the hour range in rich medium. Knockout mutants have major defects in their sporulation and competence development programs. Both mutants are hypersensitive to a wide range of antibiotics and have dramatic alterations to their cell morphologies, suggestive of cell envelope defects. Indeed, RNase Y mutants are significantly smaller in diameter than wild-type strains and have a very disordered peptidoglycan layer. Strains lacking RNase J1 form long filaments in tight spirals, reminiscent of mutants of the actin-like proteins (Mre) involved in cell shape determination. Finally, we combined the
rnjA
and
rny
mutations with mutations in other components of the degradation machinery and show that many of these strains are also viable. The implications for the two known RNA degradation pathways of
B. subtilis
are discussed.
RfaH Promotes the Ability of the Avian Pathogenic Escherichia coli O2 Strain E058 To Cause Avian Colibacillosis
Authors: Gao Qingqing , Xu Huiqing , Wang Xiaobo , Zhang Debao , Ye Zhengqin , Gao Song , Liu Xiufan
Published: March 2013

Avian pathogenic
Escherichia coli
(APEC) infection causes avian colibacillosis, which refers to any localized or systemic infection, such as acute fatal septicemia or subacute pericarditis and airsacculitis. The RfaH transcriptional regulator in
E. coli
is known to regulate a number of phenotypic traits. The direct effect of RfaH on the virulence of APEC has not been investigated yet. Our results showed that the inactivation of
rfaH
significantly decreased the virulence of APEC E058. The attenuation was assessed by
in vivo
and
in vitro
assays, including chicken infection assays, an ingestion and intracellular survival assay, and a bactericidal assay with serum complement. The virulence phenotype was restored to resemble that of the wild type by complementation of the
rfaH
gene in
trans
. The results of the quantitative real-time reverse transcription-PCR (qRT-PCR) analysis and animal system infection experiments indicated that the deletion of
rfaH
correlated with decreased virulence of the APEC E058 strain.
Small-Angle X-Ray Scattering for Imaging of Surface Layers on Intact Bacteria in the Native Environment
Authors: Sekot Gerhard , Schuster David , Messner Paul , Pum Dietmar , Peterlik Herwig , Schäffer Christina
Published: March 2013

Crystalline cell surface layers (S-layers) represent a natural two-dimensional (2D) protein self-assembly system with nanometer-scale periodicity that decorate many prokaryotic cells. Here, we analyze the S-layer on intact bacterial cells of the Gram-positive organism
Geobacillus stearothermophilus
ATCC 12980 and the Gram-negative organism
Aquaspirillum serpens
MW5 by small-angle X-ray scattering (SAXS) and relate it to the structure obtained by transmission electron microscopy (TEM) after platinum/carbon shadowing. By measuring the scattering pattern of X rays obtained from a suspension of bacterial cells, integral information on structural elements such as the thickness and lattice parameters of the S-layers on intact, hydrated cells can be obtained nondestructively. In contrast, TEM of whole mounts is used to analyze the S-layer lattice type and parameters as well as the physical structure in a nonaqueous environment and local information on the structure is delivered. Application of SAXS to S-layer research on intact bacteria is a challenging task, as the scattering volume of the generally thin (3- to 30-nm) bacterial S-layers is low in comparison to the scattering volume of the bacterium itself. For enhancement of the scattering contrast of the S-layer in SAXS measurement, either silicification (treatment with tetraethyl orthosilicate) is used, or the difference between SAXS signals from an S-layer-deficient mutant and the corresponding S-layer-carrying bacterium is used for determination of the scattering signal. The good agreement of the SAXS and TEM data shows that S-layers on the bacterial cell surface are remarkably stable.
Regulation of Iron Metabolism by Pyrococcus furiosus
Authors: Zhu Yixuan , Kumar Sunil , Menon Angeli L. , Scott Robert A. , Adams Michael W. W.
Published: March 2013

Iron is an essential element for the hyperthermophilic archaeon
Pyrococcus furiosus
, and many of its iron-containing enzymes have been characterized. How iron assimilation is regulated, however, is unknown. The genome sequence contains genes encoding two putative iron-responsive transcription factors, DtxR and Fur. Global transcriptional profiles of the
dtxR
deletion mutant (ΔDTXR) and the parent strain under iron-sufficient and iron-limited conditions indicated that DtxR represses the expression of the genes encoding two putative iron transporters, Ftr1 and FeoAB, under iron-sufficient conditions. Under iron limitation, DtxR represses expression of the gene encoding the iron-containing enzyme aldehyde ferredoxin oxidoreductase and a putative ABC-type transporter. Analysis of the
dtxR
gene sequence indicated an incorrectly predicted translation start site, and the corrected full-length DtxR protein, in contrast to the truncated version, specifically bound to the promoters of
ftr1
and
feoAB
, confirming its role as a transcription regulator. Expression of the gene encoding Ftr1 was dramatically upregulated by iron limitation, but no phenotype was observed for the ΔFTR1 deletion mutant under iron-limited conditions. The intracellular iron concentrations of ΔFTR1 and the parent strain were similar, suggesting that under the conditions tested, Ftr1 is not an essential iron transporter despite its response to iron. In contrast to DtxR, the Fur protein appears not to be a functional regulator in
P. furiosus
, since it did not bind to the promoters of any of the iron-regulated genes and the deletion mutant (ΔFUR) revealed no transcriptional responses to iron availability. DtxR is therefore the key iron-responsive transcriptional regulator in
P. furiosus
.
Efficacy of diode laser in the management of oral lichen planus
Authors: Misra Neeta , Chittoria Nandita , Umapathy Deepak , Misra Pradyumna
Published: March 2013

Oral lichen planus (OLP) is a common chronic disease of uncertain aetiology. Treatment of patients with symptomatic OLP represents a therapeutic challenge. Despite numerous existing remedies, there are many treatment failures. The diode laser therapy is used as a possible alternative method in the treatment of lichen planus. The patient with OLP lesions was treated using diode laser (940 nm) for the symptomatic relief of pain and burning sensation. The patient was assessed before, during and after the completion of the treatment weekly. The treatment was performed for 2 months and the patient showed complete remission of burning sensation and pain (visual analog scale 0%). The follow-up was performed for 7 months and no recurrence of burning sensation was found. Diode laser therapy seems to be an effective alternative treatment for relieving the symptoms of OLP.
Gallstone ileus and fatal gallstone coleus: the importance of the second stone
Authors: Vaughan-Shaw Peter G , Talwar Anjay
Published: March 2013

A patient was admitted as an emergency with bowel obstruction. Recent medical history included an episode of gallstone ileus treated surgically by removal of an enteric calculus. On this admission, an obstructing calculus was removed from the descending colon (gallstone coleus) at laparotomy. However, the postoperative course was complicated by sepsis and the patient died. A CT scan on the second admission and cytology results from a liver abscess suggested gallbladder malignancy as the underlying cause of the cholecystoenteric fistula. The technical challenge and increased mortality associated with cholecystoenteric fistula repair supports simple enterolithotomy as the preferred management of gallstone ileus. However, this case supports the need for a systematic search for all enteric stones at laparotomy and consideration of concurrent or interval cholecystectomy and cholecystoenteric fistula repair to prevent recurrent gallstone ileus and determine underlying pathology.
Marfan syndrome presenting with headache and coincidental ophthalmic artery aneurysm
Authors: Vandersteen Anthony Martin , Kenny Joanna , Khan Naheed L , Male Alison
Published: March 2013

A 24-year-old Ugandan woman was referred for a neurology opinion after complaining of a year long history of right-sided retro-orbital stabbing pain. Brain imaging revealed a coincidental 3 mm left ophthalmic artery aneurysm. Marfanoid habitus was noted; after further investigations she was diagnosed with mild aortic root dilatation, subtle lens dislocation and Marfan syndrome. Her symptoms were secondary to temporomandibular joint dysfunction, an under-recognised complication of Marfan syndrome. Her ophthalmic artery aneurysm is likely to be a coincidental finding.
Acute lymphocytic leukaemia presenting as a metabolic bone disease
Authors: Sukumar Suja P , Balachandran Karthik , Sahoo Jaya Prakash , Kamalanathan Sadishkumar
Published: March 2013

A 7-year-old boy presented with the acute onset of low backache of 2 months duration. An x-ray of thoracolumbar spine revealed multiple vertebral fractures, and biochemical evaluation showed hypercalcaemia with a suppressed parathyroid hormone which raised the possibilities of malignancy, granulomatous conditions or vitamin D toxicity. Despite the absence of blast cells in his blood, the bone marrow biopsy was unequivocally diagnostic of acute lymphoblastic leukaemia.
Incidental paraganglioma of the urinary bladder in a 66-year-old woman
Authors: Christodoulidou Michelle , Lucky Marc , Mansour Paul , Gammal Mohsen
Published: March 2013

A 66-year-old female patient was referred to drology department when a bladder mass was incidentally found on a transvaginal ultrasound scan. Cystoscopy revealed a small, smooth mass just above the trigone which appeared to be covered with normal urothelium. The histology from this growth after transurethral resection revealed a paraganglioma of the bladder. We will discuss the management of this case and literature review of this finding in this study.
Long-term antibiotic therapy in late onset pouch-urethral fistula after ileoanal anastomosis for ulcerative colitis may be effective and well tolerated
Authors: Samaha Mario , Moloney Manus
Published: March 2013

A 25-year-old male patient underwent restorative proctocolectomy and ileoanal anastomosis in 1991 for refractory ulcerative colitis. In February 2001, he presented with pneumaturia, faecaluria, pelvic ‘pressure’ and watery diarrhoea caused by passage of urine through the anal canal. A fistula between the pouch and the membranous urethra was demonstrated by a pouchogram contrast study. In October 2002, he was started on ciprofloxacin 250 mg once daily and metronidazole 400 mg twice daily. Apart from a short break in 2003 the patient has remained on this regimen until the time of writing (now over 10 years) and has had sustained remission, excellent quality of life and no adverse effects.
Social inequality in breast, lung and colorectal cancers: a sibling approach
Authors: Søndergaard Grethe , Mortensen, Laust Hvas , Andersen Anne-Marie Nybo , Andersen P K , Dalton Susanne Oksbjerg , Osler Merete
Published: March 2013

Objective

To examine whether family factors shared by siblings explained the association between education and risk of lung, colorectal and breast cancer.

Design

We used conventional cohort and intersibling Cox regression analyses to analyse the association between education and risk of cancer.

Setting

Denmark.

Participants

We retrieved register data from Statistics Denmark on individuals born in Denmark 1950–1979 with at least one full sibling. The cohorts included between 391 931 and 1 381 369 individuals followed from age 28 for incident lung, colorectal and breast cancer until the end of 2009.

Results

In the cohort analysis, low education was associated with an increased risk of colorectal cancer before age 45 and lung cancer, and with a decreased risk of colorectal cancer after age 45 and breast cancer. When compared with the cohort analyses, the intersibling associations were stronger for colorectal cancer after age 45 and weaker for lung cancer. Serious health conditions in childhood/young adulthood did not explain the associations.

Conclusions

Family factors shared by siblings confounded some of the association between education and colorectal cancer after age 45 and lung cancer, but not the associations found for colorectal cancer before age 45 or breast cancer.
The clustering of cardiovascular disease risk factors and their impacts on annual medical expenditure in Japan: community-based cost analysis using Gamma regression models
Authors: Murakami Yoshitaka , Okamura Tomonori , Nakamura Koshi , Miura Katsuyuki , Ueshima Hirotsugu
Published: March 2013

Objective

The clustering of cardiovascular disease (CVD) risk factors is a serious threat for increasing medical expenses. The age-specific proportion and distribution of medical expenditure attributable to CVD risk factors, especially focused on the elderly, is thus indispensable for formulating public health policy given the extent of the ageing population in developed countries.

Design

Cost analysis using individuals’ medical expenses and their corresponding health examination measures.

Setting

Shiga prefecture, Japan, from April 2000 to March 2006.

Participants

33 213 participants aged 40 years and over.

Main outcome measures

Mean medical expenditure per year.

Methods

Gamma regression models were applied to examine how the number of CVD risk factors affects mean medical expenditure. The four CVD risk factors analysed in this study were defined as follows: hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg), hypercholesterolaemia (serum total cholesterol ≥240 mg/dl), high blood glucose (casual blood glucose ≥200 mg/dl) and smoking (current smoker). Sex-specific and age-specific investigations were carried out on the elderly (aged 65 and over) and non-elderly (aged 40–64) populations.

Results

The mean medical expenditure (per year) for the no CVD risk-factor group was only 110 000 yen at age 50 (men, 110 708 yen; women, 107 109 yen), but this expenditure was 6–7 times higher for 80-year-olds who have three or four CVD risk factors (men, 603 351 yen; women, 765 673 yen). The total overspend (excess fraction) was larger for the non-elderly (men, 15.4%; women, 11.1%) than that for the elderly (men, 0.1%; women, 5.2%) and largely driven by people with one or two CVD risk factors, except for elderly men.

Conclusions

The age-specific proportion and distribution of medical expenditure attributable to CVD risk factors showed that a high-risk approach for the elderly and a population approach for the majority are both necessary to reduce total medical expenditure in Japan.