bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Solar System with a Human Orrery
Authors: Newbury Peter
Published: November 2010

One of the fundamental learning goals of introductory astronomy is for the students to gain some perspective on the scale and structure of the solar system. Many astronomy teachers have laid out the planets along a long strip of paper1 or across a school grounds or campus.2 Other activities that investigate the motion of the planets are often computer based,34 hiding the awe-inspiring distances between the planets. Our human orrery activity, adapted from the design at the Armagh Observatory in Ireland,567 combines the best of both approaches by creating a working model of the solar system that mimics both the scale and the motion of the planets.
Using Environmental Science as a Motivational Tool to Teach Physics to Non-science Majors
Authors: Busch Hauke C.
Published: November 2010

A traditional physical science course was transformed into an environmental physical science course to teach physics to non-science majors. The objective of the new course was to improve the learning of basic physics principles by applying them to current issues of interest. A new curriculum was developed with new labs, homework assignments, worksheets, and interactive classroom learning techniques such as Peer Instruction (PI)1 and SCALE-UP.2 It was found that the new course showed an increase in students' class participation, attendance, and overall interest, with most rating their science experience as very positive.
Experiments with Helium-Filled Balloons
Authors: Zable Anthony C.
Published: November 2010

The concepts of Newtonian mechanics, fluids, and ideal gas law physics are often treated as separate and isolated topics in the typical introductory college-level physics course, especially in the laboratory setting. To bridge these subjects, a simple experiment was developed that utilizes computer-based data acquisition sensors and a digital gram scale to estimate the molar mass of the gas in an inflated balloon. In this experiment, the comparable density of an inflated balloon to that of atmospheric air introduces a significant role for buoyancy that must be accounted for. The ideal gas law approximation is assumed for both the isolated gas mixture within the balloon and the surrounding air, which defines the relationship between the gas pressure, volume, temperature, and molar quantity. Analysis of the forces associated with the inflated balloon with the incorporation of Archimedes' principle and the ideal gas law into Newton's second law results in an experimental method for the measurement of the molar mass and mole fraction of a gas that is easy to implement yet academically challenging for students. The following narrative describes the basic setup of this experiment, along with a sample set of data as acquired and analyzed by a typical physics student from one of my classes.
Measuring Model Rocket Engine Thrust Curves
Authors: Penn Kim , Slaton William V.
Published: November 2010

This paper describes a method and setup to quickly and easily measure a model rocket engine's thrust curve using a computer data logger and force probe. Horst1 describes using Vernier's LabPro2 and force probe to measure the rocket engine's thrust curve; however, the method of attaching the rocket to the force probe is not discussed. We show how a simple engine holder can be constructed and used with Vernier's LabPro and force probe to record data that students can use to compare to sample data from the rocket manufacturer or the National Association of Rocketry's3 engine certification sheets, calculate total impulse, and make predictions for model rocket launches. PASCO markets a rocket engine test bracket4 that mounts to its PASPORT force sensor for similar measurements. The engine holder described here is very economical, and all the parts can be obtained from a local hardware store or home center.
Determining the Thickness and Refractive Index of a Mirror
Authors: Uysal Ahmet
Published: November 2010

When a laser beam reflects from a back surface glass mirror and falls on a screen, a pattern of discrete bright spots is created by partial reflection and refraction of the light at the air-glass interface and reflection at the mirror surface (Fig. 1). This paper explains how this phenomenon can be used to determine the refractive index and the thickness of the glass with a simple measurement. It is possible to utilize this experiment for geometrical optics labs and moreover it would be a nice practice for Physics Olympians.
Waves and Destruction
Authors: Riendeau Diane
Published: November 2010

Thanks to Chris Chiaverina (retired) and Frank Noschese (John Jay HS; Cross River, NY) for their contributions to this month's column.

If you have a video that you use in your classroom, please send the link and a brief description to Diane, driendeau@dist113.org.
BRAF
Gene Amplification Can Promote Acquired Resistance to MEK Inhibitors in Cancer Cells Harboring the BRAF V600E Mutation
Authors: Corcoran Ryan B. , Dias-Santagata Dora , Bergethon Kristin , Iafrate A. John , Settleman Jeffrey , Engelman Jeffrey A.
Published: November 2010

Amplification of an upstream gene leads to resistance to cancer drugs targeted downstream.
Shared Means to Distinct Ends
Authors: VanHook Annalisa M.
Published: November 2010

Different Wnt ligands use a common mechanism to activate unrelated receptors to initiate canonical or noncanonical Wnt signaling.
Interpreting the Ligand’s Message
Authors: Ray L. Bryan
Published: November 2010

Epinephrine and norepinephrine produce distinct conformational changes in their receptor and distinct signaling output.
ISAba825, a Functional Insertion Sequence Modulating Genomic Plasticity and
bla
OXA-58
Expression in
Acinetobacter baumannii
Authors: Ravasi Pablo , Limansky Adriana S. , Rodriguez Ramiro E. , Viale Alejandro M. , Mussi María A.
Published: November 2010

ISAba825, an insertion sequence found inactivating
Acinetobacter baumannii carO
, was tagged with a kanamycin (Kn) resistance cassette. ISAba825::Kn effectively transposed in
A. baumannii
, showing preference for short, AT-enriched target sequences, generating 6- to 9-bp target duplications. Additionally, we detected the presence of ISAba825 upstream of a plasmid-borne
bla
OXA-58
gene, generating a hybrid promoter largely enhancing its expression and leading to carbapenem resistance. Overall, a role for ISAba825 in carbapenem resistance modulation in
A. baumannii
is proposed.
In Vitro
Antimicrobial Activity of Wall Teichoic Acid Biosynthesis Inhibitors against
Staphylococcus aureus
Isolates
Authors: Suzuki Takashi , Swoboda Jonathan G. , Campbell Jennifer , Walker Suzanne , Gilmore Michael S.
Published: November 2010

Staphylococcus aureus
is the leading cause of invasive and superficial human infections, is increasingly antibiotic resistant, and is therefore the target for the development of new antimicrobials. Compounds (1835F03 and targocil) were recently shown to function as bacteriostatic inhibitors of wall teichoic acid (WTA) biosynthesis in
S. aureus
. To assess the value of targeting WTA biosynthesis in human infection, it was therefore of interest to verify the involvement of WTA in bacterial binding to human corneal epithelial cells (HCECs) and to assess the activities of inhibitors of WTA biosynthesis against clinical isolates of methicillin-susceptible
S. aureus
(MSSA) and methicillin-resistant
S. aureus
(MRSA) from cases of human keratitis. The 1835F03 MIC
90
s were 8 μg/ml for MSSA keratitis isolates and >32 μg/ml for MRSA keratitis isolates. The MIC
90
for the analog of 1835F03, targocil, was 2 μg/ml for both MRSA and MSSA. Targocil exhibited little toxicity at concentrations near the MIC, with increased toxicity occurring at higher concentrations and with longer exposure times. Targocil activity was moderately sensitive to the presence of serum, but it inhibited extracellular and intracellular bacteria in the presence of HCECs better than vancomycin. Targocil-resistant strains exhibited a significantly reduced ability to adhere to HCECs.
A Novel Chimeric Lysin Shows Superiority to Mupirocin for Skin Decolonization of Methicillin-Resistant and -Sensitive
Staphylococcus aureus
Strains
Authors: Pastagia Mina , Euler Chad , Chahales Peter , Fuentes-Duculan Judilyn , Krueger James G. , Fischetti Vincent A.
Published: November 2010

Staphylococcus aureus
is a major human pathogen responsible for a number of serious and sometimes fatal infections. One of its reservoirs on the human body is the skin, which is known to be a source of invasive infection. The potential for an engineered staphylococcus-specific phage lysin (ClyS) to be used for topical decolonization is presented. We formulated ClyS into an ointment and applied it to a mouse model of skin colonization/infection with
S. aureus
. Unlike the standard topical antibacterial agent mupirocin, ClyS eradicated a significantly greater number of methicillin-susceptible
S. aureus
(MSSA) and -resistant
S. aureus
(MRSA) bacteria: a 3-log reduction with ClyS as opposed to a 2-log reduction with mupirocin in our model. The use of ClyS also demonstrated a decreased potential for the development of resistance by MRSA and MSSA organisms compared to that from the use of mupirocin
in vitro
. Because antibodies may affect enzyme function, we tested antibodies developed after repeated ClyS exposure for their effect on ClyS killing ability. Our results showed no inhibition of ClyS activity at various antibody titers. These data demonstrate the potential of developing ClyS as a novel class of topical antimicrobial agents specific to staphylococcus.
Use of Inverse PCR for Analysis of Class 1 Integrons Carrying an Unusual 3′ Conserved Segment Structure
Authors: Lee Mei-Feng , Peng Chien-Fang , Hsu Hui-Jine , Toh Han-Siong
Published: November 2010

By using inverse PCR and DNA sequencing, 13
sul3
-associated mutational integrons, 2 defective class 1 integrons, and 1
qnrB2
-associated complex
sul1
-type class 1 integrons were identified in
Salmonella enterica
serovar Choleraesuis,
Pseudomonas aeruginosa
, and
Enterobacter cloacae
, respectively. In addition, conjugation and Southern hybridization demonstrated that unusual class 1 integrons were located on plasmids or integrated into chromosomal DNA. Thus, an inverse PCR assay can be a valuable tool for the analysis of unusual structures of the 3′ conserved region of class 1 integrons.
Expression of Multidrug Efflux Pump Genes
acrAB-tolC
,
mdfA
, and
norE
in
Escherichia coli
Clinical Isolates as a Function of Fluoroquinolone and Multidrug Resistance
Authors: Swick Michelle C. , Morgan-Linnell Sonia K. , Carlson Kimberly M. , Zechiedrich Lynn
Published: November 2010

In a single quantitative study, we measured
acrA
,
acrB
,
tolC
,
mdfA
, and
norE
expression in
Escherichia coli
clinical isolates by using real-time PCR.
acrA
and
acrB
overexpression strongly correlated with fluoroquinolone and multidrug resistance;
tolC
,
mdfA
, and
norE
expression did not. The order of abundance of efflux pump transcripts in all fluoroquinolone-susceptible isolates was
tolC
(highest), then
acrA
and
acrB
, and then
mdfA
and
norE.
Our findings suggest
acrAB
overexpression is an indicator of multidrug resistance.
Combinatorial Phenotypic Signatures Distinguish Persistent from Resolving Methicillin-Resistant
Staphylococcus aureus
Bacteremia Isolates
Authors: Seidl Kati , Bayer Arnold S. , Fowler Vance G. , McKinnell James A. , Abdel Hady Wessam , Sakoulas George , Yeaman Michael R. , Xiong Yan Q.
Published: November 2010

Persistent methicillin-resistant
Staphylococcus aureus
(MRSA) bacteremia (PB) (positive blood cultures after ≥7 days of therapy) represents a clinically challenging subset of invasive MRSA infections. In this investigation, we examined the potential correlation of specific virulence signatures with PB versus resolving MRSA bacteremia (RB) (negative blood cultures within 2 to 4 days of therapy) strains. Thirty-six MRSA isolates from patients enrolled in a recent multinational clinical trial were studied for (i) susceptibility to host defense cationic peptides (HDPs) (i.e., thrombin-induced platelet microbicidal proteins [tPMPs] and human neutrophil peptide 1 [hNP-1]); (ii) adherence to host endovascular ligands (fibronectin) and cells (endothelial cells); and (iii) biofilm formation. We found that PB isolates exhibited significantly reduced susceptibilities to tPMPs and hNP-1 (
P
< 0.001 and
P
= 0.023, respectively). There was no significant association between the PB outcome and fibronectin binding, endothelial cell binding, or biofilm formation (
P
= 0.25, 0.97, and 0.064 versus RB strains, respectively). However, multiple logistic regression analysis revealed that the PB outcome was significantly associated with the combination of reduced susceptibilities to HDPs and extent of biofilm formation (
P
< 0.0001). Similar results were obtained in a second analysis using days of bacteremia as a continuous outcome, showing that reduced HDP susceptibilities and increased biofilm formation cocontributed to predict the duration of bacteremia. Our data indicate that PB isolates have specific pathogenic signatures independent of conventional antimicrobial susceptibility. These combinatorial mosaics can be defined and used to prospectively distinguish PB from RB strains in advance and potentially to predict ultimate clinical outcomes.
The Antibiotic Monensin Causes Cell Cycle Disruption ofToxoplasma gondiiMediated through the DNA Repair Enzyme TgMSH-1
Authors: Lavine Mark D. , Arrizabalaga Gustavo
Published: November 2010

Monensin is a polyether ionophore antibiotic that is widely used in the control of coccidia in animals. Despite its significance in veterinary medicine, little is known about its mode of action and potential mechanisms of resistance in coccidian parasites. Here we show that monensin causes accumulation of the coccidianToxoplasma gondiiat an apparent late-S-phase cell cycle checkpoint. In addition, experiments utilizing a monensin-resistantT. gondiimutant show that this effect of monensin is dependent on the function of a mitochondrial homologue of the MutS DNA damage repair enzyme (TgMSH-1). Furthermore, the same TgMSH-1-dependent cell cycle disruption is observed with the antiparasitic ionophore salinomycin and the DNA alkylating agent methyl nitrosourea. Our results suggest a novel mechanism for the mode of action of monensin and salinomycin on coccidial parasites, in which the drug activates an MSH-1-dependent cell cycle checkpoint by an unknown mechanism, ultimately leading to the death of the parasite. This model would indicate that cell cycle disruption is an important mediator of drug susceptibility and resistance to ionophoric antibiotics in coccidian parasites.
Development and Validation of a High-Performance Liquid Chromatography Method for Determination of Cefquinome Concentrations in Sheep Plasma and Its Application to Pharmacokinetic Studies
Authors: Uney Kamil , Altan Feray , Elmas Muammer
Published: November 2010

Cefquinome has a broad spectrum of antibacterial activity and was developed especially for use in animals. A simple and sensitive high-performance liquid chromatography (HPLC) method with UV-visible detection for quantification of cefquinome concentrations in sheep plasma was developed and validated. Separation of cefquinome from plasma components was achieved on a Phenomenex Gemini C
18
column (250 mm by 4.6 mm; internal diameter [i.d.], 5 μm). The mobile phase consisted of acetonitrile and 0.1% trifluoroacetic acid in water and was delivered at a rate of 0.9 ml/min. A simple and rapid sample preparation involved the addition of methanol to 200 μl of plasma to precipitate plasma proteins followed by direct injection of 50 μl of supernatant into the high-performance liquid chromatography system. The linearity range of the proposed method was 0.02 to 12 μg/ml. The intraday and interday coefficients of variation obtained from cefquinome were less than 5%, and biases ranged from −3.76% to 1.24%. Mean recovery based on low-, medium-, and high-quality control standards ranged between 92.0 and 93.9%. Plasma samples were found to be stable in various storage conditions (freeze-thaw, postpreparative, short-term, and long-term stability). The method described was found to be readily available, practicable, cheap, rapid, sensitive, precise, and accurate. It was successfully applied to the study of the pharmacokinetics of cefquinome in sheep. This method can be very useful and an alternate to performing pharmacokinetic studies in the determination of cefquinome for clinical use.
Whole-Genome Analysis ofSalmonella entericaSerovar Typhimurium T000240 Reveals the Acquisition of a Genomic Island Involved in Multidrug Resistance via IS1Derivatives on the Chromosome
Authors: Izumiya Hidemasa , Sekizuka Tsuyoshi , Nakaya Hideo , Taguchi Masumi , Oguchi Akio , Ichikawa Natsuko , Nishiko Rika , Yamazaki Shuji , Fujita Nobuyuki , Watanabe Haruo , Ohnishi Makoto , Kuroda Makoto
Published: November 2010

Salmonella entericaserovar Typhimurium is frequently associated with life-threatening systemic infections, and the recent global emergence of multidrug resistance inS. entericaisolates from agricultural and clinical settings has raised concerns. In this study, we determined the whole-genome sequence of fluoroquinolone-resistantS. entericaserovar Typhimurium T000240 strain (DT12) isolated from human gastroenteritis in 2000. Comparative genome analysis revealed that T000240 displays high sequence similarity to strain LT2, which was originally isolated in 1940, indicating that progeny of LT2 might be reemerging. T000240 possesses a unique 82-kb genomic island, designated as GI-DT12, which is composed of multidrug resistance determinants, including a Tn2670-like composite transposon (class 1 integron [intI1,blaoxa-30,aadA1,qacEΔ1, andsul1], mercury resistance proteins, and chloramphenicol acetyltransferase), a Tn10-like tetracycline resistance protein (tetA), the aerobactin iron-acquisition siderophore system (lutAandlucABC), and an iron transporter (sitABCD). Since GI-DT12 is flanked by IS1derivatives, IS1-mediated recombination likely played a role in the acquisition of this genomic island through horizontal gene transfer. The aminoglycoside-(3)-N-acetyltransferase (aac(3)) gene and a class 1 integron harboring thedfrA1gene cassette responsible for gentamicin and trimethoprim resistance, respectively, were identified on plasmid pSTMDT12_L and appeared to have been acquired through homologous recombination with IS26. This study represents the first characterization of the unique genomic island GI-DT12 that appears to be associated with possible IS1-mediated recombination inS. entericaserovar Typhimurium. It is expected that future whole-genome studies will aid in the characterization of the horizontal gene transfer events for the emergingS. entericaserovar Typhimurium strains.
Complementarity-Determining Region 3 Size Spectratypes of T Cell Receptor β Chains in CD8+T Cells following Antiviral Treatment of Chronic Hepatitis B
Authors: Ma Shi-Wu , Li Yong-Yin , Zhang Guang-Wen , Huang Xuan , Sun Jian , Li Chris , Abbott William G. H. , Hou Jin-Lin
Published: November 2010

An increased CD8+T cell response to hepatitis B virus (HBV) peptides occurs between 12 and 24 weeks after starting antiviral therapy for chronic hepatitis B. It is not known whether these cells have antiviral function. The aim of this study was to determine whether clonal expansions of CD8+T cells at these time points predict the virological response to therapy. Peripheral blood CD8+T cells were obtained from 20 patients treated with lamivudine or telbivudine for chronic hepatitis B at baseline, 12 weeks, and 24 weeks. The CDR3 spectratype of each T cell receptor (TCR) β chain variable region (Vβ) gene family was analyzed, and the changes in the numbers of Vβ families with clonal expansions were compared in subjects with (n= 12) and without (n= 8) a virological response (52 week HBV DNA < 300 copies/ml). The number of CD8+TCR Vβ families with clonal expansions at 12 weeks relative to baseline (median [10th to 90th percentile], +2.5 [0 to +7] versus +1 [0 to +2],P= 0.03) and at 24 weeks relative to 12 weeks (+1 [0 to +2] versus −1 [−3 to +4],P= 0.006) was higher in subjects with a virological response versus subjects without a virological response, as were interleukin-2 (IL-2) but not IL-21 mRNA levels in peripheral blood mononuclear cells. The duration of new expansions at 12 weeks was higher (P< 0.0001) in responders. Increased numbers of CD8+T cell expansions after antiviral therapy are associated with a virological response to treatment. These CD8+T cells are a potential target for a therapeutic vaccine for chronic hepatitis B.
Diversity of the Early Step of the Futalosine Pathway
Authors: Arakawa Chisato , Kuratsu Masahiro , Furihata Kazuo , Hiratsuka Tomoshige , Itoh Nobuya , Seto Haruo , Dairi Tohru
Published: November 2010

We recently demonstrated that the futalosine pathway was operating in some bacteria for the biosynthesis of menaquinone and that futalosine was converted into dehypoxanthinyl futalosine (DHFL) by an MqnB of
Thermus thermophilus
. In this study, we found that aminodeoxyfutalosine, which has adenine instead of hypoxanthine in futalosine, was directly converted into DHFL by an MqnB of
Helicobacter pylori
. Therefore, this step is potentially an attractive target for the development of specific anti-
H. pylori
drugs.
NALP1 Influences Susceptibility to Human Congenital Toxoplasmosis, Proinflammatory Cytokine Response, and Fate ofToxoplasma gondii-Infected Monocytic Cells
Authors: Witola William H. , Mui Ernest , Hargrave Aubrey , Liu Susan , Hypolite Magali , Montpetit Alexandre , Cavailles Pierre , Bisanz Cordelia , Cesbron-Delauw Marie-France , Fournié Gilbert J. , McLeod Rima
Published: November 2010

NALP1 is a member of the NOD-like receptor (NLR) family of proteins that form inflammasomes. Upon cellular infection or stress, inflammasomes are activated, triggering maturation of proinflammatory cytokines and downstream cellular signaling mediated through the MyD88 adaptor.Toxoplasma gondiiis an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines that are important in innate immunity. In this study, susceptibility alleles for human congenital toxoplasmosis were identified in the NALP1 gene. To investigate the role of the NALP1 inflammasome during infection withT. gondii, we genetically engineered a human monocytic cell line for NALP1 gene knockdown by RNA interference. NALP1 silencing attenuated progression ofT. gondiiinfection, with accelerated host cell death and eventual cell disintegration. In line with this observation, upregulation of the proinflammatory cytokines interleukin-1β (IL-1β), IL-18, and IL-12 uponT. gondiiinfection was not observed in monocytic cells with NALP1 knockdown. These findings suggest that the NALP1 inflammasome is critical for mediating innate immune responses toT. gondiiinfection and pathogenesis. Although there have been recent advances in understanding the potent activity of inflammasomes in directing innate immune responses to disease, this is the first report, to our knowledge, on the crucial role of the NALP1 inflammasome in the pathogenesis ofT. gondiiinfections in humans.
Enhanced Virulence of
Salmonella enterica
Serovar Typhimurium after Passage through Mice
Authors: Mastroeni Pietro , Morgan Fiona J. E. , McKinley Trevelyan J. , Shawcroft Ewan , Clare Simon , Maskell Duncan J. , Grant Andrew J.
Published: November 2010

The interaction between
Salmonella enterica
and the host immune system is complex. The outcome of an infection is the result of a balance between the
in vivo
environment where the bacteria survive and grow and the regulation of fitness genes at a level sufficient for the bacteria to retain their characteristic rate of growth in a given host. Using bacteriological counts from tissue homogenates and fluorescence microscopy to determine the spread, localization, and distribution of
S. enterica
in the tissues, we show that, during a systemic infection,
S. enterica
adapts to the
in vivo
environment. The adaptation becomes a measurable phenotype when bacteria that have resided in a donor animal are introduced into a recipient naïve animal. This adaptation does not confer increased resistance to early host killing mechanisms but can be detected as an enhancement in the bacterial net growth rate later in the infection. The enhanced growth rate is lost upon a single passage
in vitro
, and it is therefore transient and not due to selection of mutants. The adapted bacteria on average reach higher intracellular numbers in individual infected cells and therefore have patterns of organ spread different from those of nonadapted bacteria. These experiments help in developing an understanding of the influence of passage in a host on the fitness and virulence of
S. enterica
.
The Vi Capsular Polysaccharide Prevents Complement Receptor 3-Mediated Clearance of
Salmonella enterica
Serotype Typhi
Authors: Wilson R. Paul , Winter Sebastian E. , Spees Alanna M. , Winter Maria G. , Nishimori Jessalyn H. , Sanchez Jesus F. , Nuccio Sean-Paul , Crawford Robert W. , Tükel Çagla , Bäumler Andreas J.
Published: November 2010

Capsular polysaccharides are important virulence factors of invasive bacterial pathogens. Here we studied the role of the virulence (Vi) capsular polysaccharide of
Salmonella enterica
serotype Typhi (
S.
Typhi) in preventing innate immune recognition by complement. Comparison of capsulated
S.
Typhi with a noncapsulated mutant (Δ
tviBCDE vexABCDE
mutant) revealed that the Vi capsule interfered with complement component 3 (C3) deposition. Decreased complement fixation resulted in reduced bacterial binding to complement receptor 3 (CR3) on the surface of murine macrophages
in vitro
and decreased CR3-dependent clearance of Vi capsulated
S.
Typhi from the livers and spleens of mice. Opsonization of bacteria with immune serum prior to intraperitoneal infection increased clearance of capsulated
S.
Typhi from the liver. Our data suggest that the Vi capsule prevents CR3-dependent clearance, which can be overcome in part by a specific antibody response.
Adsorption of Components of the Plasma Kinin-Forming System on the Surface ofPorphyromonas gingivalisInvolves Gingipains as the Major Docking Platforms
Authors: Rapala-Kozik Maria , Bras Grazyna , Chruscicka Barbara , Karkowska-Kuleta Justyna , Sroka Aneta , Herwald Heiko , Nguyen Ky-Anh , Eick Sigrun , Potempa Jan , Kozik Andrzej
Published: November 2010

Enhanced production of proinflammatory bradykinin-related peptides, the kinins, has been suggested to contribute to the pathogenesis of periodontitis, a common inflammatory disease of human gingival tissues. In this report, we describe a plausible mechanism of activation of the kinin-generating system, also known as the contact system or kininogen-kallikrein-kinin system, by the adsorption of its plasma-derived components such as high-molecular-mass kininogen (HK), prekallikrein (PK), and Hageman factor (FXII) to the cell surface of periodontal pathogenPorphyromonas gingivalis. The adsorption characteristics of mutant strains deficient in selected proteins of the cell envelope suggested that the surface-associated cysteine proteinases, gingipains, bearing hemagglutinin/adhesin domains (RgpA and Kgp) serve as the major platforms for HK and FXII adhesion. These interactions were confirmed by direct binding tests using microplate-immobilized gingipains and biotinylated contact factors. Other bacterial cell surface components such as fimbriae and lipopolysaccharide were also found to contribute to the binding of contact factors, particularly PK. Analysis of kinin release in plasma upon contact withP. gingivalisshowed that the bacterial surface-dependent mechanism is complementary to the previously described kinin generation system dependent on HK and PK proteolytic activation by the gingipains. We also found that severalP. gingivalisclinical isolates differed in the relative significance of these two mechanisms of kinin production. Taken together, these data show the importance of this specific type of bacterial surface-host homeostatic system interaction in periodontal infections.
TheN-Ethyl-N-Nitrosourea-InducedGoldenticketMouse Mutant Reveals an Essential Function ofStingin theIn VivoInterferon Response toListeria monocytogenesand Cyclic Dinucleotides
Authors: Sauer John-Demian , Sotelo-Troha Katia , von Moltke Jakob , Monroe Kathryn M. , Rae Chris S. , Brubaker Sky W. , Hyodo Mamoru , Hayakawa Yoshihiro , Woodward Joshua J. , Portnoy Daniel A. , Vance Russell E.
Published: November 2010

Type I interferons (IFNs) are central regulators of the innate and adaptive immune responses to viral and bacterial infections. Type I IFNs are induced upon cytosolic detection of microbial nucleic acids, including DNA, RNA, and the bacterial second messenger cyclic-di-GMP (c-di-GMP). In addition, a recent study demonstrated that the intracellular bacterial pathogenListeria monocytogenesstimulates a type I IFN response due to cytosolic detection of bacterially secreted c-di-AMP. The transmembrane signaling adaptor Sting (Tmem173, Mita, Mpys, Eris) has recently been implicated in the induction of type I IFNs in response to cytosolic DNA and/or RNA. However, the role of Sting in response to purified cyclic dinucleotides or duringin vivo L. monocytogenesinfection has not been addressed. In order to identify genes important in the innate immune response, we have been conducting a forward genetic mutagenesis screen in C57BL/6 mice using the mutagenN-ethyl-N-nitrosourea (ENU). Here we describe a novel mutant mouse strain,Goldenticket(Gt), that fails to produce type I IFNs uponL. monocytogenesinfection. By genetic mapping and complementation experiments, we found thatGtmice harbor a single nucleotide variant (T596A) ofStingthat functions as a null allele and fails to produce detectable protein. Analysis of macrophages isolated fromGtmice revealed thatStingis absolutely required for the type I interferon response to both c-di-GMP and c-di-AMP. Additionally,Stingis required for the response to c-di-GMP andL. monocytogenes in vivo. Our results provide new functions forStingin the innate interferon response to pathogens.
Clostridium perfringens
TpeL Glycosylates the Rac and Ras Subfamily Proteins
Authors: Nagahama Masahiro , Ohkubo Akiko , Oda Masataka , Kobayashi Keiko , Amimoto Katsuhiko , Miyamoto Kazuaki , Sakurai Jun
Published: November 2010

Clostridium perfringens
TpeL belongs to a family of large clostridial cytotoxins that encompasses
Clostridium difficile
toxin A (TcdA) and B (TcdB) and
Clostridium sordellii
lethal toxin (TcsL). We report here the identification of the TpeL-catalyzed modification of small GTPases. A recombinant protein (TpeL1-525) derived from the TpeL N-terminal catalytic domain in the presence of streptolysin O (SLO) induced the rounding of Vero cells and the glycosylation of cellular Rac1. Among several hexoses tested, UDP-
N
-acetyl-glucosamine (UDP-GlcNAc) and UDP-glucose (UDP-Glc) served as cosubstrates for TpeL1-525-catalyzed modifications. TpeL1-525 catalyzed the incorporation of UDP-Glc into Ha-Ras, Rap1B, and RalA and of UDP-GlcNAc into Rac1, Ha-Ras, Rap1B, and RalA. In Rac1, TpeL and TcdB share the same acceptor amino acid for glycosylation, Thr-35. In Vero cells treated with TpeL1-525 in the presence of SLO, glycosylation leads to a translocation of the majority of Rac1 and Ha-Ras to the membrane. We demonstrate for first time that TpeL uses both UDP-GlcNAc and UDP-Glc as donor cosubstrates and modifies the Rac1 and Ras subfamily by glycosylation to mediate its cytotoxic effects.
Identification of Subtilase Cytotoxin (SubAB) Receptors Whose Signaling, in Association with SubAB-Induced BiP Cleavage, Is Responsible for Apoptosis in HeLa Cells
Authors: Yahiro Kinnosuke , Satoh Mamoru , Morinaga Naoko , Tsutsuki Hiroyasu , Ogura Kohei , Nagasawa Sayaka , Nomura Fumio , Moss Joel , Noda Masatoshi
Published: November 2010

Subtilase cytotoxin (SubAB), which is produced by certain strains of Shiga-toxigenic
Escherichia coli
(STEC), causes the 78-kDa glucose-regulated protein (GRP78/BiP) cleavage, followed by induction of endoplasmic reticulum (ER) stress, leading to caspase-dependent apoptosis via mitochondrial membrane damage by Bax/Bak activation. The purpose of the present study was to identify SubAB receptors responsible for HeLa cell death. Four proteins, NG2, α2β1 integrin (ITG), L1 cell adhesion molecule (L1CAM), and hepatocyte growth factor receptor (Met), were identified to be SubAB-binding proteins by immunoprecipitation and purification, followed by liquid chromatography-tandem mass spectrometry analysis. SubAB-induced Bax conformational change, Bax/Bak complex formation, caspase activation, and cell death were decreased in β1 ITG, NG2, and L1CAM small interfering RNA-transfected cells, but unexpectedly, BiP cleavage was still observed. Pretreatment of cells with a function-blocking β1 ITG antibody (monoclonal antibody [MAb] P5D2) enhanced SubAB-induced caspase activation; MAb P5D2 alone had no effect on caspase activation. Furthermore, we found that SubAB induced focal adhesion kinase fragmentation, which was mediated by a proteasome-dependent pathway, and caspase activation was suppressed in the presence of proteasome inhibitor. Thus, β1 ITG serves as a SubAB-binding protein and may interact with SubAB-signaling pathways, leading to cell death. Our results raise the possibility that although BiP cleavage is necessary for SubAB-induced apoptotic cell death, signaling pathways associated with functional SubAB receptors may be required for activation of SubAB-dependent apoptotic pathways.
Distinct Time-Resolved Roles for Two Catabolite-Sensing Pathways during
Streptococcus pyogenes
Infection
Authors: Kietzman Colin C. , Caparon Michael G.
Published: November 2010

Many Gram-positive pathogens link the expression of virulence genes to the presence of carbon source substrates using overlapping pathways for global control of carbon catabolite regulation. However, how these pathways are integrated to control the behavior of the transcriptome in time- and compartment-specific patterns is typically not well understood. In the present study, global transcriptome profiling was used to determine the extent to which glucose alters gene expression in
Streptococcus pyogenes
(group A streptococcus) and the contributions of the CcpA and LacD.1 catabolite control pathways to the regulation of this response
in vitro
. This analysis revealed that the expression of as many as 15% of the genes examined was regulated and that CcpA and LacD.1 together contribute to the regulation of 60% of this subset. However, numerous patterns were observed, including both CcpA- and LacD.1-specific and independent regulation, coregulation, and regulation of genes by these pathways independently of glucose. In addition, CcpA and LacD.1 had antagonistic effects on most coregulated genes. To resolve the roles of these regulators during infection, the expression of selected transcripts representative of different regulatory patterns was examined in a murine model of soft tissue infection. This revealed distinct patterns of misregulation with respect to time in CcpA
−
versus LacD.1
−
mutants. Taken together, these data support an important role for carbohydrate in the regulation of the transcriptome in tissue and suggest that the CcpA and LacD.1 pathways are organized to function at different times during the course of an infection.
Identification of Gene Products Involved in the Oxidative Stress Response of
Moraxella catarrhalis
Authors: Hoopman Todd C. , Liu Wei , Joslin Stephanie N. , Pybus Christine , Brautigam Chad A. , Hansen Eric J.
Published: November 2010

Moraxella catarrhalis
is subjected to oxidative stress from both internal and environmental sources. A previous study (C. D. Pericone, K. Overweg, P. W. Hermans, and J. N. Weiser, Infect. Immun.
68
:3990-3997, 2000) indicated that a wild-type strain of
M. catarrhalis
was very resistant to killing by exogenous hydrogen peroxide (H
2
O
2
). The gene encoding OxyR, a LysR family transcriptional regulator, was identified and inactivated in
M. catarrhalis
strain O35E, resulting in an increase in sensitivity to killing by H
2
O
2
in disk diffusion assays and a concomitant aerobic serial dilution effect. Genes encoding a predicted catalase (KatA) and an alkyl hydroperoxidase (AhpCF) showed dose-dependent upregulation in wild-type cells exposed to H
2
O
2
. DNA microarray and real-time reverse transcription-PCR (RT-PCR) analyses identified
M. catarrhalis
genes whose expression was affected by oxidative stress in an OxyR-dependent manner. Testing of
M. catarrhalis
O35E
katA
and
ahpC
mutants for their abilities to scavenge exogenous H
2
O
2
showed that the KatA catalase was responsible for most of this activity in the wild-type parent strain. The introduction of the same mutations into
M. catarrhalis
strain ETSU-4 showed that the growth of a ETSU-4
katA
mutant was markedly inhibited by the addition of 50 mM H
2
O
2
but that this mutant could still form a biofilm equivalent to that produced by its wild-type parent strain.
Priority to registered donors on the waiting list for postmortal organs? A critical look at the objections
Authors: Hartogh Govert den
Published: November 2010

It has often been proposed to restrict access to postmortal organs to registered donors, or at least to give them priority on the waiting list. Such proposals are motivated by considerations of fairness: everyone benefits from the existence of a pool of available organs and of an organised system of distributing them and it is unfair that people who are prepared to contribute to this public good are duped by people who are not. This paper spells out this rationale and goes on to discuss the main principled objections that have been brought forward to such proposals. The most fundamental objection is that healthcare resources should be allocated in accordance with need, not with merit. The reply to this objection is that the principle of allocation according to need only holds in cases in which the provision of such resources and the fair distribution of the burdens of contribution are independently secured, as they are in an obligatory insurance system.
Neurobehavioral effects of long-term exposure to pesticides: results from the 4-year follow-up of the PHYTONER Study
Authors: Baldi Isabelle , Gruber Anne , Rondeau Virginie , Lebailly Pierre , Brochard Patrick , Fabrigoule Colette
Published: November 2010

Objective

The aim of the PHYTONER study is to investigate the role of pesticides on neurobehavioral performances in French vineyard workers.

Methods

929 workers affiliated to the health insurance system for farmers in the Bordeaux area of south-western France were enrolled in the study in 1997–1998. They were contacted for a first follow-up in 2001–2003. Participants completed a questionnaire and nine neurobehavioral tests. They were classified according to their life-long pesticide exposure, as directly exposed, indirectly exposed or non-exposed. Educational level, age, sex, alcohol consumption, smoking, psychotropic drug use and depressive symptoms were taken into account in the analysis.

Results

614 subjects were available for investigation at follow-up. Follow-up analysis confirmed that the risk of obtaining a low performance on the tests was higher in exposed subjects, with ORs ranging from 1.35 to 5.60. Evolution of performances over the follow-up period demonstrated that exposed subjects had the worst decreases in performance. The risk of having a two-point lower score on the Mini-Mental State Examination was 2.15 (95% CI 1.18 to 3.94) in exposed subjects.

Conclusion

These results suggest long-term cognitive effects of chronic exposure to pesticides and raise the issue of the risk of evolution towards dementia. The PHYTONER study is the first to provide prospective data on the natural history of neurological disorders associated with pesticide exposure.
Long-term effects on humoral immunity among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
Authors: Saberi Hosnijeh Fatemeh , Boers Daisy , Portengen Lützen , Bueno-de-Mesquita H Bas , Heederik Dick , Vermeulen Roel
Published: November 2010

Objectives

Epidemiological studies have shown inconsistent effects on immunological parameters in subjects exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this study we investigated changes in humoral immunity and prevalence of atopic diseases among workers from a Dutch historical cohort occupationally exposed to chlorophenoxy herbicides and contaminants including TCDD.

Methods

45 workers who had been exposed to high levels of TCDD in the past and 108 non-exposed workers (39 from the same factory as the exposed subjects (internal control group) and 69 from a comparable factory but without TCDD exposure (external control group)) were included in the study. Blood immunoglobulin (Ig) and complement factor (C) concentrations and specific IgE antibodies to a panel of common allergens were measured using quantitative nephelometry or ELISA. TCDD plasma levels were measured and back-extrapolated to the time of last exposure (TCDDmax) using a one-compartment first order kinetic model.

Results

A borderline significant negative association between both current and predicted TCDD levels and C4 was found in multivariate analyses (β=−0.020; 95% CI=−0.040–0.010 and β=−0.020; 95% CI=−0.030–0.00, respectively). History of eczema was significantly associated with current TCDD levels in both crude (OR=1.5; 95% CI=1.03−2.2) and adjusted models (OR=1.7; 95% CI=1.08−2.7).

Conclusions

Our results do not support an association between TCDD exposure and markers of humoral immunity except possibly C4. Interestingly, decreased levels of C4 have been linked to lymphoma risk, which provides some support to the putative link between TCDD and non-Hodgkin lymphoma.
A NOTE ON THE OPTIMAL SUPPLY CYCLE WHEN THE WHOLE PERIOD IS STOCKOUT
Authors: CHEN MIAO-SHENG , CHEN YING-CHIEH
Published: November 2010

The purpose of this article is to construct a stochastic-demand inventory model which assumes that the whole period is stockout and the goods supply is at the end of the period. Furthermore, it also assumes that the waiting willingness of the customer depends on the length of waiting time. Based on these assumptions, the optimal supply cycle is then found so that the profit per unit time is maximized.
BIO-INSPIRED COVERAGE OF INVISIBLE HAZARDOUS SUBSTANCES IN THE ENVIRONMENT
Authors: OYEKAN JOHN O. , HU HUOSHENG , GU DONGBING
Published: November 2010

Inspired by the simplicity of how nature solves its problems, a controller based upon the bacteria chemotaxis behavior and flocking of starlings in nature is developed and presented. It would enable the localization and subsequent mapping of pollutants in the environment. The pollutants could range from chemical leaks to invisible air borne hazardous materials. Simulation is used to explore the feasibility of the proposed controller and then a brief discussion on how to implement it onto a real robotic platform is presented. By using the advantages offered by swarm robotics, it is possible to achieve a collective mapping of an invisible pollutant spread over a large area. The approach presented is very simple, computational efficient, easily tuned and yet highly effective (desirable characteristics of biological systems) in generating a representation of an invisible pollutant.
NONLINEAR MODELING WITH CAVITATION PHENOMENON OF A NOVEL SHOCK ABSORBER FOR ABOVE-KNEE PROSTHESIS
Authors: MAO Y. C.
Published: November 2010

The shock wave of ground reaction forces during walking and running is suggested as a primary etiological agent in some conditions, such as degenerative joint disease, prosthetic joint loosening, plantar fasciitis or muscle tears. This study proposes a novel shock absorber design with an adjustable automatic smooth tuning range of the damping coefficient and rapid rebounds after impact loads, equipped in the above-knee prosthesis tibia section without any electronic devices. This absorber is also capable of automatic locking-out and releasing for stance and heel-strike phases without manual switching. It absorbs the impact load of the ground reaction force at each heel strike and adapts itself to the input force speed, feasible for patients to tolerate a wide range of athletic and inert situations. This study constructs a high order nonlinear dynamic model for its pressure-sensitive plunger and check valve systems and considers the cavitation phenomenon during speedy fluid flows. Simulation results show that both the damper resistant force and the damping coefficient reduce as the ground reaction force velocity increases, providing a desirable tendency of diminishing shock wave influences on the biological musculoskeletal system.
A SCANNER BASED PALMPRINT VERIFICATION SYSTEM FOR CIVIL APPLICATION
Authors: ZHANG HUAN , HU DEWEN
Published: November 2010

The concept of capturing a palmprint using a scanner is not new, but the current palmprint capture devices based on a scanner have the limitations of low speed and large weight. A new palmprint capture device based on a scanner has been developed, which can overcome these limitations. A scanner based palmprint verification system (PVS) has also been designed using the proposed palmprint capture device. A commercially available mobile internet device (MID) was used to execute the whole program and to store the collected palmprint images. A small palmprint database was built using the developed palmprint capture device and the experimental results on this palmprint database showed that the designed system achieved an acceptable level of performance. The proposed PVS has a stable performance, small size and low price, and can meet the practical needs of civil palmprint applications.
MULTI-CAMERA POSITIONING FOR AUTOMATED TRACKING SYSTEMS IN DYNAMIC ENVIRONMENTS
Authors: YAO YI , CHEN CHUNG-HAO , ABIDI BESMA , PAGE DAVID , KOSCHAN ANDREAS , ABIDI MONGI
Published: November 2010

Most existing camera placement algorithms focus on coverage and/or visibility analysis, which ensures that the object of interest is visible in the camera's field of view (FOV). According to recent literature, handoff safety margin is introduced to sensor planning so that sufficient overlapped FOVs among adjacent cameras are reserved for successful and smooth target transition. In this paper, we investigate the sensor planning problem when considering the dynamic interactions between moving targets and observing cameras. The probability of camera overload is explored to model the aforementioned interactions. The introduction of the probability of camera overload also considers the limitation that a given camera can simultaneously monitor or track a fixed number of targets and incorporates the target's dynamics into sensor planning. The resulting camera placement not only achieves the optimal balance between coverage and handoff success rate but also maintains the optimal balance in environments with various target densities. The proposed camera placement method is compared with a reference algorithm by Erdem and Sclaroff. Consistently improved handoff success rate is illustrated via experiments using typical office floor plans with various target densities.
PRESSURE DROP CHARACTERISTICS OF R410A-OIL MIXTURE FLOW BOILING IN SMALL SMOOTH TUBES
Authors: GAO YIFENG , DENG BIN , DING GUOLIANG , HU HAITAO , HUANG XIANGCHAO
Published: November 2010

This study presents experimental frictional pressure drop for R410A/oil mixture flow boiling in small horizontal smooth tubes with inside diameters of 4.18 mm and 2.0 mm. Experimental conditions cover nominal oil concentrations from 0 to 5%. The test results show that the presence of oil enhances two-phase frictional pressure drop about 0–120% and 0–90% at present test conditions for 4.18 mm I.D. smooth tube and 2.0 mm I.D. smooth tube, respectively, and the enhanced effect is more evident at higher vapor qualities where the local oil concentrations are higher. A new correlation to predict the local frictional pressure drop of R410A/oil mixture flow boiling inside conventional size and small smooth tubes is developed based on local properties of refrigerant–oil mixture, and the experimental data of 4.18 mm I.D. and 2.0 mm I.D. smooth tubes and that of 6.34 mm I.D. smooth tube (Hu et al., 2008) are well-correlated with the new correlation.