bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic variability, heritability and correlation among agronomic and disease resistance traits in a diversity panel and elite breeding material of spelt wheat
Authors: Longin Carl Friedrich Horst , Würschum Tobias
Published: April 2014

Spelt wheat (Triticum spelta L.) is an old‐world crop that has attracted increased attention since the 1970s accompanied by a constant increase in spelt production. Our objectives were to (i) study the genetic variability and heritability of important agronomic traits and (ii) examine the correlation among these traits for an efficient design of spelt breeding schemes. To this end, we compared a diversity panel of 150 old and new spelt varieties with current elite‐breeding material. Phenotypic data were recorded at multiple locations for yield, plant height, lodging, heading time, number of spikelets, ear snapping and susceptibility to powdery mildew, brown rust and Septoria tritici blotch. We observed highly significant genetic variances for almost all traits in both germplasm sets. Heritability estimates ranged from 0.23 for Septoria tritici blotch to 0.97 for plant height. A significant correlation between yield and plant height of −0.56 as well as yield and lodging of −0.39 was determined but no other correlation of yield with any of the examined traits. Thus, pedigree selection with early generation screenings on plant height and lodging can be recommended for further spelt improvement.
Sublethal metal stress response of larvae of Aedes aegypti
Authors: Perez Mario H. , Noriega Fernando G.
Published: April 2014

Aedes aegypti (Diptera: Culicidae) has adapted to urban environments. The urbanization process provides suitable habitats for this disease vector, subsequently increasing the probability of the transmission of pathogens in high‐density environments. Urban environments provide metal‐stressed larval habitats. However, little is known about the physiological cost of metal stress or how this might affect the performance of this mosquito species. The present study aims to characterize the sublethal physiological consequences of metal stress in Aedes aegypti. Various parameters of mosquito physiology under larval metal stress are assessed, including larval metallothionein expression and the effects of larval metal stress on adult performance and their progeny. The results show that environmentally relevant larval metal stress compromises larval and adult development and performance, and also results in larval metal tolerance along with an increase in lipid consumption. These performance costs are coupled with a dramatic increase in metallothionein expression in the midgut. Metal stress results in a lowered adult body mass and neutral storage lipids at emergence, starvation tolerance, fecundity and starvation tolerance of offspring compared with non‐metal‐stressed individuals. Ironically, larval metal stress results in increased adult longevity. Taken together, these findings indicate that even low levels of environmentally relevant larval metal stress have considerable physiological consequences for this important disease vector.
Observation of Magnetic Field Effects on Transient Fluorescence Spectra of Cryptochrome 1 From Homing Pigeons
Authors: Du Xian‐li , Wang Jing , Pan Wei‐song , Liu Qi‐jun , Wang Xiao‐jie , Wu Wen‐jian
Published: April 2014

Cryptochromes are suggested to be involved in the bird magnetoreception based on the radical pair mechanism (RPM), a well established theory of weak magnetic field effects on chemical reactions. Two members of cryptochrome/photolyase family were found to respond to magnetic field, however, no direct responses of bird cryptochrome to magnetic field as weak as the Earth's magnetic field have been obtained so far. In this study, we used transient fluorescence spectroscopy to characterize the weak magnetic field effects of bird cryptochromes. To do this, we cloned the cryptochrome 1 gene (clCRY1) from the retina of homing pigeons (Columba livia), expressed it in insect Sf9 cells and analyzed the transient fluorescence of purified clCRY1 by application of 45–300 μT magnetic fields. The flavin adenine dinucleotide (FADox) and glucose oxidase (GOD) in PBS buffer were set as controls which could be excited by light to generate radicals, but would not be sensitive to magnetic field. We observed that the transient fluorescence spectra of clCRY1 were sensitive to the applied magnetic field at room temperature. Our result provides a new proof of the cryptochrome‐based model of avian magnetoreception in vitro.
Want to Increase Trust in Government? Update Our Public Participation Laws
Authors: Leighninger Matt
Published: April 2014

Leighninger Podcast Episode
The Change in Suicide Rates between 2002 and 2011 in China
Authors: Zhang Jie , Sun Long , Liu Yuxin , Zhang Jianwei
Published: April 2014

Chinese suicide rates have been reported in various studies in the past two decades, but few of them were based on national data. The most recent mortality data (2002–2011) provided by the China Ministry of Health and the detailed census data provided by the National Population Census were used in this study. We calculated the age‐, gender‐, and region‐specific suicide rates and their trends in the past 10 years between 2002 and 2011. The overall suicide rates in China decreased during the study period. The rural/urban ratio of the suicide rates has been significantly reduced from the ratio in the 1990s, and male suicide rates have exceeded those of females. Age was positively associated with suicide rates without the two peaks found in the suicide rates over 20 years ago. The Chinese suicide rates have significantly declined in the past decade, with withering of the unique suicide rate patterns previously found in Chinese suicides about 20 years ago.
Preparation for Practice: Elementary Preservice Teachers Learning and Using Scientific Classroom Discourse Community Instructional Strategies
Authors: Lewis Elizabeth , Dema Oxana , Harshbarger Dena
Published: April 2014

Despite historical national efforts to improve elementary science education, science instruction continues to be marginalized, varying by state. This study was designed to address the ongoing challenge of educating elementary preservice teachers (PSTs) to teach science. Elementary PSTs are one of the science education community's major links to schools and science education reform. However, they often lack a strong background in science, knowledge of effective science teaching strategies, and consequently have low confidence and self‐efficacy. This investigation explored the initial learning of elementary PSTs using an interdisciplinary model of a scientific classroom discourse community during a science methods course. Findings post‐methods course suggested that the PSTs gained confidence in how to teach inquiry‐based elementary science and recognized inquiry‐based science as an effective means for engaging student learning. Additionally, PSTs embraced the interdisciplinary model as one that benefits students' learning and effectively uses limited time in a school day.
RADIOGRAPHIC DIAGNOSIS OF MECHANICAL OBSTRUCTION IN DOGS BASED ON RELATIVE SMALL INTESTINAL EXTERNAL DIAMETERS
Authors: Finck Cyrielle , D'Anjou Marc‐André , Alexander Kate , Specchi Swan , Beauchamp Guy
Published: April 2014

Mechanical obstruction is a frequent cause of acute vomiting in dogs requiring prompt diagnosis to improve patient management and prognosis. The purpose of this retrospective study was to compare small intestinal radiographic characteristics in dogs with versus without mechanical intestinal obstruction. Fifty dogs with gastrointestinal clinical signs and abdominal radiographs were recruited from hospital record archives and assigned to groups (group 1, obstructive, n = 25; group 2, nonobstructive n = 25). Abdominal radiographs were randomized and independently interpreted by three examiners who were unaware of group status. Intestinal dilation was subjectively scored based on distribution (segmental, regional or diffuse), and severity (absent, mild, moderate or severe). Small intestinal maximal diameter (SImax), L5 vertebral body height, small intestinal minimal diameter (SImin), and an estimated average of small intestinal diameters (SIave) were measured and three ratios were calculated: SImax/L5, SImax/SImin, and SImax/SIave. Segmental dilation was more prevalent in obstructed dogs for all examiners (P ≤ 0.03) and most nonobstructed dogs had no dilation (P ≤ 0.05). All ratios were higher in obstructed dogs (P < 0.002). Subjective dilation scores and ratio measurements had low interobserver agreement (absent to fair, with kappa values between −0.06 and 0.57) and reproducibility (coefficients of 0.35–0.61). Findings indicated that dogs with SImax/L5 ≤ 1.4, SImax/SImin ≤ 2, and SImax/SIave ≤ 1.3 values are very unlikely to be mechanically obstructed; dogs with SImax/L5 ≥ 2.4, SImax/SImin ≥ 3.4 and SImax/SIave ≥ 1.9 are very likely obstructed, particularly if segmental dilation (less than 25% of the small intestine) is present. Dogs with ratios falling between these thresholds may need further testing unless other signs justify surgical exploration or endoscopy.
Pre‐exposure to adenosine, acting via A2A receptors on endothelial cells, alters the protein kinase A dependence of adenosine‐induced dilation in skeletal muscle resistance arterioles
Authors: Maimon Nir , Titus Patricia A. , Sarelius Ingrid H.
Published: April 2014

Key points

The adenosine‐dependent component of functional dilation of small resistance arterioles acts via A2A receptors located on endothelium to activate KATP channels on associated vascular smooth muscle.

A2A receptors are Gs‐coupled, hence receptor occupancy should activate cAMP/protein kinase A (PKA) cell signalling pathways However, pre‐exposure to adenosine alters the PKA dependence of the response and renders the vessel insensitive to PKA inhibition.

The adenosine pre‐exposure effect is mimicked by pre‐activation of PKA and is specific to adenosine, as the PKA dependence of dilation to isoproterenol (another Gs‐coupled agonist) is not affected by pre‐exposure.

Activation of PKA alone does not induce dilation. An additional signalling mechanism, dependent on increased EC Ca2+ via activation of cyclic nucleotide gated channels, is required together with PKA activation to produce A2A‐dependent vasodilation.

This novel identification of variability in signalling downstream from a single receptor to produce the same response may reflect a mechanism for integration of key homeostatic responses.

Adenosine (ADO) is an endogenous vasodilatory purine widely recognized to be a significant contributor to functional hyperaemia. Despite this, many aspects of the mechanisms by which ADO induces dilation in small resistance arterioles are not established, or appear contradictory. These include: identification of the primary receptor subtype; its location on endothelial (EC) or vascular smooth muscle cells; whether ADO acts on KATP channels in these resistance vessels; and the contribution of cAMP/protein kinase A (PKA) signalling to the response. In intravital microscopy studies of intact or EC‐denuded skeletal muscle arterioles, we show that ADO acts via A2A receptors located on ECs to produce vasodilation via activation of KATP channels located on vascular smooth muscle cells. Importantly, we found that the signalling pathway involves cAMP as expected, but that a requirement for PKA activation is demonstrable only if the vessel is not pre‐exposed to ADO. That is, PKA‐dependent signalling varies with pre‐exposure to ADO. Further, we show that PKA activation alone is not sufficient to dilate these arterioles; an additional EC calcium‐dependent signalling mechanism is required for vasodilation to ADO. The ability of arterioles in situ to respond to occupancy of a specific receptor by utilizing different cell signalling pathways under different conditions to produce the same response allows the arteriole to respond to key homeostatic requirements using more than a single signalling mechanism. Clearly, this is likely to be physiologically advantageous, but the role for this signalling flexibility in the integrated arteriolar response that underlies functional hyperaemia will require further exploration.
Numerical Investigation of Fluid Flow in a Chandler Loop
Authors: Touma Hisham , Sahin Iskender , Gaamangwe Tidimogo , Gorbet Maud B. , Peterson Sean D.
Published: April 2014

The Chandler loop is an artificial circulatory platform for in vitro hemodynamic experiments. In most experiments, the working fluid is subjected to a strain rate field via rotation of the Chandler loop, which, in turn, induces biochemical responses of the suspended cells. For low rotation rates, the strain rate field can be approximated using laminar flow in a straight tube. However, as the rotation rate increases, the effect of the tube curvature causes significant deviation from the laminar straight tube approximation. In this manuscript, we investigate the flow and associated strain rate field of an incompressible Newtonian fluid in a Chandler loop as a function of the governing nondimensional parameters. Analytical estimates of the strain rate from a perturbation solution for pressure driven steady flow in a curved tube suggest that the strain rate should increase with Dean number, which is proportional to the tangential velocity of the rotating tube, and the radius to radius of curvature ratio of the loop. Parametrically varying the rotation rate, tube geometry, and fill ratio of the loop show that strain rate can actually decrease with Dean number. We show that this is due to the nonlinear relationship between the tube rotation rate and height difference between the two menisci in the rotating tube, which provides the driving pressure gradient. An alternative Dean number is presented to naturally incorporate the fill ratio and collapse the numerical data. Using this modified Dean number, we propose an empirical formula for predicting the average fluid strain rate magnitude that is valid over a much wider parameter range than the more restrictive straight tube-based prediction.
Residual Shear Deformations in the Coronary Artery
Authors: Wang Ruoya , Gleason Rudolph L.
Published: April 2014

Quantifying arterial residual deformations is critical for understanding the stresses and strains within the arterial wall during physiological and pathophysiological conditions. This study presents novel findings on residual shear deformations in the left anterior descending coronary artery. Residual shear deformations are most evident when thin, long axial strips are cut from the artery. These strips deform into helical configurations when placed in isotonic solution. A residual shear angle is introduced as a parameter to quantify the residual shear deformations. Furthermore, a stress analysis is performed to study the effects of residual shear deformations on the intramural shear stress distribution of an artery subjected to pressure, axial stretch, and torsion using numerical simulation. The results from the stress analyses suggest that residual shear deformations can significantly modulate the intramural shear stress across the arterial wall.
Dynamic Modeling and Vibration Response Simulation for High Speed Rolling Ball Bearings With Localized Surface Defects in Raceways
Authors: Niu Linkai , Cao Hongrui , He Zhengjia , Li Yamin
Published: April 2014

A dynamic model is developed to investigate vibrations of high speed rolling ball bearings with localized surface defects on raceways. In this model, each bearing component (i.e., inner raceway, outer raceway and rolling ball) has six degrees of freedom (DOFs) to completely describe its dynamic characteristics in three-dimensional space. Gyroscopic moment, centrifugal force, lubrication traction/slip between bearing component are included owing to high speed effects. Moreover, local defects are modeled accurately and completely with consideration of additional deflection due to material absence, changes of Hertzian contact coefficient and changes of contact force directions due to raceway curvature variations. The obtained equations of motion are solved numerically using the fourth order Runge–Kutta–Fehlberg scheme with step-changing criterion. Vibration responses of a defective bearing with localized surface defects are simulated and analyzed in both time domain and frequency domain, and the effectiveness of fault feature extraction techniques is also discussed. An experiment is carried out on an aerospace bearing test rig. By comparing the simulation results with experiments, it is confirmed that the proposed model is capable of predicting vibration responses of defective high speed rolling ball bearings effectively.
Visualizing and Manipulating Temporal Signaling Dynamics with Fluorescence-Based Tools
Authors: Doupé David P. , Perrimon Norbert
Published: April 2014

Fluorescent sensors and optogenetic tools reveal temporal dynamics in cellular signaling.
Move and Countermove
Authors: Hines Pamela J.
Published: April 2014

A plant pathogen and its host compete for control over a key phosphorylation site in an innate immune receptor.
Circadian Rhythms
Authors: Hines Pamela J.
Published: April 2014

Behavioral rhythms emerge from the interactions of many independent oscillators rather than from a group of master pacemakers.
Preventing Stress with Sugar
Authors: Berndt Jason D.
Published: April 2014

Hexosamine biosynthesis and metabolism limits cellular damage due to stress.
Natural Killer Cells on the Attack
Authors: Gough Nancy R.
Published: April 2014

Genetically or pharmacologically disrupting the activity of an E3 ubiquitin ligase promotes the antitumor activity of natural killer cells.
Antifungal Susceptibility Patterns of Opportunistic Fungi in the Genera Verruconis and Ochroconis
Authors: Seyedmousavi S. , Samerpitak K. , Rijs A. J. M. M. , Melchers W. J. G. , Mouton J. W. , Verweij P. E. , de Hoog G. S.
Published: April 2014

Species of
Verruconis
and species of
Ochroconis
are dematiaceous fungi generally found in the environment but having the ability to infect humans, dogs, cats, poultry, and fish. This study presents the antifungal susceptibility patterns of these fungi at the species level. Forty strains originating from clinical and environmental sources were phylogenetically identified at the species level by using sequences of the ribosomal DNA internal transcribed spacer (rDNA ITS).
In vitro
antifungal susceptibility testing was performed against eight antifungals, using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. The geometric mean MICs for amphotericin B (AMB), flucytosine (5FC), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), and posaconazole (POS) and minimum effective concentrations (MECs) for caspofungin (CAS) and anidulafungin (AFG) across the
Ochroconis
and
Verruconis
species were as follows, in increasing order. For
Verruconis
species, the values (μg/ml) were as follows: AFG, 0.04; POS, 0.25; ITC, 0.37; AMB, 0.50; CAS, 0.65; VRC, 0.96; 5FC, 10.45; and FLC, 47.25. For
Ochroconis
species, the values (μg/ml) were as follows: AFG, 0.06; POS, 0.11; CAS, 0.67; VRC, 2.76; ITC, 3.94; AMB, 5.68; 5FC, 34.48; and FLC, 61.33. Antifungal susceptibility of
Ochroconis
and
Verruconis
was linked with phylogenetic distance and thermotolerance. Echinocandins and POS showed the greatest
in vitro
activity, providing possible treatment options for
Ochroconis
and
Verruconis
infections.
Population Pharmacokinetic/Pharmacodynamic Analysis of the Bactericidal Activities of Sutezolid (PNU-100480) and Its Major Metabolite against Intracellular Mycobacterium tuberculosis in
Ex Vivo
Whole-Blood Cultures of Patients with Pulmonary Tuberculosis
Authors: Zhu Tong , Friedrich Sven O. , Diacon Andreas , Wallis Robert S.
Published: April 2014

Sutezolid (PNU-100480 [U-480]) is an oxazolidinone antimicrobial being developed for the treatment of tuberculosis. An active sulfoxide metabolite (PNU-101603 [U-603]), which reaches concentrations in plasma several times those of the parent, has been reported to drive the killing of extracellular
Mycobacterium tuberculosis
by sutezolid in hollow-fiber culture. However, the relative contributions of the parent and metabolite against intracellular
M. tuberculosis
in vivo
are not fully understood. The relationships between the plasma concentrations of U-480 and U-603 and intracellular whole-blood bactericidal activity (WBA) in
ex vivo
cultures were examined using a direct competitive population pharmacokinetic (PK)/pharmacodynamic 4-parameter sigmoid model. The data set included 690 PK determinations and 345 WBA determinations from 50 tuberculosis patients enrolled in a phase 2a sutezolid trial. The model parameters were solved iteratively. The median U-603/U-480 concentration ratio was 7.1 (range, 1 to 28). The apparent 50% inhibitory concentration of U-603 for intracellular
M. tuberculosis
was 17-fold greater than that of U-480 (90% confidence interval [CI], 9.9- to 53-fold). Model parameters were used to simulate
in vivo
activity after oral dosing with sutezolid at 600 mg twice a day (BID) and 1,200 mg once a day (QD). Divided dosing resulted in greater cumulative activity (−0.269 log
10
per day; 90% CI, −0.237 to −0.293 log
10
per day) than single daily dosing (−0.186 log
10
per day; 90% CI, −0.160 to −0.208 log
10
per day). U-480 accounted for 84% and 78% of the activity for BID and QD dosing, respectively, despite the higher concentrations of U-603. Killing of intracellular
M. tuberculosis
by orally administered sutezolid is mainly due to the activity of the parent compound. Taken together with the findings of other studies in the hollow-fiber model, these findings suggest that sutezolid and its metabolite act on different mycobacterial subpopulations.
Altered Pharmacokinetics of Piperacillin in Febrile Neutropenic Patients with Hematological Malignancy
Authors: Sime Fekade Bruck , Roberts Michael S. , Warner Morgyn S. , Hahn Uwe , Robertson Thomas A. , Yeend Sue , Phay Andy , Lehman Sheila , Lipman Jeffrey , Peake Sandra L. , Roberts Jason A.
Published: April 2014

This study assessed the pharmacokinetics and dosing adequacy of piperacillin in febrile neutropenic patients after the first dose. Pharmacokinetic analysis was performed using noncompartmental methods. We observed an elevated volume of distribution (29.7 ± 8.0 liters [mean ± standard deviation]) and clearance (20.2 ± 7.5 liters/h) compared to data from other patient populations. Antibiotic exposure did not consistently result in therapeutic targets. We conclude that alternative dosing strategies guided by therapeutic drug monitoring may be required to optimize exposure.
In Vitro
and
In Vivo
Activities of Tigecycline-Colistin Combination Therapies against Carbapenem-Resistant Enterobacteriaceae
Authors: Betts Jonathan W. , Phee Lynette M. , Hornsey Michael , Woodford Neil , Wareham David W.
Published: April 2014

We assessed the activity of tigecycline (TGC) combined with colistin (COL) against carbapenem-resistant enterobacteria. Synergy occurred
in vitro
against the majority of isolates, with the exception of
Serratia marcescens
. In a simple animal model (
Galleria mellonella
), TGC-COL was superior (
P
< 0.01) in treating
Escherichia coli
,
Klebsiella pneumoniae
, and
Enterobacter
infections, including those with TGC-COL resistance. Clinical studies are needed to determine whether TGC-COL regimens may be a viable option.
Role of Capsule and Suilysin in Mucosal Infection of Complement-Deficient Mice with Streptococcus suis
Authors: Seitz Maren , Beineke Andreas , Singpiel Alena , Willenborg Jörg , Dutow Pavel , Goethe Ralph , Valentin-Weigand Peter , Klos Andreas , Baums Christoph G.
Published: April 2014

Virulent
Streptococcus suis
serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against
S. suis
. Experimental infection of wild-type (WT) and C3
−/−
mice demonstrated for the first time that the complement system protects naive mice against invasive mucosal
S. suis
infection.
S. suis
WT but not an unencapsulated mutant caused mortality associated with meningitis and other pathologies in C3
−/−
mice. The capsule contributed also substantially to colonization of the upper respiratory tract. Experimental infection of C3
−/−
mice with a suilysin mutant indicated that suilysin expression facilitated an early disease onset and the pathogenesis of meningitis. Flow cytometric analysis revealed C3 antigen deposition on the surface of ca. 40% of
S. suis
WT bacteria after opsonization with naive WT mouse serum, although to a significantly lower intensity than on the unencapsulated mutant.
Ex vivo
multiplication in murine WT and C3
−/−
blood depended on capsule but not suilysin expression. Interestingly,
S. suis
invasion of inner organs was also detectable in C5aR
−/−
mice, suggesting that chemotaxis and activation of immune cells via the anaphylatoxin receptor C5aR is, in addition to opsonization, a further important function of the complement system in defense against mucosal
S. suis
infection. In conclusion, we unequivocally demonstrate here the importance of complement against mucosal
S. suis
serotype 2 infection and that the capsule of this pathogen is also involved in escape from complement-independent immunity.
Phosphoethanolamine Decoration of Neisseria gonorrhoeae Lipid A Plays a Dual Immunostimulatory and Protective Role during Experimental Genital Tract Infection
Authors: Packiam Mathanraj , Yedery Roshan D. , Begum Afrin A. , Carlson Russell W. , Ganguly Jhuma , Sempowski Gregory D. , Ventevogel Melissa S. , Shafer William M. , Jerse Ann E.
Published: April 2014

The induction of an intense inflammatory response by
Neisseria gonorrhoeae
and the persistence of this pathogen in the presence of innate effectors is a fascinating aspect of gonorrhea. Phosphoethanolamine (PEA) decoration of lipid A increases gonococcal resistance to complement-mediated bacteriolysis and cationic antimicrobial peptides (CAMPs), and recently we reported that wild-type
N. gonorrhoeae
strain FA1090 has a survival advantage relative to a PEA transferase A (
lptA
) mutant in the human urethral-challenge and murine lower genital tract infection models. Here we tested the immunostimulatory role of this lipid A modification. Purified lipooligosaccharide (LOS) containing lipid A devoid of the PEA modification and an
lptA
mutant of strain FA19 induced significantly lower levels of NF-κB in human embryonic kidney Toll-like receptor 4 (TLR4) cells and murine embryonic fibroblasts than wild-type LOS of the parent strain. Moreover, vaginal proinflammatory cytokines and chemokines were not elevated in female mice infected with the isogenic
lptA
mutant, in contrast to mice infected with the wild-type and complemented
lptA
mutant bacteria. We also demonstrated that
lptA
mutant bacteria were more susceptible to human and murine cathelicidins due to increased binding by these peptides and that the differential induction of NF-κB by wild-type and unmodified lipid A was more pronounced in the presence of CAMPs. This work demonstrates that PEA decoration of lipid A plays both protective and immunostimulatory roles and that host-derived CAMPs may further reduce the capacity of PEA-deficient lipid A to interact with TLR4 during infection.
ALOX12
in Human Toxoplasmosis
Authors: Witola William H. , Liu Susan Ruosu , Montpetit Alexandre , Welti Ruth , Hypolite Magali , Roth Mary , Zhou Ying , Mui Ernest , Cesbron-Delauw Marie-France , Fournie Gilbert J. , Cavailles Pierre , Bisanz Cordelia , Boyer Kenneth , Withers Shawn , Noble A. Gwendolyn , Swisher Charles N. , Heydemann Peter T. , Rabiah Peter , Muench Stephen P. , McLeod Rima
Published: April 2014

ALOX12
is a gene encoding arachidonate 12-lipoxygenase (12-LOX), a member of a nonheme lipoxygenase family of dioxygenases.
ALOX12
catalyzes the addition of oxygen to arachidonic acid, producing 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can be reduced to the eicosanoid 12-HETE (12-hydroxyeicosatetraenoic acid). 12-HETE acts in diverse cellular processes, including catecholamine synthesis, vasoconstriction, neuronal function, and inflammation. Consistent with effects on these fundamental mechanisms, allelic variants of
ALOX12
are associated with diseases including schizophrenia, atherosclerosis, and cancers, but the mechanisms have not been defined.
Toxoplasma gondii
is an apicomplexan parasite that causes morbidity and mortality and stimulates an innate and adaptive immune inflammatory reaction. Recently, it has been shown that a gene region known as
Toxo1
is critical for susceptibility or resistance to
T. gondii
infection in rats. An orthologous gene region with
ALOX12
centromeric is also present in humans. Here we report that the human
ALOX12
gene has susceptibility alleles for human congenital toxoplasmosis (rs6502997 [
P
, <0.000309], rs312462 [
P
, <0.028499], rs6502998 [
P
, <0.029794], and rs434473 [
P
, <0.038516]). A human monocytic cell line was genetically engineered using lentivirus RNA interference to knock down
ALOX12
. In
ALOX12
knockdown cells,
ALOX12
RNA expression decreased and levels of the
ALOX12
substrate, arachidonic acid, increased.
ALOX12
knockdown attenuated the progression of
T. gondii
infection and resulted in greater parasite burdens but decreased consequent late cell death of the human monocytic cell line. These findings suggest that
ALOX12
influences host responses to
T. gondii
infection in human cells.
ALOX12
has been shown in other studies to be important in numerous diseases. Here we demonstrate the critical role
ALOX12
plays in
T. gondii
infection in humans.
Inhibition of the Alternative Pathway of Nonhuman Infant Complement by Porin B2 Contributes to Virulence of Neisseria meningitidis in the Infant Rat Model
Authors: Lewis Lisa A. , Vu David M. , Granoff Dan M. , Ram Sanjay
Published: April 2014

Neisseria meningitidis
utilizes capsular polysaccharide, lipooligosaccharide (LOS) sialic acid, factor H binding protein (fHbp), and neisserial surface protein A (NspA) to regulate the alternative pathway (AP) of complement. Using meningococcal mutants that lacked all four of the above-mentioned molecules (quadruple mutants), we recently identified a role for PorB2 in attenuating the human AP; inhibition was mediated by human fH, a key downregulatory protein of the AP. Previous studies showed that fH downregulation of the AP via fHbp or NspA is specific for human fH. Here, we report that PorB2-expressing quadruple mutants also regulate the AP of baby rabbit and infant rat complement. Blocking a human fH binding region on PorB2 of the quadruple mutant of strain 4243 with a chimeric protein that comprised human fH domains 6 and 7 fused to murine IgG Fc enhanced AP-mediated baby rabbit C3 deposition, which provided evidence for an fH-dependent mechanism of nonhuman AP regulation by PorB2. Using isogenic mutants of strain H44/76 that differed only in their PorB molecules, we confirmed a role for PorB2 in resistance to killing by infant rat serum. The PorB2-expressing strain also caused higher levels of bacteremia in infant rats than its isogenic PorB3-expressing counterpart, thus providing a molecular basis for increased survival of PorB2 isolates in this model. These studies link PorB2 expression with infection of infant rats, which could inform the choice of meningococcal strains for use in animal models, and reveals, for the first time, that PorB2-expressing strains of
N. meningitidis
regulate the AP of baby rabbits and rats.
Phase Variation Mediates Reductions in Expression of Surface Proteins during Persistent Meningococcal Carriage
Authors: Alamro Mohamed , Bidmos Fadil A. , Chan Hannah , Oldfield Neil J. , Newton Emma , Bai Xilian , Aidley Jack , Care Rory , Mattick Claire , Turner David P. J. , Neal Keith R. , Ala'Aldeen Dlawer A. A. , Feavers Ian , Borrow Ray , Bayliss Christopher D.
Published: April 2014

Asymptomatic and persistent colonization of the upper respiratory tract by
Neisseria meningitidis
occurs despite elicitation of adaptive immune responses against surface antigens. A putative mechanism for facilitating host persistence of this bacterial commensal and pathogen is alterations in expression of surface antigens by simple sequence repeat (SSR)-mediated phase variation. We investigated how often phase variation occurs during persistent carriage by analyzing the SSRs of eight loci in multiple isolates from 21 carriers representative of 1 to 6 months carriage. Alterations in repeat number were detected by a GeneScan analysis and occurred at 0.06 mutations/gene/month of carriage. The expression states were determined by Western blotting and two genes,
fetA
and
nadA
, exhibited trends toward low expression states. A critical finding from our unique examination of combinatorial expression states, “phasotypes,” was for significant reductions in expression of multiple phase-variable surface proteins during persistent carriage of some strains. The immune responses in these carriers were examined by measuring variant-specific PorA IgG antibodies, capsular group Y IgG antibodies and serum bactericidal activity in concomitant serum samples. Persistent carriage was associated with high levels of specific IgG antibodies and serum bactericidal activity while recent strain acquisition correlated with a significant induction of antibodies. We conclude that phase-variable genes are driven into lower expression states during long-term persistent meningococcal carriage, in part due to continuous exposure to antibody-mediated selection, suggesting localized hypermutation has evolved to facilitate host persistence.
Fibronectin-Binding Protein of Borrelia hermsii Expressed in the Blood of Mice with Relapsing Fever
Authors: Lewis Eric R. G. , Marcsisin Renee A. , Campeau Miller Shelley A. , Hue Fong , Phillips April , AuCoin David P. , Barbour Alan G.
Published: April 2014

To identify and characterize surface proteins expressed by the relapsing fever (RF) agent
Borrelia hermsii
in the blood of infected mice, we used a cell-free filtrate of their blood to immunize congenic naive mice. The resultant antiserum was used for Western blotting of cell lysates, and gel slices corresponding to reactive bands were subjected to liquid chromatography-tandem mass spectrometry, followed by a search of the proteome database with the peptides. One of the immunogens was identified as the BHA007 protein, which is encoded by a 174-kb linear plasmid. BHA007 had sequence features of lipoproteins, was surface exposed by the criteria of
in situ
protease susceptibility and agglutination of Vtp
−
cells by anti-BHA007 antibodies, and was not essential for
in vitro
growth. BHA007 elicited antibodies during experimental infection of mice, but immunization with recombinant protein did not confer protection against needle-delivered infection. Open reading frames (ORFs) orthologous to BHA007 were found on large plasmids of other RF species, including the coding sequences for the CihC proteins of
Borrelia duttonii
and
B. recurrentis
, but not in Lyme disease
Borrelia
species. Recombinant BHA007 bound both human and bovine fibronectin with

K
d

(dissociation constant) values of 22 and 33 nM, respectively, and bound to C4-binding protein with less affinity. The distant homology of BHA007 and its orthologs to BBK32 proteins of Lyme disease species, as well as to previously described BBK32-like proteins in relapsing fever species, indicates that BHA007 is a member of a large family of multifunctional proteins in
Borrelia
species that bind to fibronectin as well as other host proteins.
Identification of Early Interactions between Francisella and the Host
Authors: Roberts Lydia M. , Tuladhar Shraddha , Steele Shaun P. , Riebe Kristina J. , Chen Ching-ju , Cumming R. Ian , Seay Sarah , Frothingham Richard , Sempowski Gregory D. , Kawula Thomas H. , Frelinger Jeffrey A.
Published: April 2014

The adaptive immune response to
Francisella tularensis
is dependent on the route of inoculation. Intradermal inoculation with the
F. tularensis
live vaccine strain (LVS) results in a robust Th1 response in the lungs, whereas intranasal inoculation produces fewer Th1 cells and instead many Th17 cells. Interestingly, bacterial loads in the lungs are similar early after inoculation by these two routes. We hypothesize that the adaptive immune response is influenced by local events in the lungs, such as the type of cells that are first infected with
Francisella
. Using fluorescence-activated cell sorting, we identified alveolar macrophages as the first cell type infected in the lungs of mice intranasally inoculated with
F. novicida
U112, LVS, or
F. tularensis
Schu S4. Following bacterial dissemination from the skin to the lung, interstitial macrophages or neutrophils are infected. Overall, we identified the early interactions between
Francisella
and the host following two different routes of inoculation.
Unusual sites for primary hydatid cysts: self experience with five cases
Authors: Attash Saad Muwafaq
Published: April 2014

Hydatid disease is a zoonotic disease caused by the tapewormEchinococcus granulosus. It is common in the sheep-raising countries including Iraq. The usual site for involvement is the liver, followed by the lungs. Other sites may be affected less commonly and require a high index of suspicion for diagnosis. We present our experience with five cases of unusual sites of primary hydatid cyst, including the pancreas, the abdominal wall, the spleen, the back and the thigh. Three patients were females and two patients were males; their ages were between 15 and 39 years. All the patients were operated at our centre, and after a period of follow-up ranging between 2 and 6 years, there was no reported recurrence in any of the patients, neither at the primary site nor at other sites.
Children reporting rescuing other children drowning in rural Bangladesh: a descriptive study
Authors: Mecrow Tom Stefan , Rahman Aminur , Linnan Michael , Scarr Justin , Mashreky Saidur Rahman , Talab Abu , Rahman A K M Fazlur
Published: April 2014

Background

SwimSafe, a basic swimming and safer rescue curriculum, has been taught to large numbers of Bangladeshi children since 2006. This study examines the frequency and characteristics of rescues reported by children who graduated from SwimSafe and compares them with age-matched and sex-matched children who did not participate in SwimSafe.

Methods

Interviews were conducted during the swimming season in Raiganj, Bangladesh. Data were collected from 3890 SwimSafe graduates aged 6–14. Two age-matched and sex-matched controls were selected; one who had learned to swim naturally, the other who had not learned to swim.

Results

188 rescues were reported by the three groups. The 12–14-year age groups reported the highest monthly rate of rescues (SwimSafe 10.5/100 000 (95% CI 3.4 to 24.5), natural swimmers 8.5/100 000 (95% CI 2.2 to 21.2)) and annual rate of rescue reported (SwimSafe 25.4/100 000 (95% CI 13.2 to 43.9), natural swimmers 35.4/100 000 (20.8 to 56.2)). Reported rescue numbers among both swimming groups was similar. Mean victim age was 4.1 years and 92.5% were under 7 years. All victims were younger than their rescuer (mean 5.9 years less). Most rescues (73.7%) took place in ponds or ditches with most (86.6%) within 10 m of the bank. Most victims had entered the water to bathe (53.8%). A large majority of reported rescues (90.9%) were conducted with the rescuer in the water, half requiring the rescuer to swim.

Conclusions

Children report frequent drowning rescues of younger children in rural Bangladesh. Most reported are contact rescues with the rescuer in the water. Formal training for in-water rescue techniques may be needed to reduce the risk to the child rescuer.
Significance of oestrogen-related receptor γ on biliary epithelial cells in the pathogenesis of primary biliary cirrhosis
Authors: Harada Kenichi , Yuko Kakuda , Sato Yasunori , Ikeda Hiroko , Nakanuma Yasuni
Published: April 2014

Aims

Oestrogen has been speculated to play an important role in the pathogenesis of primary biliary cirrhosis (PBC), which mainly affects middle-aged and old-aged females because biliary epithelial cells (BECs) are known to express oestrogen receptors (ERs). Oestrogen-related receptors (ERRs) are constitutively active without oestrogen and competitively inhibit the ER-dependent effects of oestrogen. We clarified the effects of oestrogen and the significance of ERRs along with their association with the pathogenesis of cholangiopathy in PBC.

Methods

We investigated the expression of ERs and ERRs and the apoptosis-related cell kinetics in BECs using cultured human BECs and human liver specimens.

Results

Although cultured human BECs and the interlobular bile ducts in the liver expressed ERβ, in cultured BECs, oestrogen treatment did not induce significant cell proliferation but increased the expression of a negative cell proliferation regulator (14-3-3σ protein). The cultured BECs constantly expressed ERRα and ERRγ, and oestrogen downregulated the ERRγ expression. Furthermore, the ERRγ expression was determined in the intrahepatic bile ducts and was stronger in the middle-aged and old-aged females, particularly those with PBC, than in the younger females. The ERRγ ligand activated a transcription factor, SP1, and enhanced the expression of the pro-apoptotic Bcl-2 family molecules and Bcl-2 inhibitor-induced apoptosis in cultured BECs.

Conclusions

Although oestrogen downregulates the ERRγ expression, the increased ERRγ expression under oestrogen-deficient conditions increases the susceptibility to Bcl-2 family-mediated apoptosis in cultured human BECs of females, particularly those with PBC. Understanding the oestrogen-mediated cell kinetics is important for elucidating the pathogenesis of cholangiopathy in PBC.
Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis of Health Survey for England data
Authors: Oyebode Oyinlola , Gordon-Dseagu Vanessa , Walker Alice , Mindell Jennifer S
Published: April 2014

Background

Governments worldwide recommend daily consumption of fruit and vegetables. We examine whether this benefits health in the general population of England.

Methods

Cox regression was used to estimate HRs and 95% CI for an association between fruit and vegetable consumption and all-cause, cancer and cardiovascular mortality, adjusting for age, sex, social class, education, BMI, alcohol consumption and physical activity, in 65 226 participants aged 35+ years in the 2001–2008 Health Surveys for England, annual surveys of nationally representative random samples of the non-institutionalised population of England linked to mortality data (median follow-up: 7.7 years).

Results

Fruit and vegetable consumption was associated with decreased all-cause mortality (adjusted HR for 7+ portions 0.67 (95% CI 0.58 to 0.78), reference category <1 portion). This association was more pronounced when excluding deaths within a year of baseline (0.58 (0.46 to 0.71)). Fruit and vegetable consumption was associated with reduced cancer (0.75 (0.59–0.96)) and cardiovascular mortality (0.69 (0.53 to 0.88)). Vegetables may have a stronger association with mortality than fruit (HR for 2 to 3 portions 0.81 (0.73 to 0.89) and 0.90 (0.82 to 0.98), respectively). Consumption of vegetables (0.85 (0.81 to 0.89) per portion) or salad (0.87 (0.82 to 0.92) per portion) were most protective, while frozen/canned fruit consumption was apparently associated with increased mortality (1.17 (1.07 to 1.28) per portion).

Conclusions

A robust inverse association exists between fruit and vegetable consumption and mortality, with benefits seen in up to 7+ portions daily. Further investigations into the effects of different types of fruit and vegetables are warranted.
Daylight savings time and myocardial infarction
Authors: Sandhu Amneet , Seth Milan , Gurm Hitinder S
Published: April 2014

Background

Prior research has shown a transient increase in the incidence of acute myocardial infarction (AMI) after daylight savings time (DST) in the spring as well as a decrease in AMI after returning to standard time in the fall. These findings have not been verified in a broader population and if extant, may have significant public health and policy implications.

Methods

We assessed changes in admissions for AMI undergoing percutaneous coronary intervention (PCI) in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) database for the weeks following the four spring and three fall DST changes between March 2010 and September 2013. A negative binomial regression model was used to adjust for trend and seasonal variation.

Results

There was no difference in the total weekly number of PCIs performed for AMI for either the fall or spring time changes in the time period analysed. After adjustment for trend and seasonal effects, the Monday following spring time changes was associated with a 24% increase in daily AMI counts (p=0.011), and the Tuesday following fall changes was conversely associated with a 21% reduction (p=0.044). No other weekdays in the weeks following DST changes demonstrated significant associations.

Conclusions

In the week following the seasonal time change, DST impacts the timing of presentations for AMI but does not influence the overall incidence of this disease.
Variations in the effects of local foliar damage on life span of individual leaves of downy birch (Betula pubescens)
Authors: Kozlov Mikhail V. , Zvereva Elena L.
Published: April 2014

Although the premature abscission of leaves damaged by herbivores has been discovered decades ago, the reduction in leaf life span caused by herbivory remains poorly documented, and the sources of variation in the magnitude of this effect have only rarely been studied. We aimed at exploring the effects of several herbivore species (at their background densities) and simulated herbivory on the leaf life span of downy birch, Betula pubescens Ehrh. Leaves damaged by herbivores abscised on average 12.6 days earlier and punched leaves 3.5 days earlier than the intact leaves of the control shoots. Different herbivores reduced the life span of the birch leaves from 0% to 27% depending on the intensity and timing of the damage but not on the insect feeding guild. The reduction in leaf life span was greater when the damage was imposed on expanding and growing leaves compared with mature leaves. However, the effect of herbivore species remained significant after accounting for intensity and timing of damage. This fact, together with greater reduction in leaf life span due to natural herbivory compared with mechanical damage, indicates that premature abscission in response to injury is considerably enhanced by insect-specific elicitors.
Jumping behaviour for a wheeled quadruped robot: simulation and experiments
Authors: Harmat Adam , Trentini Michael , Sharf Inna
Published: April 2014

In this paper, we describe a new jumping behaviour developed for the quadruped robot, PAW (Platform for Ambulating Wheels). The robot has very few degrees of freedom and no knee joints. It employs springy legs and wheels at the distal ends of the legs to achieve various modes of legged, wheeled, and hybrid locomotion, such as high-speed breaking, bounding, and presently jumping. The jumping maneuver developed in this manuscript is designed specifically to take advantage of the wheels on the robot and compliance in its legs and it involves the following principal stages: acceleration to jumping speed, body positioning via front hip thrusting, rear leg compression and thrusting, and flight. A high-fidelity MSC.ADAMS/Simulink co-simulation was developed and used to test and optimize the jumping process. Because of the strong coupling between the parameters defining the jump maneuver, manual parameter tuning is difficult and thus a genetic algorithm is employed for the optimization process. The data generated by the genetic algorithm is further used for the fitting of a quadratic response surface, which allows identifying those parameters that contribute most to a successful jump. Finally, the jumping maneuver is implemented on the physical PAW to demonstrate its feasibility on a hybrid quadruped, and to provide insights into the robot response during this highly dynamic maneuver.