bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the Lizard Teira dugesii as a Potential Host for Ixodes ricinus Tick-Borne Pathogens
Authors: De Sousa R. , de Carvalho I. Lopes , Santos A. S. , Bernardes C. , Milhano N. , Jesus J. , Menezes D. , Núncio M. S.
Published: March 2012

PCR screening of ticks and tissue samples collected from 151
Teira dugesii
lizards seems to indicate a potential role of this lizard species in the maintenance and transmission cycle of some
Ixodes ricinus
tick-borne agents, such as
Rickettsia monacensis
,
Rickettsia helvetica
, and
Borrelia lusitaniae
, that are circulating on Madeira Island.
Histone H3 Variants in Trichomonas vaginalis
Authors: Zubáčová Zuzana , Hostomská Jitka , Tachezy Jan
Published: March 2012

The parabasalid protist
Trichomonas vaginalis
is a widespread parasite that affects humans, frequently causing vaginitis in infected women. Trichomonad mitosis is marked by the persistence of the nuclear membrane and the presence of an asymmetric extranuclear spindle with no obvious direct connection to the chromosomes. No centromeric markers have been described in
T. vaginalis
, which has prevented a detailed analysis of mitotic events in this organism. In other eukaryotes, nucleosomes of centromeric chromatin contain the histone H3 variant CenH3. The principal aim of this work was to identify a CenH3 homolog in
T. vaginalis
. We performed a screen of the
T. vaginalis
genome to retrieve sequences of canonical and variant H3 histones. Three variant histone H3 proteins were identified, and the subcellular localization of their epitope-tagged variants was determined. The localization of the variant TVAG_185390 could not be distinguished from that of the canonical H3 histone. The sequence of the variant TVAG_087830 closely resembled that of histone H3. The tagged protein colocalized with sites of active transcription, indicating that the variant TVAG_087830 represented H3.3 in
T. vaginalis
. The third H3 variant (TVAG_224460) was localized to 6 or 12 distinct spots at the periphery of the nucleus, corresponding to the number of chromosomes in G
1
phase and G
2
phase, respectively. We propose that this variant represents the centromeric marker CenH3 and thus can be employed as a tool to study mitosis in
T. vaginalis
. Furthermore, we suggest that the peripheral distribution of CenH3 within the nucleus results from the association of centromeres with the nuclear envelope throughout the cell cycle.
Motor Protein Myo5p Is Required To Maintain the Regulatory Circuit Controlling
WOR1
Expression in Candida albicans
Authors: Kachurina Nadezda , Turcotte Bernard , Whiteway Malcolm
Published: March 2012

The
Candida albicans MYO5
gene encodes myosin I, a protein required for the formation of germ tubes and true hyphae. Because the polarized growth of opaque-phase cells in response to pheromone results in mating projections that can resemble germ tubes, we examined the role of Myo5p in this process. We localized green fluorescent protein (GFP)-tagged Myo5p in opaque-phase cells of
C. albicans
during both bud and shmoo formation. In vegetatively growing opaque cells, Myo5p is found at sites of bud emergence and bud growth, while in pheromone-stimulated cells, Myo5p localizes at the growing tips of shmoos. Intriguingly, cells homozygous for
MTL
a
in which the
MYO5
gene was deleted failed to switch efficiently from the white phase to the opaque phase, although ectopic expression of
WOR1
from the
MET3
promoter can convert
myo5
mutants into mating-competent opaque cells. However, when
WOR1
expression was shut off, the
myo5
-defective cells rapidly lost both their opaque phenotype and mating competence, suggesting that Myo5p is involved in the maintenance of the opaque state. When
MYO5
is expressed conditionally in opaque cells, the opaque phenotype, as well as the mating ability of the cells, becomes unstable under repressive conditions, and quantitative real-time PCR demonstrated that the shutoff of
MYO5
expression correlates with a dramatic reduction in
WOR1
expression. It appears that while myosin I is not directly required for mating in
C. albicans
, it is involved in
WOR1
expression and the white-opaque transition and thus is indirectly implicated in mating.
The Arthroderma benhamiae Hydrophobin HypA Mediates Hydrophobicity and Influences Recognition by Human Immune Effector Cells
Authors: Heddergott Christoph , Bruns Sandra , Nietzsche Sandor , Leonhardt Ines , Kurzai Oliver , Kniemeyer Olaf , Brakhage Axel A.
Published: March 2012

Dermatophytes are the most common cause of superficial mycoses in humans and animals. They can coexist with their hosts for many years without causing significant symptoms but also cause highly inflammatory diseases. To identify mechanisms involved in the modulation of the host response during infection caused by the zoophilic dermatophyte
Arthroderma benhamiae
, cell wall-associated surface proteins were studied. By two-dimensional gel electrophoresis, we found that a hydrophobin protein designated HypA was the dominant cell surface protein. HypA was also detected in the supernatant during the growth and conidiation of the fungus. The
A. benhamiae
genome harbors only a single hydrophobin gene, designated
hypA
. A
hypA
deletion mutant was generated, as was a complemented
hypA
mutant strain (
hypA
C
). In contrast to the wild type and the complemented strain, the
hypA
deletion mutant exhibited “easily wettable” mycelia and conidia, indicating the loss of surface hydrophobicity of both morphotypes. Compared with the wild type, the
hypA
deletion mutant triggered an increased activation of human neutrophil granulocytes and dendritic cells, characterized by an increased release of the immune mediators interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor alpha (TNF-α). For the first time, we observed the formation of neutrophil extracellular traps against dermatophytes, whose level of formation was increased by the Δ
hypA
mutant compared with the wild type. Furthermore, conidia of the Δ
hypA
strain were killed more effectively by neutrophils. Our data suggest that the recognition of
A. benhamiae
by the cellular immune defense system is notably influenced by the presence of the surface rodlet layer formed by the hydrophobin HypA.
The LovK-LovR Two-Component System Is a Regulator of the General Stress Pathway in Caulobacter crescentus
Authors: Foreman Robert , Fiebig Aretha , Crosson Sean
Published: March 2012

A conserved set of regulators control the general stress response in
Caulobacter crescentus
, including σ
T
, its anti-σ factor NepR, the anti-anti-σ factor PhyR, and the transmembrane sensor kinase PhyK. We report that the soluble histidine kinase LovK and the single-domain response regulator LovR also function within the
C. crescentus
general stress pathway. Our genetic data support a model in which LovK-LovR functions upstream of σ
T
by controlling the phosphorylation state and thus anti-anti-σ activity of PhyR. Transcription of
lovK
and
lovR
is independently activated by stress through a mechanism that requires
sigT
and
phyR
. Conversely,
lovK
and
lovR
function together to repress transcription of the general stress regulon. Concordant with a functional role of the LovK-LovR two-component system as a negative regulator of the general stress pathway,
lovK
-
lovR
-null mutants exhibit increased cell survival after osmotic stress, while coordinate overexpression of
lovK
and
lovR
attenuates cell survival relative to that of the wild type. Notably,
lovK
can complement the transcriptional and cell survival defects of a
phyK
-null mutant when
lovR
is deleted. Moreover, in this same genetic background, σ
T
-dependent transcription is activated in response to osmotic stress. This result suggests that flavin-binding LOV (light, oxygen, or voltage) histidine kinases are competent to perceive cytoplasmic signals in addition to the environmental signal blue light. We conclude that the PhyK-PhyR and LovK-LovR two-component signaling systems coordinately regulate stress physiology in
C. crescentus
.
A retrospective analysis of cervical spine radiography in a specialist trauma unit for head injury
Authors: Baneke Alex Jan , Shafei Rachelle , Costello Jonathan
Published: March 2012

Objectives

The performance of an adequate and complete series of cervical radiographs in the trauma patient is essential in order to ensure safe trauma management. Eastern Association for the Surgery of Trauma (EAST) has produced widely recognised guidelines with which trauma units should comply. The aim of the study is to ascertain the adequacy of cervical spine imaging of trauma patients in a specialist trauma unit (head injury) using EAST guidelines as gold standard. An additional assessment of institutional reporting accuracy is conducted.

Methods

Data were examined from 81 consecutive trauma patients requiring cervical spine radiography. EAST guidelines were applied retrospectively to this cohort in order to define guideline compliance. An additional cohort assessment was conducted addressing the accuracy and adequacy of the formal institutional reports associated with these radiographs.

Results

99% of patients undergoing a full cervical trauma series had at least one inadequate initial image. Of these, 85% had at least one inadequate lateral or peg view (of which 26% did not have repeat radiographs performed). Over one-third of all trauma patients left the emergency department with inadequate cervical spine imaging (incomplete cervical spine series or inadequate films). From the institutional reporting perspective, only 27% of all inadequate initial and repeat lateral or peg views were subsequently explicitly reported as being inadequate.

Discussion

These findings call into question current practice. Clearly, multiple confounders exist in the context of process variability in a heterogeneous population such as that attending an emergency department. This study offer solutions to address this problem.
Acute embolization of ruptured brain arteriovenous malformations
Authors: Stemer Andrew B , Bank William O , Armonda Rocco A , Liu Ai-Hsi , Herzig David W , Bell Randy S
Published: March 2012

Background

Ruptured brain arteriovenous malformations (bAVMs) are at increased risk of re-hemorrhage but management has historically been conservative. This is because: (1) ruptured bAVMs have not been considered as catastrophic as ruptured cerebral aneurysms, (2) surgical resection is aided by waiting for brain edema to resolve and clot to liquefy and (3) fear exists that partially treated bAVMs may be more dangerous than those untreated. The purpose of this study was to determine the feasibility and safety of acute embolization in patients with ruptured bAVMs.

Methods

21 consecutive patients who underwent acute embolization of ruptured bAVMs from 2007 to 2011 were retrospectively reviewed. All treatments consisted of embolization exclusively using Onyx liquid embolic agent. Neurological outcomes were assessed using the Glasgow Outcome Scale (GOS) at hospital discharge following initial treatment.

Results

Nine patients (43%) were male, mean age was 38 years (range 8–75) and initial embolization was performed at a median of 4 days after ictus (mean 5.8, range 0–19). Spetzler–Martin grades ranged from I to VI (mean 3, median 3). In seven patients (33%) the AVM was completely occluded with a single treatment. With subsequent embolizations, complete occlusion occurred in four additional patients (19%). Six patients (29%) had post-embolization AVM resection and one patient (5%) had post-embolization gamma knife irradiation. None has suffered subsequent hemorrhages (mean follow-up 7.5 months). The mean discharge GOS of all patients was 4.4 (range 1–5).

Conclusion

Treatment of ruptured bAVMs is often delayed but our experience with Onyx suggests that acute embolization is safe and feasible.
The challenges of stem cell therapy
Authors: Di Nardo Paolo , Singla Dinender , Li Ren-Ke
Published: March 2012

The actual repairing power of stem cells has yet to be fully realized because of insufficient knowledge about the basic mechanisms regulating their fate and unsuitable protocols to implant them in injured tissues. Novel strategies must be formulated to fully exploit stem cell potential in the clinical setting.
Transcription factor CHF1/Hey2 regulates EC coupling and heart failure in mice through regulation of FKBP12.6
Authors: Liu Yonggang , Korte F. Steven , Moussavi-Harami Farid , Yu Man , Razumova Maria , Regnier Michael , Chin Michael T.
Published: March 2012

Heart failure is a leading cause of morbidity and mortality in Western society. The cardiovascular transcription factor CHF1/Hey2 has been linked to experimental heart failure in mice, but the mechanisms by which it regulates myocardial function remain incompletely understood. The objective of this study was to determine how CHF1/Hey2 affects development of heart failure through examination of contractility in a myocardial knockout mouse model. We generated myocardial-specific knockout mice. At baseline, cardiac function was normal, but, after aortic banding, the conditional knockout mice demonstrated a greater increase in ventricular weight-to-body weight ratio compared with control mice (5.526 vs. 4.664 mg/g) and a significantly decreased ejection fraction (47.8 vs. 72.0% control). Isolated cardiac myocytes from these mice showed decreased calcium transients and fractional shortening after electrical stimulation. To determine the molecular basis for these alterations in excitation-contraction coupling, we first measured total sarcoplasmic reticulum calcium stores and calcium-dependent force generation in isolated muscle fibers, which were normal, suggesting a defect in calcium cycling. Analysis of gene expression demonstrated normal expression of most genes known to be involved in myocardial calcium cycling, with the exception of the ryanodine receptor binding protein FKBP12.6, which was expressed at increased levels in the conditional knockout hearts. Treatment of the isolated knockout myocytes with FK506, which inhibits the association of FKBP12.6 with the ryanodine receptor, restored contractile function. These findings demonstrate that conditional deletion of CHF1/Hey2 in the myocardium leads to abnormalities in calcium handling mediated by FKBP12.6 that predispose to pressure overload-induced heart failure.
O-GlcNAc signaling is essential for NFAT-mediated transcriptional reprogramming during cardiomyocyte hypertrophy
Authors: Facundo Heberty T. , Brainard Robert E. , Watson Lewis J. , Ngoh Gladys A. , Hamid Tariq , Prabhu Sumanth D. , Jones Steven P.
Published: March 2012

The regulation of cardiomyocyte hypertrophy is a complex interplay among many known and unknown processes. One specific pathway involves the phosphatase calcineurin, which regulates nuclear translocation of the essential cardiac hypertrophy transcription factor, nuclear factor of activated T-cells (NFAT). Although metabolic dysregulation is frequently described during cardiac hypertrophy, limited insights exist regarding various accessory pathways. One metabolically derived signal, beta-O-linked N-acetylglucosamine (O-GlcNAc), has emerged as a highly dynamic posttranslational modification of serine and threonine residues regulating physiological and stress processes. Given the metabolic dysregulation during hypertrophy, we hypothesized that NFAT activation is dependent on O-GlcNAc signaling. Pressure overload-induced hypertrophy (via transverse aortic constriction) in mice or treatment of neonatal rat cardiac myocytes with phenylephrine significantly enhanced global O-GlcNAc signaling. NFAT-luciferase reporter activity revealed O-GlcNAc-dependent NFAT activation during hypertrophy. Reversal of enhanced O-GlcNAc signaling blunted cardiomyocyte NFAT-induced changes during hypertrophy. Taken together, these results demonstrate a critical role of O-GlcNAc signaling in NFAT activation during hypertrophy and provide evidence that O-GlcNAc signaling is coordinated with the onset and progression of cardiac hypertrophy. This represents a potentially significant and novel mechanism of cardiac hypertrophy, which may be of particular interest in future in vivo studies of hypertrophy.
Differential effects of high-fat diet on myocardial lipid metabolism in failing and nonfailing hearts with angiotensin II-mediated cardiac remodeling in mice
Authors: Pellieux Corinne , Montessuit Christophe , Papageorgiou Irène , Pedrazzini Thierry , Lerch René
Published: March 2012

Normal myocardium adapts to increase of nutritional fatty acid supply by upregulation of regulatory proteins of the fatty acid oxidation pathway. Because advanced heart failure is associated with reduction of regulatory proteins of fatty acid oxidation, we hypothesized that failing myocardium may not be able to adapt to increased fatty acid intake and therefore undergo lipid accumulation, potentially aggravating myocardial dysfunction. We determined the effect of high-fat diet in transgenic mice with overexpression of angiotensinogen in the myocardium (TG1306/R1). TG1306/R1 mice develop ANG II-mediated left ventricular hypertrophy, and at one year of age approximately half of the mice present heart failure associated with reduced expression of regulatory proteins of fatty acid oxidation and reduced palmitate oxidation during ex vivo working heart perfusion. Hypertrophied hearts from TG1306/R1 mice without heart failure adapted to high-fat feeding, similarly to hearts from wild-type mice, with upregulation of regulatory proteins of fatty acid oxidation and enhancement of palmitate oxidation. There was no myocardial lipid accumulation or contractile dysfunction. In contrast, hearts from TG1306/R1 mice presenting heart failure were unable to respond to high-fat feeding by upregulation of fatty acid oxidation proteins and enhancement of palmitate oxidation. This resulted in accumulation of triglycerides and ceramide in the myocardium, and aggravation of contractile dysfunction. In conclusion, hearts with ANG II-induced contractile failure have lost the ability to enhance fatty acid oxidation in response to increased fatty acid supply. The ensuing accumulation of lipid compounds may play a role in the observed aggravation of contractile dysfunction.
Ras dexamethasone-induced protein 1 is a modulator of hormone secretion in the volume overloaded heart
Authors: McGrath Monica Forero , Ogawa Tsuneo , de Bold Adolfo J.
Published: March 2012

Because of the crucial role of the endocrine heart in maintaining homeostasis, considerable effort has been focused on the elucidation of the mechanistic underlying gene expression and secretion of the cardiac hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). However, much remains to be determined regarding specific molecular events involved in cardiocyte secretory function. In this work, we identified genes involved in the transcriptional response of the endocrine heart to volume overload (VO) and signaling pathways involved in its regulation. To this end, the cardiac atrial and ventricular transcriptomes were analyzed in the heart of rats subjected to experimentally induced aorto-caval shunt VO. Pathway analysis revealed unique gene expression profiles in the VO atria for G-protein signaling, notably a significant downregulation of Ras dexamethasone-induced protein 1 (RASD1). In vitro, knockdown of RASD1 in the atrial-derived HL-1 cells, significantly increased ANF secretion. Concurrent knockdown of RASD1 and its effectors Gαo1or Gβ1γ2abrogated the endocrine response, demonstrating a previously unknown negative modulator role for RASD1. RASD1 thus emerges as a tonic inhibitor of ANF secretion and illustrates for the first time the concept of inhibitory protein regulators of ANF release. The novel molecular function identified herein for RASD1 is of considerable importance given its therapeutic implications for cardiovascular disease.
Congenital heart disease and the specification of left-right asymmetry
Authors: Francis Richard J. B. , Christopher Adam , Devine William A. , Ostrowski Lawrence , Lo Cecilia
Published: March 2012

Complex congenital heart disease (CHD) is often seen in conjunction with heterotaxy, the randomization of left-right visceral organ situs. However, the link between cardiovascular morphogenesis and left-right patterning is not well understood. To elucidate the role of left-right patterning in cardiovascular development, we examined situs anomalies and CHD in mice with a loss of function allele of Dnaic1, a dynein protein required for motile cilia function and left-right patterning. Dnaic1 mutants were found to have nodal cilia required for left-right patterning, but they were immotile. Half the mutants had concordant organ situs comprising situs solitus or mirror symmetric situs inversus. The remaining half had randomized organ situs or heterotaxy. Looping of the heart tube, the first anatomical lateralization, showed abnormal L-loop bias rather than the expected D-loop orientation in heterotaxy and nonheterotaxy mutants. Situs solitus/inversus mutants were viable with mild or no defects consisting of azygos continuation and/or ventricular septal defects, whereas all heterotaxy mutants had complex CHD. In heterotaxy mutants, but not situs solitus/inversus mutants, the morphological left ventricle was thin and often associated with a hypoplastic transverse aortic arch. Thus, in conclusion, Dnaic1 mutants can achieve situs solitus or inversus even with immotile nodal cilia. However, the finding of abnormal L-loop bias in heterotaxy and nonheterotaxy mutants would suggest motile cilia are required for normal heart looping. Based on these findings, we propose motile nodal cilia patterns heart looping but heart and visceral organ lateralization is driven by signaling not requiring nodal cilia motility.
Sympathetic neural responses to 24-hour sleep deprivation in humans: sex differences
Authors: Carter Jason R. , Durocher John J. , Larson Robert A. , DellaValla Joseph P. , Yang Huan
Published: March 2012

Sleep deprivation has been linked to hypertension, and recent evidence suggests that associations between short sleep duration and hypertension are stronger in women. In the present study we hypothesized that 24 h of total sleep deprivation (TSD) would elicit an augmented pressor and sympathetic neural response in women compared with men. Resting heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were measured in 30 healthy subjects (age, 22 ± 1; 15 men and 15 women). Relations between spontaneous fluctuations of diastolic arterial pressure and MSNA were used to assess sympathetic baroreflex function. Subjects were studied twice, once after normal sleep and once after TSD (randomized, crossover design). TSD elicited similar increases in systolic, diastolic, and mean BP in men and women (time, P < 0.05; time × sex, P > 0.05). TSD reduced MSNA in men (25 ± 2 to 16 ± 3 bursts/100 heart beats; P = 0.02), but not women. TSD did not alter spontaneous sympathetic or cardiovagal baroreflex sensitivities in either sex. However, TSD shifted the spontaneous sympathetic baroreflex operating point downward and rightward in men only. TSD reduced testosterone in men, and these changes were correlated to changes in resting MSNA ( r = 0.59; P = 0.04). Resting HR, respiratory rate, and estradiol were not altered by TSD in either sex. In conclusion, TSD-induced hypertension occurs in both sexes, but only men demonstrate altered resting MSNA. The sex differences in MSNA are associated with sex differences in sympathetic baroreflex function (i.e., operating point) and testosterone. These findings may help explain why associations between sleep deprivation and hypertension appear to be sex dependent.
Use of endogenous NADH fluorescence for real-time in situ visualization of epicardial radiofrequency ablation lesions and gaps
Authors: Mercader Marco , Swift Luther , Sood Sumit , Asfour Huda , Kay Matthew , Sarvazyan Narine
Published: March 2012

Radiofrequency ablation (RFA) aims to produce lesions that interrupt reentrant circuits or block the spread of electrical activation from sites of abnormal activity. Today, there are limited means for real-time visualization of cardiac muscle tissue injury during RFA procedures. We hypothesized that the fluorescence of endogenous NADH could be used as a marker of cardiac muscle injury during epicardial RFA procedures. Studies were conducted in blood-free and blood-perfused hearts from healthy adult Sprague-Dawley rats and New Zealand rabbits. Radiofrequency was applied to the epicardial surface of the heart using a 4-mm standard blazer ablation catheter. A dual camera optical mapping system was used to monitor NADH fluorescence upon ultraviolet illumination of the epicardial surface and to record optical action potentials using the voltage-sensitive probe RH237. Epicardial lesions were seen as areas of low NADH fluorescence. The lesions appeared immediately after ablation and remained stable for several hours. Real-time monitoring of NADH fluorescence allowed visualization of viable tissue between the RFA lesions. Dual recordings of NADH and epicardial electrical activity linked the gaps between lesions to postablation reentries. We found that the fluorescence of endogenous NADH aids the visualization of injured epicardial tissue caused by RFA. This was true for both blood-free and blood-perfused preparations. Gaps between NADH-negative regions revealed unablated tissue, which may promote postablation reentry or provide pathways for the conduction of abnormal electrical activity.
Kocher-Debre-Semelaigne Syndrome: Hypothyroid Muscular Pseudohypertrophy—A Rare Report of Two Cases
Authors: Shaw Chandan , Shaw Prachi
Published: March 2012

Kocher-Debre-Semelaigne syndrome (KDSS) is a rare association of muscular pseudohypertrophy and long-standing moderate-to-severe hypothyroidism in the pediatric age group. It may be confused with primary muscle disorders, lest one is cautious enough to investigate for hypothyroidism. The striking clinical features, availability of a simple treatment and a good prognosis for the condition makes it worthwhile to report the case so that all practitioners be aware of the condition and its management.
A Paratransgenic Strategy for the Control of Chagas Disease
Authors: Hurwitz Ivy , Fieck Annabeth , Klein Nichole , Jose Christo , Kang Angray , Durvasula Ravi
Published: March 2012

Chagas disease results from infection with the parasiteTrypanosoma cruzi. This disease remains a significant cause of morbidity and mortality in central and south America. Chagas disease now exists and is detected worldwide because of human migration. Control of Chagas disease has relied mainly on vector eradication however, the development of insect resistance to pesticides, coupled with cost and adverse health effects of insecticide treatments, has prompted our group to investigate novel methods of transmission control. Our laboratory has been instrumental in the development of the paratransgenic strategy to control vectorial transmission ofT. cruzi. In this paper, we discuss various components of the paratransgenic approach. Specifically, we describe classes of molecules that can serve as effectors, including antimicrobial peptides, endoglucanases, and highly specific single chain antibodies that target surface glycoprotein tags on the surface ofT. cruzi. Furthermore, we address evolving concepts related to field dispersal of engineered bacteria as part of the paratransgenic control strategy and attendant risk assessment evaluation.
Interactions among Carbon Dioxide, Heat, and Chemical Lures in Attracting the Bed Bug,Cimex lectulariusL. (Hemiptera: Cimicidae)
Authors: Singh Narinderpal , Wang Changlu , Cooper Richard , Liu Chaofeng
Published: March 2012

Commercial bed bug (Cimex lectulariusL.) monitors incorporating carbon dioxide (CO2), heat, and chemical lures are being used for detecting bed bugs; however, there are few reported studies on the effectiveness of chemical lures in bed bug monitors and the interactions among chemical lure, CO2, and heat. We screened 12 chemicals for their attraction to bed bugs and evaluated interactions among chemical lures, CO2, and heat. The chemical lure mixture consisting of nonanal, 1-octen-3-ol, spearmint oil, and coriander Egyptian oil was found to be most attractive to bed bugs and significantly increased the trap catches in laboratory bioassays. Adding this chemical lure mixture when CO2was present increased the trap catches compared with traps baited with CO2alone, whereas adding heat did not significantly increase trap catches when CO2was present. Results suggest a combination of chemical lure and CO2is essential for designing effective bed bug monitors.
Modulation of Apoptosis Pathways by Oxidative Stress and Autophagy in β Cells
Authors: Wang Maorong , Crager Mia , Pugazhenthi Subbiah
Published: March 2012

Human islets isolated for transplantation are exposed to multiple stresses including oxidative stress and hypoxia resulting in significant loss of functional β cell mass. In this study we examined the modulation of apoptosis pathway genes in islets exposed to hydrogen peroxide, peroxynitrite, hypoxia, and cytokines. We observed parallel induction of pro- and antiapoptotic pathways and identified several novel genes including BFAR, CARD8, BNIP3, and CIDE-A. As BNIP3 is an inducer of autophagy, we examined this pathway in MIN6 cells, a mouse beta cell line and in human islets. Culture of MIN6 cells under low serum conditions increased the levels of several proteins in autophagy pathway, including ATG4, Beclin 1, LAMP-2, and UVRAG. Amino acid deprivation led to induction of autophagy in human islets. Preconditioning of islets with inducers of autophagy protected them from hypoxia-induced apoptosis. However, induction of autophagy during hypoxia exacerbated apoptotic cell death. ER stress led to induction of autophagy and apoptosis in β cells. Overexpression of MnSOD, an enzyme that scavenges free radicals, resulted in protection of MIN6 cells from cytokine-induced apoptosis. Ceramide, a mediator of cytokine-induced injury, reduced the active phosphorylated form of Akt and downregulated the promoter activity of the antiapoptotic gene bcl-2. Furthermore, cytokine-stimulated JNK pathway downregulated the bcl-2 promoter activity which was reversed by preincubation with SP600125, a JNK inhibitor. Our findings suggest that β cell apoptosis by multiple stresses in islets isolated for transplantation is the result of orchestrated gene expression in apoptosis pathway.
Tumor Angiogenesis Mediated by Myeloid Cells Is Negatively Regulated by CEACAM1
Authors: Lu Rongze , Kujawski Maciej , Pan Hao , Shively John E.
Published: March 2012

Bv8 (prokineticin 2) expressed by Gr1+CD11b+ myeloid cells is critical for VEGF-independent tumor angiogenesis. Although granulocyte colony-stimulating factor (G-CSF) has been shown to be a key inducer of Bv8 expression, the basis for Bv8 production in driving tumor angiogenesis is undefined. Because the cell adhesion molecule CEACAM1, which is highly expressed on Gr1+CD11b+ myeloid cells, is known to regulate G-CSF receptor (G-CSFR) signaling, we hypothesized that CEACAM1 would regulate Bv8 production in these cells. In support of this hypothesis, we found that Bv8 expression was elevated in Gr1+CD11b+ cells from Ceacam1-deficient mice implanted with B16 melanoma, increasing the infiltration of Gr1+CD11b+ myeloid cells in melanoma tumors and enhancing their growth and angiogenesis. Furthermore, treatment with anti-Gr1 or anti-Bv8 or anti-G-CSF monoclonal antibody reduced myeloid cell infiltration, tumor growth, and angiogenesis to levels observed in tumor-bearing wild-type (WT) mice. Reconstitution of CEACAM1-deficient mice with WT bone marrow cells restored tumor infiltration of Gr1+CD11b+ cells along with tumor growth and angiogenesis to WT levels. Treatment of tumor-bearing WT mice with anti-CEACAM1 antibody limited tumor outgrowth and angiogenesis, albeit to a lesser extent. Tumor growth in Ceacam1-deficient mice was not affected significantly in Rag−/− background, indicating that CEACAM1 expression in T and B lymphocytes had a negligible role in this pathway. Together, our findings show that CEACAM1 negatively regulates Gr1+CD11b+ myeloid cell–dependent tumor angiogenesis by inhibiting the G-CSF-Bv8 signaling pathway. Cancer Res; 72(9); 2239–50. ©2012 AACR.
Novel MT1-MMP Small-Molecule Inhibitors Based on Insights into Hemopexin Domain Function in Tumor Growth
Authors: Remacle Albert G. , Golubkov Vladislav S. , Shiryaev Sergey A. , Dahl Russell , Stebbins John L. , Chernov Andrei V. , Cheltsov Anton V. , Pellecchia Maurizio , Strongin Alex Y.
Published: March 2012

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a promising drug target in malignancy. The structure of MT1-MMP includes the hemopexin domain (PEX) that is distinct from and additional to the catalytic domain. Current MMP inhibitors target the conserved active site in the catalytic domain and, as a result, repress the proteolytic activity of multiple MMPs instead of MT1-MMP alone. In our search for noncatalytic inhibitors of MT1-MMP, we compared the protumorigenic activity of wild-type MT1-MMP with an MT1-MMP mutant lacking PEX (ΔPEX). In contrast to MT1-MMP, ΔPEX did not support tumor growth in vivo, and its expression resulted in small fibrotic tumors that contained increased levels of collagen. Because these findings suggested an important role for PEX in tumor growth, we carried out an inhibitor screen to identify small molecules targeting the PEX domain of MT1-MMP. Using the Developmental Therapeutics Program (National Cancer Institute/NIH), virtual ligand screening compound library as a source and the X-ray crystal structure of PEX as a target, we identified and validated a novel PEX inhibitor. Low dosage, intratumoral injections of PEX inhibitor repressed tumor growth and caused a fibrotic, ΔPEX-like tumor phenotype in vivo. Together, our findings provide a preclinical proof of principle rationale for the development of novel and selective MT1-MMP inhibitors that specifically target the PEX domain. Cancer Res; 72(9); 2339–49. ©2012 AACR.
Metformin-Mediated Bambi Expression in Hepatic Stellate Cells Induces Prosurvival Wnt/β-Catenin Signaling
Authors: Subramaniam Nanthakumar , Sherman Mara H. , Rao Renuka , Wilson Caroline , Coulter Sally , Atkins Annette R. , Evans Ronald M. , Liddle Christopher , Downes Michael
Published: March 2012

AMP-activated protein kinase (AMPK) regulates lipid, cholesterol, and glucose metabolism in specialized metabolic tissues, such as muscle, liver, and adipose tissue. Agents that activate AMPK, such as metformin and 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), have beneficial effects on liver glucose and lipid metabolism. In addition, AMPK activation in proliferating hepatic stellate cells (HSC) induces growth arrest and inhibits hepatic fibrosis. As metformin and AICAR act in different ways to achieve their effects, our aim was to examine the effects of AMPK activation in quiescent HSCs with these two agents on HSC function. We found that phospho-AMPK levels were markedly upregulated by both AICAR and metformin in quiescent HSCs. However, although AICAR treatment induced cell death, cells treated with metformin did not differ from untreated controls. AICAR-mediated HSC cell death was paralleled by loss of expression of the TGF-β decoy receptor Bambi, whereas metformin increased Bambi expression. Transfection of siRNA-Bambi into HSCs also induced cell death, mimicking the effects of AICAR, whereas overexpression of Bambi partially rescued AICAR-treated cells. As Bambi has previously been shown to promote cell survival through Wnt/β-catenin signaling, a reporter incorporating binding sites for a downstream target of this pathway was transfected into HSCs and was induced. We conclude that although AICAR and metformin both activate AMPK in quiescent HSCs, AICAR rapidly induced cell death, whereas metformin-treated cells remained viable. The finding that metformin increases Bambi expression and activates Wnt/β-catenin signaling provides a possible mechanistic explanation for this observation. These results suggest that AICAR and metformin may confer disease-specific therapeutic benefits. Cancer Prev Res; 5(4); 553–61. ©2012 AACR.
Electrophysiological Characteristics of Canine Superior Vena Cava Sleeve Preparations
Authors: Sicouri Serge , Blazek Jonathan , Belardinelli Luiz , Antzelevitch Charles
Published: March 2012

Background—

In addition to extrasystoles of pulmonary vein (PV) origin, those arising from the superior vena cava (SVC) can precipitate atrial fibrillation (AF). The present study evaluates the electrophysiological properties of canine SVC sleeve preparations and the effect of ranolazine on late phase 3 early and delayed afterdepolarization (EAD and DAD)-induced triggered activity in SVC sleeves and compares SVC and PV sleeve electrophysiological properties.

Methods and Results—

Action potentials (APs) were recorded from superfused SVC and PV sleeves using microelectrode techniques. Acetylcholine (1 μmol/L), isoproterenol (1 μmol/L), high calcium ([Ca
2+
]
o
=5.4 mmol/L), or a combination were used to induce EADs, DADs, and triggered activity. A marked diversity of action potential characteristics was observed in the SVC sleeve, including action potentials with short and long APs, with and without phase 4 depolarization. Rapid pacing induced hyperpolarization, accentuating the slope of phase 4 depolarization. Phase 4 depolarization and rapid pacing-induced hyperpolarization were reduced or eliminated after atropine (10 μmol/L) or ranolazine (10 μmol/L). APs displaying phase 4 depolarization (n=19) had longer APDs, smaller amplitude and V
max
, and a more positive take-off potential than APs lacking phase 4 depolarization (n=15). Ranolazine (5–10 μmol/L) eliminated late phase 3 EAD- and DAD-induced triggered activity as well as isoproterenol-induced automaticity elicited in SVC sleeves. Compared with PV, SVC sleeves display phase 4 depolarization, smaller V
max
, and longer APs.

Conclusions—

Autonomic influences promote spontaneous automaticity and triggered activity in SVC sleeves, thus generating extrasystolic activity capable of initiating atrial arrhythmias. Ranolazine can effectively suppress these triggers.
Familial Effects on Ischemic Stroke
Authors: Kasiman Katherine , Lundholm Cecilia , Sandin Sven , Malki Ninoa , Sparén Pär , Ingelsson Erik
Published: March 2012

Background—

Previous studies on familial risk of ischemic stroke have supported genetic influence on the disease incidence. This study aimed to characterize these familial effects in a nationwide population-based study by taking into account sibling relations, sex of siblings, and age of onset, with respect to ischemic stroke incidence.

Methods and Results—

Incident ischemic stroke cases identified from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007 were linked to their stroke-free siblings (study participants), forming an exposed sib-pair. Each exposed sib-pair was matched up to 5 unexposed sib-pairs from the Multi-Generation Registry by birth and calendar years. Incident ischemic stroke risk was assessed using hazard estimates obtained from stratified Cox regression analyses. A total of 30 735 exposed and 152 391 unexposed study participants were included in the analyses. The overall risk of incident ischemic stroke when exposed was significantly increased (relative risk, 1.61; 95% confidence interval, 1.48–1.75;
P
<0.001). Familial risk was higher in full (relative risk, 1.64; 95% confidence interval, 1.50–1.81;
P
<0.001) than in half (relative risk, 1.41; 95% confidence interval, 1.10–1.82;
P
=0.007) siblings. Familial risk of early ischemic stroke almost doubled when exposed to early ischemic stroke (relative risk, 1.94; 95% confidence interval, 1.41–2.67;
P
<0.001).

Conclusions—

There was a 60% increased risk for ischemic stroke in individuals having a sibling with prior stroke. The familial effect was even higher for full-sibling relations. Familial effects were observed in both male and female individuals, and no differential effects depending on the sex of either of the siblings were found.
Left Ventricular Function Impairment in Patients With Normal-Weight Obesity
Authors: Kosmala Wojciech , Jedrzejuk Diana , Derzhko Roksolana , Przewlocka-Kosmala Monika , Mysiak Andrzej , Bednarek-Tupikowska Grazyna
Published: March 2012

Background—

Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities.

Methods and Results—

One hundred sixty-eight subjects (age, 38±7 years) with BMI <25kg/m
2
and no history of any disease affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (β=−0.17,
P
<0.006), C-reactive protein (β=−0.20,
P
<0.002) and abdominal fat deposit (β=−0.20,
P
<0.003); for tissue S velocity, PICP (β=−0.21,
P
<0.002) and abdominal fat deposit (β=−0.43,
P
<0.0001); for tissue E velocity, abdominal fat deposit (β=−0.30,
P
<0.0001), PICP (β=−0.31,
P
<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; β=−0.20,
P
<0.002); and for E/e′-PICP, IL-18 (both β=0.18,
P
<0.01) and HOMA IR (β=0.16,
P
<0.04).

Conclusions—

In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.
Patterns of Choice: The Prix Ars Electronica Jury Sessions
Authors: Offenhuber Dietmar
Published: March 2012

This article investigates the social structures reflected in the annual jury sessions of the Prix Ars Electronica, a major media art competition—the composition, the temporal evolution and ultimately the decisions of these juries. The author focuses on three different structures: the network of co-jurors across different categories and years, the co-artist network formed by the jury decisions, and finally the interaction between these two networks. The results not only reveal different roles of individuals in the jury process but also reflect the evolution of the field in general. Based solely on public data, the results show a multifaceted picture of a dynamic field.
Music and Naturoids: The Third Reality
Authors: Negrotti Massimo
Published: March 2012

At a high level of abstraction, it can be shown by analogy that attempts to reproduce natural phenomena occur not only in technological endeavors but also in human communication and the arts, including music. This paper presents the parallel development of artificial devices—or “naturoids”—in the fields of technology, message communication and musical composition, highlighting the transfiguration that unavoidably affects the resulting device, message or musical work. In the technological field and, to an extent, in the communications field, the transfiguration of the natural object is taken as a more or less unsatisfying outcome. By contrast, in the arts, and mainly in music, the transfiguration effect is exactly what the artist pursues through placing him- or herself at a nonordinary observation level.
Culture, Data and Algorithmic Organization
Authors: Legrady George
Published: March 2012

The author presents his interactive digital installations of the past decade, featured in museums, media arts festivals and galleries, that engage the audience to contribute data that is then transformed into content and visually projected large scale in the exhibition space. Collected over time, the data occasions further data-mining, algorithmic processing, with visualization of the results.
ParaSites: Initial Report and Research Context
Authors: Colle Cécile , Nuhn Ralf
Published: March 2012

This research explores the potential for using behaviors and strategies of parasites as a model for sculptural propositions in the built environment, and investigates how these interventions might resonate with concerns in architecture, urbanism and sociocultural politics.
Glint: Audiovisual Glitches
Authors: Tunali Funda Senova
Published: March 2012

This paper explores the idea of glitch through an audiovisual project called Glint and how the concept of glitch can be marked as a manifestation of digital culture.
Does Government Intervention Matter? Revisiting Recent Rice Price Increases in Bangladesh
Authors: Misra Manoj
Published: March 2012

Abstract

The specter of food crisis is haunting the world again in 2011. This comes after a short period of decline in food prices since they peaked in the summer of 2008. The addition of seven point five million people during the 2007-08 food crisis with the estimated food insecure population of sixty-five point three million in Bangladesh (FAO/WFP 2008) underlines the magnitude of food insecurity in the country. In this article I trace the volatility in Bangladesh’s rice market since the 2007-8 food crisis in terms of the country’s deregulation of agricultural sector and the gradual elimination of market regulatory mechanisms. I demonstrate that despite Bangladesh’s relatively minor dependence on the international rice market and a steady domestic supply, the lack of strong government regulation and monitoring of the market resulted in irrational rice-price increases. I argue that the alleged connections between the domestic and the international rice markets are largely hypothetical, and therefore the domestic price increases must be analyzed in terms of internal management of the market. The methodology of this article involves critical review of literature and data collected from secondary sources. Referring to Stiglitz I conclude that the Bangladesh rice market is far from developed and thus warrants a strong regulatory regime.
Resistance to Neo-Liberalism: France, Greece, Spain, and the US
Authors: Mann Keith
Published: March 2012

Abstract

The mass mobilizations against neo-liberal austerity drives that took place in Greece, France, Spain, and Madison, Wisconsin from 2010 into the summer of 2011 reflect deeply global forces and suggest several trends in contemporary global capitalism. These include an emerging pattern of inequality among member states of the European Union, deep alienation of workers from the Social Democracy and other traditional labor organizations who have championed neo-liberal economic policies and implemented austerity drives, and new forms of collective action.
Mexico’s Concentration on Consular Services in the United States
Authors: Joseph Daniel Hernández
Published: March 2012

Summary

No other foreign service has as strong a consular concentration, or is as centered in a single other country, as the Mexican Foreign Service and its consular network in the United States. Mexico has 73 embassies and 67 consulates throughout the world — with 50 of these consulates in the United States. Clearly, consular work and particularly the consular tasks that are performed in the United States take up a large part of the resources, attention and priority of Mexican foreign policy.