bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Binding Specificity of K88ac and K88ad Fimbriae of EnterotoxigenicEscherichia coliby Constructing K88ac/K88ad Chimeric FaeG Major Subunits
Authors: Zhang Weiping , Fang Ying , Francis David H.
Published: November 2008

EnterotoxigenicEscherichia coli(ETEC) strains expressing K88 (F4) fimbriae are the major cause of diarrhea in young pigs. Three antigenic variants of K88 fimbriae (K88ab, K88ac, and K88ad) have been identified among porcine ETEC strains. Each K88 fimbrial variant shows a unique pattern in binding to different receptors on porcine enterocytes. Such variant specificity in fimbrial binding is believed to be controlled by the major subunit (FaeG) of the K88 fimbriae, because the genes coding for the only other fimbrial subunit are identical among the three variants. Uniqueness in binding to host receptors may be responsible for differences in the virulence levels of porcine diarrhea disease caused by K88 ETEC strains. To better understand the relationships between the structure of FaeG proteins and fimbrial binding function, and perhaps virulence in disease, we constructed and expressed various K88ac/K88adfaeGgene chimeras and characterized the binding activity of each K88 chimeric fimbria. After verifying biosynthesis of the chimeric fimbriae, we examined their binding specificities in bacterial adherence assays by using porcine brush border vesicles that are specific to either the K88ac or K88ad fimbria. Results showed that each fimbria switched binding specificity to that of the reciprocal type when a peptide comprising amino acids 125 to 163 was exchanged with that of its counterpart. Substitutions of a single amino acid within this region negatively affected the binding capacity of each fimbria. These data indicate that the peptide including amino acids 125 to 163 of the FaeG subunit is essential for K88 variant-specific binding.
Characterization of the Mycobacterial NER System Reveals Novel Functions of theuvrD1Helicase
Authors: Güthlein Carolin , Wanner Roger M. , Sander Peter , Davis Elaine O. , Bosshard Martin , Jiricny Josef , Böttger Erik C. , Springer Burkhard
Published: November 2008

In this study, we investigated the role of the nucleotide excision repair (NER) pathway in mycobacterial DNA repair.Mycobacterium smegmatislacking the NER excinuclease componentuvrBor the helicaseuvrD1gene and a double knockout lacking both genes were constructed, and their sensitivities to a series of DNA-damaging agents were analyzed. As anticipated, the mycobacterial NER system was shown to be involved in the processing of bulky DNA adducts and interstrand cross-links. In addition, it could be shown to exert a protective effect against oxidizing and nitrosating agents. Interestingly, inactivation ofuvrBanduvrD1significantly increased marker integration frequencies in gene conversion assays. This implies that in mycobacteria (which lack the postreplicative mismatch repair system) NER, and particularly the UvrD1 helicase, is involved in the processing of a subset of recombination-associated mismatches.
Genome-Wide Identification of H-NS-Controlled, Temperature-Regulated Genes in
Escherichia
coli
K-12
Authors: White-Ziegler Christine A. , Davis Talya R.
Published: November 2008

DNA microarrays demonstrate that H-NS controls 69% of the temperature regulated genes in
Escherichia
coli
K-12. H-NS is shown to be a common regulator of multiple iron and other nutrient acquisition systems preferentially expressed at 37°C and of general stress response, biofilm formation, and cold shock genes highly expressed at 23°C.
Two Kdo-Heptose Regions Identified inHafnia alvei32 Lipopolysaccharide: the Complete Core Structure and Serological Screening of DifferentHafniaO Serotypes
Authors: Lukasiewicz Jolanta , Niedziela Tomasz , Jachymek Wojciech , Kenne Lennart , Lugowski Czeslaw
Published: November 2008

Hafnia alvei, a gram-negative bacterium, is an opportunistic pathogen associated with mixed hospital infections, bacteremia, septicemia, and respiratory diseases. Various 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo)-containing fragments different from known structures of core oligosaccharides were previously found among fractions obtained by mild acid hydrolysis of someH. alveilipopolysaccharides (LPSs). However, the positions of these segments in the LPS structure were not known. Analysis of de-N,O-acylated LPS by nuclear magnetic resonance spectroscopy and mass spectrometry allowed the determination of the location of a Kdo-containing trisaccharide in the structure ofH. alveiPCM 32 LPS. It was established that the trisaccharide {l-α-d-Hepp-(1→4)-[α-d-Galp6OAc-(1→7)]-α-Kdop-(2→} is an integral part of the outer-core oligosaccharide ofH. alvei32 LPS. The very labile ketosidic linkage between →4,7)-α-Kdopand →2)-Glcpin the core oligosaccharide was identified. Screening for this Kdo-containing trisaccharide was performed on the group of 37 O serotypes ofH. alveiLPSs using monospecific antibodies recognizing the structure. It was established that this trisaccharide is a characteristic component of the outer-core oligosaccharides ofH. alvei2, 32, 600, 1192, 1206, and 1211 LPSs. The weaker cross-reactions with LPSs of strains 974, 1188, 1198, 1204, and 1214 suggest the presence of similar structures in these LPSs, as well. Thus, we have identified new examples of endotoxins among those elucidated so far. This type of core oligosaccharide deviates from the classical scheme by the presence of the structural Kdo-containing motif in the outer-core region.
1,3-Propanediol Dehydrogenase fromKlebsiella pneumoniae: Decameric Quaternary Structure and Possible Subunit Cooperativity
Authors: Marçal David , Rêgo Ana Toste , Carrondo Maria Arménia , Enguita Francisco J.
Published: November 2008

Klebsiella pneumoniaeis a nosocomial pathogen frequently isolated from opportunistic infections, especially in clinical environments. In spite of its potential pathogenicity, this microorganism has several metabolic potentials that could be used in biotechnology applications.K. pneumoniaeis able to metabolize glycerol as a sole source of carbon and energy. 1,3-Propanediol dehydrogenase is the core of the metabolic pathway for the use of glycerol. We have determined the crystallographic structure of 1,3-propanediol dehydrogenase, a type III Fe-NAD-dependent alcohol dehydrogenase, at 2.7-Å resolution. The structure of the enzyme monomer is closely related to that of other alcohol dehydrogenases. The overall arrangement of the enzyme showed a decameric structure, formed by a pentamer of dimers, which is the catalytic form of the enzyme. Dimers are associated by strong ionic interactions that are responsible for the highly stable in vivo packing of the enzyme. Kinetic properties of the enzyme as determined in the article would suggest that this decameric arrangement is related to the cooperativity between monomers.
The Ether-Cleaving Methyltransferase System of the Strict Anaerobe
Acetobacterium dehalogenans
: Analysis and Expression of the Encoding Genes
Authors: Schilhabel Anke , Studenik Sandra , Vödisch Martin , Kreher Sandra , Schlott Bernhard , Pierik Antonio Y. , Diekert Gabriele
Published: November 2008

Anaerobic
O
-demethylases are inducible multicomponent enzymes which mediate the cleavage of the ether bond of phenyl methyl ethers and the transfer of the methyl group to tetrahydrofolate. The genes of all components (methyltransferases I and II, CP, and activating enzyme [AE]) of the vanillate- and veratrol-
O
-demethylases of
Acetobacterium dehalogenans
were sequenced and analyzed. In
A. dehalogenans
, the genes for methyltransferase I, CP, and methyltransferase II of both
O
-demethylases are clustered. The single-copy gene for AE is not included in the
O
-demethylase gene clusters. It was found that AE grouped with COG3894 proteins, the function of which was unknown so far. Genes encoding COG3894 proteins with 20 to 41% amino acid sequence identity with AE are present in numerous genomes of anaerobic microorganisms. Inspection of the domain structure and genetic context of these orthologs predicts that these are also
r
eductive
a
ctivases for
c
orrinoid
e
nzymes (RACEs), such as carbon monoxide dehydrogenase/acetyl coenzyme A synthases or anaerobic methyltransferases. The genes encoding the
O
-demethylase components were heterologously expressed with a C-terminal
Strep
-tag in
Escherichia coli
, and the recombinant proteins methyltransferase I, CP, and AE were characterized. Gel shift experiments showed that the AE comigrated with the CP. The formation of other protein complexes with the
O
-demethylase components was not observed under the conditions used. The results point to a strong interaction of the AE with the CP. This is the first report on the functional heterologous expression of acetogenic phenyl methyl ether-cleaving
O
-demethylases.
Spatial Clustering of the Curlin Secretion Lipoprotein Requires Curli Fiber Assembly
Authors: Epstein Elisabeth Ashman , Reizian Margeaux A. , Chapman Matthew R.
Published: November 2008

Gram-negative bacteria assemble functional amyloid surface fibers called curli. CsgB nucleates the major curli subunit protein, CsgA, into a self-propagating amyloid fiber on the cell surface. The CsgG lipoprotein is sufficient for curlin transport across the outer membrane and is hypothesized to be the central molecule of the curli fiber secretion and assembly complex. We tested the hypothesis that the curli secretion protein, CsgG, was restricted to certain areas of the cell to promote the interaction of CsgA and CsgB during curli assembly. Here, electron microscopic analysis of curli-producing strains showed that relatively few cells in the population contacted curli fibers and that curli emanated from spatially discrete points on the cell surface. Microscopic analysis revealed that CsgG was surface exposed and spatially clustered around curli fibers. CsgG localization to the outer membrane and exposure of the surface domain were not dependent on any othercsg-encoded protein, but the clustering of CsgG required thecsg-encoded proteins CsgE, CsgF, CsgA, and CsgB. CsgG formed stable oligomers in all thecsgmutant strains, but these oligomers were distinct from the CsgG complexes assembled in wild-type cells. Finally, we found that efficient fiber assembly was required for the spatial clustering of CsgG. These results suggest a new model where curli fiber formation is spatially coordinated with the CsgG assembly apparatus.
The Flat-Ribbon Configuration of the Periplasmic Flagella of
Borrelia burgdorferi
and Its Relationship to Motility and Morphology
Authors: Charon Nyles W. , Goldstein Stuart F. , Marko Michael , Hsieh Chyongere , Gebhardt Linda L. , Motaleb M. Abdul , Wolgemuth Charles W. , Limberger Ronald J. , Rowe Nancy
Published: November 2008

Electron cryotomography was used to analyze the structure of the Lyme disease spirochete,
Borrelia burgdorferi
. This methodology offers a new means for studying the native architecture of bacteria by eliminating the chemical fixing, dehydration, and staining steps of conventional electron microscopy. Using electron cryotomography, we noted that membrane blebs formed at the ends of the cells. These blebs may be precursors to vesicles that are released from cells grown in vivo and in vitro. We found that the periplasmic space of
B. burgdorferi
was quite narrow (16.0 nm) compared to those of
Escherichia coli
and
Pseudomonas aeruginosa
. However, in the vicinity of the periplasmic flagella, this space was considerably wider (42.3 nm). In contrast to previous results, the periplasmic flagella did not form a bundle but rather formed a tight-fitting ribbon that wraps around the protoplasmic cell cylinder in a right-handed sense. We show how the ribbon configuration of the assembled periplasmic flagella is more advantageous than a bundle for both swimming and forming the flat-wave morphology. Previous results indicate that
B. burgdorferi
motility is dependent on the rotation of the periplasmic flagella in generating backward-moving waves along the length of the cell. This swimming requires that the rotation of the flagella exerts force on the cell cylinder. Accordingly, a ribbon is more beneficial than a bundle, as this configuration allows each periplasmic flagellum to have direct contact with the cell cylinder in order to exert that force, and it minimizes interference between the rotating filaments.
YtxR Acts as an Overriding Transcriptional Off Switch for the
Yersinia enterocolitica
Ysc-Yop Type 3 Secretion System
Authors: Axler-DiPerte Grace L. , Hinchliffe Stewart J. , Wren Brendan W. , Darwin Andrew J.
Published: November 2008

The
Yersinia enterocolitica
YtxR protein is a LysR-type transcriptional regulator that induces expression of the
ytxAB
locus, which encodes a putative ADP-ribosylating toxin. The
ytxR
and
ytxAB
genes are not closely linked in the
Y. enterocolitica
chromosome, and whereas
ytxR
is present in all sequenced
Yersinia
spp., the
ytxAB
locus is not. These observations suggested that there might be other YtxR-regulon members besides
ytxAB
and prompted us to investigate coregulated genes and gene products by using transcriptional and proteomic approaches. Microarray and reverse transcription-PCR analysis showed that YtxR strongly activates expression of the
yts2
locus, which encodes a putative type 2 secretion system, as well as several uncharacterized genes predicted to encode extracytoplasmic proteins. Strikingly, we also discovered that under Ysc-Yop type 3 secretion system-inducing conditions, YtxR prevented the appearance of Yop proteins in the culture supernatant. Microarray and
lacZ
operon fusion analysis showed that this was due to specific repression of
ysc-yop
gene expression. YtxR was also able to repress VirF-dependent Φ(
yopE-lacZ
) and Φ(
yopH-lacZ
) expression in a strain lacking the virulence plasmid, which suggested a direct repression mechanism. This was supported by DNase I footprinting, which showed that YtxR interacted with the
yopE
and
yopH
control regions. Therefore, YtxR is a newly identified regulator of the
ysc-yop
genes that can act as an overriding off switch for this critical virulence system.
Genome Sequence of the Probiotic Bacterium
Bifidobacterium animalis
subsp.
lactis
AD011
Authors: Kim Jihyun F. , Jeong Haeyoung , Yu Dong Su , Choi Sang-Haeng , Hur Cheol-Goo , Park Myeong-Soo , Yoon Sung Ho , Kim Dae-Won , Ji Geun Eog , Park Hong-Seog , Oh Tae Kwang
Published: November 2008

Bifidobacterium animalis
subsp.
lactis
is a probiotic bacterium that naturally inhabits the guts of most mammals, including humans. Here we report the complete genome sequence of
B. animalis
subsp.
lactis
AD011 that was isolated from an infant fecal sample. Biological functions encoded in a single circular chromosome of 1,933,695 bp, smallest among the completely sequenced bifidobacterial genomes, are suggestive of their probiotic functions, such as utilization of bifidogenic factors and a variety of glycosidic enzymes and biosynthesis of polysaccharides.
The impact of temporary employment and job tenure on work-related sickness absence
Authors: Tompa E , Scott-Marshall H , Fang M
Published: November 2008

Objectives:

To investigate the impact of temporary employment and job tenure on work-related sickness absence of 1 week or more.

Methods:

A longitudinal analysis was undertaken of the time to work-related sickness absence from the start of a job using the Canadian Survey of Labour and Income Dynamics. The sample consisted of 4777 individuals who experienced 7953 distinct job episodes and 167 absences. There were 114 488 person-job-month observational units. The major variables of interest in this study were a variable identifying whether the job was temporary or permanent, and tenure on the job.

Results:

Individuals in temporary jobs were as likely to have a work-related sickness absence as individuals in permanent jobs. Individuals with job tenure of 4–6 months were 64% less likely to have an absence than individuals with longer tenures. Individuals in a union were more likely to have an absence. Firm size was not associated with absence.

Conclusions:

Previous studies have suggested that temporary employment and job tenure are associated with work-related health risk exposures and the ability to take a sickness absence, but these studies have not considered the nature of the employment contract in a longitudinal framework. This analysis did not find temporary employment to be associated with differential absence rate after controlling for tenure, prior health status, and several other individual and job characteristics. Short tenure is negatively related to the probability of work-related sickness absence, union membership is positively related, and firm size is not related to this variable.
Depression in primary care: three key challenges
Authors: Lester H , Howe A
Published: November 2008

The recognition and treatment of depression is a challenging area of clinical practice, especially in primary care where there are many patients with various presentations and a multitude of causes for distress. The prevalence of depression is increasing, and it is predicted to become second only to ischaemic heart disease as a cause of morbidity worldwide. Fortunately, the research evidence on effective approaches is increasing. This article looks at how we can best identify, treat and understand the perspectives of people with depression who are seen in primary care.

Simple questionnaires can provide effective screening in generalist settings, particularly when targeting high-risk groups such as those with cardiovascular comorbidity or recurrent unexplained symptoms. Guidelines now exist for use of antidepressants and cognitive behavioural therapy for mild to moderate depression, although the latter needs effective policy implementation in clinical practice to maximise its impact for patients. However, there is also consistent evidence from service users that people with depression want individualised care which takes into account their preferences and concerns, even if this entails departure from guidelines. Adherence to treatment is low in many studies, and remodelling of services can easily lead to gaps in consistent approaches to personal care.

The research challenges for the future include clarification of which patient groups merit proactive screening, how to enhance adherence, and the relative merits and outcomes of pharmacological versus behavioural therapies. Changes in policy and service configuration can improve or destabilise effective care, but high-quality and flexible intervention with patients with mild to moderate depression is likely to be cost-effective in view of the high prevalence and disease burden of this distressing problem.
Ordovician and Silurian nautiloid cephalopods from Anticosti Island: traject across the Ordovician–Silurian (O–S) mass extinction boundary
Authors: Holland Charles Hepworth , Copper Paul
Published: November 2008

Well-preserved shells of Ashgill (Katian–Hirnantian) and Llandovery nautiloids from Anticosti Island include the type species of 10 genera. From a diversity high of some 40 described nektic and nektobenthic species during the deeper water, distal shelf facies of the Vaureal Formation (late Katian, Richmondian), the succeeding Hirnantian shows a decline to ca. 19 species in the shallower water Ellis Bay Formation. A number of Katian species possessed very large orthoconchs (>1 m in length), but Hirnantian species were less than half that size. The initial earliest Silurian (Rhuddanian, Becscie Formation) recovery nautiloid fauna is impoverished, with low diversity (one sp.?), and generally dwarfed, to shells with diameters of <1 cm. Nautiloid diversity expanded and progressed to some 22 species in the late Aeronian through Telychian Jupiter and Chicotte formations, with an apparent peak in the Goéland Member of the Jupiter Formation. Three new species, Actinoceras lesperancei , Eridites barnesi , and Diestoceras macgilvrayoceras , are described. The distribution of shells within the succession defines the fauna’s stratigraphic and paleobiogeographic significance, with a changing mix of Baltic and Laurentian taxa.
Investigating feedforward neural regulation of circulation from analysis of spontaneous arterial pressure and heart rate fluctuations in conscious rats
Authors: Legramante Jacopo M. , Sacco Sergio , Raimondi Gianfranco , Di Lecce Vito N. , Pallante Marco , Di Nardo Paolo , Galante Alberto
Published: November 2008

It has been suggested in anesthetized animals that the occurrence of sequences of consecutive beats characterized by systolic arterial pressure (SAP) and RR or pulse interval (PI) changing in the opposite direction (SAP+/RR− and SAP−/RR+, nonbaroreflex sequences) might represent the expression of neural cardiovascular regulatory mechanisms operating with feedforward characteristics. The aim of the present study was to study nonbaroreflex sequences in a more physiological experimental model, i.e., in conscious freely moving rats. We studied conscious rats before and after 1) complete autonomic blockade ( n = 12), 2) sympathetic blockade ( n = 10), 3) α ( n = 7)- and β ( n = 8)-adrenergic blockade, and 4) parasympathetic blockade ( n = 10). Nonbaroreflex sequences were defined as three or more beats in which SAP and PI of the following beat changed in the opposite direction. Complete autonomic blockade reduced the number of nonbaroreflex sequences (95.6 ± 9.0 vs. 45.2 ± 4.1, P < 0.001), as did sympathetic blockade (80.9 ± 12.6 vs. 30.9 ± 6.1, P < 0.001). The selective α-receptor blockade did not induce significant changes (80.9 ± 12.5 in baseline vs. 79.0 ± 14.7 after prazosin), whereas β-receptor blockade significantly reduced nonbaroreflex sequence occurrence (80.9 ± 12.5 in baseline vs. 48.9 ± 15.3 after propranolol). Parasympathetic blockade produced a significant increase of nonbaroreflex sequences (95.1 ± 6.9 vs. 136.0 ± 12.4, P < 0.01). These results demonstrate the physiological role of the nonbaroreflex sequences as an expression of a feedforward type of short-term cardiovascular regulation able to interact dynamically with the feedback mechanisms of baroreflex origin in the neural control of the sinus node.
Chronic stimulation of farnesoid X receptor impairs nitric oxide sensitivity of vascular smooth muscle
Authors: Kida Taiki , Murata Takahisa , Hori Masatoshi , Ozaki Hiroshi
Published: November 2008

Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily that is highly expressed in enterohepatic tissue, is implicated in bile acid, lipid, and glucose metabolisms. Although recent studies showed that FXR is also expressed in vascular endothelial cells and smooth muscle cells, its physiological and/or pathological roles in vasculature tissue remain unknown. The aim of this study is to examine the chronic effect of synthetic FXR agonist GW4064 on vascular contraction and endothelium-dependent relaxation using tissue culture procedure. In cultured rabbit mesenteric arteries, the treatment with 0.1–10 μM GW4064 for 7 days did not influence vascular contractility induced by high K+(15–65 mM), norepinephrine (0.1–100 μM), and endothelin-1 (0.1–100 nM). However, the chronic treatment with GW4064 (1–10 μM for 7 days) dose dependently impaired endothelium-dependent relaxation induced by substance P (0.1–30 nM). In hematoxylin-eosin cross sectioning and en face immunostaining, GW4064 had no effects on the morphology of endothelial and smooth muscle cells. In endothelium-denuded arteries treated with GW4064 (1–10 μM) for 7 days, 3 nM–100 μM sodium nitroprusside-induced vasorelaxation, but not membrane-permeable cGMP analog 8-bromoguanosine-cGMP (8-Br-cGMP; 1–100 μM)-induced vasorelaxation, was significantly impaired. In these GW4064-treated arteries, 1 μM sodium nitroprusside-induced intracellular cGMP elevations were impaired. In RT-PCR, any changes were detected in mRNA expression level of α1- and β1-subunit of soluble guanylyl cyclase. These results suggest that chronic stimulation of FXR impairs endothelium-dependent relaxation, which is due to decreased sensitivity of smooth muscle cells to nitric oxide.
The involvement of heating rate and vasoconstrictor nerves in the cutaneous vasodilator response to skin warming
Authors: Hodges Gary J. , Kosiba Wojciech A. , Zhao Kun , Johnson John M.
Published: November 2008

Slow local skin heating (LH) causes vasodilator responses, some of which are dependent on sympathetic nerve function. It is not known, however, how the rate of LH affects either the sympathetic or the nonadrenergic components of the responses to LH and whether the adrenergic effects of LH depend on tonic sympathetic activity or whether LH stimulates transmitter release. In part 1, cutaneous vascular conductance (CVC) responses to slow and fast LH (+0.1° and +2°C/min) from 34° to 40°C were compared both at control sites and at sites pretreated with bretylium tosylate (BT; blocks transmitter release from adrenergic terminals). We confirmed, as previously found, the axon reflex (AR) response to slow LH to be blocked by BT ( P < 0.05). Pretreatment with BT reduced the AR only with fast LH. BT inhibited the peak vasodilation achieved with both rates of LH ( P < 0.05). Longer-term LH was associated with a slow fall in CVC, the classical “die away” phenomenon, at untreated sites ( P < 0.05) but not at BT-pretreated sites. Thus the LH-stimulated AR is only partially dependent on intact sympathetic function, and the “die away” phenomenon is dependent on such function. In part 2, we tested whether the conditions in part 1 (whole body and local skin temperatures of 34°C) completely suppressed sympathetic nerve activity. The infusion of BT by microdialysis did not change the CVC ( P > 0.05), suggesting the absence of tonic activity in those conditions and therefore that the adrenergic components of the responses in part 1 are via the stimulation of the transmitter release by LH.
Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart
Authors: Chao Wei
Published: November 2008

Toll-like receptors (TLRs) represent the first line of host defense against microbial infection and play a pivotal role in both innate and adaptive immunity. TLRs recognize invading pathogens through molecular pattern recognition, transduce signals via distinct intracellular pathways involving a unique set of adaptor proteins and kinases, and ultimately lead to the activation of transcription factors and inflammatory responses. Among 10 TLRs identified in humans, at least two exist in the heart, i.e., TLR2 and TLR4. In addition to the critical role of these in mediating cardiac dysfunction in septic conditions, emerging evidence suggests that the TLRs can also recognize endogenous ligands and may play an important role in modulating cardiomyocyte survival and in ischemic myocardial injury. In animal models of ischemia-reperfusion injury or in hypoxic cardiomyocytes in vitro, the administration of a sublethal dose of lipopolysaccharide, which signals through TLR4, reduces subsequent myocardial infarction, improves cardiac functions, and attenuates cardiomyocyte apoptosis. By contrast, a systemic deficiency of TLR2, TLR4, or myeloid differentiation primary-response gene 88, an adaptor critical for all TLR signaling, except TLR3, leads to an attenuated myocardial inflammation, a smaller infarction size, a better preserved ventricular function, and a reduced ventricular remodeling after ischemic injury. These loss-of-function studies suggest that both TLRs contribute to myocardial inflammation and ischemic injury in the heart although the exact contribution of cardiac (vs. circulatory cell) TLRs remains to be defined. These recent studies demonstrate an emerging role for TLRs as a critical modulator in both cell survival and tissue injury in the heart.
Morphology of Exertion-Triggered Plaque Rupture in Patients With Acute Coronary Syndrome
Authors: Tanaka Atsushi , Imanishi Toshio , Kitabata Hironori , Kubo Takashi , Takarada Shigeho , Tanimoto Takashi , Kuroi Akio , Tsujioka Hiroto , Ikejima Hideyuki , Ueno Satoshi , Kataiwa Hideaki , Okouchi Keishi , Kashiwaghi Manabu , Matsumoto Hiroki , Takemoto Kazushi , Nakamura Nobuo , Hirata Kumiko , Mizukoshi Masato , Akasaka Takashi
Published: November 2008

Background—

Plaque rupture and secondary thrombus formation play key roles in the onset of acute coronary syndrome (ACS). One pathological study suggested that the morphologies of plaque rupture differed between rest-onset and exertion-triggered rupture in men who experienced sudden death. The aim of the present study was to use optical coherence tomography to investigate the relationship in patients with ACS between the morphology of a ruptured plaque and the patient’s activity at the onset of ACS.

Methods and Results—

The study population was drawn from 43 consecutive ACS patients (with or without ST-segment elevation) who underwent optical coherence tomography and presented with a ruptured plaque at the culprit site. Patients were divided into a rest group and an exertion group on the basis of their activities at the onset of ACS. The thickness of the broken fibrous cap correlated positively with activity at the onset of ACS. The culprit plaque ruptured at the shoulder more frequently in the exertion group than in the rest group (rest 57% versus exertion 93%,
P
=0.014). The thickness of the broken fibrous cap in the exertion group was significantly higher than in the rest-onset group (rest onset: 50 μm [interquartile median 15 μm]; exertion: 90 μm [interquartile median 65 μm],
P
<0.01).

Conclusions—

The morphologies of exertion-triggered and rest-onset ruptured plaques differ in ACS patients. Our data suggest that a thin-cap fibroatheroma is a lesion predisposed to rupture both at rest and during the patient’s day-to day activity, and some plaque rupture may occur in thick fibrous caps depending on exertion levels.
Electrophysiological Consequences of Acute Regional Ischemia/Reperfusion in Neonatal Rat Ventricular Myocyte Monolayers
Authors: de Diego Carlos , Pai Rakesh K. , Chen Fuhua , Xie Lai-Hua , De Leeuw Jan , Weiss James N. , Valderrábano Miguel
Published: November 2008

Background—

Electrophysiological changes promoting arrhythmias during acute regional ischemia/reperfusion are challenging to study in intact cardiac tissue because of complex 3-dimensional myocardial and vascular geometry. We characterized electrophysiological alterations and arrhythmias during regional ischemia/reperfusion in a simpler 2-dimensional geometry of cultured neonatal rat ventricular myocyte monolayers.

Methods and Results—

Optical mapping of intracellular Ca (Ca
i
) and voltage was performed with the use of Rhod 2-AM and Rh-237, respectively. Regional ischemia was mimicked by covering the central portion of monolayer with a glass coverslip, and reperfusion was mimicked by removing the coverslip. Monolayers were stained with fluorescent antibodies to detect total and dephosphorylated connexin-43 at various time points. During coverslip ischemia, action potential duration shortened, Ca
i
transient duration was prolonged, and local conduction velocity (CV) slowed progressively, with loss of excitability after 10.6±3.6 minutes. CV slowing was accompanied by connexin-43 dephosphorylation. During ischemia, spontaneous reentry occurred in 5 of 11 monolayers, initiated by extrasystoles arising from the border zone or unidirectional conduction block of paced beats. On reperfusion, excitability recovered within 1.0±0.8 minutes, but CV remained depressed for 9.0±3.0 minutes, promoting reentry in the reperfused zone. As connexin-43 phosphorylation recovered in the reperfused zone, CV normalized, and arrhythmias resolved.

Conclusions—

Acute regional ischemia/reperfusion in neonatal rat ventricular myocyte monolayers recapitulates electrophysiological alterations and arrhythmias similar to those observed during acute coronary occlusion/reperfusion in intact hearts. During early reperfusion, slow recovery from connexin-43 dephosphorylation leads to persistent CV slowing, creating a highly arrhythmogenic substrate.
Cornell Product Left Ventricular Hypertrophy in Electrocardiogram and the Risk of Stroke in a General Population
Authors: Ishikawa Joji , Ishikawa Shizukiyo , Kabutoya Tomoyuki , Gotoh Tadao , Kayaba Kazunori , Schwartz Joseph E. , Pickering Thomas G. , Shimada Kazuyuki , Kario Kazuomi
Published: November 2008

Left ventricular hypertrophy (LVH), assessed by ECG, is associated with an increased risk for cardiovascular events among hypertensive subjects. We evaluated the risks of LVH in a Japanese general population including normotensive and prehypertensive subjects. We measured ECG and blood pressure in 10 755 subjects at baseline. The Cornell product (CP) and Sokolow-Lyon (SL) voltage were calculated as markers of LVH (CP ≥2440 mm×ms and SL voltage ≥38 mm). Follow-up was performed for 10 years, and the incidence of stroke and myocardial infarction was evaluated. The prevalence of CP-LVH was 2.7% for normotensives, 5.2% for prehypertensives, and 11.0% for hypertensives, and the prevalence of SL-LVH was 5.0%, 8.2%, and 15.2%, respectively. In all of the subjects, CP-LVH and SL-LVH were both predictors of stroke (CP-LVH: hazard risk: 1.62, 95% CI: 1.19 to 2.20,
P
=0.002; SL-LVH: hazard risk: 1.29, 95% CI: 0.98 to 1.71,
P
=0.07) after adjustment for confounding factors but were not predictors of myocardial infarction. The adjusted hazard ratio of CP-LVH predicting stroke was especially high in the normotensives (hazard risk: 7.53; 95% CI: 3.39 to 16.77). In the normotensives, diabetes mellitus and hyperlipidemia were significant determinants of CP-LVH but not of SL-LVH. In all of the hypertensive subgroups (normotensives, prehypertensives, and hypertensives), the c-statistic for the equation predicting stroke increased when CP-LVH was added to the model but not when SL-LVH was added. In conclusion, both CP-LVH and SL-LVH are risk factors for stroke in the Japanese general population. CP-LVH is related to glucose abnormality, and its predictive value for stroke is seen even in normotensives and prehypertensives.
Chronic Blockade of Phosphatidylinositol 3-Kinase in the Nucleus Tractus Solitarii Is Prohypertensive in the Spontaneously Hypertensive Rat
Authors: Zubcevic Jasenka , Waki Hidefumi , Diez-Freire Carlos , Gampel Alexandra , Raizada Mohan K. , Paton Julian F.R.
Published: November 2008

Phosphatidylinositol 3-kinase (PI3K) within brain stem neurons has been implicated in hypertension in the spontaneously hypertensive rat (SHR). Previously, we demonstrated elevated expression of PI3K subunits in rostral ventrolateral medulla and paraventricular nucleus of SHRs compared with Wistar-Kyoto rats. Here, we considered expression levels of PI3K in the nucleus tractus solitarii, a pivotal region in reflex regulation of arterial pressure, and determined its functional role for arterial pressure homeostasis in SHRs and Wistar-Kyoto rats. We found elevated mRNA levels of p110β and p110δ catalytic PI3K subunits in the nucleus tractus solitarii of adult (12 to 14 weeks old) SHRs relative to the age-matched Wistar-Kyoto rats (fold differences relative to β-actin: 1.7±0.2 versus 1.01±0.08 for p110β, n=6,
P
<0.05; 1.62±0.15 versus 1.02±0.1 for p110δ, n=6,
P
<0.05). After chronic blockade of PI3K signaling in the nucleus tractus solitarii by lentiviral-mediated expression of a mutant form of p85α, systolic pressure increased from 175±3 mm Hg to 191±6 mm Hg (
P
<0.01) in SHRs but not in Wistar-Kyoto rats. In addition, heart rate increased (from 331±6 to 342±6 bpm;
P
<0.05) and spontaneous baroreflex gain decreased (from 0.7±0.07 to 0.5±0.04 ms/mm Hg;
P
<0.001) in the SHRs. Thus, PI3K signaling in the nucleus tractus solitarii of SHR restrains arterial pressure in this animal model of neurogenic hypertension.
Attention-spreading Based on Hierarchical Spatial Representations for Connected Objects
Authors: Kasai Tetsuko
Published: November 2008

Attention selects objects or groups as the most fundamental unit, and this may be achieved through a process in which attention automatically spreads throughout their entire region. Previously, we found that a lateralized potential relative to an attended hemifield at occipito-temporal electrode sites reflects attention-spreading in response to connected bilateral stimuli [Kasai, T., & Kondo, M. Electrophysiological correlates of attention-spreading in visual grouping. NeuroReport, 18, 93–98, 2007]. The present study examined the nature of object representations by manipulating the extent of grouping through connectedness, while controlling the symmetrical structure of bilateral stimuli. The electrophysiological results of two experiments consistently indicated that attention was guided twice in association with perceptual grouping in the early phase (N1, 150–200 msec poststimulus) and with the unity of an object in the later phase (N2pc, 310/330–390 msec). This suggests that there are two processes in object-based spatial selection, and these are discussed with regard to their cognitive mechanisms and object representations.
The Neural Development of an Abstract Concept of Number
Authors: Cantlon Jessica F. , Libertus Melissa E. , Pinel Philippe , Dehaene Stanislas , Brannon Elizabeth M. , Pelphrey Kevin A.
Published: November 2008

As literate adults, we appreciate numerical values as abstract entities that can be represented by a numeral, a word, a number of lines on a scorecard, or a sequence of chimes from a clock. This abstract, notation-independent appreciation of numbers develops gradually over the first several years of life. Here, using functional magnetic resonance imaging, we examine the brain mechanisms that 6- and 7-year-old children and adults recruit to solve numerical comparisons across different notation systems. The data reveal that when young children compare numerical values in symbolic and nonsymbolic notations, they invoke the same network of brain regions as adults including occipito-temporal and parietal cortex. However, children also recruit inferior frontal cortex during these numerical tasks to a much greater degree than adults. Our data lend additional support to an emerging consensus from adult neuroimaging, nonhuman primate neurophysiology, and computational modeling studies that a core neural system integrates notation-independent numerical representations throughout development but, early in development, higher-order brain mechanisms mediate this process.
Induced Alpha-band Oscillations Reflect Ratio-dependent Number Discrimination in the Infant Brain
Authors: Libertus Melissa E. , Pruitt Laura B. , Woldorff Marty G. , Brannon Elizabeth M.
Published: November 2008

Behavioral studies show that infants are capable of discriminating the number of objects or events in their environment, while also suggesting that number discrimination in infancy may be ratio-dependent. However, due to limitations of the dependent measures used with infant behavioral studies, the evidence for ratio dependence falls short of the vast psychophysical datasets that have established ratio dependence, and thus, adherence to Weber's Law in adults and nonhuman animals. We addressed this issue in two experiments that presented 7-month-old infants with familiar and novel numerosities while electroencephalogram measures of their brain activity were recorded. These data provide convergent evidence that the brains of 7-month-old infants detected numerical novelty. Alpha-band and theta-band oscillations both differed for novel and familiar numerical values. Most importantly, spectral power in the alpha band over midline and right posterior scalp sites was modulated by the ratio between the familiar and novel numerosities. Our findings provide neural evidence that numerical discrimination in infancy is ratio dependent and follows Weber's Law, thus indicating continuity of these cognitive processes over development. Results are also consistent with the idea that networks in the frontal and parietal cortices support ratio-dependent number discrimination in the first year of human life, consistent with what has been reported in neuroimaging studies in adults and older children.
Eight Arabic Block Prints from the Collection of Aziz S. Atiya
Authors: Muehlhaeusler Mark
Published: November 2008

This article describes a group of medieval Arabic block prints from the collection of Aziz S. Atiya preserved (with one exception) at the J. Willard Marriott Library at the University of Utah. It provides transcriptions of the texts, translations and notes, and discusses some aspects of the history of block-printing in the Middle East. This article also considers the place of block-printed amulets within the larger Islamic magical tradition, and examines parallels in a variety of sources.
L'énigme du manuscrit 1218b de la Baladiyya d'Alexandrie : un étrange vadémécum attribué faussement au traditionniste Ibn Huzayma
Authors: Gimaret Daniel
Published: November 2008

Contrairement à ce qui se lit dans Sezgin, GAS, I, 601, le Kitāb al-Tawhīd figurant dans un manuscrit d'Alexandrie et prétendument attribué à Ibn Huzayma (m. 311/924) s'avère à l'examen sans rapport aucun avec le célèbre ouvrage du non moins célèbre traditionniste. Divisé en une cinquantaine de chapitres, chacun consacré à l'explication d'un terme donné, le livre se présente comme un lexique à l'attention des ahl al-sunna wa-l-ğamāa. Y sont développées d'abord majoritairement les thèses classiques du sunnisme traditionaliste de type hanbalite, tant au plan théologique (foi indissociable des œuvres, contre les murği'ites ; réalité des attributs anthopomorphiques « sans chercher comment », contre les mu'tazilites ; etc.) que politique (légitimité des trois premiers califes, contre les chiites). Très vite cependant interviennent d'autres notions caractéristiques, elles, de la spiritualité soufie ou apparentée, où domine l'idée de renoncement au monde (zuhd), mais où se retrouvent aussi tous les mots-phares du vocabulaire mystique tels que mahabba, sabr, adab, ma'rifa, tawakkul, riyā, 'uğb, etc. Diverses raisons, de forme comme de fond, montrent à l'évidence, selon nous, que l'auteur du livre – où se remarquent par ailleurs bon nombre d'étrangetés – ne saurait être Ibn Huzayma. Quant à savoir qui est l'auteur véritable, la question reste pour l'instant sans réponse.
Les dialectes arabes modernes : état et nouvelles perspectives pour la classification géo-sociologique
Authors: Embarki Mohamed
Published: November 2008

La classification géographique et/ou sociologique des dialectes arabes modernes s'appuie, entre autres, sur certaines unités phonologiques qui, confrontées à une comparaison très minutieuse, ne s'avèrent pas fortement discriminantes. Les mêmes unités se retrouvent dans les parlers de plusieurs régions et variétés sociologiques à la fois en synchronie et en diachronie. Ont été revisitées plusieurs unités consonantiques et vocaliques dans diverses variétés linguistiques arabes (protoarabe, dialectes arabes anciens, arabe classique, arabe moyen, arabe moderne et dialectes arabes modernes). Devant cette extrême variabilité, la présente étude discute d'une part les éléments qui permettent de déceler dans les unités phonologiques celles produites par des développements parallèles vs celles qui sont le fruit des mécanismes de diffusion vs celles issues d'un processus d'héritage. L'hypothèse défendue dans cette étude est que certaines unités phonologiques, considérées comme discriminantes, sont le résultat soit d'un long héritage passé de l'arabe ancien aux dialectes arabes modernes, soit d'un processus de diffusion ample qui s'était développé à une époque très lointaine. D'autre part, elle verse dans le champ de la dialectologie arabe, à des fins de classification, des indices acoustiques fins dépendant de deux phénomènes différents, la coarticulation et la prosodie.
Declaratory Judgments and Official Apologies as Forms of Reparation for the Non-Material Damage Suffered by the State: the Djibouti-France Case
Authors: Fasoli Elena
Published: November 2008

The present article deals with the different manifestations of the non-material damage in inter-State legal relations. The recent decision rendered by the International Court of Justice on 4 June 2008 regarding certain questions of mutual assistance in criminal matters between Djibouti and France provides an opportunity to examine the intricate distinction between legal and moral damage and the consequences deriving therefrom, in terms of reparation. The judgment confirms a tendency emerging from legal literature as well as by international practice, that different types of non-material damage require different forms of reparation. Official apologies or public acknowledgment of the wrongful act – although also theoretically applicable as reparation for legal damage – are considered the most appropriate forms of reparation for the moral damage caused to a State. On the other hand, the judicial declaration of the unlawful character of an act appears an important reparatory result for the legal damage implicit in the breach of any international obligation.
Stimulating Research and Development of Pharmaceutical Products for Neglected Diseases
Authors: Stirner Beatrice
Published: November 2008

This article provides an introduction to the problem of pharmaceutical research and development of medicinal products for neglected diseases in developing countries. The prevailing market-based intellectual property incentive model of global pharmaceutical innovation has focussed health research priorities mainly on needs of industrialized countries. Increased international attention to the lack of health tools to prevent or treat diseases affecting impoverished regions has raised the discussion on how to encourage sustainable innovation in this area with little or no market. Proposals include models such as for example prize funds, advanced purchase commitments patent pools or creative licensing strategies and seek to complement the current intellectual property based incentive mechanism and government's innovation policy instruments such as tax credits or public research funds. Indispensable requirement to tackle the issue of neglected diseases, however, is a concerted commitment of all stakeholders on national and international levels.
The Rule of Exhaustion of Local Remedies in the Context of the Responsibility of International Organisations
Authors: Thallinger Gerhard
Published: November 2008

In the context of the responsibility of international organisations the duty to exhaust local remedies shall apply as a modified exhaustion of the internal remedies rule. Thereby, international organisations, like states, can avail themselves of the opportunity to rectify the behaviour of their organs by their own means. Against the backdrop of the raison d'être of international organisations, internal remedies do not necessarily have to meet the same stringent requirements as local remedies within states but must provide comparable legal redress. In order to render a claim against an international organisation admissible, such internal remedies have to be invoked beforehand. In toto, such an approach might serve as an incentive for international organisations to enhance means of legal review and promote legal protection of individuals against acts of international organisations that do today exercise state-like jurisdiction in an incremental number of instances.