bluuebunny/crossref_metadata_2025 huggingface dataset:
Noroviruses Distinguish between Type 1 and Type 2 Histo-Blood Group Antigens for Binding
Authors: Shirato Haruko , Ogawa Satoko , Ito Hiromi , Sato Takashi , Kameyama Akihiko , Narimatsu Hisashi , Xiaofan Zheng , Miyamura Tatsuo , Wakita Takaji , Ishii Koji , Takeda Naokazu
Published: August 2008

Norovirus (NoV) is a causative agent of acute gastroenteritis. NoV binds to histo-blood group antigens (HBGAs), namely, ABH antigens and Lewis (Le) antigens, in which type 1 and type 2 carbohydrate core structures constitute antigenically distinct variants. Norwalk virus, the prototype strain of norovirus, binds to the gastroduodenal junction, and this binding is correlated with the presence of H type 1 antigen but not with that of H type 2 antigen (S. Marionneau, N. Ruvoen, B. Le Moullac-Vaidye, M. Clement, A. Cailleau-Thomas, G. Ruiz-Palacois, P. Huang, X. Jiang, and J. Le Pendu, Gastroenterology
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:1967-1977, 2002). It has been unknown whether NoV distinguishes between the type 1 and type 2 chains of A and B antigens. In this study, we synthesized A type 1, A type 2, B type 1, and B type 2 pentasaccharides in vitro and examined the function of the core structures in the binding between NoV virus-like particles (VLPs) and HBGAs. The attachment of five genogroup I (GI) VLPs from 5 genotypes and 11 GII VLPs from 8 genotypes, GI/1, GI/2, GI/3, GI/4, GI/8, GII/1, GII/3, GII/4, GII/5, GII/6, GII/7, GII/12, and GII/14, to ABH and Le HBGAs was analyzed by enzyme-linked immunosorbent assay-based binding assays and Biacore analyses. GI/1, GI/2, GI/3, GI/4, GI/8, and GII/4 VLPs were more efficiently bound to A type 2 than A type 1, and GI/8 and GII/4 VLPs were more efficiently bound to B type 2 than B type 1, indicating that NoV VLPs distinguish between type 1 and type 2 carbohydrates. The dissociation of GII/4 VLPs from B type 1 was slower than that from B type 2 in the Biacore experiments; moreover, the binding to B type 1 was stronger than that to B type 2 in the ELISA experiments. These results indicated that the type 1 carbohydrates bind more tightly to NoV VLPs than the type 2 carbohydrates. This property may afford NoV tissue specificity. GII/4 is known to be a global epidemic genotype and binds to more HBGAs than other genotypes. This characteristic may be linked with the worldwide transmission of GII/4 strains. GI/2, GI/3, GI/4, GI/8, GII/4, and GII/7 VLPs bound to Le
a
expressed by nonsecretors, suggesting that NoV can infect individuals regardless of secretor phenotype. Overall, our results indicated that HBGAs are important factors in determining tissue specificity and the risk of transmission.
A Viral Noncoding RNA Generated bycis-Element-Mediated Protection against 5′→3′ RNA Decay Represses both Cap-Independent and Cap-Dependent Translation
Authors: Iwakawa Hiro-oki , Mizumoto Hiroyuki , Nagano Hideaki , Imoto Yuka , Takigawa Kazuma , Sarawaneeyaruk Siriruk , Kaido Masanori , Mise Kazuyuki , Okuno Tetsuro
Published: August 2008

Positive-strand RNA viruses use diverse mechanisms to regulate viral and host gene expression for ensuring their efficient proliferation or persistence in the host. We found that a small viral noncoding RNA (0.4 kb), named SR1f, accumulated inRed clover necrotic mosaic virus(RCNMV)-infected plants and protoplasts and was packaged into virions. The genome of RCNMV consists of two positive-strand RNAs, RNA1 and RNA2. SR1f was generated from the 3′ untranslated region (UTR) of RNA1, which contains RNA elements essential for both cap-independent translation and negative-strand RNA synthesis. A 58-nucleotide sequence in the 3′ UTR of RNA1 (Seq1f58) was necessary and sufficient for the generation of SR1f. SR1f was neither a subgenomic RNA nor a defective RNA replicon but a stable degradation product generated by Seq1f58-mediated protection against 5′→3′ decay. SR1f efficiently suppressed both cap-independent and cap-dependent translation both in vitro and in vivo. SR1ftransinhibited negative-strand RNA synthesis of RCNMV genomic RNAs via repression of replicase protein production but not via competition of replicase proteins in vitro. RCNMV seems to use cellular enzymes to generate SR1f that might play a regulatory role in RCNMV infection. Our results also suggest that Seq1f58 is an RNA element that protects the 3′-side RNA sequences against 5′→3′ decay in plant cells as reported for the poly(G) tract and stable stem-loop structure inSaccharomyces cerevisiae.
Targeting the Retinoblastoma Protein by MC007L, Gene Product of the Molluscum Contagiosum Virus: Detection of a Novel Virus-Cell Interaction by a Member of the Poxviruses
Authors: Mohr Stefan , Grandemange Stéphanie , Massimi Paola , Darai Gholamreza , Banks Lawrence , Martinou Jean-Claude , Zeier Martin , Muranyi Walter
Published: August 2008

The human pathogenic poxvirus molluscum contagiosum virus (MCV) is the causative agent of benign neoplasm, with worldwide incidence, characterized by intraepidermal hyperplasia and hypertrophy of cells. Here, we present evidence that the MC007L protein of MCV targets retinoblastoma protein (pRb) via a conserved LxCxE motif, which is present in many viral oncoproteins. The deregulation of the pRb pathway plays a central role in tumor pathogenesis. The oncoproteins of small DNA viruses contain amino acid sequences that bind to and inactivate pRb. Isolated expression of these oncoproteins induces apoptosis, cell proliferation, and cellular transformation. The MC007L gene displays no homology to other genes within the poxvirus family. The protein anchors into the outer mitochondrial membrane via an N-terminal mitochondrial targeting sequence. Through the LxCxE motifs, MC007L induces a cytosolic sequestration of pRb at mitochondrial membranes, leading to the inactivation of the protein by mislocalization. MC007L precipitates the endogenous pRb/E2F-1 complex. Moreover, MC007L is able to cooperate to transform primary rat kidney cells. The interaction between MC007L and pRb provides a novel mechanism by which a virus can perturb the cell cycle.
Who does not need a statin: too late in end-stage renal disease or heart failure?
Authors: Laufs U , Custodis F , Böhm M
Published: August 2008

Current guidelines from large randomised trials recommend that all patients with diabetes type 2 or coronary artery disease after myocardial infarction should be treated with statin drugs. However, the recent 4D and CORONA trials show no improvement in mortality in elderly patients with ischaemic heart failure and patients with diabetes and end-stage renal disease receiving haemodialysis with the onset of statin treatment. The survival benefit from statin treatment appears to stem primarily from the prevention of progression of coronary artery disease. In clinical conditions where coronary artery disease does not significantly contribute to the cause of death statins seem to be less effective. In patients at risk for organ damage, statin treatment, therefore, has to be started early in the course of the disease. The effect of statin withdrawal in ischaemic heart failure or in patients with advanced renal disease is not known. On the basis of the available evidence, current statin treatment should not be stopped in these patients.
FLEXOR DIGITORUM PROFUNDUS AVULSION OF THE LEFT LITTLE FINGER THROUGH ENCHONDROMA OF THE DISTAL PHALANX: PULL-OUT WIRE TECHNIQUE TREATMENT WITHOUT BONE GRAFT
Authors: Yamauchi Toru , Yoshii Takashi , Sempuku Takeo
Published: August 2008

This case report describes the rare occurrence of a flexor digitorum profundus (FDP) avulsion of the left little finger in association with a pathological fracture of an enchondroma. The enchondroma was treated by simple curettage without bone graft. The FDP tendon was re-attached to the distal phalanx using the pull-out technique with a non-absorbable polyethylene suture.

We recommend simple curettage without bone grafting in cases of enchondroma of the distal phalanx in which the bone defect is small.
CLINICAL RESULT OF OPERATIVE TREATMENT FOR SCAPHOID NON-UNION IN THE SKELETALLY IMMATURE: PERCUTANEOUS VERSUS OPEN PROCEDURE
Authors: Jeon In-Ho , Kochhar Hemanshu , Micic Ivan D. , Oh Soo-Hoon , Kim Shin-Yoon , Kim Poong Taek
Published: August 2008

This article is a retrospective study of 13 cases of scaphoid non-union in skeletally immature patients.

For the fracture fixation, three cases of stable fibrous union with minimal sclerosis, without deformity or cystic changes were considered for the percutaneous Herbert screw fixation. Ten cases were managed with the open reduction and internal fixation with or without bone grafting.

The average union time was 10.5 weeks post-operatively. The average union time was lesser in percutaneous Herbert screw fixation group (nine weeks) than open procedure group (11.5 weeks). All cases achieved union without any supplemental procedures. According to Cooney's clinical scoring, 12 cases were rated excellent result and one good result.

The percutaneous Herbert screw fixation for scaphoid non-union in skeletally immature patients can be a good treatment option when it is fibrous union with no deformity.
DELAYED RUPTURE OF FLEXOR TENDONS CAUSED BY PROTRUSION OF A SCREW HEAD OF A VOLAR PLATE FOR DISTAL RADIUS FRACTURE: A CASE REPORT
Authors: Yamazaki Hiroshi , Hattori Yasunori , Doi Kazuteru
Published: August 2008

We report a rare occurrence of attritional rupture of flexor tendons caused by protrusion of the screw head of the volar radius plate. The cause of the protrusion was plate placement on the prominent distal volar lip of the radius and secondary loss of the original reduction due to using a non-locking osteosynthesis system for the treatment of displaced intra-articular fracture of the distal radius.
ENDOSCOPIC CARPAL TUNNEL RELEASE: OUR EXPERIENCE WITH 12,702 CASES
Authors: Pajardi Giorgio , Pegoli Loris , Pivato Giorgio , Zerbinati Paolo
Published: August 2008

Carpal tunnel syndrome (CTS) is still today the most common nerve entrapment syndrome at the level of the upper extremity. When surgery is indicated, the surgical treatment of choice is the opening of the retinaculum. The authors describe their experience on 12,702 carpal tunnel decompressions, by the endoscopic procedure in a period of 14 years, outlining the indications, post-operative treatment, complications and results.
GRID APPLICATION FAULT DIAGNOSIS USING WRAPPER SERVICES AND MACHINE LEARNING
Authors: HOFER JÜRGEN , FAHRINGER THOMAS
Published: August 2008

Quick and accurate identification of the root cause of failures is an important prerequisite for any reliable system. However with increasing Grid size and complexity, the manual diagnosis of application faults becomes impractical, tedious and time-consuming. So far there has been a lack of systematic and comprehensive studies in organization and classification of Grid faults. We address this gap with a multi-perspective Grid fault taxonomy precisely describing an incident using eight different characteristics. Based on that, we develop a pragmatic model-based technique for application-specific fault diagnosis using indicators, symptoms and rules. Customized wrapper services then apply this knowledge to reason about the root causes of failures. In addition to applying user-provided diagnosis models we demonstrate that given a set of past classified fault events it is possible to automatically extract new models through learning. We investigated and compared several supervised classification learning and cluster analysis algorithms for this purpose. Our approach was implemented as part of the Otho Toolkit, a framework for "service-enabling" legacy applications by synthesizing tailor-made wrapper service.
SERVICE LICENSING COMPOSITION AND COMPATIBILITY ANALYSIS
Authors: GANGADHARAN G. R. , D'ANDREA VINCENZO , WEISS MICHAEL
Published: August 2008

Services enable the transformation of the World Wide Web as distributed interoperable systems interacting beyond organizational boundaries. Service licensing enables broader usage of services and a means for designing business strategies and relationships. A service license describes the terms and conditions for the use and access of the service in a machine interpretable way that services could be able to understand. Service-based applications are largely grounded on composition of independent services. In that scenario, license compatibility is a complex issue, requiring careful attention before attempting to merge licenses. The permissions and the prohibitions imposed by the licenses of services would deeply impact the composition. Thus, service licensing requires a comprehensive analysis on composition of these rights and requirements conforming to the nature of operations performed and compensation of services used in composition. In this paper, we analyze the compatibility of service license by describing a matchmaking algorithm. Further, we illustrate the composability of service licenses by creating a composite service license that is compatible with the licenses being composed.
ONTOLOGY- AND BEHAVIOR-AWARE DISCOVERY OF WEB SERVICE COMPOSITIONS
Authors: BROGI ANTONIO , CORFINI SARA
Published: August 2008

Web service discovery is one of the key issues in the emerging area of Service-oriented Computing. In this paper, we present a complete composition-oriented, ontology-based methodology for discovering semantic Web services, which exploits functional and behavioral properties contained in OWL-S service advertisements to satisfy functional and behavioral client queries. To this aim, we build on top of the results contained in two recent articles, where we presented (1) a suitable data structure (viz. a dependency hypergraph) to collect functional information of services, and (2) a suitable notion of behavioral equivalence for Web services. We also discuss the architecture and the main implementation choices of the matchmaking system applying such a methodology.
WS-CONTRACT ESTABLISHMENT WITH QOS: AN APPROACH BASED ON FEATURE MODELING
Authors: FANTINATO MARCELO , DE TOLEDO MARIA BEATRIZ FELGAR , DE SOUZA GIMENES ITANA MARIA
Published: August 2008

Electronic contracts describe inter-organizational business processes in terms of supply and consumption of electronic services (commonly Web services). The establishment of e-contracts in a particular business domain usually involves a set of well-defined common and variable properties. These properties are not fully exploited by the existing e-contract establishment approaches. Feature modeling is a software engineering technique that has been widely used for capturing and managing commonalities and variabilities of product families in the context of software product line. This paper presents a feature-based approach to support Web services e-contract (WS-contract) establishment. The approach aims at improving the information structure and reuse of WS-contracts, including the QoS attributes. Features are used to represent possible WS-contract elements in order to drive WS-contract template instantiation, thus acting as a configuration space manager. A toolkit named FeatureContract was developed to automatically support the proposed approach. A case study was carried out within the telecom context to show the approach feasibility.
TNF induction of atrogin-1/MAFbx mRNA depends on Foxo4 expression but not AKT-Foxo1/3 signaling
Authors: Moylan Jennifer S. , Smith Jeffrey D. , Chambers Melissa A. , McLoughlin Thomas J. , Reid Michael B.
Published: August 2008

Murine models of starvation-induced muscle atrophy demonstrate that reduced protein kinase B (AKT) function upregulates the atrophy-related gene atrogin-1/MAFbx (atrogin). The mechanism involves release of inhibition of Forkhead transcription factors, namely Foxo1 and Foxo3. Elevated atrogin mRNA also corresponds with elevated TNF in inflammatory catabolic states, including cancer and chronic heart failure. Exogenous tumor necrosis factor (TNF) increases atrogin mRNA in vivo and in vitro. We used TNF-treated C2C12 myotubes to test the hypothesis that AKT-Foxo1/3 signaling mediates TNF regulation of atrogin mRNA. Here we confirm that exposure to TNF increases atrogin mRNA (+125%). We also confirm that canonical AKT-mediated regulation of atrogin is active in C2C12 myotubes. Inhibition of phosphoinositol-3 kinase (PI3K)/AKT signaling with wortmannin reduces AKT phosphorylation (−87%) and increases atrogin mRNA (+340%). Activation with insulin-like growth factor (IGF) increases AKT phosphorylation (+126%) and reduces atrogin mRNA (−15%). Although AKT regulation is intact, our data suggest it does not mediate TNF effects on atrogin. TNF increases AKT phosphorylation (+50%) and stimulation of AKT with IGF does not prevent TNF induction of atrogin mRNA. Nor does TNF appear to signal through Foxo1/3 proteins. TNF has no effect on Foxo1/3 mRNA or Foxo1/3 nuclear localization. Instead, TNF increases nuclear Foxo4 protein (+55%). Small interfering RNA oligos targeted to two distinct regions of Foxo4 mRNA reduce the TNF-induced increase in atrogin mRNA (−34% and −32%). We conclude that TNF increases atrogin mRNA independent of AKT via Foxo4. These results suggest a mechanism by which inflammatory catabolic states may persist in the presence of adequate growth factors and nutrition.
Nonmuscle myosin II is responsible for maintaining endothelial cell basal tone and stress fiber integrity
Authors: Goeckeler Zoe M. , Bridgman Paul C. , Wysolmerski Robert B.
Published: August 2008

Cultured confluent endothelial cells exhibit stable basal isometric tone associated with constitutive myosin II regulatory light chain (RLC) phosphorylation. Thrombin treatment causes a rapid increase in isometric tension concomitant with myosin II RLC phosphorylation, actin polymerization, and stress fiber reorganization while inhibitors of myosin light chain kinase (MLCK) and Rho-kinase prevent these responses. These findings suggest a central role for myosin II in the regulation of endothelial cell tension. The present studies examine the effects of blebbistatin, a specific inhibitor of myosin II activity, on basal tone and thrombin-induced tension development. Although blebbistatin treatment abolished basal tension, this was accompanied by an increase in myosin II RLC phosphorylation. The increase in RLC phosphorylation was Ca2+dependent and mediated by MLCK. Similarly, blebbistatin inhibited thrombin-induced tension without interfering with the increase in RLC phosphorylation or in F-actin polymerization. Blebbistatin did prevent myosin II filament incorporation and association with polymerizing or reorganized actin filaments leading to the disappearance of stress fibers. Thus the inhibitory effects of blebbistatin on basal tone and induced tension are consistent with a requirement for myosin II activity to maintain stress fiber integrity.
Apoptosis-induced alkalinization by the Na+/H+ exchanger isoform 1 is mediated through phosphorylation of amino acids Ser726 and Ser729
Authors: Grenier Amy L. , Abu-ihweij Khaled , Zhang Ge , Ruppert Shannon Moore , Boohaker Rebecca , Slepkov Emily R. , Pridemore Kathryn , Ren Jian-Jian , Fliegel Larry , Khaled Annette R.
Published: August 2008

Apoptosis is a complex process essential for normal tissue development and cellular homeostasis. While biochemical events that occur late in the apoptotic process are better characterized, early physiological changes that initiate the progression of cell death remain poorly understood. Previously, we observed that lymphocytes, undergoing apoptosis in response to growth factor withdrawal, experienced a rapid and transient rise in cytosolic pH. We found that the protein responsible was the pH-regulating, plasma membrane protein Na+/H+ exchanger isoform 1 (NHE1), and that its activity was impeded by inhibition of the stress-activated kinase, p38 MAP kinase. In the current study, we examined how NHE1 is activated during apoptosis. We identified the phosphorylation sites on NHE1 that regulate its alkalinizing activity in response to a cell death stimulus. Performing targeted mutagenesis, we observed that substitution of Ser726 and Ser729 for alanines produced a mutant form of NHE1 that did not alkalinize in response to an apoptotic stimulus, and expression of which protected cells from serum withdrawal- induced death. In contrast, substitution of Ser726 and Ser729 for glutamic acids raised the basal pH and induced susceptibility to death. Analysis of serine phosphorylation showed that phosphorylation of NHE1 during apoptosis decreased upon mutation of Ser726 and Ser729. Our findings thus confirm a necessary function for NHE1 during apoptosis and reveal the critical regulatory sites that when phosphorylated mediate the alkalinizing activity of NHE1 in the early stages of a cell death response.
The gut does not contribute to systemic ammonia release in humans without portosystemic shunting
Authors: van de Poll Marcel C. G. , Ligthart-Melis Gerdien C. , Olde Damink Steven W. M. , van Leeuwen Paul A. M. , Beets-Tan Regina G. H. , Deutz Nicolaas E. P. , Wigmore Stephen J. , Soeters Peter B. , Dejong Cornelis H. C.
Published: August 2008

The gut is classically seen as the main source of circulating ammonia. However, the contribution of the intestines to systemic ammonia production may be limited by hepatic extraction of portal-derived ammonia. Recent data suggest that the kidney may be more important than the gut for systemic ammonia production. The aim of this study was to quantify the role of the kidney, intestines, and liver in interorgan ammonia trafficking in humans with normal liver function. In addition, we studied changes in interorgan nitrogen metabolism caused by major hepatectomy. From 21 patients undergoing surgery, blood was sampled from the portal, hepatic, and renal veins to assess intestinal, hepatic, and renal ammonia metabolism. In seven cases, blood sampling was repeated after major hepatectomy. At steady state during surgery, intestinal ammonia release was equaled by hepatic ammonia uptake, precluding significant systemic release of intestinal-derived ammonia. In contrast, the kidneys released ammonia to the systemic circulation. Major hepatectomy led to increased concentrations of ammonia and amino acids in the systemic circulation. However, transsplanchnic concentration gradients after major hepatectomy were similar to baseline values, indicating the rapid institution of a new metabolic equilibrium. In conclusion, since hepatic ammonia uptake exactly equals intestinal ammonia release, the splanchnic area, and hence the gut, probably does not contribute significantly to systemic ammonia release. After major hepatectomy, hepatic ammonia clearance is well preserved, probably related to higher circulating ammonia concentrations.
Caloric restriction optimizes the proteasome pathway with aging in rat plantaris muscle: implications for sarcopenia
Authors: Hepple Russell T. , Qin Maggie , Nakamoto Hideko , Goto Sataro
Published: August 2008

To gain insight into the significance of alterations in the proteasome pathway for sarcopenia and its attenuation by calorie restriction, we examined protein oxidation and components of the proteasome pathway in plantaris muscle in 8-, 30-, and 35-mo-old ad libitum-fed (AL) rats; and in 8-, 35-, and 40-mo-old calorie-restricted (CR) rats. We hypothesized that CR rats would exhibit a lesser accumulation of protein carbonyls with aging and that this would be associated with a better maintenance of skeletal muscle proteasome activity and function with aging. Consistent with this view, whereas AL rats had a significant increase in protein carbonylation with aging, there was no such increase in CR rats. Protein levels of the ubiquitin ligases MuRF1 and MAFbx increased similarly with aging in both AL and CR rats. On the other hand, chymotrypsin-like activity of the proteasome increased with aging more gradually in CR rats, and this increase was paralleled by increases in the expression of the C2 subunit in both groups, suggesting that differences in activity were not related to differences in proteasome function with aging. Interestingly, the plot of muscle mass vs. proteasome activity showed that the oldest animals in both diets had a lower muscle mass than would be predicted by their proteasome activity, suggesting that other factors explain the acceleration of sarcopenia at advanced age. Since calorie restriction better protects skeletal muscle function than muscle mass with aging (Hepple RT, Baker DJ, Kaczor JJ, Krause DJ, FASEB J 19: 1320–1322, 2005), and our current results show that this protection of function is associated with a prevention of oxidative protein damage accumulation, we suggest that calorie restriction optimizes the proteasome pathway to preserve skeletal muscle function at the expense of modest muscle atrophy.
Birdsong Decreases Protein Levels of FoxP2, a Molecule Required for Human Speech
Authors: Miller Julie E. , Spiteri Elizabeth , Condro Michael C. , Dosumu-Johnson Ryan T. , Geschwind Daniel H. , White Stephanie A.
Published: August 2008

Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.
Threshold Tuning Curves of Chinchilla Auditory-Nerve Fibers. I. Dependence on Characteristic Frequency and Relation to the Magnitudes of Cochlear Vibrations
Authors: Temchin Andrei N. , Rich Nola C. , Ruggero Mario A.
Published: August 2008

Frequency-threshold tuning curves were recorded in thousands of auditory-nerve fibers (ANFs) in chinchilla. Synthetic tuning curves with 21 characteristic frequencies (187 Hz to 19.04 kHz, spaced every 1/3 octave) were constructed by averaging individual tuning curves within 2/3-octave frequency bands. Tuning curves undergo a gradual transition in symmetry at characteristic frequencies (CFs) of 1 kHz and an abrupt change in shape at CFs of 3–4 kHz. For CFs ≤3 kHz, the lower limbs of tuning curves have similar slopes, about −18 dB/octave, but the upper limbs have slopes that become increasingly steep with increasing frequency and CF. For CFs >4 kHz, tuning curves normalized to the CF are nearly identical and consist of three segments. A tip segment, within 30–40 dB of CF threshold, has lower- and upper-limb slopes of −60 and +120 dB/octave, respectively, and is flanked by a low-frequency (“tail”) segment, with shallow slope, and a terminal high-frequency segment with very steep slope (several hundreds of dB/octave). The tuning curves of fibers innervating basal cochlear sites closely resemble basilar-membrane tuning curves computed with low isovelocity criteria. At the apex of the chinchilla cochlea, frequency tuning is substantially sharper for ANFs than for available recordings of organ of Corti vibrations.
Different Atrophic Patterns in Early- and Late-Onset Alzheimer’s Disease and Evaluation of Clinical Utility of a Method of Regional z-Score Analysis Using Voxel-Based Morphometry
Authors: Shiino Akihiko , Watanabe Toshiyuki , Kitagawa Tadashi , Kotani Emi , Takahashi June , Morikawa Shigehiro , Akiguchi Ichiro
Published: August 2008

Background/Aims: We evaluated the differential patterns of brain atrophy in early- and late-onset Alzheimer’s disease (AD) by measuring regional z-scores of voxel-based morphometry and assessed the availability of the method for clinical use. Methods: The first 50 patients with probable AD were compared to 83 age-matched control subjects to identify the brain atrophy. Regions of interest were set in the areas showing z-scores >4. To find substantial differences in the atrophy pattern, principal component analysis was performed. The second group of 56 patients with memory complaints entered the study for evaluation of the clinical use of the model. Results: The centers of the regions of interest were the amygdala, anterior hippocampi, posterior hippocampi, temporal cortices and subcallosal cortex, and left posterior cingulate cortex (PCC). Eigenvectors of the temporal cortices and left PCC showed counter-directions to those of patient age, suggesting that patients with younger onset age were preferentially associated with atrophy of those regions. Differential analyses of the second group showed high availability for the detection of abnormal brain atrophy in people with subjective memory complaints. Conclusion: AD with earlier onset is preferentially related to PCC and temporal lobe atrophy. Voxel-based morphometry can be statistically analyzed, and this method has the potential for bias-free assessment of brain atrophy.
The Survival of Herpes Simplex Virus in Preserved Murine Corneas
Authors: Robert Pierre-Yves , Ducher Virginie , Pleyer Uwe , Denis François , Adenis Jean-Paul , Ranger-Rogez Sylvie
Published: August 2008

Background/Aims: This study investigates the survival of HSV in infected mouse corneas, in the conditions of normal human eye bank preservation. Methods: Hundred seventy-two BALB/C mice infected with herpes simplex virus 1 (HSV-1) (KOS) were randomly assigned to either: no preservation in group 1 (n = 62), 31°C preservation for 3 weeks in group 2 (n = 70) or 4°C preservation for 8 days in group 3 (n = 40). The presence of HSV-1 was thereafter detected by viral culture and PCR. Results: In groups 1, 2 and 3, HSV-1 was detected by culture in 22 (35.5%), 1 (1.4%) and 0 (0.0%) of the corneas, and by PCR in 27 (43.7%), 3 (4.2%) and 7 (17.5%) of the corneas respectively. When compared to group 1, HSV was detected significantly less often in groups 2 (p < 0.0001) and 3 (p < 0.0001). Conclusions: HSV-1 DNA undergoes a degradation during corneal preservation.
Computer-Based Visual Evaluation as a Screening Tool after Intravitreal Injections of Vascular Endothelial Growth Factor Inhibitors
Authors: Meyer Carsten H. , Lapolice Deborah J.
Published: August 2008

Purpose: To evaluate the visual acuity (VA) of patients following intravitreal (IVT) injections. Methods: 15 patients received 3 anti-vascular-endothelial-growth-factor (VEGF) injections on a monthly basis. Prior to each injection as well as 2 months after, the patients received a standardized examination including Snellen VA and optical coherence tomography (OCT). During this time the patients were trained to evaluate their central VA by 3 computer-based tests: (a) VA was examined by the patient on a computer-based vision chart and (b) subjectively categorized as ‘same’, ‘worse’ or ‘better’; (c) the edge of metamorphopsia was outlined on a digital Amsler grid. Results: VA improved during the 3 injections by ≥2 lines (13/15). The assessment demonstrated subjective improvement (13/15), i.e. a gain of 2 or more lines or decreased central metamorphopsia (12/15). Reevaluation 2 months later demonstrated a decline of ≥1 Snellen line or increased retinal thickness on OCT (8/15), and a decline of ≥1 line or an enlarged metamorphopsia in the computer-based tests (6/15). Conclusion: Our pilot study demonstrated a good correlation between the professional examination and the computer-based assessment. Selected patients can define their visual impairment. A web-based VA evaluation may help to screen patients after IVT injections on a regular basis at home.
UVA/Riboflavin-Induced Apoptosis in Mouse Cornea
Authors: Wang F.
Published: August 2008

Background: A mouse model of combined UVA/riboflavin irradiation to eliminate stromal cells and other antigen-presenting cells in the cornea provides the basis for a probably low risk of corneal transplantation. Methods: After abrasion of the epithelium, the central corneas of mouse eyes were treated with UVA/riboflavin in vitro. Histological studies of hematoxylin-eosin and immunohistochemical staining with caspase 3 were performed. Dissected mouse corneas were analyzed by Western blot. Results: Apoptotic cells were shown on the central corneal stroma; a cell-free zone was displayed in the cornea. Numbers of dead cells increased according to cultivation time. However, the endothelium survived due to the adjustment of the irradiation dose. Conclusions: A cell-free zone in the stroma of the mouse cornea was produced by UVA/riboflavin irradiation in vitro. The technique makes possible to prevent or reduce immunological reactions and the risk of graft rejection by pretreatment of the donor cornea, ultimately prolonging graft survival.
Fluoroquinolone Resistance in Clinical Isolates of Klebsiella oxytoca
Authors: Horii Toshinobu , Osaki Mai , Muramatsu Hideaki
Published: August 2008

Background: Prevalence of fluoroquinolone-resistant Klebsiella oxytoca has been reported worldwide. Methods: We recovered ten clinical K. oxytoca isolates from patients with acute cystitis, asymptomatic bacteriuria or acute bacillary diarrhea in Japan. Out of ten isolates, one fluoroquinolone-susceptible isolate was included as a control. Fluoroquinolone resistance was characterized genetically by PCR and DNA sequencing methods. Outer membrane protein (OMP) profiles were determined by SDS-PAGE. Results: In nine clinical isolates of levofloxacin-resistant K. oxytoca, nucleotide sequences in the quinolone-resistance-determining regions showed amino acid mutations such as Thr83Ile and Asp87Gly in GyrA and Ser80Ile in ParC. Combined effects of reduced 36-kDa OMP production and amino acid mutations in GyrA and ParC were shown by two K. oxytoca isolates exhibiting higher minimum inhibitory concentrations for fluoroquinolones than other fluoroquinolone-resistant isolates. Conclusions: In clinical K. oxytoca isolates, the various mechanisms of fluoroquinolone resistance may include reduced 36-kDa OMP production as well as GyrA and ParC mutations.
How Has Genomics Altered Our View of Caries Microbiology?
Authors: Russell R.R.B.
Published: August 2008

Genome sequencing and other molecular techniques for the identification and characterisation of bacteria have provided us with a vast amount of new information, both on the detailed properties of certain species and on the total plaque microflora. Thus, from genomics, we have gained many valuable insights into the biology of Streptococcus mutans and the diversity within the species, while molecular techniques of identification have prompted a heightened awareness of the importance of species other than S. mutans to the caries process. S. mutans remains deserving of detailed study, both as an exemplar of an acidogenic, aciduric plaque bacterium and because it shows a strong association with caries. Nevertheless, its value as a target for inhibitors and its useful- ness as an indicator organism for monitoring the value of caries prediction or prevention need to be evaluated in the light of new discoveries.
The Influence of Pit and Fissure Sealants on Infrared Fluorescence Measurements
Authors: Diniz M.B. , Rodrigues J.A. , Hug I. , Cordeiro R.C.L. , Lussi A.
Published: August 2008

The aim of this in vitro study was to evaluate the influence of pit and fissure sealants on fluorescence readings using lasers. We selected 166 permanent molars and randomly divided them into 4 groups which were each treated with a different sealant (a commercially available clear sealant, 2 opaque sealants and an experimental nanofilled clear sealant). The teeth were independently measured twice by 2 experienced dentists using conventional laser fluorescence (LF) and a laser fluorescence pen device (LFpen), before and after sealing, and again after thermocycling to simulate the thermal stressing between the tooth and the dental materials. Friedman test showed no statistically significant changes using LF and LFpen for the commercial clear sealant group, although values tended to increase after sealing. However, the values increased significantly after thermocycling. There was a statistically significant decrease in fluorescence after application of opaque sealants. After application of the experimental nanofilled clear sealant, LF values increased only after thermocycling, whereas the LFpen values increased after sealing and after thermocycling as well. The intraclass correlation coefficient ranged from 0.87 to 0.96 for interexaminer and 0.82 to 0.94 for intraexaminer reproducibility. It was shown that pit and fissure sealants influence LF and LFpen readings, with the values increasing or decreasing according to the material used. In conclusion, both laser fluorescence devices could be useful as an adjunct to detect occlusal caries under unfilled clear sealants. Nevertheless, surfaces sealed with clear nanofilled material could be assessed using only the LF device.
Fibromodulin-Deficient Mice Reveal Dual Functions for Fibromodulin in Regulating Dental Tissue and Alveolar Bone Formation
Authors: Goldberg Michel , Ono Mitsuaki , Septier Dominique , Bonnefoix Mireille , Kilts Tina M. , Bi Yanming , Embree Mildred , Ameye Laurent , Young Marian F.
Published: August 2008

The extracellular matrix of newborn, 7- and 21-day-old fibromodulin-deficient (Fmod KO) mice was compared with age-matched wild-type (WT) mice. Western blotting of proteins from 21-day-old WT mice revealed that the molecular weight of Fmod is smaller in dental tissues (approx. 40 kDa) compared to alveolar bone extracts (approx. 52 kDa). Dentin matrix protein1 (DMP1) was slightly increased in Fmod KO versus WT tooth extracts. After chondroitinase ABC digestion, dentin sialophosphoprotein (DSPP) appeared as 2 strong bands (approx. 150 and 70 kDa) in incisors from 21-day-old Fmod KO mice, whereas the smaller-sized species of DSPP was nearly absent in WT molars and no difference was detected between WT and KO mice in molars. Dentin mineralization was altered in newborn and 7-day-old KO mice, but seemed normal in 21-day-old KO mice. DMP1 and DSPP may be involved in compensatory mechanisms. The enamel had a twisted appearance and looked porous at day 21 in KO incisor, and the outer aprismatic layer was missing in the molar. Alveolar bone formation was enhanced in Fmod KO mice at days 0 and 7, whereas no difference was detected at day 21. We conclude that Fmod may control dental tissue formation and early maturation, where it acts mostly as an inhibitor in alveolar bone accumulation, excerpting its effects only at early developing stages. These dual functions may be related to the different forms of Fmod found in bone versus teeth.
Bisphosphonates and Osteonecrosis of the Jaw: Moving from the Bedside to the Bench
Authors: Allen Matthew R.
Published: August 2008

Osteonecrosis of the jaw (ONJ) has received significant attention as a potential side effect of bisphosphonate treatment. The limited understanding of the underlying pathophysiology of the condition emphasizes the need to transition ONJ research from the bedside to the bench, supplementing ongoing clinical research with animal/basic science studies. The goal of this review is to briefly highlight the most commonly proposed mechanisms for ONJ and then summarize our laboratory’s recent efforts to begin transitioning ONJ research to an animal model. Remodeling suppression, disrupted angiogenesis and infection have all been proposed to connect bisphosphonates to ONJ, although most supportive data for each of these are either indirect or nonexistent. Our laboratory has begun studying the dog as a potential model of ONJ. We have shown regions of necrotic bone matrix within the mandible of dogs treated with oral or intravenous bisphosphonate. We hypothesize these regions are the result of remodeling suppression, and if combined with additional factors such as dental intervention or infection, would result in manifestation of exposed oral lesions, the clinical definition of ONJ. Although these findings suggest the dog may be a viable animal model to study ONJ, many questions remain unanswered. No matter what animal model is found to mimic the clinical presentation of ONJ, once established it will allow significant progress toward understanding the specific role of bisphosphonates in the pathophysiology of ONJ and if/how the entity of ONJ can best be treated and prevented.
Functional Roles of Prolines at Amelogenin C Terminal during Tooth Enamel Formation
Authors: Zhu Li , Tanimoto Kotaro , Le Thuan , DenBesten Pamela K. , Li Wu
Published: August 2008

Amelogenins, the chief proteins in enamel matrix, undergo progressive degradation by matrix metalloproteinase-20 (MMP-20) to facilitate crystal growth. Proline is the most abundant residue in amelogenin and is located upstream to all MMP-20 cleavage sites in the amelogenin sequence. Pro41 is critical for amelogenin N-terminal processing, while the role of prolines at the amelogenin C terminus have not been determined. This study sought to elucidate the effect of the C-terminal prolines on apatite binding and MMP-20 hydrolysis. To compare apatite affinity, recombinant full-length human amelogenin (rh174) and mutated variants (P156T and P164T) were incubated with hydroxyapatite (HAP), and the unbound proteins were quantified by the Bradford assay. rh174 and mutants, as well as 3 oligopeptides, including wild-type peptide and peptides containing 2 mutations, were incubated with MMP-20 both in solution and on HAP. The digested products were analyzed by SDS-PAGE, reverse-phase high-performance liquid chromatography and mass spectrometry. Mutated amelogenins displayed a significantly lower affinity to HAP than the wild type (P156T < P164T < rH174). The proline mutation at amino acid location 164 significantly reduced the initial hydrolysis of either the amelogenins in solution or the proteins bound on HAP, which was confirmed by amelogenin oligopeptide assays. It was concluded that prolines at the amelogenin C terminus are essential for the initial processing of amelogenin and amelogenin-mineral interactions.
The Potential Functional Interaction of Biglycan and WISP-1 in Controlling Differentiation and Proliferation of Osteogenic Cells
Authors: Inkson Colette A. , Ono Mitsuaki , Bi Yanming , Kuznetsov Sergei A. , Fisher Larry W. , Young Marian F.
Published: August 2008

Biglycan (BGN) and WISP-1 are 2 extracellular matrix proteins that bind to each other and colocalize in mineralizing tissue. Here we show that WISP-1 abrogates the repression of proliferation in bone marrow stromal cells induced by BGN. We also demonstrate that WISP-1 and its variant WISP-1va can alleviate the repressed osteogenic differentiation caused by the absence of BGN. These preliminary data suggest that WISP-1 and BGN may functionally interact and control each other’s activity, thus regulating the differentiation and proliferation of osteogenic cells.
Detection of Dental Fluorosis-Associated Quantitative Trait Loci on Mouse Chromosomes 2 and 11
Authors: Everett Eric T. , Yan Dong , Weaver Marjorie , Liu Lixiang , Foroud Tatiana , Martinez-Mier E. Angeles
Published: August 2008

Systemic exposure to greater than optimal fluoride (F) can lead to dental fluorosis (DF). Parental A/J (DF-susceptible) and 129P3/J (DF-resistant) inbred mice were used for histological studies and to generate F2 progeny. Mice were treated with 0 or 50 ppm F in their drinking water for 60 days. A clinical criterion (modified Thylstrup and Fejerskov categorical scale) was used to assess the severity of DF for each individual F2 animal. Parental strains were subjected to histological examination of maturing enamel. F treatment resulted in accumulation of amelogenins in the maturing enamel of A/J mice. Quantitative trait loci (QTL) detection was performed using phenotypic extreme F2 animals genotyped for 354 single nucleotide polymorphism-based markers distributed throughout the mouse genome followed by χ2 analysis. Significant evidence of association was observed on chromosomes 2 and 11 for a series of consecutive markers (p < 0.0001). Further analyses were performed to examine whether the phenotypic effects were found in both male and female F2 mice or whether there was evidence for gender-specific effects. Analyses performed using the markers on chromosomes 2 and 11 which were significant in the mixed-gender mice were also significant when analyses were limited to only the male or female mice. The QTL detected on chromosomes 2 and 11 which influence the variation in response to fluorosis have their effect in mice of both genders. Finally, the QTL in both chromosomes appear to have an additive effect.
Expression of Adiponectin and Adiponectin Receptors in Human Pituitary Gland and Brain
Authors: Psilopanagioti Aristea , Papadaki Helen , Kranioti Elena F. , Alexandrides Theodore K. , Varakis John N.
Published: August 2008

Background/Aims: Adiponectin and its receptors, AdipoR1 and AdipoR2, constitute integral components of energy homeostatic mechanism in peripheral tissues. Recent studies have implicated adiponectin in central neural networks regulating food intake and energy expenditure. The present study aimed at investigating the possible expression and distribution of adiponectin and its receptors in human pituitary gland, hypothalamus and different brain areas. Methods: Sections of the pituitary gland, hypothalamus and adjacent basal forebrain area, cerebrum and cerebellum from 35 autopsy cases, were examined using HE, PAS-Orange G, luxol fast blue/cresyl violet stains and single and double immunohistochemistry using adiponectin, AdipoR1, AdipoR2, choline acetyltransferase, FSH, LH, TSH, GH, ACTH and prolactin-specific antibodies. Age and BMI mean values ± SD of the autopsy cases were 56 ± 18 years and 27 ± 5 kg/m2, respectively. Results: Strong adiponectin expression was observed in pituitary gland. In pars distalis (PD), adiponectin localized in GH, FSH, LH and TSH-producing cells and in pars tuberalis (PT) in FSH, LH and TSH-producing cells. Strong to moderate expression of AdipoR1 and AdipoR2 was observed in PD by the same cell types as adiponectin. No immunoreactivity for adiponectin receptors was noted in cells of PT. Intense AdipoR1 immunostaining was observed in neurons of lateral hypothalamic area and of nucleus basalis of Meynert (NBM). Conclusions: Adiponectin and its receptors expression in human pituitary might indicate the existence of a local system, modulating endocrine axes. Furthermore, the presence of AdipoR1 in hypothalamus and NBM suggests that adiponectin may participate in central neural signaling pathways controlling energy homeostasis and higher brain functions.