bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Investors Overweight Personal Experience? Evidence from IPO Subscriptions
Authors: KAUSTIA MARKKU , KNÜPFER SAMULI
Published: November 2008

We find a strong positive link between past IPO returns and future subscriptions at the investor level in Finland. Our setting allows us to trace this effect to the returns personally experienced by investors; the effect is not explained by patterns related to the IPO cycle, or wealth effects. This behavior is consistent with reinforcement learning, where personally experienced outcomes are overweighted compared to rational Bayesian learning. The results provide a microfoundation for the argument that investor sentiment drives IPO demand. The paper also contributes to understanding how popular investment styles develop, and has implications for the marketing of financial products.
Estimating the Intertemporal Risk–Return Tradeoff Using the Implied Cost of Capital
Authors: PÁSTOR ĽUBOŠ , SINHA MEENAKSHI , SWAMINATHAN BHASKARAN
Published: November 2008

We argue that the implied cost of capital (ICC), computed using earnings forecasts, is useful in capturing time variation in expected stock returns. First, we show theoretically that ICC is perfectly correlated with the conditional expected stock return under plausible conditions. Second, our simulations show that ICC is helpful in detecting an intertemporal risk–return relation, even when earnings forecasts are poor. Finally, in empirical analysis, we construct the time series of ICC for the G–7 countries. We find a positive relation between the conditional mean and variance of stock returns, at both the country level and the world market level.
Atrial Flutter Ablation in Inducible Patients during Pulmonary Vein Atrum Isolation: A Randomized Comparison
Authors: SCHMIDT MARTIN , DACCARETT MARCOS , SEGERSON NATHAN , AIREY KELLY J. , GÜNTHER JENS , MARSCHANG HARALD , FISH ERIC , RITTGER HARALD , SINHA ANIL‐MARTIN , RITSCHER GUIDO , BRACHMANN JOHANNES , MARROUCHE NASSIR F.
Published: November 2008

Background:

The incidence of atrial flutter (AFL) post pulmonary vein antrum isolation (PVAI) in patients with atrial fibrillation (AF) is reported to be between 8% and 20%. The need for right or left AFL ablation during the initial PVAI procedure remains controversial. We prospectively compared mapping and ablation versus no ablative treatment of inducible AFL during PVAI.

Methods and Results:

In 220 patients (167 men, mean age 56 ± 15 years) with symptomatic AF presenting for PVAI, burst pacing from the high right atrium and coronary sinus was performed to determine AFL inducibility. A total of 25 patients with sustained (17 patients) or reproducible (eight patients) AFL were included in this study. Patients were randomized to mapping and ablation of AFL using the CARTO 3D mapping system (Biosense Webster, Diamond Bar, CA, USA) versus no further ablation. Typical AFL was induced in 48% of the patients. During a follow‐up of 12 ± 4 months, recurrences were determined by serial 48‐h Holter and event monitors. Recurrence rates, time to recurrence, and AFL cycle length differences between both groups were not statistically significant.

Conclusion:

These data suggest that inducibility of AFL post PVAI does not predict long‐term incidence of AFL. Moreover, this study demonstrates little benefit to mapping and ablation of these arrhythmias during the PVAI procedures.
Interatrial Septum Thickness and Difficulty with Transseptal Puncture during Redo Catheter Ablation of Atrial Fibrillation
Authors: TOMLINSON DAVID R. , SABHARWAL NIKANT , BASHIR YAVER , BETTS TIMOTHY R.
Published: November 2008

Background:

Patients undergoing catheter ablation for atrial fibrillation (AF) frequently require redo procedures, but there are no data reporting interatrial septum thickness (IAS) and difficulty during repeat transseptal puncture (TSP).

Methods:

Patients undergoing two separate AF ablation procedures had preprocedural fossa ovalis (FO) thickness measured using transesophageal echocardiography (TEE). “Difficult” TSP was defined by two observers as requiring excessive force, or conversion to TEE guidance.

Results:

The study comprised 42 patients (37 male) with mean ± SD age 55 ± 9 years. Mean FO thickness was significantly greater at the time of redo TSP (2.2 ± 1.6 mm vs 2.6 ± 1.5 mm at redo, P = 0.03); however, this finding was limited to those who underwent initial dual transseptal sheath procedures, FO thickness 2.0 ± 1.5 mm and 2.5 ± 1.4 mm for TEE 1 and 2, respectively (P = 0.048). There was a trend for more frequent difficult redo TSP procedures, 7/42 (17%; 95% confidence interval [CI] 8–31) redo, versus 4/42 (10%; 95% CI 3–23) first TSP. On univariate analysis, FO thickness was not predictive of TSP difficulty; the only predictor of difficult redo TSP was diabetes.

Conclusions:

IAS thickness at the FO increased following catheter ablation of AF, yet on subgroup analysis this was limited to initial procedures utilizing dual transseptal sheaths. There was a trend toward more frequent difficulty during redo TSP, yet this was not associated with FO thickening. Diabetes may predispose to difficulty during redo TSP; this finding requires confirmation in a larger study population.
Does Atrial Fibrillation Beget Ventricular Fibrillation in Patients with Acute Myocardial Infarction?
Authors: SANKARANARAYANAN RAJIV , JAMES MICHAEL A. , NUTA BOGDAN , TOWNSEND MANDIE , KESAVAN SUJATA , BURTCHAELL STEPHANIE , HOLLOWAY RUSSELL , EWINGS, B.Sc., M.Sc. PAUL
Published: November 2008

Background:

Atrial fibrillation (AF) is associated with increased mortality and a higher complication rate postmyocardial infarction (MI), but the exact mechanisms are unknown. We investigated whether AF predisposes to ventricular arrhythmia in postmyocardial infarct patients, thereby accounting for increased mortality.

Methods:

Five hundred consecutive patients admitted to our coronary care unit with acute MI were monitored for in‐hospital arrhythmias. Detailed information was also compiled on past history, co‐morbidities, electrolyte disturbances, drug therapies, and ejection fraction. Mortality data were collected for an average of 5.5 years.

Results:

The results have shown that the incidence of ventricular fibrillation (VF) is much greater in patients presenting with AF (P = 0.03) and multivariate analysis has shown that AF is independently associated with the development of VF. This association occurs principally in patients who are admitted with AF (P = 0.01) rather than those who develop it during their admission, although these patients are also at mildly increased risk. The increased incidence of VF does account for increased mortality in the AF patients but does not explain all of their excess risk. There was no association between AF and ventricular tachycardia (VT); P = 0.50.

Conclusions:

In conclusion, AF on admission to the hospital with acute MI is associated with an increased risk of VF and subsequent mortality.
Delayed Cardiac Perforation by Defibrillator Lead Placed in the Right Ventricular Outflow Tract Resulting in Massive Pericardial Effusion
Authors: LAU ERNEST W. , SHANNON HEATHER J. , McKAVANAGH PETER
Published: November 2008

A 76‐year‐old man received a dual‐chamber implantable cardioverter defibrillator (ICD), with the defibrillator lead positioned within the right ventricular outflow tract. The lead parameters at the time of implantation were satisfactory and the postprocedure chest X‐ray showed the leads were in place. The patient was cardioverted from atrial fibrillation during defibrillation threshold testing and commenced on anticoagulation immediately. One month post implantation, he experienced multiple ventricular tachycardia episodes all successfully treated with antitachycardia pacing and shocks by his ICD, but he fell and hit his chest against a hard surface during one of these attacks. He developed a massive pericardial effusion and computed tomography confirmed cardiac perforation by the defibrillator lead. Pericardiocentesis was performed and the defibrillator lead replaced with a different model positioned at the right ventricular apex. The patient made an uneventful recovery. The management and avoidance of delayed cardiac perforation by transvenous leads were discussed.
Successful Catheter Ablation of Typical Atrial Flutter in a Patient with a Long Vertical and Diverticulum‐Like Cavotricuspid Isthmus
Authors: TSAI WEI‐CHUNG , CHU CHIH‐SHENG , WU DING‐KWO , LAI WEN‐TER , LEE KUN‐TAI
Published: November 2008

A long vertical vestibule with a diverticulum‐like morphology of cavotricuspid isthmus (CTI) was demonstrated by right atrial angiogram in a 47‐year‐old male patient in whom his typical atial flutter was difficult to be ablated. Compatible with the right atrial angiography, the diverticulum‐like CTI with a long vertical vestibule, pouch‐like recess, and a long transverse posterior component was also demonstrated on volume‐rendering reconstruction computed tomography and the virtual endoscopy showed prominent trabeculation inside the diverticulum‐like part of CTI. The bidirectional CTI conduction block was successfully achieved after ablating along the CTI guided by the right atrial angiography.
RNA Silencing: Small RNA‐Mediated Posttranscriptional Regulation of mRNA and the Implications for Heart Electropathophysiology
Authors: LATRONICO MICHAEL V. G. , CONDORELLI GIANLUIGI
Published: November 2008

Gene silencing refers to the “switching off” of genes within the cell: it can occur at transcriptional and posttranscriptional levels, controlling, respectively, how much mRNA is transcribed from each gene and how much protein is translated from this mRNA. Knowledge of its governing mechanisms is fundamental to our understanding of physiology; moreover, where there is a relevance for pathology, new diagnostic and therapeutic tools may be developed. Recently, families of noncoding RNA (ncRNA)—RNA that does not encode for a protein end‐product—have been discovered that function as regulators of gene silencing. This has revolutionized biology by challenging the credence in the centrality of proteins as the regulators of biological processes, and is changing the way we study pathophysiology. In fact, a subfamily of small ncRNAs, called microRNA (miRNA), is now known as one of the most abundant class of regulatory molecules, and over one‐third of human genes—including a growing number of key genes of the heart—may be targeted by one or more of the hundreds of miRNAs that exist. Here, we focus on how these small ncRNAs control translation, on the extraordinary consequences this class of regulator is currently known to have on aspects of cardiac excitability, and on the exciting therapeutic potential they have in this field.
Quadricuspid Pulmonary Valve Identified by Transthoracic Echocardiography
Authors: Fernández‐Armenta Juan , Villagómez David , Fernández‐Vivancos Carla , Vázquez Rafael , Pastor Luis
Published: November 2008

The quadricuspid pulmonary valve is a rare congenital anomaly. It tends to be clinically quiescent. Its diagnosis by two‐dimensional echocardiography could be very difficult because of the anatomical features. We report on the echocardiographic findings of a 66‐year‐old female patient with mitral and aortic regurgitation of rheumatic origin and severe pulmonary hypertension. There was an aneurismatic dilation of the pulmonary artery trunk allowing visualization of the short‐axis view of the pulmonary valve. It showed four cusps of similar size and an important deficit of central coaptation. Very few cases of the quadricuspid pulmonary valve are documented in live patients.
Massive Cerebral Embolism Originated from Ruptured Infective Mitral Annular Calcification in a Chronic Hemodialysis Patient
Authors: Nishida Junichi , Maeda Takuto , Yuda Satoshi , Tanaka Marenao , Hashimoto Akiyoshi , Tsuchihashi Kazufumi , Shimamoto Kazuaki
Published: November 2008

Infective endocarditis of mitral annular calcification (MAC) has been reported, however, little attention has been given to the possibility of cerebral‐embolism based infective endocarditis of MAC. We report a chronic hemodialysis patient of massive cerebral embolism originated from ruptured infective MAC.
Early Myocardial Functional Alterations in Patients with Obstructive Sleep Apnea Syndrome
Authors: Kepez Alper , Niksarlioglu Elif Yelda Ozgun , Hazirolan Tuncay , Ranci Ortenca , Kabul Hasan Kutsi , Demir Ahmet Uğur , Kaya Ergün Barış , Kocabas Ugur , Aytemir Kudret , Sahin Altay , Tokgozoglu Lale , Nazli Nasih
Published: November 2008

Background: There is limited information regarding myocardial alterations in patients with obstructive sleep apnea syndrome (OSAS) in the absence of pulmonary and cardiac comorbidity. In this study, we aimed to evaluate potential myocardial alterations of these patients and investigate the possible effects of OSAS‐related pathological variations on left and right ventricular functions. Methods: We studied 107 consecutive patients who were referred to our sleep laboratory for clinically suspected OSAS and 30 controls without any history or symptoms of sleep‐related disorders. Severity of OSAS was quantified by polysomnography. Patients with apnea–hypopnea index (AHI) < 5 were included in the OSAS (−) group (Group 1, n = 22). Subjects with AHI ≥ 5 were considered as OSAS and classified according to their AHI as mild‐to‐moderate (AHI ≥ 5 and AHI < 30) (Group 2, n = 45) and severe (AHI ≥ 30) OSAS groups (Group 3, n = 40). Conventional M‐mode, 2D, and Doppler mitral inflow parameters, tissue Doppler velocities, myocardial peak systolic strain, and strain rate values of various segments were measured and compared between groups. Results: Patients with OSAS displayed impairment of left ventricular diastolic function compared with controls. There were no significant differences between groups regarding parameters reflecting left ventricular systolic function. Myocardial strain analysis demonstrated significant decrement regarding apical right ventricular longitudinal peak systolic strain and strain rate values between groups in relation to the severity of OSAS. Conclusions: Patients with OSAS display a regional pattern of right ventricular dysfunction correlated with the severity of disease.
Right Ventricular Adaptations Along with Left Ventricular Remodeling in Older Athletes
Authors: Ozdogan Oner , Yilmaz Gulsum Meral , Gurgun Cemil , Kayikcioglu Meral , Cinar Cahide Soydas
Published: November 2008

Background: Afterload changes and anatomic interaction between the ventricles cause right ventricle (RV) adaptation along with left ventricle (LV) remodeling. This study was designed to evaluate RV adaptations along with LV remodeling and to determine the effect of aging on both ventricles in a population of older athletes. Methods: Echocardiographic characteristics of 48 endurance trained older athletes were examined by tissue Doppler imaging (TDI) and integrated backscatter (IBS). Results: Mean LV mass index was calculated as 107.8±17.0 g/m2. Twenty‐two athletes were > 55 years old. Age was found to be a risk factor for diastolic dysfunction regarding lateral TDI velocities (Em < Am) (r = 0.385, P < 0.001). RV long‐axis (LAX) diameters were associated with LA volumes and LV masses (r = 0.380, P < 0.01 and r = 0.307, P < 0.05). RV LAX diameters were correlated with RV TDI E‐wave (r =−0.285, P < 0.05), RV LAX average, and peak IBS values (r = 0.36, P < 0.05 and r = 0.348, P < 0.05). Conclusions: TDI and IBS are applicable methods to evaluate the relationship between the two ventricles in athletes' heart. Increased RV LAX IBS values indicate increased LV mass and LA volume as a result of RV changes along with LV remodeling. Our data suggest that RV TDI E‐wave and average RV IBS values reflect cardiac adaptations of both RV and LV in older athletes.
Diverticulum of the Posterior Left Atrial Wall
Authors: Herzog Bernhard A. , Husmann Lars , Jenni Rolf , Kaufmann Philipp A.
Published: November 2008

Diverticula of the left atrium are very rare malformations of unknown etiology and may be associated with arrhythmias, thromboembolism, or mitral valve regurgitation. We report a patient with suspected coronary artery disease (CAD) in whom we performed a low‐dose computed tomography coronary angiography using prospective electrocardiogram triggering. CAD could be ruled out. Incidentally, we found a diverticulum on the posterior wall of the left atrium combined with an interatrial septal aneurysm. The diagnosis was confirmed by transthoracic echocardiography.
Environmental Anthropology Engaging Permaculture: Moving Theory and Practice Toward Sustainability
Authors: Veteto James R. , Lockyer Joshua
Published: November 2008

Using a variety of theoretical rubrics, recent work in ecological and environmental anthropology has revealed that human–environment interactions within the context of global capitalism are complex and have increasingly unjust and unsustainable outcomes. As globalization proceeds and associated socio‐environmental problems become clear, it is important that ecological and environmental anthropologists use empirical research to develop both theoretical and practical approaches to addressing the sustainability challenge. We suggest that an anthropological engagement with permaculture represents an especially timely opportunity for anthropologists to move toward sustainability in ways that complement and enable us to extend our traditional areas of theoretical and practical expertise. Permaculture is a development strategy that has a history of grassroots application, but it has been largely ignored by mainstream development practitioners and anthropologists alike. We argue that permaculture deserves a closer look. In this article, we trace the historical development of permaculture, provide examples of permaculture in practice in an ecovillage context, identify compatible areas of research within environmental anthropology, and make suggestions for engagement.
Clinical and radiographic characteristics of single‐tooth replacements preceded by local ridge augmentation: a prospective randomized clinical trial
Authors: Meijndert L. , Raghoebar G. M. , Meijer H. J. A. , Vissink A.
Published: November 2008

Objectives: To assess in a randomized‐clinical trial the influence of three augmentation techniques (chinbone with or without a Bio‐Gide® membrane and Bio‐Oss® with a Bio‐Gide® membrane) on the clinical and radiographic characteristics of hard and soft tissues around implants and adjacent teeth in the reconstructed maxillary anterior region, up to 1 year after functional loading.

Materials and methods: Ninety‐three patients requesting single‐tooth replacement and presenting with a horizontal (bucco‐palatinal) bone deficiency were included. After augmentation, 93 ITI‐EstheticPlus implants were placed. Clinical variables, standardized photographs and radiographs were analysed to assess the impact on the levels of the marginal gingiva (MGL) and marginal bone (MBL) around implants and adjacent teeth, viz at pre‐augmentation, pre‐implantation (TPI) and 1 (T1) and 12 (T12) months after final crown placement.

Results: Implant survival was 97.8%. No significant differences were observed in the treatment outcomes of the three augmentation modalities. Combining the three modalities, a slight but significant increase in the implants approximal pocket depth was found between T1 and T12. Approximal bone loss at the implant between T1 and T12 was 0.14 ± 0.76 mm (mesial) and 0.14 ± 0.47 mm (distal); the approximal MGL slightly increased (mesial: 0.24 ± 0.46 mm, distal: 0.25 ± 0.66 mm), and the buccal MGL decreased (0.11 ± 0.61 mm). Bone loss at the adjacent teeth, although minor, was significant between TPI and T1. No correlations were observed in changes of MBL and MGL.

Conclusions: None of the three applied augmentation technique procedures influenced the characteristics of the MGL and MBL or the implant survival of single‐tooth replacements. Peri‐implant hard and soft tissues were very stable in the first year after loading.
Implants in fresh extraction sockets: a prospective 5‐year follow‐up clinical study
Authors: Botticelli Daniele , Renzi Antonio , Lindhe Jan , Berglundh Tord
Published: November 2008

Objective: The aim of this prospective study was to evaluate the 5‐year clinical outcome of the ‘immediate implants.’

Material and methods: One week after the cementation of the prosthesis, a clinical baseline examination was carried out. Clinical measurements were performed of the following: plaque, mucositis, probing pocket depth, and soft tissue position. The height of the keratinized mucosa was measured at the buccal/lingual aspects. Standardized intra‐oral radiographs were taken. The marginal level of bone to implant contact [radiographic (Rx) bone level] was measured, and Rx bone level change over time was evaluated. The clinical/radiographic measurements were repeated on a yearly basis. The subjects were enrolled in a carefully supervised oral hygiene program.

Results and conclusion: It was demonstrated that ‘immediate implants’ that were loaded after 5–7 months had a high success rate. During the 5‐year interval, no implant was lost, and the mean Rx bone level at the implants was maintained or even improved. The plaque and mucositis scores were low (<20%) at baseline and at all re‐examinations. Implant sites located adjacent to the teeth showed bone gain during the initial period while sites that were facing edentulous zones lost some bone.
Tibial versus iliac bone grafts: a comparative examination in 15 freshly preserved adult cadavers
Authors: Gerressen Marcus , Prescher Andreas , Riediger Dieter , Van Der Ven David , Ghassemi Alireza
Published: November 2008

Purpose: We compared autogenous bone grafts from the proximal tibia and the anterior iliac crest under standardized conditions with regard to the attainable bone amount and the histological bone density.

Material and methods: In 15 freshly preserved adult cadavers, a corticocancellous block graft from the anterior iliac crest and a purely cancellous transplant from the tibia of the homolateral side were harvested respectively, with the length of the skin incision set at 6 cm for the iliac and at 3.5 cm for the tibial approach. The size of the iliac graft was defined to be between 1/3 and 1/4 of the total iliac length. At the medial tibia the maximum possible amount of cancellous bone was collected after preparation of a cortical lid. For volume determination grafts were cautiously cut up and then put in a water‐filled measuring cylinder. In addition, bone density was measured by histomorphometry. The received data were statistically evaluated using the t‐test for related samples at P=0.05 and Pearson's correlation analysis.

Results: From both donor sites approximately equal amounts of bone were available. This result is neither dependent on age nor on gender. In contrast, bone density turned out significantly higher in the iliac graft, with the difference showing a significant age dependence (r=−0.556).

Conclusions: Provided that no cortical transplants are needed, cancellous tibial bone grafts offer an appropriate alternative to the classic iliac bone graft, especially in elderly patients.
Risk factors for tooth loss in an adult population: a radiographic study
Authors: Bahrami Golnosh , Væth Michael , Kirkevang Lise‐Lotte , Wenzel Ann , Isidor Flemming
Published: November 2008

Aim: The aim of the present study was to estimate the incidence and identify risk factors for tooth loss during a 5‐year period in a randomly selected Danish population.

Material and Methods: In 1997 and 2003, 473 randomly selected adults received a full‐mouth radiographic examination. The total number of teeth was 12,444. For each tooth, the following information was recorded from the radiographs: marginal bone level, filling, crown, root canal post, root filling, apicectomy, periapical status and caries lesion. Unconditional and conditional logistic regression analyses were used to identify risk factors for tooth loss.

Results: During the study period, 107 teeth in 60 individuals were lost. On the individual level, reduced marginal bone level and apical periodontitis (AP) were highly associated with tooth loss. On the tooth level, a reduced marginal bone level, AP and apicectomy were strongly associated with tooth loss. Canines were not lost often, whereas tooth loss was more frequently observed in molars and premolars than in incisors.

Conclusions: A reduced marginal bone level and AP were associated with tooth loss over time. Furthermore, there was a higher risk of tooth loss in the posterior regions than in the anterior region.
Novel mutations in the SH3BP2 gene associated with sporadic central giant cell lesions and cherubism
Authors: Carvalho VM , Perdigão PF , Amaral FR , De Souza PEA , De Marco L , Gomez RS
Published: November 2008

Central giant cell lesion (CGCL) is a reactive bone lesion that occurs mainly in the mandible, characterized by the multinucleated osteoclast‐like giant cells in a background of oval to spindle‐shaped mononuclear cells. The etiology is unknown and occurs more commonly in young adults. Cherubism, a rare disease found predominantly in females has histologic characteristics indistinguishable from those of CGCL and is caused by mutations mostly present in exon 9 of the SH3BP2 gene. In this study, we investigated four cases of CGCL and one case of cherubism. DNA was extracted from peripheral blood and tumor tissue and all coding and flanking regions of the SH3BP2 amplified by PCR and directly sequenced to identify underlying mutations. Two novel mutations were found; a heterozygous missense mutation c.1442A>T (Q481L) in exon 11 in one sporadic case of CGCL and a heterozygous germline and tumor tissue missense mutation c.320C>T (T107M) in exon 4 in one patient with cherubism. These findings open a new window to investigate the possible relationship between the pathogenesis of the cherubism and CGCL.
An active triple‐catalytic hybrid enzyme engineered by linking cyclo‐oxygenase isoform‐1 to prostacyclin synthase that can constantly biosynthesize prostacyclin, the vascular protector
Authors: Ruan Ke‐He , So Shui‐Ping , Cervantes Vanessa , Wu Hanjing , Wijaya Cori , Jentzen Rebecca R.
Published: November 2008

It remains a challenge to achieve the stable and long‐term expression (in human cell lines) of a previously engineered hybrid enzyme [triple‐catalytic (Trip‐cat) enzyme‐2; Ruan KH, Deng H & So SP (2006) Biochemistry45, 14003–14011], which links cyclo‐oxygenase isoform‐2 (COX‐2) to prostacyclin (PGI2) synthase (PGIS) for the direct conversion of arachidonic acid into PGI2 through the enzyme’s Trip‐cat functions. The stable upregulation of the biosynthesis of the vascular protector, PGI2, in cells is an ideal model for the prevention and treatment of thromboxane A2 (TXA2)‐mediated thrombosis and vasoconstriction, both of which cause stroke, myocardial infarction, and hypertension. Here, we report another case of engineering of the Trip‐cat enzyme, in which human cyclo‐oxygenase isoform‐1, which has a different C‐terminal sequence from COX‐2, was linked to PGI2 synthase and called Trip‐cat enzyme‐1. Transient expression of recombinant Trip‐cat enzyme‐1 in HEK293 cells led to 3–5‐fold higher expression capacity and better PGI2‐synthesizing activity as compared to that of the previously engineered Trip‐cat enzyme‐2. Furthermore, an HEK293 cell line that can stably express the active new Trip‐cat enzyme‐1 and constantly synthesize the bioactive PGI2 was established by a screening approach. In addition, the stable HEK293 cell line, with constant production of PGI2, revealed strong antiplatelet aggregation properties through its unique dual functions (increasing PGI2 production while decreasing TXA2 production) in TXA2 synthase‐rich plasma. This study has optimized engineering of the active Trip‐cat enzyme, allowing it to become the first to stably upregulate PGI2 biosynthesis in a human cell line, which provides a basis for developing a PGI2‐producing therapeutic cell line for use against vascular diseases.
Effect of the ‐Gly‐3(S)‐hydroxyprolyl‐4(R)‐hydroxyprolyl‐ tripeptide unit on the stability of collagen model peptides
Authors: Mizuno Kazunori , Peyton David H. , Hayashi Toshihiko , Engel Jürgen , Bächinger Hans Peter
Published: November 2008

In order to evaluate the role of 3(S)‐hydroxyproline [3(S)‐Hyp] in the triple‐helical structure, we produced a series of model peptides with nine tripeptide units including 0–9 3(S)‐hydroxyproline residues. The sequences are H‐(Gly‐Pro‐4(R)Hyp)l‐(Gly‐3(S)Hyp‐4(R)Hyp)m‐(Gly‐Pro‐4(R)Hyp)n‐OH, where (l, m, n) = (9, 0, 0), (4, 1, 4), (3, 2, 4), (3, 3, 3), (1, 7, 1) and (0, 9, 0). All peptides showed triple‐helical CD spectra at room temperature and thermal transition curves. Sedimentation equilibrium analysis showed that peptide H‐(Gly‐3(S)Hyp‐4(R)Hyp)9‐OH is a trimer. Differential scanning calorimetry showed that replacement of Pro residues with 3(S)Hyp residues decreased the transition enthalpy, and the transition temperature increases by 4.5 °C from 52.0 °C for the peptide with no 3(S)Hyp residues to 56.5 °C for the peptide with nine 3(S)Hyp residues. The refolding kinetics of peptides H‐(Gly‐3(S)Hyp‐4(R)Hyp)9‐OH, H‐(Gly‐Pro‐4(R)Hyp)9‐OH and H‐(Gly‐4(R)Hyp‐4(R)Hyp)9‐OH were compared, and the apparent reaction orders of refolding at 10 °C were n = 1.5, 1.3 and 1.2, respectively. Replacement of Pro with 3(S)Hyp or 4(R)Hyp has little effect on the refolding kinetics. This result suggests that the refolding kinetics of collagen model peptides are influenced mainly by the residue in the Yaa position of the ‐Gly‐Xaa‐Yaa‐ repeated sequence. The experiments indicate that replacement of a Pro residue by a 3(S)Hyp residue in the Xaa position of the ‐Gly‐Xaa‐4(R)Hyp‐ repeat of collagen model peptides increases the stability, mainly due to entropic factors.
Structural and functional studies on a mesophilic stationary phase survival protein (Sur E) from Salmonella typhimurium
Authors: Pappachan A. , Savithri H. S. , Murthy M. R. N.
Published: November 2008

SurE, the stationary‐phase survival protein of Salmonella typhimurium, forms part of a stress survival operon regulated by the stationary‐phase RNA polymerase alternative sigma factor. SurE is known to improve bacterial viability during stress conditions. It functions as a phosphatase specific to nucleoside monophosphates. In the present study we reported the X‐ray crystal structure of SurE from Salmonella typhimurium. The protein crystallized in two forms: orthorhombic F222; and monoclinic C2. The two structures were determined to resolutions of 1.7 and 2.7 Å, respectively. The protein exists as a domain‐swapped dimer. The residue D230 is involved in several interactions that are probably crucial for domain swapping. A divalent metal ion is found at the active site of the enzyme, which is consistent with the divalent metal ion‐dependent activity of the enzyme. Interactions of the conserved DD motif present at the N‐terminus with the phosphate and the Mg2+ present in the active site suggest that these residues play an important role in enzyme activity. The divalent metal ion specificity and the kinetic constants of SurE were determined using the generic phosphatase substrate para‐nitrophenyl phosphate. The enzyme was inactive in the absence of divalent cations and was most active in the presence of Mg2+. Thermal denaturation studies showed that S. typhimurium SurE is much less stable than its homologues and an attempt was made to understand the molecular basis of the lower thermal stability based on solvation free‐energy. This is the first detailed crystal structure analysis of SurE from a mesophilic organism.
A novel nucleoside kinase from Burkholderia thailandensis
Authors: Ota Hiroko , Sakasegawa Shin‐ichi , Yasuda Yuko , Imamura Shigeyuki , Tamura Tomohiro
Published: November 2008

The genome of the mesophilic Gram‐negative bacterium Burkholderia thailandensis contains an open reading frame (i.e. the Bth_I1158 gene) that has been annotated as a putative ribokinase and PFK‐B family member. Notably, although the deduced amino acid sequence of the gene showed only 29% similarity to the recently identified nucleoside kinase from hyperthermophilic archaea Methanocaldococcus jannaschii, 15 of 17 residues reportedly involved in the catalytic activity of M. jannaschii nucleoside kinase were conserved. The gene was cloned and functionally overexpressed in Rhodococcus erythropolis, and the purified enzyme was characterized biochemically. The substrate specificity of the enzyme was unusually broad for a bacterial PFK‐B protein, and the specificity extended not only to purine and purine‐analog nucleosides but also to uridine. Inosine was the most effective phosphoryl acceptor, with the highest kcat/Km value (80 s−1·mm−1) being achieved when ATP served as the phosphoryl donor. By contrast, this enzyme exhibited no activity toward ribose, indicating that the recombinant enzyme was a nucleoside kinase rather than a ribokinase. To our knowledge, this is the first detailed analysis of a bacterial nucleoside kinase in the PFK‐B family.
Structure of the putative 32 kDa myrosinase‐binding protein from Arabidopsis (At3g16450.1) determined by SAIL‐NMR
Authors: Takeda Mitsuhiro , Sugimori Nozomi , Torizawa Takuya , Terauchi Tsutomu , Ono Akira M. , Yagi Hirokazu , Yamaguchi Yoshiki , Kato Koichi , Ikeya Teppei , Jee JunGoo , Güntert Peter , Aceti David J. , Markley John L. , Kainosho Masatsune
Published: November 2008

The product of gene At3g16450.1 from Arabidopsis thaliana is a 32 kDa, 299‐residue protein classified as resembling a myrosinase‐binding protein (MyroBP). MyroBPs are found in plants as part of a complex with the glucosinolate‐degrading enzyme myrosinase, and are suspected to play a role in myrosinase‐dependent defense against pathogens. Many MyroBPs and MyroBP‐related proteins are composed of repeated homologous sequences with unknown structure. We report here the three‐dimensional structure of the At3g16450.1 protein from Arabidopsis, which consists of two tandem repeats. Because the size of the protein is larger than that amenable to high‐throughput analysis by uniform 13C/15N labeling methods, we used stereo‐array isotope labeling (SAIL) technology to prepare an optimally 2H/13C/15N‐labeled sample. NMR data sets collected using the SAIL protein enabled us to assign 1H, 13C and 15N chemical shifts to 95.5% of all atoms, even at a low concentration (0.2 mm) of protein product. We collected additional NOESY data and determined the three‐dimensional structure using the cyana software package. The structure, the first for a MyroBP family member, revealed that the At3g16450.1 protein consists of two independent but similar lectin‐fold domains, each composed of three β‐sheets.
Enzymes of creatine biosynthesis, arginine and methionine metabolism in normal and malignant cells
Authors: Bera Soumen , Wallimann Theo , Ray Subhankar , Ray Manju
Published: November 2008

The creatine/creatine kinase system decreases drastically in sarcoma. In the present study, an investigation of catalytic activities, western blot and mRNA expression unambiguously demonstrates the prominent expression of the creatine‐synthesizing enzymes l‐arginine:glycine amidinotransferase and N‐guanidinoacetate methyltransferase in sarcoma, Ehrlich ascites carcinoma and Sarcoma 180 cells, whereas both enzymes were virtually undetectable in normal muscle. Compared to that of normal animals, these enzymes remained unaffected in the kidney or liver of sarcoma‐bearing mice. High activity and expression of mitochondrial arginase II in sarcoma indicated increased ornithine formation. Slightly or moderately higher levels of ornithine, guanidinoacetate and creatinine were observed in sarcoma compared to muscle. Despite the intrinsically low level of creatine in Ehrlich ascites carcinoma and Sarcoma 180 cells, these cells could significantly take up and release creatine, suggesting a functional creatine transport, as verified by measuring mRNA levels of creatine transporter. Transcript levels of arginase II, ornithine‐decarboxylase, S‐adenosyl‐homocysteine hydrolase and methionine‐synthase were significantly upregulated in sarcoma and in Ehrlich ascites carcinoma and Sarcoma 180 cells. Overall, the enzymes related to creatine and arginine/methionine metabolism were found to be significantly upregulated in malignant cells. However, the low levels of creatine kinase in the same malignant cells do not appear to be sufficient for the building up of an effective creatine/phosphocreatine pool. Instead of supporting creatine biosynthesis, l‐arginine:glycine amidinotransferase and N‐guanidinoacetate methyltransferase appear to be geared to support cancer cell metabolism in the direction of polyamine and methionine synthesis because both these compounds are in high demand in proliferating cancer cells.
Hypoxia decreases the expression of the two enzymes responsible for producing linear and cyclic tetrapyrroles in the heme biosynthetic pathway
Authors: Vargas Patrick D. , Furuyama Kazumichi , Sassa Shigeru , Shibahara Shigeki
Published: November 2008

Heme is synthesized in all cell types in aerobic organisms. Hydroxymethylbilane synthase (HMBS) and uroporphyrinogen III synthase (UROS) catalyze two consecutive reactions in the heme biosynthetic pathway, generating the first linear and the first cyclic tetrapyrroles, respectively. Each of the HMBS and UROS genes contains the two separate promoters that generate ubiquitous and erythroid‐specific mRNAs. Despite the functional significance of HMBS and UROS, regulation of their gene expression remains to be investigated. Here, we showed that hypoxia (1% O2) decreased the expression of ubiquitous mRNAs for HMBS and UROS by three‐ and twofold, respectively, in human hepatic cells (HepG2 and Hep3B), whereas the expression of ubiquitous and erythroid HMBS and UROS mRNAs remained unchanged in erythroid cells (YN‐1 and K562). Unexpectedly, hypoxia did not decrease the half‐life of HMBS mRNA (8.4 h under normoxia versus 9.1 h under hypoxia) or UROS mRNA (9.0 versus 10.4 h) in hepatic cells. It is therefore unlikely that a change in mRNA stability is responsible for the hypoxia‐mediated decrease in the expression levels of these mRNAs. Furthermore, expression levels of HMBS and UROS mRNAs were decreased under normoxia by treatment with deferoxamine or cobalt chloride in hepatic cells, while hypoxia‐inducible factor 1α was accumulated. Thus, the decrease in the expression of ubiquitous HMBS and UROS mRNAs is associated with accumulation of hypoxia‐inducible factor 1α protein. In conclusion, the expression of HMBS and UROS mRNAs may be coordinately regulated, which represents a newly identified mechanism that is important for heme homeostasis.
Formation of highly toxic soluble amyloid beta oligomers by the molecular chaperone prefoldin
Authors: Sakono Masafumi , Zako Tamotsu , Ueda Hiroshi , Yohda Masafumi , Maeda Mizuo
Published: November 2008

Alzheimer’s disease (AD) is a neurological disorder characterized by the presence of amyloid β (Aβ) peptide fibrils and oligomers in the brain. It has been suggested that soluble Aβ oligomers, rather than Aβ fibrils, contribute to neurodegeneration and dementia due to their higher level of toxicity. Recent studies have shown that Aβ is also generated intracellularly, where it can subsequently accumulate. The observed inhibition of cytosolic proteasome by Aβ suggests that Aβ is located within the cytosolic compartment. To date, although several proteins have been identified that are involved in the formation of soluble Aβ oligomers, none of these have been shown to induce in vitro formation of the high‐molecular‐mass (> 50 kDa) oligomers found in AD brains. Here, we examine the effects of the jellyfish‐shaped molecular chaperone prefoldin (PFD) on Aβ(1–42) peptide aggregation in vitro. PFD is thought to play a general role in de novo protein folding in archaea, and in the biogenesis of actin, tubulin and possibly other proteins in the cytosol of eukaryotes. We found that recombinant Pyrococcus PFD produced high‐molecular‐mass (50–250 kDa) soluble Aβ oligomers, as opposed to Aβ fibrils. We also demonstrated that the soluble Aβ oligomers were more toxic than Aβ fibrils, and were capable of inducing apoptosis. As Pyrococcus PFD shares high sequence identity to human PFD and the PFD‐homolog protein found in human brains, these results suggest that PFD may be involved in the formation of toxic soluble Aβ oligomers in the cytosolic compartment in vivo.
Identification, characterization and activation mechanism of a tyrosine kinase of Bacillus anthracis
Authors: Mattoo Abid R. , Arora Amit , Maiti Souvik , Singh Yogendra
Published: November 2008

Bacillus subtilis has three active tyrosine kinases, PtkA, PtkB and McsB, which play an important role in the physiology of the bacterium. Genome sequence analysis and biochemical experiments indicated that the ortholog of McsB, BAS0080, is the only active tyrosine kinase present in Bacillus anthracis. The autophosphorylation of McsB of B. anthracis was enhanced in the presence of an activator protein McsA (BAS0079), a property similar to that reported for B. subtilis. However, the process of enhanced phosphorylation of McsB in the presence of McsA remains elusive. To understand the activation mechanism of McsB, we carried out spectroscopic and calorimetric experiments with McsB and McsA. The spectroscopic results suggest that the binding affinity of Mg‐ATP for McsB increased by one order from 103 to 104 in the presence of McsA. The calorimetric experiments revealed that the interaction between McsB and McsA is endothermic in nature, with unfavourable positive enthalpy (ΔH) and favourable entropy (ΔS) changes leading to an overall favourable free energy change (ΔG). Kinetics of binding of both ATP and McsA with McsB showed low association rates (ka) and fast dissociation rates (kd). These results suggest that enhanced phosphorylation of McsB in the presence of McsA is due to increased affinity of ATP for McsB.
Substrate‐dependent hysteretic behavior in StEH1‐catalyzed hydrolysis of styrene oxide derivatives
Authors: Lindberg Diana , Gogoll Adolf , Widersten Mikael
Published: November 2008

The substrate selectivity and enantioselectivity of Solanum tuberosum epoxide hydrolase 1 (StEH1) have been explored by steady‐state and pre‐steady‐state measurements on a series of styrene oxide derivatives. A preference for the (S)‐ or (S,S)‐enantiomers of styrene oxide, 2‐methylstyrene oxide and trans‐stilbene oxide was established, with E‐values of 43, 160 and 2.9, respectively. Monitoring of the pre‐steady‐state phase of the reaction with (S,S)‐2‐methylstyrene oxide revealed two observed rates for alkylenzyme formation. The slower of these rates showed a negative substrate concentration dependence, as did the rate of alkylenzyme formation in the reaction with the (R,R)‐enantiomer. Such kinetic behavior is indicative of an additional, off‐pathway step in the mechanism, referred to as hysteresis. On the basis of these data, a kinetic mechanism that explains the kinetic behavior with all tested substrates transformed by this enzyme is proposed. Regioselectivity of StEH1 in the catalyzed hydrolysis of 2‐methylstyrene oxide was determined by 13C‐NMR spectroscopy of 18O‐labeled diol products. The (S,S)‐enantiomer is attacked exclusively at the C‐1 epoxide carbon, whereas the (R,R)‐enantiomer is attacked at either position at a ratio of 65 : 35 in favor of the C‐1 carbon. On the basis of the results, we conclude that differences in efficiency in stabilization of the alkylenzyme intermediates by StEH1 are important for enantioselectivity with styrene oxide or trans‐stilbene oxide as substrate. With 2‐methylstyrene oxide, slow conformational changes in the enzyme also influence the catalytic efficiency.
Effects of Cacao Liquor Polyphenols on Cardiovascular and Autonomic Nervous Functions in Hypercholesterolaemic Rabbits
Authors: Akita Megumi , Kuwahara Masayoshi , Itoh Fumi , Nakano Yoshihisa , Osakabe Naomi , Kurosawa Tohru , Tsubone Hirokazu
Published: November 2008

Abstract:  Many epidemiological studies have shown that polyphenols can reduce the risk of mortality from cardiovascular diseases. This study tested the hypothesis that cacao liquor polyphenols have the properties to restore the cardiovascular and autonomic nervous function in an animal model of familial hypercholesterolaemia. Male Kurosawa and Kusanagi‐hypercholesterolaemic rabbits were housed in individual cages in a room where a 12‐hr light:dark cycle (lights‐on at 8:00 and lights‐off at 20:00) was maintained. At 3 months of age, they were divided into two groups (standard diet and cacao liquor polyphenol) and the animals received 100 g of the respective diets per day and were provided with tap water ad libitum. Heart rate and blood pressure were measured by a telemetry system. To clarify the autonomic nervous function, power spectral analysis of heart rate variability, baroreflex sensitivity and autonomic nervous tone were measured. After 6 months of dietary administration of cacao liquor polyphenols, heart rate and blood pressure were lowered but plasma lipid concentrations were unchanged. The area of atherosclerotic lesions in the aorta in the cacao liquor polyphenol group was significantly smaller than that in the standard diet group. The high‐frequency power of heart rate variability in the rabbits in the standard diet group was significantly decreased with ageing, but that in the cacao liquor polyphenol group was not different between short‐term and long‐term treatment. Moreover, cacao liquor polyphenols preserved parasympathetic nervous tone, although that in the standard diet group was significantly decreased with ageing. We conclude that cacao liquor polyphenols may play an important role to protect cardiovascular and autonomic nervous functions.
Use of Observations below Detection Limit for Model Calibration
Authors: LeFrancois Michael , Poeter Eileen
Published: November 2008

Censored (nondetect) values occur when chemical concentrations in water samples are near or below the level that can be measured by an analysis method. It is common to either delete or substitute values for nondetect observations for use in model calibration, but this practice can bias the estimated parameter values and the model predictions. A more realistic representation of the system is obtained from the calibration if we include such observations in a manner reflecting that we know only the value is below the detection limit. Consequently, we propose use of the censored‐residual approach to including nondetect values as observations for calibration. In this approach, residuals are calculated as the detection limit minus the simulated value when the simulated value exceeds the detection limit, and the residual is assigned a value of zero when the simulated value is below the detection limit. The new censored‐residual approach is particularly advantageous when calibrating transport models to low concentration data.
CURRENCY CRISES IN EMERGING MARKETS: THE CASE OF POST‐LIBERALIZATION TURKEY
Authors: FERIDUN Mete
Published: November 2008

This article investigates the determinants of currency crises in Turkey. It analyzes the two major currency crises of 1994 and 2000–2001 in the light of the existing theoretical models. The present study uses logit, probit, and limited dependent models to explain the currency crises in the post–capital account liberalization era. The results obtained from the three approaches are generally consistent and the coefficients obtained for the explanatory variables generally have the same sign. The findings suggest that the currency crises in Turkey are associated with global liquidity conditions, fiscal imbalances, capital outflows, and banking sector weaknesses.