bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63
Authors: Waanders E , Venselaar H , Te Morsche RHM , De Koning DB , Kamath PS , Torres VE , Somlo S , Drenth JPH 
Published: January 2010

Waanders E, Venselaar H, te Morsche RHM, de Koning DB, Kamath PS, Torres VE, Somlo S, Drenth JPH. Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63.Polycystic liver disease (PCLD) is characterized by intralobular bile duct cysts in the liver. It is caused by mutations in PRKCSH, encoding hepatocystin, and SEC63, encoding Sec63p. The main goals of this study were to screen for novel mutations and to analyze mutations for effects on protein structure and function. We screened 464 subjects including 76 probands by direct sequencing or conformation‐sensitive capillary electrophoresis. We analyzed the effects of all known and novel mutations using a combination of splice site recognition, evolutionary conservation, secondary and tertiary structure predictions, PolyPhen, and pMut and sift. We identified a total of 26 novel mutations in PRKCSH (n = 14) and SEC63 (n = 12), including four splice site mutations, eight insertions/ deletions, six non‐sense mutations, and eight missense mutations. Out of 48 PCLD mutations, 13 were predicted to affect splicing. Most mutations were located in highly conserved regions and homology modeling for two domains of Sec63p showed severe effects of the residue substitutions. In conclusion, we identified 26 novel mutations associated with PCLD and we provide in silico analysis in order to delineate the role of these mutations.
Effects of classroom education on knowledge and attitudes regarding organ donation in ethnically diverse urban high schools
Authors: Cárdenas Vicky , Thornton John D. , Wong Kristine A. , Spigner Clarence , Allen Margaret D. 
Published: January 2010

Cárdenas V, Thornton JD, Wong KA, Spigner C, Allen MD. Effects of classroom education on knowledge and attitudes regarding organ donation in ethnically diverse urban high schools.  Clin Transplant 2010: 24: 784–793. © 2010 John Wiley & Sons A/S.Abstract:  School‐based health education is a promising approach for improving organ donation rates, but little is known about its efficacy among ethnically diverse youth. The impact of a classroom intervention was examined in a multicultural high school population where students’ ethnicities were 45% African American, 30% Asian American, and 33% Caucasian (allowing for multiracial choices). A baseline survey was administered to all health classes within two wk prior to intervention. On the intervention day, classes randomly assigned to the intervention group received an educational session, followed by a second survey; in control classes, the second survey was taken before the educational session. At baseline, non‐Caucasian ethnicity and male gender were each associated with lower levels of willingness to donate. Following the intervention, students in the intervention group demonstrated a significant increase in knowledge scores (p < 0.001), as well as positive movement of opinion regarding willingness to donate (p < 0.0001). Most importantly, the positive changes in opinion occurred independently of ethnicity and gender, in spite of these both being negative predictors of opinion at baseline. These results demonstrate that even a single classroom exposure can impact knowledge levels, correct misinformation, and effect opinion change on organ donation among an ethnically diverse adolescent population.
NOTES ON NEW BOOKS
Authors: Magill C. P. , Chambers W. Walker 
Published: January 2010

Allemugnes et Allemanas.Hier ist dus Wort. Gedichte.Neue Gedichte. Mit einem Nachwort von Gerhart Pohle.The Archipelago. By Friedrich Holderlin. The text with notes and a new translation by J. B. Leishman. With an introduction by Friedrich Gundolftranslated by J. B. Leishman and Elisabeth Gundolf:Family Strife in Habsburg.A Faithful Servant of His MasterMedea. By Franz GrillparzerThe Guest‐Friend and The Argonauts.Franz Grillparzer. Der Innere Orden. Ein Brevier, Herausgegeben uon Christoph Meyer.The Stattire of Thomas Mtitin. An Anthology of Criticism.NietzscheHotbeins Dance of Death.Steirische LandbatiJi bel.New Theatres for Old.Das Wirtshazrs ZUY Verlorenert Zeit.Vormittug. Erinnertingen eittes Verlegers.Kiinig Haber. Erzuhlzrg.Das Neue Buch: Katalog der Neuerscheinungen 1945‐47
Diagenesis of the Amposta offshore oil reservoir (Amposta Marino C2 well, Lower Cretaceous, Valencia Trough, Spain)
Authors: PLAYÀ E. , TRAVÉ A. , CAJA M. A. , SALAS R. , MARTÍN‐MARTÍN J. D. 
Published: January 2010

AbstractSamples from the Amposta Marino C2 well (Amposta oil field) have been investigated in order to understand the origin of fractures and porosity and to reconstruct the fluid flow history of the basin prior, during and after oil migration. Three main types of fracture systems and four types of calcite cements have been identified. Fracture types A and B are totally filled by calcite cement 1 (CC1) and 2 (CC2), respectively; fracture type A corresponds to pre‐Alpine structures, while type B is attributed to fractures developed during the Alpine compression (late Eocene‐early Oligocene). The oxygen, carbon and strontium isotope compositions of CC2 are close to those of the host‐rock, suggesting a high degree of fluid‐rock interaction, and therefore a relatively closed palaeohydrogeological system. Fracture type C, developed during the Neogene extension and enlarged by subaerial exposure, tend to be filled with reddish (CS3r) and greenish (CS3g) microspar calcite sediment and blocky calcite cement type 4 (CC4), and postdated by kaolinite, pyrite, barite and oil. The CS3 generation records lower oxygen and carbon isotopic compositions and higher 87Sr/86Sr ratios than the host‐limestones. These CS3 karstic infillings recrystallized early within evolved‐meteoric waters having very little interaction with the host‐rock. Blocky calcite cement type 4 (CC4 generation) has the lowest oxygen isotope ratio and the most radiogenic 87Sr/86Sr values, indicating low fluid‐rock interaction. The increasingly open palaeohydrogeological system was dominated by migration of hot brines with elevated oxygen isotope ratios into the buried karstic system. The main oil emplacement in the Amposta reservoir occurred after the CC4 event, closely related to the Neogene extensional fractures. Corrosion of CC4 (blocky calcite cement type 4) occurred prior to (or during) petroleum charge, possibly related to kaolinite precipitation from relatively acidic fluids. Barite and pyrite precipitation occurred after this corrosion. The sulphur source associated with the late precipitation of pyrite was likely related to isotopically light sulphur expelled, e.g. as sulphide, from the petroleum source rock (Ascla Fm). Geofluids (2010) 10, 314–333
Partial reduction of BACE1 improves synaptic plasticity, recent and remote memories in Alzheimer’s disease transgenic mice
Authors: Kimura Ryoichi , Devi Latha , Ohno Masuo 
Published: January 2010

J. Neurochem. (2010) 10.1111/j.1471‐4159.2010.06608.xAbstractβ‐Site amyloid precursor protein cleaving enzyme 1 (BACE1) initiates amyloid‐β (Aβ) generation that is central to the pathophysiology of Alzheimer’s disease (AD). Therefore, lowering Aβ levels by BACE1 manipulations represents a key therapeutic strategy, but it remains unclear whether partial inhibition of BACE1, as expected for AD treatments, can improve memory deficits. In this study, we used heterozygous BACE1 gene knockout (BACE1+/−) mice to evaluate the effects of partial BACE1 suppression on different types of synaptic and cognitive dysfunctions in Alzheimer’s transgenic mice (5XFAD model). We found that ∼50% BACE1 reductions rescued deficits of 5XFAD mice not only in hippocampus‐dependent memories as tested by contextual fear conditioning and spontaneous alternation Y‐maze paradigms but also in cortex‐dependent remote memory stabilization during 30 days after contextual conditioning. Furthermore, 5XFAD‐associated impairments in long‐term potentiation (a synaptic model of learning and memory) and declines in synaptic plasticity/learning‐related brain‐derived neurotrophic factor‐tyrosine kinase B signaling pathways were prevented in BACE1+/−·5XFAD mice. Finally, these improvements were related with reduced levels of β‐secretase‐cleaved C‐terminal fragment (C99), Aβ peptides and plaque burden in relevant brain regions of BACE1+/−·5XFAD mice. Therefore, our findings provide compelling evidence for beneficial effects of partially BACE1‐inhibiting approaches on multiple forms of functional defects associated with AD.
Serine/threonine kinase akt activation regulates the activity of retinal serine/threonine phosphatases, PHLPP and PHLPPL
Authors: Kanan Yogita , Matsumoto Hiroyuki , Song Hongman , Sokolov Maxim , Anderson Robert E. , Rajala Raju V. S. 
Published: January 2010

J. Neurochem. (2010) 113, 477–488.AbstractIn our previous studies, we have shown that insulin receptor (IR) activation leads to the activation of phosphoinositide 3‐kinase (PI3K) and Akt activation in rod photoreceptors. This pathway is functionally important for photoreceptor survival as deletion of IR and one of the isoforms of Akt (Akt2) resulted in stress‐induced photoreceptor degeneration. However, the molecular mechanism of this degeneration is not known. Akt signaling is known to be regulated by the serine/threonine phosphatases, PH domain and leucine‐rich repeat protein phosphatases (PHLPP) and PHLPP‐like (PHLPPL). In this study, we characterized these two phosphatases in the retina and examined the role of IR, PI3K, and Akt signaling on the activity of PHLPP and PHLPPL. Most of the studies published on PHLPP and PHLPPL are directed toward Akt dephosphorylation; however, there are no studies available to date on how the enzyme activities of these phosphatases are regulated. We made a novel finding in this study that both PHLPP and PHLPPL activities were significantly decreased in the presence of insulin ex vivo. The insulin‐induced decrease of phosphatase activities were PI3K‐dependent as pre‐treatment of ex vivo retinal cultures with LY294002 significantly reversed the insulin‐induced inhibition. It has been shown previously that PHLPP and PHLPPL regulate the dephosphorylation of Akt isoforms, and our results demonstrate for the first time that retinal PHLPP and PHLPPL activities are under the control of the IR‐activated PI3K/Akt pathway.
Inhibitory effect of anticholinergics on the contraction of isolated caprine urinary bladder detrusor muscle
Authors: George N. , Shiny P. J. , Miriam J. , Nancy C. A. , Dhanasekar K. R. , Peedicayil J. 
Published: January 2010

Summary1. This study investigated whether four anticholinergics which are not clinically used for relaxing the urinary bladder detrusor muscle inhibit the contraction of isolated caprine (goat) detrusor muscle: cyclopentolate (100 nm), homatropine (5 μm), ipratropium (500 nm) and valethamate (1 μm).2. The effects of these anticholinergics were compared with tolterodine (3 μm), an anticholinergic clinically used for relaxing the detrusor muscle. The inhibitory effect of each of these five anticholinergics was studied on six strips of caprine detrusor muscle made to contract with 100 μm acetylcholine (ACh) by determining the percent inhibition of height of contraction and the area under the contractile curve (AUC).3. It was found that all five anticholinergics inhibited the ACh‐induced contraction of the caprine detrusor and that this inhibition was reversed by raising the concentration of ACh. Hence, these four anticholinergics, like tolterodine, may be useful in managing clinical conditions that require relaxation of the detrusor muscle.
Behavior of the Electrocardiographic T Peak to End Interval in Childhood
Authors: Benatar Abraham , Carbonez Karlien 
Published: January 2010

Background: The T‐wave peak to T‐wave end (TpTe) interval reflects spatial and transmural dispersion in repolarization and serves as an arrhythmogenic index. Normal TpTe interval data in children are lacking. We evaluated the effects of age, gender, heart rate, leads (II and V5) on TpTe and T‐wave voltage. Methods: Four hundred healthy children (age 4 days to 16.7 years) were enrolled. From a resting 12‐lead digital ECG, TpTe, RR, QT, JT intervals, and T amplitude were measured (leads II and V5). Bazett and Fridericia formulas were applied to TpTe for heart rate correction and TpTe/QT and TpTe/JT were calculated. Descriptive and analytical statistics were applied, significance level set at P ≤ 0.05. Results: TpTe in leads II and V5 correlate well. Contrary to adults, no gender differences in TpTe were observed in childhood. TpTe lengthens with increasing age, and is inversely related to heart rate. TpTe 98th percentile is 85 msec in first 5 years, increasing to 92 msec in adolescence. TpTe Fridericia is a good correction formula in childhood; TpTe Bazett overcorrects in the younger age. TpTe/QT and TpTe/JT are longer in younger subjects due to greater QT shortening than the TpTe interval at higher heart rates. Conclusions: In children, TpTe in lead II and V5 correlate well. The TpTe interval lengthens with advancing age as heart rate diminishes. TpTe Fridericia is a good correction formula in children. Younger subjects have higher TpTe/QT and TpTe/JT indices compared to older children. T‐wave voltage increases with age, tallest in the 5–10‐year‐age group particularly in V5. Ann Noninvasive Electrocardiol 2010;15(1):11–16
Abnormal P‐Wave Morphology Is a Predictor of Atrial Fibrillation Development and Cardiac Death in MADIT II Patients
Authors: Holmqvist Fredrik , Platonov Pyotr G. , McNitt Scott , Polonsky Slava , Carlson Jonas , Zareba Wojciech , Moss Arthur J. ,   for the MADIT II Investigators
Published: January 2010

Background: Several ECG‐based approaches have been shown to add value when risk‐stratifying patients with congestive heart failure, but little attention has been paid to the prognostic value of abnormal atrial depolarization in this context. The aim of this study was to noninvasively analyze the atrial depolarization phase to identify markers associated with increased risk of mortality, deterioration of heart failure, and development of atrial fibrillation (AF) in a high‐risk population with advanced congestive heart failure and a history of acute myocardial infarction. Methods: Patients included in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) with sinus rhythm at baseline were studied (n = 802). Unfiltered and band‐pass filtered signal‐averaged P waves were analyzed to determine orthogonal P‐wave morphology (prespecified types 1, 2, and 3/atypical), P‐wave duration, and RMS20. The association between P‐wave parameters and data on the clinical course and cardiac events during a mean follow‐up of 20 months was analyzed. Results: P‐wave duration was 139 ± 23 ms and the RMS20 was 1.9 ± 1.1 μV. None of these parameters was significantly associated with poor cardiac outcome or AF development. After adjustment for clinical covariates, abnormal P‐wave morphology was found to be independently predictive of nonsudden cardiac death (HR 2.66; 95% CI 1.41–5.04, P = 0.0027) and AF development (HR 1.75; 95% CI 1.10–2.79, P = 0.019). Conclusion: Abnormalities in P‐wave morphology recorded from orthogonal leads in surface ECG are independently predictive of increased risk of nonsudden cardiac death and AF development in MADIT II patients. Ann Noninvasive Electrocardiol 2010;15(1):63–72
First year growth among very low birth weight infants
Authors: Westerberg Ane C. , Henriksen Christine , Ellingvåg Asta , Veierød Marit B. , Júlíusson Pétur B. , Nakstad Britt , Aurvåg Anne K. , Rønnestad Arild , Grønn Morten , Iversen Per O. , Drevon Christian A. 
Published: January 2010

AbstractAim:  The aim of this study was to describe first‐year growth among very low birth weight infants and the effect of growth restriction at hospital discharge on first year growth.Method:  Anthropometric measures and background information for 118 very low birth weight infants were collected from medical records. Z‐scores were calculated based on recent Norwegian growth references.Results:  Significant catch‐up growth for weight and length was observed during the first year with mean z‐score change (SD) of 0.40 (1.05) and 1.01 (1.25) respectively. However, the very low birth weight infants remained lighter and shorter than full‐term peers until 12 months corrected age with mean z‐score of −0.93 (1.09) and −0.48 (1.06) respectively. Head circumference followed a normal growth pattern after 2 months. Infants discharged from hospital as growth restricted had increased catch‐up in weight and length, but remained smaller than infants not subjected to early growth restriction and full‐term peers. Multiple regression showed that weight below the 10th percentile at discharge is important for weight and length during the first year of life.Conclusion:  Very low birth weight infants showed catch‐up growth during the first year, but their weight and length remained less than full‐term peers. Growth deficiencies were more pronounced among infants subjected to early growth restriction, despite increased catch‐up growth.
Tumour necrosis factor‐like weak inducer of apoptosis (TWEAK) and its receptor Fn14 during cardiac remodelling in rats
Authors: Mustonen E. , Säkkinen H. , Tokola H. , Isopoussu E. , Aro J. , Leskinen H. , Ruskoaho H. , Rysä J. 
Published: January 2010

AbstractAim:  Accumulating evidence supports the concept that proinflammatory cytokines play an essential role in the failing heart. We examined the concomitant tumour necrosis factor‐like weak inducer of apoptosis (TWEAK)/Fn14 expression in myocytes in vitro as well as in vivo in cardiac remodelling.Methods:  We assessed TWEAK and its receptor Fn14 expression in response to angiotensin (Ang) II, myocardial infarction (MI) as well as to local adenovirus‐mediated p38 gene transfer in vivo. The effect of various hypertrophic factors and mechanical stretch was studied in neonatal rat ventricular myocyte cell culture.Results:  Ang II increased Fn14 levels from 6 h to 2 weeks, the greatest increase in mRNA levels being observed at 6 h (6.3‐fold, P < 0.001) and protein levels at 12 h (4.9‐fold, P < 0.01). TWEAK mRNA and protein levels remained almost unchanged during Ang II infusion. Likewise, a rapid and sustained elevation of Fn14 mRNA and protein levels in the left ventricle was observed after experimental MI. Moreover, local p38 gene transfer increased Fn14 mRNA and protein but not TWEAK levels. Fn14 immunoreactive cells were mainly proliferating non‐myocytes in the inflammation area while TWEAK immunoreactivity localized to cardiomyocytes and endothelial cells of the coronary arteries. Hypertrophic agonists and lipopolysaccharide increased Fn14 but not TWEAK gene expression in neonatal rat myocytes, while mechanical stretch upregulated Fn14 and downregulated TWEAK gene expression.Conclusions:  In conclusion, the cardiac TWEAK/Fn14 pathway is modified in response to myocardial injury, inflammation and pressure overload. Furthermore, our findings underscore the importance of Fn14 as a mediator of TWEAK/Fn14 signalling in the heart and a potential target for therapeutic interventions.
Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes
Authors: Lalande S. , Hofman P. L. , Baldi J. C. 
Published: January 2010

AbstractAim:  Although impaired left ventricular (LV) diastolic function is commonly observed in patients with type 2 diabetes, it remains unclear whether the impairment is caused by altered LV relaxation or changes in LV preload. The purpose of this study was to examine the influence of LV function and LV loading conditions on stroke volume in men with type 2 diabetes.Methods:  Cardiac magnetic resonance imaging scans were performed in eight men with type 2 diabetes and 11 non‐diabetic men matched for age, weight and physical activity level. Total blood volume was determined with the Evans blue dye dilution technique.Results:  End‐diastolic volume (EDV), the ratio of peak early to late mitral inflow velocity (E/A) and stroke volume were lower in men with type 2 diabetes than in non‐diabetic individuals. Peak filling rate and peak ejection rate were not different between diabetic and non‐diabetic individuals; however, men with type 2 diabetes had proportionally longer systolic duration than non‐diabetic individuals. Heart rate was higher and total blood volume was lower in men with type 2 diabetes. The lower total blood volume was correlated with a lower EDV in men with type 2 diabetes.Conclusions:  Men with type 2 diabetes have an altered cardiac cycle and lower end‐diastolic and stroke volume. A lower total blood volume and higher heart rate in men with type 2 diabetes suggest that changes in LV preload, independent of changes in LV relaxation or contractility, influence LV diastolic filling and stroke volume in this population.
Current insights in polymyositis and dermatomyositis
Authors: Kohsaka Hitoshi 
Published: January 2010

AbstractPolymyositis (PM) and dermatomyositis (DM) are characterized by immune‐mediated muscle damage. Early immunohistochemical studies of PM and DM muscle biopsy samples suggested that PM is mediated by cytotoxic CD8 T lymphocytes, whereas DM is a vasculopathy mediated by antibodies and complement deposition to the intramuscular microvessels. This classic view is now challenged by recent advances in immunology and molecular biology, as well as by clinical observation of the two diseases. Clonal expansion of cytotoxic CD8 T cells was found in the affected muscles and in peripheral blood from PM and DM patients. Autoantigens recognized by these clones are yet to be identified. Patient sera contain various autoantibodies. Although they are not directed to endothelial antigens, detection of specific antibodies helps when classifying the patients. Infiltrating cells, as well as muscle cells, produce cytokines and chemokines that could potentiate inflammation. Myofibers overexpress major histocompatibility complex class I and class II molecules that render themselves vulnerable to immune attacks while they also express molecules that protect themselves from apoptotic cell death. Corticosteroid administration is still a gold standard for PM/DM treatment. A major life‐threatening complication is an interstitial lung disease, the acute form of which should not be treated with corticosteroids alone. Future studies should be carried out to further elucidate their ethiopathology and to develop more effective and specific treatment. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2009.00002.x, January 2010)