bluuebunny/crossref_metadata_2025 huggingface dataset:
Flavonoids inhibit melanoma lung metastasis by impairing tumor cells endothelium interactions
Authors: Piantelli Mauro , Rossi Cosmo , Iezzi Manuela , La Sorda Rossana , Iacobelli Stefano , Alberti Saverio , Natali Pier Giorgio
Published: October 2005

Flavonoids comprise a class of low molecular weight compounds displaying a variety of biological activities including inhibition of tumor growth and metastasis. To gain insight into the mechanisms underlying metastasis inhibition, we have employed the B16‐BL6 murine melanoma metastasis model. B57BL/6N mice were injected i.v. with tumor cells and Apigenin, Quercetin, or Tamoxifen, each at 50 mg/kg given i.p., and lung tumor cell colonies counted 14–6 days thereafter. Three different injection schedules were used for each drug: (a) daily injection, starting 24 h before injection of the tumor cells; (b) single dose, 24 h preceding tumor challenge; (c) daily injection, starting 24 h after the injection of the tumor cells. All three compounds significantly reduced tumor lung deposits (Apigenin = Quercetin > Tamoxifen). However, when treatment was delayed by 24 h after tumor cells (schedule c), multiple daily doses of Apigenin or Quercetin were less effective that a single dose of the same compound given 24 h before tumor challenge (schedule b). Apigenin and Quercetin, but not Tamoxifen, were found to inhibit VCAM‐1 expression in a dose‐dependent manner in HUVEC and in murine pulmonary endothelial cells. In ex vivo experiments, the number of tumor cells adhering to lung vessels was significantly diminished in animals treated with a single dose of Apigenin and Quercetin. These findings indicate that the inhibition of tumor cell metastasis by Apigenin or Quercetin may significantly depend on the ability of these compounds to alter the host's microenvironment, further substantiating the role of the intravascular processes in the metastatic cascade. J. Cell. Physiol. 207: 23–29, 2006. © 2005 Wiley‐Liss, Inc.
D‐aspartic acid in the nervous system of Aplysia limacina: Possible role in neurotransmission
Authors: Spinelli Patrizia , Brown Euan R. , Ferrandino Gabriele , Branno Margherita , Montarolo Pier Giorgio , D'Aniello Enrico , Rastogi Rakesh K. , D'Aniello Biagio , Baccari Gabriella Chieffi , Fisher George , D'Aniello Antimo
Published: October 2005

In the marine mollusk Aplysia limacina, a substantial amount of endogenous D‐aspartic acid (D‐Asp) was found following its synthesis from L‐aspartate by an aspartate racemase. Concentrations of D‐Asp between 3.9 and 4.6 µmol/g tissue were found in the cerebral, abdominal, buccal, pleural, and pedal ganglia. In non nervous tissues, D‐Asp occurred at a very low concentration compared to the nervous system. Immunohistochemical studies conducted on cultured Aplysia neurons using an anti‐D‐aspartate antibody demonstrated that D‐Asp occurs in the soma, dendrites, and in synaptic varicosities. Synaptosomes and synaptic vesicles from cerebral ganglia were prepared and characterized by electron microscopy. HPLC analysis revealed high concentrations of D‐Asp together with L‐aspartate and L‐glutamate in isolated synaptosomes In addition, D‐Asp was released from synaptosomes by K+ depolarization or by ionomycin. D‐Asp was one of the principal amino acids present in synaptic vesicles representing about the 25% of total amino acids present in these cellular organelles. Injection of D‐Asp into live animals or addition to the incubation media of cultured neurons, caused an increase in cAMP content. Taken as a whole, these findings suggest a possible role of D‐Asp in neurotransmission in the nervous system of Aplysia limacina. © 2005 Wiley‐Liss, Inc.
Intracellular localization of ClC chloride channels and their ability to form hetero‐oligomers
Authors: Suzuki Tatsunori , Rai Tatemitsu , Hayama Atsushi , Sohara Eisei , Suda Shin , Itoh Tomohiro , Sasaki Sei , Uchida Shinichi
Published: October 2005

ClC chloride channels (ClCs) can be classified into two groups in terms of their cellular localizations: ClCs present in the plasma membranes and those residing in intracellular organelles. Members of the latter group, including ClC‐3, ClC‐4, ClC‐5, ClC‐6, and ClC‐7, are often co‐expressed in a variety of cell types in many organs. Although the localization of individual channels within cells has been investigated, the degree of overlap between the locations of different ClCs in the same cell has not been clarified. To address this question, different combinations of ClCs, engineered to encode specific epitope tags (FLAG or HA), were either transiently or stably transfected into HEK293 cells, and we then compared the intracellular localization of the expressed channel proteins by immunofluorescence microscopy. Immunofluorescence images of the alternatively labeled channels clearly showed significant co‐localization between all pair‐wise combinations of ClCs. In particular, ClC‐3, ClC‐4, and ClC‐5 showed a high degree of co‐localization. As a significant degree of co‐localization between ClCs was observed, we used co‐immunoprecipitation to evaluate oligomer formation, and found that each ClC tested could form homo‐oligomers, and that any pair‐wise combination of ClC‐3, ClC‐4, and ClC‐5 could also form hetero‐oligomers. Neither ClC‐6 nor ClC‐7 was co‐precipitated with any other channel protein. These results suggest that within cells ClC‐3, ClC‐4, and ClC‐5 may have combinatorial functions, whereas ClC‐6 and ClC‐7 are more likely to function as homo‐oligomers. © 2005 Wiley‐Liss, Inc.
Interleukin‐1β downregulates the L‐type Ca2+ channel activity by depressing the expression of channel protein in cortical neurons
Authors: Zhou Chen , Tai Chao , Ye Hai Hong , Ren Xi , Chen Jian Gou , Wang Shi‐Qiang , Chai Zhen
Published: October 2005

Interleukin‐1β (IL‐1β), a proinflammatory cytokine, has been involved in various diseases of the central nervous system (CNS). Due to the diverse, “contradictory” effects of IL‐1β on neurons during insults to the brain, the mechanisms underlying these effects have not been elucidated. Calcium influx through the L‐type Ca2+ channels (LCCs) is believed to play a critical role in the cascade of biochemical events leading to neuron death in these pathophysiological conditions. So far, the mechanism of the interaction of IL‐1β and LCCs in the initiation and progression of these diseases is unclear. In this study, we investigate systemically the effects of IL‐1β on the LCCs current, which are believed to be implicated in the cascade of biochemical events leading to neuron death in neuropathological conditions. Using patch clamp, we observe that IL‐1β treatment (10 ng/ml, 24 h) suppresses LCC currents by ∼38%, which made up half of the whole‐cell Ca2+ current determined by nifedipine. IL‐1β does not alter the characteristics of single LCC including current amplitude, open probability, and conductance, but decreases the number of the functioning channel by 40%. Moreover, immunoblot assay exhibits that IL‐1β reduces the expression of LCC proteins by 38∼42% in both whole neuron and plasma membrane fraction, and demonstrates that IL‐1β downregulates the LCC activity via the reduction of LCC density. According to early research pretreatments longer than 12 h may play a crucial role in the neuroprotective effects of IL‐1β, our findings may establish an explanation for the protective effects of this interleukin on neurons in the late stage of injury, and could raise a new issue to clinical treatment for insults to brain. © 2005 Wiley‐Liss, Inc.
An approachable human adult stem cell source for hard‐tissue engineering
Authors: Laino Gregorio , Graziano Antonio , d'Aquino Riccardo , Pirozzi Giuseppe , Lanza Vladimiro , Valiante Salvatore , De Rosa Alfredo , Naro Fabio , Vivarelli Elisabetta , Papaccio Gianpaolo
Published: October 2005

Stem cells were obtained from deciduous dental pulp of healthy subjects, aged 6–10 years. This stem cell population was cultured, expanded, and specifically selected, detecting using a FACsorter, c‐kit, CD34, and STRO‐1 antigen expression. Then, c‐kit+/CD34+/STRO‐1+cells were replaced in the culture medium added of 20% FBS, leading to osteoblast differentiation. In fact, these cells, after a week, showed a large positivity for CD44, osteocalcin, and RUNX‐2 markers. To achieve an adipocytic differentiation, cells, after sorting, were challenged with dexamethason 10−8 mM in the same culture medium. To obtain myotube fusion, sorted cells were co‐cultured in ATCC medium with mouse myogenic C2C12 cells and, after a week, human stem cell nuclei were found to be able to fuse, forming myotubes. Differentiated osteoblasts, as assessed by a large positivity to several specific antibodies, after 30 days of culture and already in vitro, started to secrete an extracellular mineralized matrix, which, 2 weeks later, built a considerable number of 3D woven bone samples, which showed a strong positivity to alkaline phosphatase (ALP), alizarin red, calcein, other than to specific antibodies. These bone samples, after in vivo transplantation into immunosuppressed rats, were remodeled in a lamellar bone containing entrapped osteocytes. Therefore, this study provides strong evidence that human deciduous dental pulp is an approachable “niche” of stromal stem cells, and that it is an ideal source of osteoblasts, as well as of mineralized tissue, ready for bone regeneration, transplantation, and tissue‐based clinical therapies. © 2005 Wiley‐Liss, Inc.
Protein loop structure prediction with flexible stem geometries
Authors: Mönnigmann M. , Floudas C.A.
Published: October 2005

The structure prediction of loops with flexible stem residues is addressed in this article. While the secondary structure of the stem residues is assumed to be known, the geometry of the protein into which the loop must fit is considered to be unknown in our methodology. As a consequence, the compatibility of the loop with the remainder of the protein is not used as a criterion to reject loop decoys. The loop structure prediction with flexible stems is more difficult than fitting loops into a known protein structure in that a larger conformational space has to be covered. The main focus of the study is to assess the precision of loop structure prediction if no information on the protein geometry is available. The proposed approach is based on (1) dihedral angle sampling, (2) structure optimization by energy minimization with a physically based energy function, (3) clustering, and (4) a comparison of strategies for the selection of loops identified in (3). Steps (1) and (2) have similarities to previous approaches to loop structure prediction with fixed stems. Step (3) is based on a new iterative approach to clustering that is tailored for the loop structure prediction problem with flexible stems. In this new approach, clustering is not only used to identify conformers that are likely to be close to the native structure, but clustering is also employed to identify far‐from‐native decoys. By discarding these decoys iteratively, the overall quality of the ensemble and the loop structure prediction is improved. Step (4) provides a comparative study of criteria for loop selection based on energy, colony energy, cluster density, and a hybrid criterion introduced here. The proposed method is tested on a large set of 3215 loops from proteins in the PdbSelect25 set and to 179 loops from proteins from the Casp6 experiment. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Tension development length and lap splice design for reinforced concrete members
Authors: Darwin David
Published: October 2005

The key factors that govern development (anchorage) and splice performance of reinforcing bars in tension are described. The bond design provisions of the AASHTO (American Association of State Highway and Transportation Officials) LRFD (Load and Resistance Factor Design) Bridge Design Specifications, the American Concrete Institute Building Code Requirements for Structural Concrete (ACI 318‐05), ACI Committee 408, CEB‐FIP Model Code 1990, and Eurocode 2 are summarized and compared with test results. In terms of the key factors, the bond strength of bars not confined by transverse reinforcement is proportional to the concrete compressive strength to the ¼ power. The contribution of transverse reinforcement to bond strength increases with the area of the transverse reinforcement per bar and the relative rib area and diameter of the bar being developed or spliced and has been found to be proportional to the concrete compressive strength to a power between ¾ and 1.0. For deep members or for high‐slump (conventional and superplasticized) concrete, the effect of bar placement may be greater than accounted for in current design provisions. Of the five design procedures compared in this paper, those developed by ACI Committee 408 provide the best match with test results for both developed and spliced bars. For developed bars, the other four design procedures result in a high percentage of tests for which the test to calculated strength ratios (T/C) are less than 1.0, with the greatest percentage of low T/C values resulting from the AASHTO requirements. The relative safety of the latter four design procedures improves for lap splices. A provision in ACI 318‐05 that allows a 20% reduction in development and lap splice length for bars smaller than 19 mm appears to be unsafe and should be removed or modified.
Spectroscopic study of Eu3+ ions in heavy metal fluoride and oxide glasses
Authors: Pisarski W. A.
Published: October 2005

Two types of fluoride and oxide systems belonging to the heavy metal glass family have been studied. From absorption and emission spectra together with Judd–Ofelt analysis, spectroscopic parameters of Eu3+ ions in both optical systems were evaluated and compared. The new oxide glassy system based on PbO–B2O3–Al2O3–WO3 exhibits interesting spectroscopic properties of Eu3+ ions for application as a red‐emitting optical material. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Magnetism in n‐type GaMnN grown by molecular beam epitaxy
Authors: Van Nostrand J. E. , Albrecht J. D. , Claflin B. , Liu Y. , Nathan M. I. , Ruden P. P.
Published: October 2005

We investigate the magnetic properties of a strongly n‐type GaMnN alloy grown by molecular beam epitaxy. Transport, X‐ray diffraction, and magnetic characterizations are presented. The carrier concentration and mobility obtained by Hall effect measurements are nearly constant with respect to temperature over the entire temperature range from 4 K to 300 K. Magnetometry data indicates a transition temperature at approximately 170 K with hysteresis measurements indicating magnetic behavior at least to 300 K. The role of alloy microstructure is investigated using X‐ray diffraction and shows the possible presence of alternate phases giving rise to magnetization. In transport, we observe a linear Hall effect dependence on magnetic field strength. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Bulk and interface contributions to the optical second‐harmonic response of native‐oxide‐covered vicinal Si(111)
Authors: McGilp J. F. , Carroll L.
Published: October 2005

The optical second‐harmonic response of native‐oxide‐covered vicinal Si(111), offcut by 3° towards [$ \bar 1 $$ \bar 1 $2], is compared with previous work at the same wavelength on similar samples, but offcut by 5° in the opposite, [11$ \bar 2 $], direction. Sample rotation plots for sS, pS, sP and pP polarisation combinations are reported using 130 fs laser pulses of 765 nm wavelength, where mN indicates m‐polarised input and N‐polarised SH output. The two offcuts have different step geometries, but the same terrace structure at the Si/SiO2 interface. In addition, the bulk quadrupolar contributions from the two offcuts are related by simple geometric factors. By using these constraints, simultaneous fitting of eight rotation plots allows the bulk and interface contributions to be estimated. These results offer the possibility of more detailed investigation of bond hyperpolarisability models, which have been applied recently to the vicinal Si/SiO2 interface. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Frequency‐domain measurement of second harmonic phase
Authors: Carriles R. , An Y. Q. , Downer M. C.
Published: October 2005

Second harmonic (SH) phase is a potentially informative component of nonlinear optical interface characterization, but is often neglected because traditional SH phase measurement methods are very cumbersome. Frequency domain interferometric second harmonic (FDISH) generation enables rapid, accurate SH phase measurement without moving parts by exploiting the wide bandwidth of ultrashort laser pulses. We illustrate the versatility of FDISH through examples of SH phase measurements from GaAs, quartz and Si interfaces. SH phase variations with azimuthal angle and time, and amongst the three tensor components of the nonlinear susceptibility χ(2) of a Si(001)‐dielectric interface, are measured. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ab initio molecular orbital study of conformational properties of cyclohexyne, cycloheptyne, and cyclooctyne
Authors: Yavari Issa , Nasiri Farough , Djahaniani Hoorieh , Jabbari Arash
Published: October 2005

The structures and relative energies for the basic conformations of cyclohexyne (1), cycloheptyne (2), and cyclooctyne (3) have been calculated by the HF/6‐31G*, MP2/6‐31G*, and B3LYP/6‐31G* methods. The C2 symmetric twist conformer of 1 is calculated to be more stable than the planar C2v geometry. Ring inversion of the envelope conformation of 2 takes place via C2 symmetric twist transition state, which is 34.0 kJ mol−1 higher than the envelope form. The C2 symmetric chair conformation of 3 is calculated to be 11.7 kJ mol−1 more stable than the unsymmetrical twist‐boat (3‐TB) geometry. Interconversion of the chair conformation and 3‐TB takes place via an unsymmetrical transition state, which is 37.6 kJ mol−1 less stable than the chair form. Conformational racemization of the chiral 3‐TB takes place via the boat transition state. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Calculations of organic‐solvent dispersions of single‐wall carbon nanotubes
Authors: Torrens Francisco
Published: October 2005

The aqueous solubility Sw and 1‐octanol–(Po), cyclohexane–(Pch), and chloroform–(Pcf) water partition coefficients are calculated. The properties of single‐wall carbon nanotubes (SWNT) are related to the indices (n, m) designating the chiral vector. SWNTs are classified in zigzag (n, 0), armchair (n, n), and chiral (n, m). These properties permit classifying SWNTs according to (n, m). Correlations between (n2 + nm + m2)1/2, log Sw, log Po, log Pch, and log Pcf show that (n, m) are adequate indices. The (10,10) is the most abundant SWNT, presenting consistency between great kinetic stability, small Sw, and great {Po, Pch, Pcf}. The room temperature solubility of SWNTs is investigated in a variety of solvents, finding a class of non‐H‐bonding Lewis bases that provides good solubility. The investigated solvents are grouped into three classes. Five solvents, all featuring high electron‐pair donicity (β) and low H‐bond parameter (α) demonstrate the ability to form stable suspensions readily. SWNTs in some organic solvents are positively charged, while those in water–Triton X are negatively charged. This is explained on the basis of permittivity and electron affinity. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Pulmonary Resection for Non‐small‐cell Lung Cancer in Patients on Hemodialysis: Clinical Outcome and Long‐term Results
Authors: Ciriaco Paola , Casiraghi Monica , Melloni Giulio , Carretta Angelo , Libretti Lidia , Augello Giuseppe , Zannini Piero
Published: October 2005

Patients on hemodialysis (HD) who undergo surgery represent a high risk group requiring careful perioperative management to avoid electrolyte imbalance and hemodynamic instability. The aim of the study was to analyze the postoperative outcome in terms of complications and survival of a group of patients on HD who had undergone pulmonary resection for non‐small cell lung cancer (NSCLC). Six patients on HD underwent seven pulmonary resections at our institution from 1998 to 2003. The underlying kidney disease was nephrosclerosis in two patients and glomerulonephritis in four. The mean levels of blood urea nitrogen and serum creatinine were 107 ± 11.5 mg/dl and 7.9 ± 0.64 mg/dl, respectively. The mean preoperative PO2 and FEV1 were 77.6 ± 2.4 mmHg and 2.4 ± 0.16 liters, respectively. The histologic diagnosis was squamous cell carcinoma in four cases and adenocarcinoma in three. One patient underwent two lung resections in 4 years for two primary lung cancers. Five patients underwent lobectomy, one underwent a wedge resection, and in one case pneumonectomy was performed after neoadjuvant chemotherapy. There was no operative mortality. Postoperatively, atrial fibrillation occurred in two patients associated with sputum retention in both, and two other patients had hyperkalemia (complication rate 57%). One patient died of cardiac complications 27 months after surgery. The remaining five patients are currently alive with no evidence of disease. Patients on HD who undergo lung resection have a high rate of postoperative complications. Although the underlying disease influences long‐term survival, radical lung resection in NSCLC patients is recommended in selected cases. Careful metabolic, hematologic, and pharmaceutical management is mandatory during the perioperative period.
Clinical and Radiologic Evaluation of Foramen of Morgagni Hernias and the Transthoracic Approach
Authors: Sırmalı Mehmet , Türüt Hasan , Gezer Suat , Fındık Göktürk , Kaya Sadi , Tastepe Ýrfan , Çetin Güven
Published: October 2005

The limited number of publications on repair of the foramen of Morgagni hernia concentrates mainly on the laparotomy approach. We present our experience with the transthoracic approach. Patients who were diagnosed as having a foramen of Morgagni hernia and were operated on via the transthoracic approach between December 1991 and June 2004 are reviewed retrospectively for their age, sex, presenting symptoms, and diagnostic and surgical procedures. Surgical repair was carried out via the transthoracic approach in all cases. Of the 24 patients who underwent transthoracic diaphragmatic repair of the defect, 16 were women and 8 were men, with an overall mean age of 55.1 years (range 42–69 years). In most cases the defect was on the right side; there was only one case of a left‐sided defect. The most common presenting symptoms were dyspnea and gastrointestinal discomfort; five (20.8%) patients were asymptomatic. In 21 cases (87.5%) the diagnoses were established radiologically. The defect was accessed surgically via a posterolateral thoracotomy. No postoperative morbidity or mortality was observed. The mean follow‐up was 8.3 years (14 months to 14 years), and no recurrence was noted. As important as the surgical repair of the foramen of Morgagni hernia itself is selection of the surgical approach so adhesions of the hernial sac from the surrounding tissues in the thoracic cavity are easily released. The transthoracic approach is amenable to safe primary repair of the defect and the release of adhesions, even in elderly and obese patients, in whom adhesions may be excessive.
Early Onset of Lysosomal Storage Disease in a Murine Model of Mucopolysaccharidosis Type VII: Undegraded Substrate Accumulates in Many Tissues in the Fetus and Very Young MPS VII Mouse
Authors: Vogler Carole , Levy Beth , Galvin Nancy , Lessard Mark , Soper Brian , Barker Jane
Published: October 2005

Lysosomal storage diseases (LSDs), due to deficiency of a lysosomal enzyme, are inherited, progressive disorders that are often fatal during childhood. The mucopolysaccharidoses (MPS) are LSDs caused by deficiency of a lysosomal enzyme needed for the stepwise degradation of glycosaminoglycans. A murine model of MPS VII shares many clinical, biochemical, and pathologic features with human MPS and has proved valuable for the study of the pathophysiology of MPS and for evaluation of therapies for LSDs. Early therapy of MPS VII mice, initiated in the first weeks of life, is much more effective in decreasing clinical and morphologic evidence of disease than treatment begun in mature animals. Whether such early therapy decreases existing storage or prevents its accumulation is incompletely investigated. We performed an analysis of storage in very young MPS VII mice to define the extent of disease at and before the time of initiation of early treatments. MPS VII pups from 12 days postcoitus (dpc) to 31 days postnatal (dpn) were studied. Storage accumulated in fixed tissue macrophages in the liver and cartilage as soon as 12 dpc and was present in central nervous system glia, leptomeninges, and perivascular cells by 15 dpc. Osteoblast and primitive neocortical cell storage was apparent at 18 to 19 dpc. At 2 dpn, lysosomal distention appeared in circulating leukocytes. Abundant lysosomal storage was present in many sites by 14 dpn. Secondary accumulation of β-hexosaminidase paralleled increasing glycosaminoglycan storage. These results confirm the presence of widespread storage even in utero and in the very young MPS VII mouse and highlight the importance of early treatment to prevent storage accumulation.
Striking Facial Dysmorphisms and Restricted Thymic Development in a Fetus with a 6-Megabase Deletion of Chromosome 14q
Authors: De Pater J. M. , Nikkels P. G. J. , Poot M. , Eleveld M. J. , Stigter R. H. , Van Der Sijs-Bos C. J. M. , Loneus W. H. , Engelen J. J. M.
Published: October 2005

During routine ultrasound screening at 12 weeks 5 days of gestation, a nuchal translucency of 7 mm, an omphalocele, and fetal hydrops were found and prompted chorionic villus sampling at 13 weeks 2 days. Chromosome analysis showed an unbalanced karyotype with an abnormal chromosome 14. The mother was a carrier of a translocation karyotype 46,XX,t(13;14) (q34;q32.2). In the fetus this gave rise to a partial trisomy 13q and partial monosomy 14q (fetal karyotype: 46,XX,der[14]t[13;14][q34;q32.2]). By Array-CGH on DNA extracted from a postmortem skin culture, a duplication of approximately 1.7 Mbp of the distal part of chromosome 13q34 and a deletion of approximately 6.0 Mbp of the distal part of chromosome 14q32.2 was demonstrated. Postmortem findings after termination of pregnancy at 14 weeks 6 days included, among others, a severe hypoplasia of the median part of the maxilla, no recognizable nose, a broad median palatoschisis, nonlobulated lungs, a horseshoe kidney with multicystic dysplasia, and decreased development of cortical cellularity in the thymus. These clinical manifestations and autopsy findings of the fetus are compared with those of previously published cases and the possible involvement in this pathology of the YY1 and JAG2 transcription factors and the BCL11b and SIVA-1 regulators of thymic development is discussed.
Differential Detection of Deletion 22q11.2 Syndrome by Specialty and Indication
Authors: Katzman P. J. , Wang B. , Sawhney M. , Wang N.
Published: October 2005

This study identified cytogenetic abnormalities in a population screened for deletion 22q11.2 syndrome (D22S) by fluorescence in situ hybridization (FISH) and G-banding and correlated these abnormalities to referring specialty and submitted indications. Requests for the D22S FISH assay were retrospectively reviewed over a 29-month period in our institution. Positive test results for D22S FISH and other abnormalities found by other FISH assays and G-banding were correlated to submitting specialist and indication. Thirteen medical services ordered D22S FISH testing on 297 patients over29 months. The detection rate for all cytogenetic aberrations was 9.4% (28 of 297) including 5.4% (16 of 297) for D22S detection by FISH and 2.7% (8 of 297) for detection of additional cytogenetic anomalies by G-banding cytogenetics. Sixty-six of 297 patients negative by D22S FISH and G-banding were screened using other FISH assays and 3 of 47 (6.4%) patients screened using subtelomeric probes were positive for deletion and 1 of 3 (33%) patients screened for Prader-Willi syndrome was positive for deletion. Pediatric geneticists requested 53.9% (160 of 297) of the tests, yielding 60.7% (17 of 28) of positive test results. Tetralogy of Fallot and developmental delay were the indications associated with the most positive test results. In our institution, pediatric geneticists identify the largest spectrum of indications with D22S and appear most aware of the association of developmental delay with D22S. Performing conventional cytogenetics and other FISH assays, in addition to FISH for D22S, is important because there is considerable overlap between D22S and the phenotype of several other syndromes.
Phosphoproteome Analysis
Authors: Raggiaschi Roberto , Gotta Stefano , Terstappen Georg C.
Published: October 2005

Protein phosphorylation is directly or indirectly involved in all important cellular events. The understanding of its regulatory role requires the discovery of the proteins involved in these processes and how, where and when protein phosphorylation takes place. Investigation of the phosphoproteome of a cell is becoming feasible today although it still represents a very difficult task especially if quantitative comparisons have to be made. Several different experimental strategies can be employed to explore phosphoproteomes and this review will cover the most important ones such as incorporation of radiolabeled phosphate into proteins, application of specific antibodies against phosphorylated residues and direct staining of phosphorylated proteins in polyacrylamide gels. Moreover, methods to enrich phosphorylated proteins such as affinity chromatography (IMAC) and immunoprecipitation as well as mass spectrometry for identification of phosphorylated peptides and phosphorylation sites are also described.
Interaction Proteomics
Authors: Monti Maria , Orrù Stefania , Pagnozzi Daniela , Pucci Piero
Published: October 2005

The term proteome is traditionally associated with the identification of a large number of proteins within complex mixtures originating from a given organelle, cell or even organism. Current proteome investigations are basically focused on two major areas, expression proteomics and functional proteomics. Both approaches rely on the fractionation of protein mixtures essentially by two-dimensional polyacrylamide gel electrophoresis (2D-gel) and the identification of individual protein bands by mass spectrometric techniques (2D-MS). Functional proteomics approaches are basically addressing two main targets, the elucidation of the biological function of unknown proteins and the definition of cellular mechanisms at the molecular level. In the cell many processes are governed not only by the relative abundance of proteins but also by rapid and transient regulation of activity, association and localization of proteins and protein complexes. The association of an unknown protein with partners belonging to a specific protein complex involved in a particular process would then be strongly suggestive of its biological function. The identification of interacting proteins in stable complexes in a cellular system is essentially achieved by affinity-based procedures. Different strategies relying on this simple concept have been developed and a brief overview of the main approaches presently used in functional proteomics studies is described.
An Arabidopsis Rhomboid homolog is an intramembrane protease in plants
Authors: Kanaoka Masahiro M. , Urban Sinisa , Freeman Matthew , Okada Kiyotaka
Published: October 2005

Regulated intramembrane proteolysis (RIP) is a fundamental mechanism for controlling a wide range of cellular functions. The Drosophila protein Rhomboid‐1 (Rho‐1) is an intramembrane serine protease that cleaves epidermal growth factor receptor (EGFR) ligands to release active growth factors. Despite differences in the primary structure of Rhomboid proteins, the proteolytic activity and substrate specificity of these enzymes has been conserved in diverse organisms. Here, we show that an Arabidopsis Rhomboid protein AtRBL2 has proteolytic activity and substrate specificity. AtRBL2 cleaved the Drosophila ligands Spitz and Keren, but not similar proteins like TGFα, when expressed in mammalian cells, leading to the release of soluble ligands into the medium. These studies provide the first evidence that the determinants of RIP are present in plants.
AlFx affects the formation of focal complexes by stabilizing the Arf‐GAP ASAP1 in a complex with Arf1
Authors: Klein Stéphanie , Franco Michel , Chardin Pierre , Luton Frédéric
Published: October 2005

Aluminum fluoride (AlFx) is known to activate directly the α subunit of G‐proteins but not the homologous small GTP‐binding proteins. However, AlFx can stabilize complexes formed between Ras, RhoA or Cdc42 and their corresponding GTPase‐activating proteins (GAPs). Here, we demonstrate that Arf1GDP can be converted into an active conformation by AlFx to form a complex with the Arf‐GAP ASAP1 in vitro and in vivo. Within this complex ASAP1, which GAP activity is inoperative, can still alter the recruitment of paxillin to the focal complexes, thus indicating that ASAP1 interferes with focal complexes independently of its GAP activity.
Malaria parasite‐infected erythrocytes inhibit glucose utilization in uninfected red cells
Authors: Mehta Monika , Sonawat Haripalsingh M. , Sharma Shobhona
Published: October 2005

The erythrocytic stages of the malaria parasite depend on anaerobic glycolysis for energy. Using [2‐13C]glucose and nuclear magnetic resonance, the glucose utilization rate and 2,3‐diphosphoglycerate (2,3‐DPG) level produced in normal RBCs and Plasmodium falciparum infected red blood cell populations (IRBCs, with <4% parasite infected red cells), were measured. The glucose flux in IRBCs was several‐folds greater, was proportional to parasitemia, and maximal at trophozoite stage. The 2,3‐DPG levels were disproportionately lower in IRBCs, indicating a downregulation of 2,3‐DPG flux in non‐parasitized RBCs. This may be due to lowered pH leading to selective differential inhibition of the regulatory glycolytic enzyme phosphofructokinase. This downregulation of the glucose utilization rate in the majority (>96%) of uninfected RBCs in an IRBC population may have physiological implications in malaria patients.
Persönlichkeitspsychologie: Stand und Perspektiven
Authors: Borkenau Peter , Egloff Boris , Eid Michael , Hennig Jürgen , Kersting Martin , Neubauer Aljoscha C. , Spinath Frank M.
Published: October 2005

Zusammenfassung. Es wird gezeigt, dass die Persönlichkeitspsychologie eine zur Zeit sehr dynamische sowie interdisziplinär stark vernetzte Teildisziplin der Psychologie ist. Dies geschieht exemplarisch anhand von sechs Forschungsfeldern: (a) Entwicklung statistischer und mathematischer Methoden (z.B. Strukturgleichungsmodelle, Mischverteilungsmodelle), welche an individuellen Unterschieden ansetzen und deren Analyse optimieren; (b) Implizite Assoziationstests als Ergänzung zu Selbstberichten im Rahmen der Persönlichkeitsmessung; (c) Forschungen zu den kognitiven und neuronalen Quellen individueller Unterschiede in der Intelligenz; (d) Forschungen zu biologischen Einflussfaktoren auf Temperamentsmerkmale; (e) quantitative und molekulare Verhaltensgenetik unter besonderer Berücksichtigung der Beziehung zwischen normaler Variation und psychischen Störungen; und (f) Vorhersage von Ausbildungs- und Berufserfolg.
Effekt des Metawissens beim kollaborativen Aufbau eines Informationspools
Authors: Cress Ulrike
Published: October 2005

Zusammenfassung. In Organisationen ermöglicht der Einsatz einer geteilten Datenbank den kollaborativen Aufbau eines Informationspools. Die Entscheidung des Einzelnen, eigenes Wissen in eine Datenbank einzugeben, stellt ein öffentliches-Gut-Dilemma dar. Jede Person spart Zeit und Kosten, wenn sie keine Information in die Datenbank eingibt, wenn aber alle Personen so verfahren, bleibt die Datenbank leer und für alle nutzlos. Dieses Dilemma wird durch die hohe Anonymität der Datenbanksituation verstärkt, in der Personen über nur wenig prospektives Metawissen (Wissen über die Wichtigkeit ihrer Information für andere) und retrospektives Metawissen (Wissen über das Verhalten der anderen Gruppenmitglieder) verfügen. In zwei Experimenten wird der Einfluss dieser beiden Faktoren untersucht. Es zeigt sich, dass prospektives Metawissen die Qualität der Datenbankinhalte beeinflusst, während retrospektives Metawissen Auswirkungen auf die Quantität der Inhalte hat.
Iron in the Sargasso Sea (Bermuda Atlantic Time‐series Study region) during summer: Eolian imprint, spatiotemporal variability, and ecological implications
Authors: Sedwick P. N. , Church T. M. , Bowie A. R. , Marsay C. M. , Ussher S. J. , Achilles K. M. , Lethaby P. J. , Johnson R. J. , Sarin M. M. , McGillicuddy D. J.
Published: October 2005

We report iron measurements for water column and aerosol samples collected in the Sargasso Sea during July‐August 2003 (summer 2003) and April‐May 2004 (spring 2004). Our data reveal a large seasonal change in the dissolved iron (dFe) concentration of surface waters in the Bermuda Atlantic Time‐series Study region, from ∼1–2 nM in summer 2003, when aerosol iron concentrations were high (mean 10 nmol m−3), to ∼0.1–0.2 nM in spring 2004, when aerosol iron concentrations were low (mean 0.64 nmol m−3). During summer 2003, we observed an increase of ∼0.6 nM in surface water dFe concentrations over 13 days, presumably due to eolian iron input; an estimate of total iron deposition over this same period suggests an effective solubility of 3–30% for aerosol iron. Our summer 2003 water column profiles show potentially growth‐limiting dFe concentrations (0.02–0.19 nM) coinciding with a deep chlorophyll maximum at 100–150 m depth, where phytoplankton biomass is typically dominated by Prochlorococcus during late summer.
Irreversible nitrate fluxes due to turbulent mixing in a coastal upwelling system
Authors: Hales B. , Moum J. N. , Covert P. , Perlin A.
Published: October 2005

Detailed and repeated measurements of nitrate across the Oregon shelf, made coincident with turbulence measurements, reveal the importance of cross‐isopycnal mixing via turbulence in providing nitrate to the upper water column. Spatial distributions of vertical gradients and turbulent fluxes in the Oregon coastal ocean reveal variability that could not have been resolved with traditional sampling approaches. Nitrate‐rich near‐bottom waters are drawn up the shelf during upwelling and back down the shelf during downwelling. Continuous turbulent mixing in the bottom boundary layer increases nitrate on intermediate isopycnals by several μM toward the shelf. This increased nitrate is consistent with measured turbulent flux of nitrate of O(0.1 μmol m−2 s−1) for a period of 3 days, roughly the timescale for changes in the wind and hence to the upwelling circulation. Our flux estimates are consistent with high‐biomass, nutrient‐replete, incubation‐based primary productivity estimates in this area and suggest that turbulent vertical nitrate transport plays a significant role in supporting the high productivity seen here. Offshore of 30 m depth, we estimate the irreversible transport of nitrate from nitrate‐rich near‐bottom waters to be about 25% of the rate at which it is provided by upwelling. The total irreversible transport is greater by some unknown amount when we consider the transport inshore of 30 m depth. We suggest that the onshore transport of offshore water, whether deep water during upwelling or surface water during relaxation, forces the juxtaposition of strong gradients and mixing regimes such that turbulent vertical fluxes are consistently elevated in the shoreward reaches of the coastal ocean.
Recent primary production increases in arctic lakes
Authors: Michelutti Neal , Wolfe Alexander P. , Vinebrooke Rolf D. , Rivard Benoit , Briner Jason P.
Published: October 2005

A new application of reflectance spectroscopy enables inferences of lake sediment chlorophyll a concentrations and hence of historical trends in lacustrine primary production. In a survey of six arctic lakes on Baffin Island (Nunavut, Canada), pronounced increases of spectrally‐inferred chlorophyll a concentrations are consistently expressed in sediments deposited during the 20th century. Climate warming appears to be increasing both aquatic chlorophyll a production and its sequestration to sediments, as these lakes enter new biological regimes that are largely unique in the context of the late Holocene.
Regional cooling in the South Pacific sector of the Southern Ocean due to global warming
Authors: Kim Dong‐Hoon , Nakashiki Norikazu , Yoshida Yoshikatsu , Maruyama Koki , Bryan Frank O.
Published: October 2005

This study investigates processes leading to regional cooling in global warming experiments conducted with the NCAR fully coupled Community Climate System Model (CCSM3). While several previous studies have investigated regional cooling in the South Pacific sector of the Southern Ocean, the mechanism leading to this response remains unclear. We find that changes in ocean circulation offer the key to understanding the regional cooling. The regional cooling in the South Pacific sector of the Southern Ocean, especially the area north of the Ross Sea, results mainly through an advective mechanism. The ocean topography contributes strongly to the change of ocean circulation through changes in bottom vortex stretching associated with a decrease in the Antarctic Circumpolar Current transport.
Cluster encounter of a magnetic reconnection diffusion region in the near‐Earth magnetotail on September 19, 2003
Authors: Borg A. L. , Øieroset M. , Phan T. D. , Mozer F. S. , Pedersen A. , Mouikis C. , McFadden J. P. , Twitty C. , Balogh A. , Rème H.
Published: October 2005

We report a clear encounter by the Cluster spacecraft of a magnetic reconnection diffusion region in the near‐Earth magnetotail at XGSM = −17.5 RE on September 19, 2003. In addition to the reversals of the plasma jets and of GSM‐z (∼normal) component of the magnetic field, clear signatures of Hall quadrupolar (GSM‐y) magnetic fields as well as bipolar Hall (GSM‐z) electric fields with amplitude up to 80 mV/m directed toward the neutral sheet in both hemispheres were observed. Furthermore, large fluctuations in the electric field perpendicular to the magnetic field with amplitudes reaching 65 mV/m were observed near the separatrices in both hemispheres and in association with local density minima.
Parameterization of the cloud droplet single scattering albedo based on aerosol chemical composition for LES modelling of boundary layer clouds
Authors: Sandu Irina , Tulet Pierre , Brenguier Jean‐Louis
Published: October 2005

Absorption of solar radiation by cloud particles is a key factor controlling the evolution of a stratocumulus cloud, hence LES simulations of their diurnal cycle are particularly sensitive to the parameterization of this process. Absorption however depends on the type of aerosol particles incorporated in cloud droplets. Current parameterizations are tested here against a more detailed scheme that accounts for the chemical composition of the aerosol. The impact on the simulated diurnal cycle is quantified.
Fluvial and lacustrine activity on layered deposits in Melas Chasma, Valles Marineris, Mars
Authors: Quantin C. , Allemand P. , Mangold N. , Dromart G. , Delacourt C.
Published: October 2005

Valley networks on Mars are the most obvious features attesting that different geologic processes and possibly climatic conditions existed in the past. THEMIS images reveal valley networks within Melas Chasma, in Valles Marineris, a Hesperian‐age canyon system. The valley networks in Melas Chasma are dense and highly organized, and the heads of the valleys are scattered at different elevations. All these features suggest that the networks were fed by precipitation. The morphological details reveal inner channels on some valley floors, attesting that water flowed within these valleys. On the DEM, the valleys flow into a completely enclosed depression. The edge of this feature follows a MOLA contour line, and the depression shows many sedimentary morphologies suggesting lacustrine environment. These landforms are located on remnants of layered deposits possibly composed of sulfate layers suggesting that fluvial activity could have contributed to the erosion of the layered terrains in Valles Marineris. Collectively, the features in Melas Chasma are a maximum of Hesperian in age. These results suggest that warm, wet environmental conditions on Mars persisted through the Hesperian and were present during the formation of Valles Marineris. The evidence for a paleolake in Melas Chasma attests to adequate environmental conditions for life development through the Hesperian period.
Flow-Induced Cerebral Vasodilatation in Vivo Involves Activation of Phosphatidylinositol-3 Kinase, NADPH-Oxidase, and Nitric Oxide Synthase
Authors: Paravicini Tamara M , Miller Alyson A , Drummond Grant R , Sobey Christopher G
Published: October 2005

Reactive oxygen species (ROS) such as superoxide (O•−2) and hydrogen peroxide (H2O2) are known cerebral vasodilators. A major source of vascular ROS is the flavin-containing enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase. Activation of NADPH-oxidase leads to dilatation of the basilar artery in vivo via production of H2O2, but the endogenous stimuli for this unique vasodilator mechanism are unknown. Shear stress is known to activate both NADPH-oxidase and phosphatidylinositol-3 kinase (PI3-K) in cultured cells. Hence, this study used a cranial window preparation in anesthetized rats to investigate whether increased intraluminal blood flow could induce cerebral vasodilatation via the activation of NADPH-oxidase and/or PI3-K. Bilateral occlusion of the common carotid arteries to increase basilar artery blood flow caused reproducible, reversible vasodilatation. Topical treatment of the basilar artery with the NADPH-oxidase inhibitor diphenyleneiodonium (DPI) (0.5 and 5 μmol/L) inhibited flow-induced dilatation by up to 50% without affecting dilator responses to acetylcholine. Treatment with the H2O2 scavenger, catalase similarly attenuated flow-induced dilatation, suggesting a role for NADPH-oxidase-derived H2O2 in this response. The nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) partially reduced flow-induced dilatation, and combined treatment with a ROS inhibitor (DPI or catalase) and l-NAME caused a greater reduction in flow-induced dilatation than that seen with any of these inhibitors alone. Flow-induced dilatation was also markedly inhibited by the PI3-K inhibitor, wortmannin. Increased O•−2 production in the endothelium of the basilar artery during acute increases in blood flow was confirmed using dihydroethidium. Thus, flow-induced cerebral vasodilatation in vivo involves production of ROS and nitric oxide, and is dependent on PI3-K activation.