bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, Synthesis, and Evaluation of 3,4‐Disubstituted Pyrazole Analogues as Antitumor CDK Inhibitors.
Authors: Lin Ronghui , Chiu George , Yu Yang , Connolly Peter J. , Li Shengjian , Lu Yanhua , Adams Mary , Fuentes‐Pesquera Angel R. , Emanuel Stuart L. , Greenberger Lee M.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Reaction of 3‐Benzoyl‐1‐methyl‐4‐phenyl‐γ‐piperidol with Arylamines and Arylhydrazines. Synthesis of 3‐Arylamino‐1‐oxo‐1‐phenylpropanes and 1,3‐Diarylpyrazoles and Their Fragmentation under Electron Impact.
Authors: Volkov S. V. , Kutyakov S. V. , Levov A. N. , Polyakova E. I. , Anh Le Tuan , Soldatova S. A. , Terentiev P. B. , Soldatenkov A. T.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of Novel 4(5)‐(5‐Aminotetrahydropyran‐2‐yl)imidazole Derivatives and Their in vivo Release of Neuronal Histamine Measured by Brain Microdialysis.
Authors: Harusawa Shinya , et al. et al.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis and Structure of 4‐Arylspirodihydropyranochromen‐2‐one Derivatives.
Authors: Moskvina V. S. , Garazd Ya. L. , Garazd M. M. , Turov A. V. , Khilya V. P.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis and Halogenation of Allylthioethers of Pyrazolo[3,4‐d]pyrimidine.
Authors: Onisko M. Yu. , Svalyavin O. V. , Lendel V. G.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Microwave‐Assisted Reductive Cyclization of N‐Allyl 2‐Nitroanilines: A New Approach to Substituted 1,2,3,4‐Tetrahydroquinoxalines.
Authors: Merisor Elena , Conrad Juergen , Mika Sabine , Beifuss Uwe
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Nucleophilic Cleavage of Selenaheterocyclic Ring in Benzisoselenazol‐3(2H)‐ones and 1,3,2‐Benzodiselenazoles.
Authors: Lisiak R. , Mlochowski J. , Palus J.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Isolation and Chemical Modification of Clerodane Diterpenoids from Salvia Species as Potential Agonists at the ϰ‐Opioid Receptor.
Authors: Li Yiqiang , Husbands Stephen M. , Mahon Mary F. , Traynor John R. , Rowan Michael G.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Two New 1‐Oxygenated ent‐Kaurane‐Type Diterpenes from Croton kongensis.
Authors: Chen Wei , Yang Xiao‐Dong , Zhao Jing‐Feng , Zhang Hong‐Bin , Li Liang
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Apply Peptide C‐Terminal Semicarbazides to Peptide Segment Coupling Using Transfer Active Ester Condensation Technology.
Authors: Wang Pu
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
First Total Synthesis of Antitumor Natural Product (+)‐ and (‐)‐Pericosine A (I): Determination of Absolute Stereo Structure.
Authors: Usami Yoshihide , Takaoka Isao , Ichikawa Hayato , Horibe Yusuke , Tomiyama Syunsuke , Ohtsuka Misako , Imanishi Yumi , Arimoto Masao
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Short and Efficient Total Synthesis of Luotonin A (Ia) and 22‐Hydroxyacuminatine (Ib) Using a Common Cascade Strategy.
Authors: Zhou Hai‐Bin , Liu Guan‐Sai , Yao Zhu‐Jun
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Total Synthesis of Neooxazolomycin.
Authors: Onyango Evans Otieno , Tsurumoto Joji , Imai Naoko , Takahashi Keisuke , Ishihara Jun , Hatakeyama Susumi
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Enantioselective Synthesis of Arglabin
Authors: Kalidindi Srinivas , Jeong Won Boo , Schall Andreas , Bandichhor Rakeshwar , Nosse Bernd , Reiser Oliver
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Total Synthesis of Pederin.
Authors: Jewett John C. , Rawal Viresh H.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Stereoselective Synthesis of Cytotoxic Anhydrophytosphingosine Pachastrissamine [Jaspine B] (I).
Authors: Prasad Kavirayani R. , Chandrakumar Appayee
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of (‐)‐Tabtoxinine‐β‐lactam, the Phytotoxin of Tobacco Wildfire Disease.
Authors: Kiyota Hiromasa , Takai Takafumi , Shimasaki Yasuharu , Saitoh Masatoshi , Nakayama Osamu , Takada Tomoko , Kuwahara Shigefumi
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Cephalimysin A, a Potent Cytotoxic Metabolite from an Aspergillus Species Separated from a Marine Fish.
Authors: Yamada Takeshi , Imai Eiji , Nakatuji Kazuyo , Numata Atsushi , Tanaka Reiko
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Inhibitors of Anthrax Lethal Factor.
Authors: Gaddis Brandon D. , Avramova Larisa V. , Chmielewski Jean
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Introductory Guide to Organonickel Chemistry
Authors: Tamaru Yoshinao
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Study of the By‐Products of Benzo[f]indolizines Syntheses: A Quest Towards Structural Diversity
Authors: Rigo Benoit , Akue‐Gedu Rufine
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Development of Environmentally Friendly Organometallic Catalysis for Drug Discovery and Its Application to Heterocyclic Chemistry
Authors: Arisawa Mitsuhiro
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Reaction Mechanisms. Part 2. Pericyclic Reactions
Authors: Tantillo Dean J. , Lee Jeehiun K.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Reaction Mechanisms. Part 1. Radical and Radical Ion Reactions
Authors: Tanko J. M.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Vibrational Spectroscopy Studies on Linear Polyamines
Authors: Marques M. P. M. , Batista de carvalho L. A. E.
Published: December 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Knallquecksilber
Authors: Bensmann Katja
Published: December 2007

Die explosiven Eigenschaften und die Darstellung des Quecksilberfulminats oder auch Knallquecksilbers sind seit mehr als drei Jahrhunderten bekannt. Nun ist es gelungen, die Struktur dieser Verbindung mittels einer Einkristallstrukturanalyse aufzuklären.
Mindfulness‐based stress reduction and attentional control
Authors: Anderson Nicole D. , Lau Mark A. , Segal Zindel V. , Bishop Scott R.
Published: December 2007

This study was designed to test the hypothesis that mindfulness involves sustained attention, attention switching, inhibition of elaborative processing and non‐directed attention. Healthy adults were tested before and after random assignment to an 8‐week Mindfulness‐Based Stress Reduction (MBSR) course (n = 39) or a wait‐list control (n = 33). Testing included measures of sustained attention, attention switching, Stroop interference (as a measure of inhibition of elaborative processing), detection of objects in consistent or inconsistent scenes (as a measure of non‐directed attention), as well as self‐report measures of emotional well‐being and mindfulness. Participation in the MBSR course was associated with significantly greater improvements in emotional well‐being and mindfulness, but no improvements in attentional control relative to the control group. However, improvements in mindfulness after MBSR were correlated with improvements in object detection. We discuss the implications of these results as they relate to the role of attention in mindfulness. Copyright © 2007 John Wiley & Sons, Ltd.
The Y‐OQ‐12: psychosocial screening of youth in primary care medicine using items from an outcome measure
Authors: Tzoumas Anthony C. , Tzoumas Jennifer L. , Burlingame Gary M. , Nelson Philip L. , Wells M. Gawain , Gray Douglas D.
Published: December 2007

The studies reported herein describe the successful development and validation of a youth mental health screening instrument for identifying psychosocial distress in pediatric care patients. As a subset of 12 items from the well‐established Youth Outcome Questionnaire‐2.01 (Y‐OQ‐2.01), the Youth Outcome Questionnaire‐12 (Y‐OQ‐12) screen intends to be the first stage in a two‐stage screening process. Patients screened as positive complete the full‐length Y‐OQ‐2.01 in the second stage. A stage two score in the clinical range can serve as a baseline in continuous outcome tracking using the Y‐OQ‐2.01. The 12 parent‐report items of the Y‐OQ‐12 were selected using a combination of items from the Y‐OQ‐2.01 using a known‐groups approach based on community (n = 500) and outpatient psychiatric (n = 500) samples. The sensitivity of the Y‐OQ‐12 was 0.84, with a specificity of 0.82 and an internal consistency of 0.90. Two factors emerged, accounting for 48% and 9% of the variance (‘mood/behavioural symptom distress’ and ‘quality of life’, respectively). A second validation study involving 371 youth from pediatric settings in three US states compared the Y‐OQ‐12 with the Pediatric Symptom Checklist (PSC) and the Diagnostic Interview Schedule for Children‐Present State. The Y‐OQ‐12 demonstrated sensitivity, specificity and predictive power that were comparable to the PSC and shows promise for screening in routine practice. The authors encourage the use of the Y‐OQ‐12 in practice and await the replication of these findings in future research. Copyright © 2007 John Wiley & Sons, Ltd.
Multiparametric analysis of normal and postchemotherapy bone marrow: Implication for the detection of leukemia‐associated immunophenotypes
Authors: Olaru D. , Campos L. , Flandrin P. , Nadal N. , Duval A. , Chautard S. , Guyotat D.
Published: December 2007

Background:

The knowledge of normal marrow is mandatory to assess the malignant counterpart of normal cells and define leukemia‐associated immunophenotypes (LAIPs). In this study, the expression of a variety of antigens expressed in normal and postchemotherapy bone marrow (BM) was analyzed to provide a frame of reference for the identification of myeloid LAIPs.

Methods:

Multiparameter four‐ and six‐color flow cytometry was used to define antigen combinations totally absent or present at very minimal levels in marrow cells of normal individuals (n = 20) and patients receiving chemotherapy for acute lymphoblastic leukemia (n = 20). Immature (blast) cells were gated according to CD45/SSC properties. Fifty‐three acute myeloid leukemia (AML) samples were studied in six‐color combinations.

Results:

In six‐color flow cytometry, 47 phenotypes were totally absent from blast gate in all normal samples. Forty‐one other phenotypes were identified in less than 0.05% of blast cells. There was no difference between normal and postchemotherapy BMs. The four‐color panel allowed to identify only 30 phenotypes present at a frequency <0.05%. Using the six‐color panel, 58% of the absent or infrequent phenotypes in normal BM were found in at least one of 53 AML samples. All AML cases exhibited at least one LAIP.

Conclusion:

Our results show that the ability to distinguish leukemic from healthy cells is considerably increased by a six‐color approach. Furthermore, these absent or infrequent phenotypes in normal BM are identified in AML and can be utilized for minimal residual disease study. © 2007 Clinical Cytometry Society
Unusual direct phycoerythrin labeling of B‐cells from a splenic marginal zone lymphoma
Authors: Tabary T. , Staal‐Viliare A. , Rault J. P. , Didion J. , Latger‐Cannard V. , Reveil B. , Cohen J. H. M. , Rio Y.
Published: December 2007

Flow cytometry is the most widely used method for lymphocyte subset characterization. Two types of antibodies, directly labeled with fluorochrome, are currently used for immunological diagnosis of B‐cell lymphoproliferation: monoclonal antibodies against leukocyte differentiation antigens and polyclonal antibodies against immunoglobulins and light chains. In this study is described the case of a patient with an uncommon immunophenotyping of a B‐cell lymphoproliferative disorder. B‐cells from peripheral blood and from bone marrow reacted positively with all the tested phycoerythrin (PE)‐conjugated antibodies, including the isotypic control. So we thought about a B‐cell proliferation carrying a surface receptor recognizing PE: these B‐cells were directly labeled with streptavidin‐PE, indeed. Moreover, the immunodots from the patient were able to fix the streptavidin‐PE. Finally, this unusual immunophenotyping was solved by using antibodies labeled with other fluorochromes than PE. © 2007 Clinical Cytometry Society.
CD158k/KIR3DL2 is a useful marker for identifying neoplastic T‐cells in Sézary syndrome by flow cytometry
Authors: Bahler David W. , Hartung Leah , Hill Sally , Bowen Glen M. , Vonderheid Eric C.
Published: December 2007

Enumeration of neoplastic T‐cells in peripheral blood specimens is necessary for the diagnosis of Sézary syndrome (SS) and monitoring treatment responses. Because neoplastic T‐cells in SS can be difficult to identify by morphology alone, flow cytometry immunophenotyping is often utilized. However, the reported immunophenotypic criteria for identifying neoplastic T‐cells in SS are variable, not present in all cases, or sometimes found in reactive T‐cell populations. Peripheral blood lymphocytes from 33 cases of SS were evaluated for the expression of pan‐T cell antigens and killer cell immunoglobulin‐like MHC receptors (KIR) CD158a, CD158b, CD158e, CD158i, and CD158k by multiparameter flow cytometry using monoclonal antibodies EB6, GL183, FES172, Z27, and Q66. A variety of abnormalities related to expression of pan‐T‐cell antigens typical of neoplastic T‐cells were observed. Expression of CD158k was observed in 32/33 cases and restricted to the phenotypically abnormal T‐cell populations, while expression of other KIR was mostly negative. Our findings confirm and extend recent reports by one group that CD158k is expressed by most SS cases. Moreover, our observation that CD4 positive, CD7 negative T‐cells are mostly CD158k negative further suggests that CD158k may be able to help identify and enumerate neoplastic T‐cells in SS even when present at low levels.
Endoscopic ultrasound‐guided fine needle aspiration is useful for nodal staging in patients with pleural mesothelioma
Authors: Bean Sarah M. , Eloubeidi Mohamad A. , Cerfolio Robert , Chhieng David C. , Eltoum Isam A.
Published: December 2007

Patients with malignant pleural mesothelioma and negative N2 stage lymph nodes may benefit from extrapleural pneumonectomy with adjuvant therapy. The objective of this study is to describe the use of EUS‐FNA to determine N2 stage status in patients with mesothelioma and its impact in the management of such patients. Six patients (mean age, 62 yr; median age, 63 yr; range, 52–70 yr; 5 men; 1 woman) underwent EUS‐FNA for staging of N2 lymph nodes from July 2000 to July 2006. Follow‐up included operative notes, treatment summaries, and surgical pathology. Eight sites were aspirated: four subcarinal lymph nodes, three aorto‐pulmonary window lymph nodes, and one paraesophageal mass. Two of 8 (25%) aspirates were positive for metastatic disease in two different patients. Two false negative EUS‐FNAs were observed and were attributed to sampling error not diagnostic error. No complications were observed. EUS‐FNA is a safe N2 node staging technique in patients with mesothelioma. A positive N2 lymph node by EUS‐FNA may be a contraindication to definitive surgery in patients with malignant mesothelioma. Diagn. Cytopathol. 2008;36:32–37. © 2007 Wiley‐Liss, Inc.
Nephrogenic adenoma identified on urine cytology using PAX‐2 immunostaining
Authors: Herlitz Leal C. , Tong Guo‐Xia , Hamele‐Bena Diane , Greenebaum Ellen
Published: December 2007

Urine cytology is a sensitive and specific method in detecting urothelial carcinoma of the urinary bladder, particularly the high‐grade ones. However, the cytologic features of nonneoplastic lesions of the lower urinary tract, including nephrogenic adenoma, are nonspecific and may cause false positive diagnosis. Recent evidence has demonstrated that nephrogenic adenoma is a true “nephrogenic” lesion derived from the exfoliated and implanted renal tubular cells in the urinary tract. This has promoted the use of immunostaining of renal transcription factor PAX2 in tissue biopsies to differentiate nephrogenic adenoma from the common malignant tumors of the lower urinary tract. We report here that PAX2 immunostaining can also be used in urine cytology specimen to identify nephrogenic adenoma. Combination of PAX2 immunostaining and cytologic analysis may increase the accuracy in identifying this benign lesion in urine cytology specimen and therefore reduce unnecessary repeat cystoscopy and biopsy procedures. This may be a cost effective follow‐ up method for patients with an established diagnosis of nephrogenic adenoma. Diagn. Cytopathol. 2008;36:47–49. © 2007 Wiley‐Liss, Inc.
Influence of the Copper Coordination Geometry on the DNA Cleavage Activity of Clip‐Phen Complexes Studied by DFT
Authors: de Hoog Paul , Louwerse Manuel J. , Gamez Patrick , Pitié Marguerite , Baerends Evert Jan , Meunier Bernard , Reedijk Jan
Published: December 2007

Six different Cu(Clip‐Phen)2+/+ complexes, with or without a coordinating chloride ligand, have been investigated by DFT calculations to evaluate the influence of the length and functional substituents of the bridge linking the two phenanthroline units on the DNA cleavage activity. The changes of the structural and energetic profiles imposed by the bridge of these complexes have been analyzed by comparison with the well studied nuclease active agent Cu(phen)22+/+. The present studies show that the bridge length of these complexes is critical for the consequent geometry, and both the strain and ligand binding energies. Upon reduction (needed for the DNA cleavage activity), the geometry of Cu(phen)2 changes drastically. The behavior of the complexes with a 4‐ or 5‐carbon bridge resembles the behavior of Cu(phen)22+/+. However, the geometries of the complexes with two‐ or three‐carbon bridges are markedly different from the one of unbridged Cu(phen)2+, as a result of constraints enforced by the short bridge. The results suggest that the cleaving activities of these bis‐phenanthroline complexes are influenced by the different ligand environment geometries imposed by the bridge, and not by the change of the redox properties. It appears that the influence of the different bridges on the redox properties of the complexes is minor.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
A polymerase chain reaction‐restriction fragment length polymorphism method based on the analysis of a 16S rRNA/tRNAVal mitochondrial region for species identification of commercial penaeid shrimps (Crustacea: Decapoda: Penaeoidea) of food interest
Authors: Pascoal Ananías , Barros‐Velázquez Jorge , Cepeda Alberto , Gallardo José M. , Calo‐Mata Pilar
Published: December 2007

A simple PCR‐RFLP method has been developed for the identification of 19 penaeid shrimp species of food interest belonging to the superfamily Penaeoidea. Preliminary amplification, sequencing and alignment of a 960 bp fragment of the 16S rRNA/tRNAVal/12S rRNA mitochondrial region allowed the design of 16Scru4/16Scru4 primers, constructed on well‐conserved mitochondrial sequences of the penaeid shrimp species considered. Such primers afforded the amplification of an internal 515–535 bp region of the 16S rRNA/tRNAVal genes that, when subjected to cleavage with AluI, TaqI and HinfI, provided species‐specific restriction patterns. Moreover, the proposed method also allowed the definition of different intraspecific restriction types between different populations of Litopenaeus vannamei, Farfantepenaeus notialis, Fenneropenaeus merguiensis, Metapenaeus sp., Melicertus latisulcatus and Pleoticus muelleri of different origins. The method described here was also successfully applied for the identification of penaeid shrimps in complex processed precooked foods, where this type of shellfish is used as an added‐value food ingredient. Sequencing analysis provided new information about the genetic relationships among shrimps not only at the levels of species and genus, but also among different populations at intraspecific level. The 16S rRNA/tRNAVal fragment considered in this study seems to be accurate for shrimp species identification in raw and processed foodstuffs and for phylogenetic analysis among penaeid shrimp species.
SOS1 mutations are rare in human malignancies: Implications for Noonan syndrome patients
Authors: Swanson Kenneth D. , Winter Jordan M. , Reis Marcelo , Bentires‐Alj Mohamed , Greulich Heidi , Grewal Rupinder , Hruban Ralph H. , Yeo Charles J. , Yassin Yosuf , Iartchouk Oleg , Montgomery Kate , Whitman Susan P. , Caligiuri Michael A. , Loh Mignon L. , Gilliland D. Gary , Look A. Thomas , Kucherlapati Raju , Kern Scott E. , Meyerson Matthew , Neel Benjamin G.
Published: December 2007

Germ line gain‐of‐function mutations in several members of the RAS/ERK pathway, including PTPN11, KRAS, and RAF1, cause the autosomal dominant genetic disorder Noonan Syndrome (NS). NS patients are at increased risk of leukemia/myeloproliferative disease and possibly some solid tumors, such as neuroblastoma. Recently, SOS1 gain of function mutations have also been shown to cause NS. Somatic PTPN11, KRAS, and RAF1 mutations occur (although at different frequencies) in a variety of sporadic neoplasms, but whether SOS1 mutations are associated with human cancer has not been evaluated. We sequenced DNA from a total of 810 primary malignancies, including pancreatic, lung, breast, and colon carcinomas, and acute myelogenous leukemia, as well as several neuroblastoma cell lines. From this large, diverse series, missense SOS1 mutations were identified in a single pancreatic tumor, one lung adenocarcinoma, and a T‐cell acute lymphoblastic leukemia cell line. Our findings suggest that SOS1 is not a significant human oncogene in most cancers. Furthermore, NS patients with SOS1 mutations may not be at increased risk of developing cancer. © 2007 Wiley‐Liss, Inc.
Detecting brain growth patterns in normal children using tensor‐based morphometry
Authors: Hua Xue , Leow Alex D. , Levitt Jennifer G. , Caplan Rochelle , Thompson Paul M. , Toga Arthur W.
Published: December 2007

Previous magnetic resonance imaging (MRI)‐based volumetric studies have shown age‐related increases in the volume of total white matter and decreases in the volume of total gray matter of normal children. Recent adaptations of image analysis strategies enable the detection of human brain growth with improved spatial resolution. In this article, we further explore the spatio‐temporal complexity of adolescent brain maturation with tensor‐based morphometry. By utilizing a novel non‐linear elastic intensity‐based registration algorithm on the serial structural MRI scans of 13 healthy children, individual Jacobian growth maps are generated and then registered to a common anatomical space. Statistical analyses reveal significant tissue growth in cerebral white matter, contrasted with gray matter loss in parietal, temporal, and occipital lobe. In addition, a linear regression with age and gender suggests a slowing down of the growth rate in regions with the greatest white matter growth. We demonstrate that a tensor‐based Jacobian map is a sensitive and reliable method to detect regional tissue changes during development. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.
Assessment of the increase in variability when combining volumetric data from different scanners
Authors: Reig Santiago , Sánchez‐González Javier , Arango Celso , Castro Josefina , González‐Pinto Ana , Ortuño Felipe , Crespo‐Facorro Benedicto , Bargalló Nuria , Desco Manuel
Published: December 2007

In multicenter MRI studies, pooling of volumetric data requires a prior evaluation of compatibility between the different machines used. We tested the compatibility of five different scanners (2 General Electric Signa, 2 Siemens Symphony, and a Philips Gyroscan) at five different sites by repeating the scans of five volunteers at each of the sites. Using a semiautomatic method based on the Talairach atlas, and SPM algorithms for tissue segmentation (multimodal T1 and T2, or T1‐only), we obtained volume measurements of the main brain lobes (frontal, parietal, occipital, temporal) and for each tissue type. Our results suggest that pooling of multisite data adds small error for whole brain measurements, intersite coefficient of variation (CV) ranging from 1.8 to 5.2%, respectively, for GM and CSF. However, in the occipital lobe, intersite CV can be as high as 11.7% for WM and 17.3% for CSF. Compared with the intersite, intrasite CV values were always much lower. Whenever possible, T1 and T2 tissue segmentation methods should be used because they yield more consistent volume measurements between sites than T1‐only, especially when some of the scans were obtained with different sequence parameters and pixel size from those of the other sites. Our study shows that highest compatibility among scanners would be obtained using equipments of the same manufacturer and also image acquisition parameters as similar as possible. After validation, data from a specific ROI or scanner showing values markedly different from the other sites might be excluded from the analysis. Hum Brain Mapp, 2009. © 2007 Wiley‐Liss, Inc.
Mature adipocyte‐derived dedifferentiated fat cells exhibit multilineage potential
Authors: Matsumoto Taro , Kano Koichiro , Kondo Daisuke , Fukuda Noboru , Iribe Yuji , Tanaka Nobuaki , Matsubara Yoshiyuki , Sakuma Takahiro , Satomi Aya , Otaki Munenori , Ryu Jyunnosuke , Mugishima Hideo
Published: December 2007

When mature adipocytes are subjected to an in vitro dedifferentiation strategy referred to as ceiling culture, these mature adipocytes can revert to a more primitive phenotype and gain cell proliferative ability. We refer to these cells as dedifferentiated fat (DFAT) cells. In the present study, we examined the multilineage differentiation potential of DFAT cells. DFAT cells obtained from adipose tissues of 18 donors exhibited a fibroblast‐like morphology and sustained high proliferative activity. Flow cytometric analysis revealed that DFAT cells comprised a highly homogeneous cell population compared with that of adipose‐derived stem/stromal cells (ASCs), although the cell‐surface antigen profile of DFAT cells was very similar to that of ASCs. DFAT cells lost expression of mature adipocytes marker genes but retained or gained expression of mesenchymal lineage‐committed marker genes such as peroxisome proliferator‐activated receptor gamma (PPARγ), RUNX2, and SOX9. In vitro differentiation analysis revealed that DFAT cells could differentiate into adipocytes, chondrocytes, and osteoblasts under appropriate culture conditions. DFAT cells also formed osteoid matrix when implanted subcutaneously into nude mice. In addition, clonally expanded porcine DFAT cells showed the ability to differentiate into multiple mesenchymal cell lineages. These results indicate that DFAT cells represent a type of multipotent progenitor cell. The accessibility and ease of culture of DFAT cells support their potential application for cell‐based therapies. J. Cell. Physiol. 215: 210–222, 2008. © 2007 Wiley‐Liss, Inc.
Pressure loading and ethanol exposure differentially modulate rat hepatic stellate cell activation
Authors: Okada Yoshikiyo , Tsuzuki Yoshikazu , Hokari Ryota , Miyazaki Jyunichi , Matsuzaki Koji , Mataki Norikazu , Komoto Shunsuke , Watanabe Chikako , Kawaguchi Atsushi , Nagao Shigeaki , Itoh Kazuro , Miura Soichiro
Published: December 2007

Ethanol may cause an increase in sinusoidal pressure accompanied by portal hypertension. Hepatic stellate cells (HSCs) located in hepatic sinusoids may therefore be frequently exposed to dual stimulations of mechanical pressure and ethanol exposure in alcoholic liver injury. In this study, the effects of pressure loading and ethanol exposure on activation of rat cultured HSCs were investigated using an in vitro pressure‐inducing apparatus. HSCs were cultured in media containing ethanol (0–100 mM) under different pressures (1–40 mmHg). Morphological changes and migration index were determined. We also determined the expression levels of α‐smooth muscle actin (α‐SMA) and mitogen‐activated protein kinases (MAPKs) by Western blot analysis and the level of collagen IV and transforming growth factor β1 (TGF‐β1) by ELISA. Pressure loading alone induced up‐regulation of α‐SMA via the extracellular signal‐regulated kinases 1 and 2 (ERK1/2) and c‐jun N‐terminal kinase (JNK) signaling pathways, prolonged extension of marginal length, and increased production of collagen IV. In contrast, ethanol exposure alone increased only extension of marginal length and cell migration. Dual stimulations of pressure loading and ethanol exposure enhanced the production of TGF‐β1 and migration index. The TGF‐β1‐dependent p38 MAPK pathway may operate for production of extracellular matrix (ECM) or enhanced migration in the case of dual stimulations. In conclusion, static pressure loading is an important factor directly accelerating the activation of HSCs. Although increased sinusoidal pressure and ethanol exposure might differentially modulate HSC activation, both stimuli are involved in an additive manner in some situations. J. Cell. Physiol. 215: 472–480, 2008. © 2007 Wiley‐Liss, Inc.
Lipocalin 2‐mediated growth suppression is evident in human erythroid and monocyte/macrophage lineage cells
Authors: Miharada Kenichi , Hiroyama Takashi , Sudo Kazuhiro , Danjo Inaho , Nagasawa Toshiro , Nakamura Yukio
Published: December 2007

Lipocalin 2 (LCN2), a secreted protein of the lipocalin family, induces apoptosis in some types of cells and inhibits bacterial growth by sequestration of the iron‐laden bacterial siderophore. We have recently reported that LCN2 inhibits the production of red blood cells in the mouse. Here we analyzed the role of LCN2 in human hematopoiesis. Expression of LCN2 was observed not only in mature cells such as those of the granulocyte/macrophage and erythroid lineages but also in hematopoietic stem/progenitor cells. We also examined expression of two candidate receptors for LCN2, brain type organic cation transporter (BOCT) and megalin, in various cell types. BOCT showed relatively high levels of expression in erythroid and hematopoietic stem/progenitor cells but lower levels in granulocyte/macrophage and T lymphoid cells. Megalin was expressed at high levels in T lymphoid and erythroid cells but at lower levels in granulocyte/macrophage lineage cells. LCN2 suppressed the growth of erythroid and monocyte/macrophage lineages in vitro, but did not have this effect on cells of other lineages. In addition, immature hematopoietic stem/progenitor cells were not sensitive to LCN2. These results demonstrate a lineage‐specific role for LCN2 in human hematopoiesis that is reminiscent of its effects upon mouse hematopoiesis and strongly suggest an important in vivo function of LCN2 in the regulation of human hematopoiesis. J. Cell. Physiol. 215: 526–537, 2008. © 2007 Wiley‐Liss, Inc.
Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes mellitus
Authors: Stosic‐Grujicic Stanislava , Stojanovic Ivana , Maksimovic‐Ivanic Danijela , Momcilovic Miljana , Popadic Dusan , Harhaji Ljubica , Miljkovic Djordje , Metz Christine , Mangano Katia , Papaccio Gianpaolo , Al‐Abed Yousef , Nicoletti Ferdinando
Published: December 2007

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine of the innate immune system that plays a major role in the induction of immunoinflammatory responses. To examine the role of endogenous MIF in the pathogenesis of type 1 diabetes (TID) we evaluated the effects of administration of neutralizing anti‐MIF antibodies to NOD mice with accelerated forms of diabetes induced by injection of cyclophosphamide or by transfer of diabetogenic spleen cells. Both accelerated forms of diabetes were markedly reduced by anti‐MIF antibody. Furthermore, MIF‐deficient (MIF−/−) mice were less susceptible to the induction of immunoinflammatory diabetes, insulitis and apoptosis within the endocrine pancreas by multiple low doses of streptozotocin (MLD‐STZ) than genetically matched wild type (WT) mice. MIF deficiency resulted in lower proliferation and lymphocyte adhesion, as well as reduced production from the spleens and peritoneal cells of a variety of inflammatory mediators typically associated with development of the disease including IL‐12, IL‐23, TNF‐α, and IL‐1β. Furthermore, MIF deletion affected the production of IL‐18, TNF‐α, IL‐1β, and iNOS in the islets of Langerhans. These data, along with the higher expression of IL‐4 and TGF‐β observed in the periphery and in the pancreas of MLD‐STZ‐challenged MIF−/− mice as compared to WT controls suggest that MIF deficiency has induced an immune deviation towards protective type 2/3 response. These results suggest that MIF participates in T1D by controlling the functional activity of monocytes/macrophages and T cells and modulating their secretory capacity of pro‐ and anti‐inflammatory molecules. J. Cell. Physiol. 215: 665–675, 2008. © 2007 Wiley‐Liss, Inc.
Mechanism of extracellular ubiquitination in the mammalian epididymis
Authors: Baska Kathleen M. , Manandhar Gaurishankar , Feng Dawn , Agca Yuksel , Tengowski Mark W. , Sutovsky Miriam , Yi Young‐Joo , Sutovsky Peter
Published: December 2007

Posttranslational modification by ubiquitination marks defective or outlived intracellular proteins for proteolytic degradation by the 26S proteasome. The ATP‐dependent, covalent ligation and formation of polyubiquitin chains on substrate proteins requires the presence and activity of a set of ubiquitin activating and conjugating enzymes. While protein ubiquitination typically occurs in the cell cytosol or nucleus, defective mammalian spermatozoa become ubiquitinated on their surface during post‐testicular sperm maturation in the epididymis, suggesting an active molecular mechanism for sperm quality control. Consequently, we hypothesized that the bioactive constituents of ubiquitin‐proteasome pathway were secreted in the mammalian epididymal fluid (EF) and capable of ubiquitinating extrinsic substrates. Western blotting indeed detected the presence of the ubiquitin‐activating enzyme E1 and presumed E1‐ubiquitin thiol–ester intermediates, ubiquitin‐carrier enzyme E2 and presumed E2‐ubiquitin thiol–ester intermediates and the ubiquitin C‐terminal hydrolase PGP 9.5/UCHL1 in the isolated bovine EF. Thiol–ester assays utilizing recombinant ubiquitin‐activating and ubiquitin‐conjugating enzymes, biotinylated substrates, and isolated bovine EF confirmed the activity of the ubiquitin activating and conjugating enzymes within EF. Ubiquitinated proteins were found to be enriched in the defective bull sperm fraction and appropriate proteasomal deubiquitinating and proteolytic activities were measured in the isolated EF by specific fluorescent substrates. The apocrine secretion of cytosolic proteins was visualized in transgenic mice and rats expressing the enhanced green fluorescent protein (eGFP) under the direction of ubiquitin‐C promoter. Accumulation of eGFP, ubiquitin and proteasomes was detected in the apical blebs, the apocrine secretion sites of the caput epididymal epithelia of both the rat and mouse epididymal epithelium, although region‐specific differences exist. Secretion of eGFP and proteasomes continued during the prolonged culture of the isolated rat epididymal epithelial cells in vitro. This study provides evidence that the activity of the ubiquitin system is not limited to the intracellular environment, contributing to a greater understanding of the sperm maturation process during epididymal passage. J. Cell. Physiol. 215: 684–696, 2008. © 2007 Wiley‐Liss, Inc.
The role of insulin receptor substrate‐1 in transformation by v‐src
Authors: Sun Hongzhi , Baserga Renato
Published: December 2007

The insulin receptor substrate‐1 (IRS‐1), a docking protein for both the insulin (InR) and the insulin‐like growth factor‐1 (IGF‐IR) receptors, sends a mitogenic, anti‐differentiation and transforming signal. We now show that down‐regulation of IRS‐1 in cells transformed by v‐src reverses the transformed phenotype (growth in serum‐free medium and colony formation in soft agar). IRS‐1 translocates to nuclei and is found in the cyclin D1 and rDNA promoters. Stat3, which is activated by src, requires both IRS‐1 and src for promoter occupancy. IRS‐1 (by itself or in combination with src) also markedly increases transcription from these two promoters. We also show that IRS‐1 binds to src via its two PI3‐K binding tyrosine residues, and that these two residues are required for transformation of mammary cancer cells expressing v‐src. Taken together, these results indicate a significant role of IRS‐1 in the activation of cell cycle progression genes and transformation of cells by v‐src. J. Cell. Physiol. 215: 725–732, 2008. © 2007 Wiley‐Liss, Inc.
Epac/Rap and PKA are novel mechanisms of ANP‐induced Rac‐mediated pulmonary endothelial barrier protection
Authors: Birukova Anna A. , Zagranichnaya Tatiana , Alekseeva Elena , Bokoch Gary M. , Birukov Konstantin G.
Published: December 2007

Acute lung injury, sepsis, lung inflammation, and ventilator‐induced lung injury are life‐threatening conditions associated with lung vascular barrier dysfunction, which may lead to pulmonary edema. Increased levels of atrial natriuretic peptide (ANP) in lung circulation reported in these pathologies suggest its potential role in the modulation of lung injury. Besides well recognized physiological effects on vascular tone, plasma volume, and renal function, ANP may exhibit protective effects in models of lung vascular endothelial cell (EC) barrier dysfunction. However, the molecular mechanisms of ANP protective effects are not well understood. The recently described cAMP‐dependent guanine nucleotide exchange factor (GEF) Epac activates small GTPase Rap1, which results in activation of small GTPase Rac‐specific GEFs Tiam1 and Vav2 and Rac‐mediated EC barrier protective responses. Our results show that ANP stimulated protein kinase A and the Epac/Rap1/Tiam/Vav/Rac cascade dramatically attenuated thrombin‐induced pulmonary EC permeability and the disruption of EC monolayer integrity. Using pharmacological and molecular activation and inhibition of cAMP‐and cGMP‐dependent protein kinases (PKA and PKG), Epac, Rap1, Tiam1, Vav2, and Rac we linked ANP‐mediated protective effects to the activation of Epac/Rap and PKA signaling cascades, which dramatically inhibited the Rho pathway of thrombin‐induced EC hyper‐permeability. These results suggest a novel mechanism of ANP protective effects against agonist‐induced pulmonary EC barrier dysfunction via inhibition of Rho signaling by Epac/Rap1‐Rac and PKA signaling cascades. J. Cell. Physiol. 215: 715–724, 2008. © 2007 Wiley‐Liss, Inc.
A further analysis of the spatio‐temporal variability in aerosols across North America: Incorporation of lower tropospheric (850‐hPa) flow
Authors: Sheridan Scott C. , Power Helen C. , Senkbeil Jason C.
Published: December 2007

In our previous research (Power et al., 2006), we analysed the variability in spectral aerosol optical depth (τa), as well as Ångström's wavelength exponent (α), which represents the relative size distribution of aerosols, at 27 sites across North America. The variability was assessed by incorporating the Spatial Synoptic Classification (SSC) surface weather type across each of these sites. In this research, we further our analysis by examining the effect of different 850‐hPa flow patterns within the lower troposphere on variability in τa and α. To accomplish this, an 850‐hPa flow classification was first developed from principal components analysis (PCA) and cluster analysis on National Centers for Environmental Prediction (NCEP)/The National Center for Atmospheric Research (NCAR) reanalysis geopotential‐height data, normalized by month of year. Nine flow types were identified.

Cluster analyses yielded five clusters for both τa and α. For τa, spatially cohesive regions were identified, with a western cluster with low aerosol optical depth and minimal synoptic variability, and eastern clusters that showed higher turbidity as well as synoptic variability. In these clusters, higher turbidity was associated with southerly advection. For α, results were less cohesive, with clusters largely representing the different seasonal patterns of the variable, with synoptic variability difficult to interpret.

Jackknifing was also utilized to evaluate whether τa and α could be predicted based on SSC weather type and 850‐hPa flow type. Results varied at the three stations evaluated, with the method yielding potentially useful results for τa across the two eastern sites, where synoptic variability at the surface and 850‐hPa is greater. At the western site, τa could not be successfully predicted. Synoptic variability is too weak for α to be predicted effectively at any of the sites examined. Copyright © 2007 Royal Meteorological Society
Expanded measurement uncertainty of soil parameters derived from proficiency‐testing data
Authors: Munzert Manfred , Kießling Günter , Übelhör Walter , Nätscher Ludwig , Neubert Karl‐Heinz
Published: December 2007

Basic parameters for the calculation of the expanded measurement uncertainty (U) of 33 soil parameters were derived from the data base of proficiency tests of the Association of German Agricultural Analytical and Research Institutes (VDLUFA) over the years 1993–2005. The underlying statistical model was the regression of the standard deviations of the means for all participating laboratories on the mean of all laboratories. In general, the linear model fits U very well. Only in three cases, a curvilinear equation showed a better significance. The calculated regressions were nonsignificant only in the cases of copper (using the Westerhoff method), pH, and the percentage of sand in the soil samples. All regressions were tested for plausibility using the Horwitz equation (HORRAT). Given a medium range of concentrations, practically all analytes fell well within a ratio of 2, only the results for manganese (Schachtschabel method) did not comply. Plausibility could be proven also for higher‐concentration ranges with the single exception of boron (hot‐water extraction). At very low–concentration ranges, for some of the analytes a HORRAT value of 2 was exceeded, presumably due to the proximity of the limit of detection in conjunction with some methodological problems. For all of these cases, a concentration limit for the reliability range of the regression for the analytes was calculated, at which the HORRAT values just met the critical ratio of 2. Laboratories are recommended to integrate the regression functions for U into their specific laboratory information and management system (LIMS) or other documentation systems in order to specify U for the measured values. Results are also considered as a solid basis for the evaluation of legally defined limits in agricultural fertilization of soils.