bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic influences on mannan‐binding lectin (MBL) and mannan‐binding lectin associated serine protease‐2 (MASP‐2) activity
Authors: Sorensen Grith L. , Petersen Inge , Thiel Steffen , Fenger Mogens , Christensen Kaare , Kyvik Kirsten O. , Sørensen Thorkild I. A. , Holmskov Uffe , Jensenius Jens Christian
Published: November 2006

The lectin pathway of the complement system is activated when Mannan‐binding lectin (MBL) in complex with MASP‐2 binds microorganisms. Polymorphisms in both genes are responsible for low serum levels, which associate with increased risk of infection and autoimmune disease. The present study includes 1215 MBL measurements and 1214 MASP‐2 activity measurements in healthy Danish adult twins. Total MASP‐2 activity was estimated by C4 cleaving activity of samples diluted in an excess of MBL. Twin‐twin correlations were higher in monozygotic (MZ) than in dizygotic (DZ) twins for both traits. Heritabilites of MBL levels and MASP‐2 activity were estimated using structural equation modeling allowing assessment of the contribution of common genes affecting both traits. The estimated heritability was 0.77 [95% CI 0.64;0.91] for MBL levels and 0.75 [95% CI 0.59;0.81] for MASP‐2 activity with the presence of additive genetic factors, shared environmental factors, and non‐shared environmental factors. The genetic correlation, i.e., common genetic factors affecting MBL and MASP‐2 activity was estimated to rg = 0.34 [0.25;0.42]. The data indicate a strong genetic influence for the serum levels of MBL and for MASP‐2 activity with a significant genetic correlation between the two traits. Genet. Epidemiol. © 2006 Wiley‐Liss, Inc.
T cells contribute to lysophosphatidylcholine‐induced macrophage activation and demyelination in the CNS
Authors: Ghasemlou Nader , Jeong Suh Young , Lacroix Steve , David Samuel
Published: November 2006

We have previously shown that intraspinal microinjection of lysophosphatidylcholine (LPC), a potent demyelinating agent, results in a rapid but brief influx of T cells (between 6 and 12 h). This is accompanied by a robust activation of macrophages/microglia that leads to demyelination by 48 h. In the present study, we examined whether this brief influx of T cells contributes to the activation of macrophages/microglia and demyelination by injecting LPC into the dorsal column white matter of athymic Nude mice that lack T cells. We show that there is a significant reduction in macrophage/microglial activation and myelin clearance after LPC injection in Nude mice as compared with wildtype controls. We also show that there is no difference in the recruitment of hematogenous macrophages into the spinal cord after LPC injection in the two mouse strains. Of the T cell cytokines assessed, there was a marked reduction in the mRNA expression of interleukin‐2 (IL‐2) in Nude mice compared with wildtype animals. Neutralizing IL‐2 with function‐blocking antibodies in wildtype animals resulted in a significant decrease in the number of phagocytic macrophages/microglia and a reduction in demyelination induced by LPC. While there may be other defects in Nude mice that might contribute to the effects shown here, these data suggest that the brief influx of T cells in this model of chemically‐induced demyelination could play a role in macrophage/microglial activation and demyelination. These results may also have implications for remyelination in this and other types of CNS damage. © 2006 Wiley‐Liss, Inc.
The development of hippocampal interneurons in rodents
Authors: Danglot Lydia , Triller Antoine , Marty Serge
Published: November 2006

Interneurons are GABAergic neurons responsible for inhibitory activity in the adult hippocampus, thereby controlling the activity of principal excitatory cells through the activation of postsynaptic GABAA receptors. Subgroups of GABAergic neurons innervate specific parts of excitatory neurons. This specificity indicates that particular interneuron subgroups are able to recognize molecules segregated on the membrane of the pyramidal neuron. Once these specific connections are established, a quantitative regulation of their strength must be performed to achieve the proper balance of excitation and inhibition. We will review when and where interneurons are generated. We will then detail their migration toward and within the hippocampus, and the maturation of their morphological and neurochemical characteristics. We will finally review potential mechanisms underlying the development of GABAergic interneurons. © 2006 Wiley‐Liss, Inc.
From grid cells to place cells: A mathematical model
Authors: Solstad Trygve , Moser Edvard I. , Einevoll Gaute T.
Published: November 2006

Anatomical connectivity and recent neurophysiological results imply that grid cells in the medial entorhinal cortex are the principal cortical inputs to place cells in the hippocampus. The authors propose a model in which place fields of hippocampal pyramidal cells are formed by linear summation of appropriately weighted inputs from entorhinal grid cells. Single confined place fields could be formed by summing input from a modest number (10–50) of grid cells with relatively similar grid phases, diverse grid orientations, and a biologically plausible range of grid spacings. When the spatial phase variation in the grid‐cell input was higher, multiple, and irregularly spaced firing fields were formed. These observations point to a number of possible constraints in the organization of functional connections between grid cells and place cells. © 2006 Wiley‐Liss, Inc.
αvβ3 Integrin‐targeting of intraperitoneally growing tumors with a radiolabeled RGD peptide
Authors: Dijkgraaf Ingrid , Kruijtzer John A.W. , Frielink Cathelijne , Corstens Frans H.M. , Oyen Wim J.G. , Liskamp Rob M.J. , Boerman Otto C.
Published: November 2006

Ovarian cancer is the fourth most common cause of cancer deaths among females in the western world after cancer of the breast, colon and lung. The inability to control the disease within the peritoneal cavity is the major cause of treatment failure in patients with ovarian cancer. The majority of ovarian carcinomas express the αvβ3 integrin. Here we studied the tumor targeting potential of an 111In‐labeled cyclic RGD peptide in athymic BALB/c mice with intraperitoneally (i.p.) growing NIH:OVCAR‐3 human ovarian carcinoma tumors. The cyclic RGD peptide, c(RGDfK)E, was synthesized, conjugated with DOTA and radiolabeled with 111In. The targeting potential of 111In‐DOTA‐E‐c(RGDfK) was studied in athymic mice with i.p. growing NIH:OVCAR‐3 xenografts and the optimal dose of this compound was determined (0.01 μg up to 10 μg). The biodistribution at optimal peptide dose was determined at various time points (0.5 up to 72 hr). Furthermore, the therapeutic potential of 177Lu‐DOTA‐E‐c(RGDfK) was studied in this model. Two hours after i.p. administration, 111In‐DOTA‐E‐c(RGDfK) showed high and specific uptake in the i.p. growing tumors. Optimal uptake in the i.p. growing tumors was observed at a 0.03–0.1 μg dose range. Tumor uptake of 111In‐DOTA‐E‐c(RGDfK) peaked 4 hr p.i. [(38.8 ± 2.7)% ID/g], gradually decreasing at later time points [(24.0 ± 4.1)% ID/g at 48 hr p.i.]. Intraperitoneal growth of OVCAR‐3 could be significantly delayed by injecting 37 MBq 177Lu‐labeled peptide i.p. Radiolabeled DOTA‐E‐c(RGDfK) is suitable for targeting of i.p. growing tumors and potentially can be used for peptide receptor radionuclide therapy of these tumors. © 2006 Wiley‐Liss, Inc.
TGFβ1 and TGFα contrarily affect alveolar survival and tumorigenesis in mouse mammary epithelium
Authors: Booth Brian W. , Jhappan Chamelli , Merlino Glenn , Smith Gilbert H.
Published: November 2006

Growth factors and hormones are responsible for development of the mammary gland and can contribute to mammary carcinogenesis. The transforming growth factors (TGF) α and β1 demonstrate opposing effects on the mammary epithelium. TGFα is a mitogen and survival factor for mammary secretory cells and is often upregulated in cancer, while TGFβ1 may act as a growth suppressor and has been shown to inhibit alveolar development and lactogenesis. To examine the contradistinct effects of TGFα and TGFβ1 on normal mammary epithelium, we crossed MT‐TGFα mice with WAP‐TGFβ1 transgenic mice. The newly generated bitransgenic mice failed to nurse their pups and were resistant to mammary tumorigenesis (0% at 12 months of age), compared to single transgenic MT‐TGFα in which the majority (65% at 12 months of age) of the mice developed hyperplastic alveolar mammary lesions. Transplantation studies showed that bitransgenic tissue was highly resistant to tumor formation even after multiple pregnancies. WAP‐TGFβ1 mammary transplants often failed to grow and fully fill cleared mammary fat pads upon transplantation. This repression of growth was completely reversed in the bitransgenic implants, which grew as well as normal epithelium upon transplantation. In addition, TGF and bitransgenic TGFα/TGFβ1 mice had reduced rates of apoptosis during involution as compared to wild type and TGFβ1. These data demonstrate that TGFβ1 and TGFα exhibit opposing effects upon the proliferation and survival of mammary epithelium when expressed alone but when expressed together result in reciprocally suppressive effects upon one another in the context of mammary development and tumorigenesis. © 2006 Wiley‐Liss, Inc.
Ala394Thr polymorphism in the clock gene NPAS2: A circadian modifier for the risk of non‐Hodgkin's lymphoma
Authors: Zhu Yong , Leaderer Derek , Guss Carly , Brown Heather N. , Zhang Yawei , Boyle Peter , Stevens Richard G. , Hoffman Aaron , Qin Qin , Han Xuesong , Zheng Tongzhang
Published: November 2006

Circadian disruption is theorized to cause immune dysregulation, which is the only established risk factor for non‐Hodgkin's lymphoma (NHL). Genes responsible for circadian rhythm are also involved in cancer‐related biological pathways as potential tumor suppressors. However, no previous studies have examined associations between circadian genes and NHL risk. In this population‐based case control study (n = 455 cases; 527 controls), we examined the only identified nonsynonymous polymorphism (Ala394Thr; rs2305160) in the largest circadian gene, neuronal PAS domain protein 2 (NPAS2), in order to examine its impact on NHL risk. Our results demonstrate a robust association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with reduced risk of NHL (OR = 0.66, 95% CI: 0.51–0.85, p = 0.001), especially B‐cell lymphoma (OR = 0.61, 95% CI: 0.47–0.80, p ≤≤ 0.0001). These findings provide the first molecular epidemiologic evidence supporting a role of circadian genes in lymphomagenesis, which suggests that genetic variations in circadian genes might be a novel panel of promising biomarkers for NHL and warrants further investigation. © 2006 Wiley‐Liss, Inc.
Development of resistance to chemotherapeutic drugs in human osteosarcoma cell lines largely depends on up‐regulation of clusterin/apolipoprotein J
Authors: Lourda Magda , Trougakos Ioannis P. , Gonos Efstathios S.
Published: November 2006

Clusterin/Apolipoprotein J (CLU) is differentially regulated during in vivo cancer progression. We have addressed the role of CLU during the acquisition and maintenance of human cancer cells resistance to chemotherapeutic drugs. We used two osteosarcoma (OS) cell lines, namely U‐2 OS and KH OS, and selected three generations of doxorubicin (DXR)‐resistant cells (R1, R2 and R3; resistant to 0.0035, 0.035 and 0.35 μM DXR, respectively) by continuous exposure to increasing, clinically relevant, DXR concentrations. Our studies showed that the DXR‐resistant OS cell lines were cross‐resistant to a variety of unrelated cytotoxic agents. Analysis of the CLU mRNA and protein expression levels revealed a minimal CLU up‐regulation in the U‐2 OS R2 cells and a significant, more than 4‐fold, induction in the KH OS R2 and R3 cells. Antibody‐mediated neutralization of the extracellular CLU, or silencing of CLU gene expression via small interfering RNA (siRNA) partially sensitized KH OS R2 cells to the drugs assayed. Moreover, siRNA‐mediated CLU knock down in the absence of DXR induced high levels of endogenous spontaneous apoptosis in both the parental and R2 OS cell lines. This effect was enhanced by more than 60% in the KH OS R2 cells as compared to their parental counterparts, indicating that the high CLU levels in the KH OS R2 cells are essential for survival. Overall, we suggest that CLU up‐regulation in the multi‐drug resistant OS cells relates to enhanced drug resistance. Therefore, CLU may represent a predictive marker, which correlates to response of cancer cells to chemotherapy. © 2006 Wiley‐Liss, Inc.
Whole genome tiling path array CGH analysis of segmental copy number alterations in cervical cancer cell lines
Authors: Lockwood William W. , Coe Bradley P. , Williams Ariane C. , MacAulay Calum , Lam Wan L.
Published: November 2006

Cervical cancer is the second most common malignancy in women worldwide, with high risk subtypes of human papillomavirus (HPV) constituting the major etiological agent. However, only a small percentage of women infected by the virus develop disease, suggesting that additional host genetic alterations are necessary for disease progression. In this study we examined the genomes of a panel of commonly used model cervical cancer cell lines using a recently developed whole genome tiling path array for CGH analysis. Detailed analysis of genomic profiles enabled the detection of many novel aberrations, which may have been missed by conventional cytogenetic methods. In total, 27 minimal regions of recurrent copy number alteration were identified that are potentially involved in tumorigenesis. Interestingly, fine mapping of the 3q gain, which is associated with the progression of precursor lesions to invasive cervical cancer, identified a minimal region of alteration harboring genes distinct from previous candidates. Novel regions of gene amplification, including the coamplification of both the Birc and MMP gene clusters on 11q22, were also evident. Lastly, characterization of genomic structure at sites of HPV integration identified the copy number gain of host cellular sequences between the viral‐host genomic boundaries in both SiHa and SW756, suggesting a direct role for HPV integration in the development of genetic abnormalities that initiate cervical cancer. This work represents the highest resolution look at a cervical cancer genome to date and offers definitive characterization of the alteration status of these cancer cell lines. © 2006 Wiley‐Liss, Inc.
Familial adenomatous polyposis patients have high levels of arachidonic acid and docosahexaenoic acid and low levels of linoleic acid and α‐linolenic acid in serum phospholipids
Authors: Almendingen Kari , Höstmark Arne T. , Fausa Olav , Mosdöl Annhild , Aabakken Lars , Vatn Morten H.
Published: November 2006

Familial adenomatous polyposis (FAP) provides a model of APC inactivation as an early genetic event for the ∼85% of colorectal cancers that develop from polyps. Abnormal fatty acid composition of tissues and serum phospholipids has been linked to cancer risk. Our aim was to describe the composition of fatty acids in serum phospholipids in 38 colectomized FAP patients as compared to 160 healthy subjects. Mean fatty acid intakes were similar between the groups. Colectomy was done on average 16 years prior to inclusion, and 18% were diagnosed with colorectal cancer at colectomy. The levels (weight %) of linoleic and α‐linolenic acid were higher among the reference subjects (difference: 3.96, 95% confidence interval (CI) = 2.87, 5.04, and difference: 0.06, 95% CI = 0.04, 0.08, respectively), and the levels of arachidonic and docosahexaenoic acid were lower (difference: −3.70, 95% CI = −4.35, −3.06, and difference: −5.26, 95% CI = −6.25, −4.28, respectively) as compared to the FAP patients (all p ≤ 0.0001). The abnormal fatty acid composition was not related to time since colectomy, intestinal reconstruction or history of colorectal cancer for any of the fatty acids assessed. Compositional differences in the fatty acid profile of serum phospholipids have not been described before in FAP patients. Further studies are needed to confirm these findings and assess clinical significances of a possible distorted fatty acid metabolism, including a potentially different dietary need of essential fatty acids. The relevance of these findings for APC induced cancers remains unclear. © 2006 Wiley‐Liss, Inc.
Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer
Authors: Slattery Martha L. , Curtin Karen , Sweeney Carol , Levin Theodore R. , Potter John , Wolff Roger K. , Albertsen Hans , Samowitz Wade S.
Published: November 2006

It has been proposed that dietary factors such as folate, alcohol and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large population‐based case‐control study of incident colon cancer were used to evaluate whether intake of dietary, obesity, physical activity and nonsteroidal antiinflammatory drugs are associated with a CpG island methylator phenotype (CIMP). The BRAF V600E mutation and 5 CpG island markers (MINT1, MINT2, MINT31, p16 and hMLH1) were assessed in 1154 cases of colon cancer. We hypothesized that dietary factors involved in DNA methylation, cruciferous vegetables and use of aspirin/NSAIDs would be associated with CIMP‐high tumors. Dietary folate, vitamins B6 and B12, methionine and alcohol were not associated with increased likelihood of colon tumors with the CIMP‐high (2 or more markers methylated) phenotype. Dietary fiber, physical activity and aspirin and other nonsteroidal antiinflammatory drugs were inversely associated with both CIMP‐low and CIMP‐high tumors. Our results also suggested non‐CIMP pathways as well. Obese individuals were at 2‐fold increased risk of having a CIMP‐low tumor. Alcohol was associated with an increased risk of tumors that were MSI+ and CIMP‐low. In the presence of smoking 20 or more cigarettes per day, use of NSAIDs did not protect against a BRAF mutation. Our data suggest multiple pathways to colon cancer. They do not support a unique role for dietary folate, alcohol, vitamins B6 and B12 and methionine in a CpG island methylator phenotype. © 2006 Wiley‐Liss, Inc.
Second malignancies among survivors of germ‐cell testicular cancer: A pooled analysis between 13 cancer registries
Authors: Richiardi Lorenzo , Scélo Ghislaine , Boffetta Paolo , Hemminki Kari , Pukkala Eero , Olsen Jorgen H. , Weiderpass Elisabete , Tracey Elizabeth , Brewster David H. , McBride Mary L. , Kliewer Erich V. , Tonita Jon M. , Pompe‐Kirn Vera , Kee‐Seng Chia , Jonasson Jon G. , Martos Carmen , Brennan Paul
Published: November 2006

We investigated the risk of second malignancies among 29,511 survivors of germ‐cell testicular cancer recorded in 13 cancer registries. Standardized incidence ratios (SIRs) were estimated comparing the observed numbers of second malignancies with the expected numbers obtained from sex‐, age‐, period‐ and population‐specific incidence rates. Seminomas and nonseminomas, the 2 main histological groups of testicular cancer, were analyzed separately. During a median follow‐up period of 8.3 years (0–35 years), we observed 1,811 second tumors, with a corresponding SIR of 1.65 (95% confidence interval (CI): 1.57–1.73). Statistically significant increased risks were found for fifteen cancer types, including SIRs of 2.0 or higher for cancers of the stomach, gallbladder and bile ducts, pancreas, bladder, kidney, thyroid, and for soft‐tissue sarcoma, nonmelanoma skin cancer and myeloid leukemia. The SIR for myeloid leukemia was 2.39 (95% CI: 1.41–3.77) after seminomas, and 6.77 (95% CI: 4.14–10.5) after nonseminomas. It increased to 37.9 (95% CI: 18.9–67.8; based on 11 observed cases of leukemia) among nonseminoma patients diagnosed since 1990. SIRs for most solid cancers increased with follow‐up duration, whereas they did not change with year of testicular cancer diagnosis. Among subjects diagnosed before 1980, 20 year survivors of seminoma had a cumulative risk of solid cancer of 9.6% (95% CI: 8.7–10.5%) vs. 6.5% expected, whereas 20 years survivors of nonseminoma had a risk of 5.0% (95% CI: 4.2–6.0%) vs. 3.1% expected. In conclusion, survivors of testicular cancers have an increased risk of several second primaries, where the effect of the treatment seems to play a major role. © 2006 Wiley‐Liss, Inc.
Associations between serum carotenoids and tocopherols and type‐specific HPV persistence: The Ludwig‐McGill cohort study
Authors: Siegel Erin M. , Craft Neal E. , Duarte‐Franco Eliane , Villa Luisa L. , Franco Eduardo L. , Giuliano Anna R.
Published: November 2006

Although oncogenic HPV infections have been established as the necessary cause of cervical cancer, most HPV infections are transient and rarely progress to cervical lesions. Current research is focused on identifying factors associated with viral persistence and clearance, such as nutritional status. We evaluated the association between serum antioxidant nutrients (retinol, 10 carotenoids and 3 tocopherols) and type‐specific HPV persistence over 4 visits among 405 women participating in the Ludwig‐McGill cohort study. We measured circulating carotenoids and tocopherol at 4 different clinical visits for each woman. We report the results from different analytic approaches (a case–control approach at both the woman and viral level, and a prospective approach based on persistent events) that examined the association between these micronutrients and type‐specific oncogenic and nononcogenic HPV persistence. In the case–control analysis at the viral level, midcirculating levels of α‐tocopherol were inversely associated with nononcogenic HPV persistent infection (adjusted odds ratio (AOR) = 0.28, 95% CI 0.14–0.57), while high levels were marginally associated (AOR = 0.59, 95% CI 0.28–1.19). Similarly, utilizing generalized estimating equation models, circulating levels of α‐ and δ‐tocopherol in the middle or upper tertiles were inversely associated with type‐specific nononcogenic HPV persistence (AOR = 0.44, 95% CI 0.19–0.97 and AOR = 0.46, 95% CI 0.19–1.11, respectively). Our study among Brazilian women suggests that serum levels of tocopherols may be protective against nononcogenic HPV persistence. However, we did not find a strong protective effect (as hypothesized) of other serum antioxidant nutrients and type‐specific oncogenic HPV persistence measured over 4 clinical visits. © 2006 Wiley‐Liss, Inc.
Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome
Authors: Renkonen‐Sinisalo Laura , Bützow Ralf , Leminen Arto , Lehtovirta Pentti , Mecklin Jukka‐Pekka , Järvinen Heikki J.
Published: November 2006

The estimated lifetime risk for endometrial carcinoma (EC) in hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is 32–60%, thus supporting surveillance. The survival rate of EC patients is, however, favourable questioning the need for surveillance. Yet, the effectiveness of gynecological surveillance remains to be shown. The 2 previously published studies were based on transvaginal ultrasound (TVUS) alone. Intrauterine biopsy has not been tested in surveillance for EC in HNPCC families. The effect of gynecological surveillance was evaluated among 175 Finnish mutation carriers. During 759 person years at risk, there were 503 surveillance visits including TVUS and intrauterine biopsy of endometrium at 94% and 74% of the visits, respectively. EC occurred in 14 cases, 11 of which were diagnosed by surveillance, 8 by intrauterine biopsies. TVUS indicated only 4 EC patients but missed 6 other cases. Intrauterine sampling detected 14 additional cases of potentially premalignant hyperplasia. The stage distribution and survival tended to be more favorable in the 14 EC cases of the surveilled group (no deaths) than in the group of 83 symptomatic mutation carriers of whom 6 died of EC, but with no statistical significance. Four cases of ovarian cancer occurred but none was detected by surveillance in TVUS examinations. In conclusion, EC surveillance in HNPCC seems more effective with endometrial biopsies than with TVUS alone. A definite improvement in survival remains to be shown. The detection of early cancer stages and premalignant lesions offers the opportunity to avoid extensive adjuvant treatment. © 2006 Wiley‐Liss, Inc.
Analysis of the extracellular matrix vesicle proteome in mineralizing osteoblasts
Authors: Xiao Zhen , Camalier Corinne E. , Nagashima Kunio , Chan King C. , Lucas David A. , Cruz M. Jason de la , Gignac Michelle , Lockett Stephen , Issaq Haleem J. , Veenstra Timothy D. , Conrads Thomas P. , Beck George R.
Published: November 2006

Many key processes central to bone formation and homeostasis require the involvement of osteoblasts, cells responsible for accumulation and mineralization of the extracellular matrix (ECM). During this complex and only partially understood process, osteoblasts generate and secrete matrix vesicles (MVs) into the ECM to initiate mineralization. Although they are considered an important component of mineralization process, MVs still remain a mystery. To better understand their function and biogenesis, a proteomic analysis of MVs has been conducted. MVs were harvested by two sample preparation approaches and mass spectrometry was utilized for protein identification. A total of 133 proteins were identified in common from the two MV preparations, among which were previously known proteins, such as annexins and peptidases, along with many novel proteins including a variety of enzymes, osteoblast‐specific factors, ion channels, and signal transduction molecules, such as 14‐3‐3 family members and Rab‐related proteins. To compare the proteome of MV with that of the ECM we conducted a large‐scale proteomic analysis of collagenase digested mineralizing osteoblast matrix. This analysis resulted in the identification of 1,327 unique proteins. A comparison of the proteins identified from the two MV preparations with the ECM analysis revealed 83 unique, non‐redundant proteins identified in all three samples. This investigation represents the first systematic proteomic analysis of MVs and provides insights into both the function and origin of these important mineralization‐regulating vesicles. J. Cell. Physiol. 210: 325–335, 2007. © 2006 Wiley‐Liss, Inc.
MicroRNAs and their regulatory roles in animals and plants
Authors: Zhang Baohong , Wang Qinglian , Pan Xiaoping
Published: November 2006

microRNAs (miRNAs) are an abundant class of newly identified endogenous non‐protein‐coding small RNAs. They exist in animals, plants, and viruses, and play an important role in gene silencing. Translational repression, mRNA cleavage, and mRNA decay initiated by miRNA‐directed deadenylation of targeted mRNAs are three mechanisms of miRNA‐guided gene regulation at the post‐transcriptional levels. Many miRNAs are highly conserved in animals and plants, suggesting that they play an essential function in plants and animals. Lots of investigations indicate that miRNAs are involved in multiple biological processes, including stem cell differentiation, organ development, phase change, signaling, disease, cancer, and response to biotic and abiotic environmental stresses. This review provides a general background and current advance on the discovery, history, biogenesis, genomics, mechanisms, and functions of miRNAs. J. Cell. Physiol. 210: 279–289, 2007. © 2006 Wiley‐Liss, Inc.
Skp2‐mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia
Authors: Auld Corinth A. , Fernandes Karishma M. , Morrison Ron F.
Published: November 2006

p27(Kip1), an important regulator of Cdk2 activity and G1/S transition, is tightly regulated in a cell‐type and condition‐specific manner to integrate mitogenic and differentiation signals governing cell cycle progression. We show that p27 protein levels progressively declined from mid‐G1 through late‐G2 phase as density‐arrested 3T3‐L1 preadipocytes synchronously reentered the cell cycle during early stages of adipocyte differentiation. This dramatic fall in p27 protein accumulation was due, at least in part, to a decrease in protein stability. Specific inhibitors of the 26S proteasome were shown to completely block the decrease in p27 protein levels throughout G1, increase the abundance of ubiquitylated p27 protein, and inhibit G1/S transition resulting in G1 arrest. It is further demonstrated that p27 was phosphorylated on threonine 187 during S phase progression by Cdk2 and that phosphorylated p27 was polyubiquitylated and degraded. Furthermore, we demonstrate that Skp2 and Cks1 dramatically increased during S/G2 phase progression concomitantly with the maximal fall in p27 protein. Complete knockdown of Skp2 with RNA interference partially prevented p27 degradation equivalent to that observed with Cdk2 blockade suggesting that the SCFSkp2 E3 ligase and other proteasome‐dependent mechanisms contribute to p27 degradation during preadipocyte replication. Interestingly, Skp2‐mediated p27 degradation was not essential for G1/S or S/G2 transition as preadipocytes shifted from quiescence to proliferation during adipocyte hyperplasia. Finally, evidence is presented suggesting that elevated p27 protein in the absence of Skp2 was neutralized by sequestration of p27 protein into Cyclin D1/Cdk4 complexes. J. Cell. Physiol. 211: 101–111, 2007. © 2006 Wiley‐Liss, Inc.
Education or employment—choices facing young people in Kazakhstan
Authors: Kalyuzhnova Yelena , Kambhampati Uma
Published: November 2006

This paper considers the links between education and employment in Kazakhstan. Using a sample of 12 000 Kazakhstani households, we analyse the factors determining the choice made by young adults between education and work within a multinomial logit framework. Our results confirm that while men are more likely to work and to remain unemployed, women are actually much more likely than men to study further. The main findings of the paper are firstly, contrary to studies elsewhere in the world, the family's income level does not influence the probability of study but influences all other choices significantly. Secondly, like studies conducted on most other countries of the world, the educational status of parents significantly influences the choices made by their offspring. In addition, the regional (location) characteristics play a role in the choice of post‐compulsory education. Copyright © 2006 John Wiley & Sons, Ltd.
An unconventional IAP‐binding motif revealed by target‐assisted iterative screening (TAIS) of the BIR3‐cIAP1 domain
Authors: Kurakin Alexei , Bredesen Dale E.
Published: November 2006

Target‐assisted iterative screening (TAIS) has been applied to a random phage‐displayed peptide library in a search for novel ligands of the third baculovirus IAP (‘inhibitors of apoptosis’) repeat (BIR) domain of cIAP1. The peptides selected in the screen fall into two distinct specificity groups, one that conforms to a known IAP‐binding motif (IBM) and another one that reveals a novel BIR domain interacting motif, NH2‐SR(V/P)W. The biochemical profiling of selected sequences with synthetic peptides, which included alanine scanning and N‐ and C‐terminal truncations as well as competition with the Smac peptide, suggests a major energetic contribution of tryptophan at the +4 position of peptide ligands to binding and identifies the latter together with the respective pocket on the BIR domain surface as a ‘hot spot’ of the interaction. A peptide featuring the novel motif selectively binds the full‐length cIAP1 protein in cell lysates. A ‘two‐pocket’ model of BIR domain recognition mechanism is proposed as the basis of differential BIR domain interactions with different IBMs. Copyright © 2006 John Wiley & Sons, Ltd.
DENSE and HARP: Two views on the same technique of phase‐based strain imaging
Authors: Kuijer Joost P.A. , Hofman Mark B.M. , Zwanenburg Jaco J.M. , Marcus J. Tim , van Rossum Albert C. , Heethaar Rob. M.
Published: November 2006

Purpose

To discuss differences between displacement encoding with stimulated echoes (DENSE) and the harmonic phase (HARP) in imaging and reconstruction strategies.

Materials and Methods

HARP and DENSE are presented in their historical context: while the HARP method was developed from the framework of myocardial tagging, DENSE arose from the framework of stimulated echo and displacement encoding using bipolar gradients. Both techniques have evolved since their introduction, thereby becoming more similar over time and losing their distinct features. Newly introduced improvements have successfully been applied in both methods. Differences between both methods are discussed point by point.

Results

From this discussion it follows that almost all apparent differences are in fact nonexistent.

Conclusion

In the literature, both techniques are still regarded as distinctly different techniques, where a more general treatment of the technique is justified. Once it is realized that both frameworks are easily merged, the benefits are 1) less confusion about the (dis)advantages of either technique, and 2) understanding of phase‐based strain imaging that is more general than HARP or DENSE alone. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Intravascular hematocrit layering in equilibrium phase contrast‐enhanced MR angiography of the peripheral vasculature
Authors: Wang Maisie S. , Haynor David R. , Wilson Gregory J. , Maki Jeffrey H.
Published: November 2006

Purpose

To evaluate intravenous hematocrit (HCT) layering detected in patent calf veins that potentially simulate filling defects seen in deep venous thrombosis (DVT).

Materials and Methods

Flow characteristics, vessel size, and enhancement patterns of veins with HCT layering were examined and compared with those of normal veins in vivo. Ex vivo studies were conducted with conventional and blood pool contrast agents to study the effects of MRI parameters and intrinsic variables on detecting HCT layering.

Results

HCT layering was detected in high resolution equilibrium phase images in one of six healthy subjects, and five of five patients with peripheral vascular occlusive disease (PVOD). Layering occurred only in deep veins that had significantly slower flow and larger diameter (P < 0.001) compared to normal veins. Enhancement patterns observed in vivo were similar to those found in the ex vivo study.

Conclusion

The HCT layering effect in MR venography has not been previously reported, likely because delayed equilibrium phase venous imaging is not frequently performed. The use of blood pool contrast agents and high resolution equilibrium phase imaging allows intravascular HCT layering to be observed within a 30–60‐minute time frame. Several imaging characteristics that distinguish HCT layering from DVT are discussed. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
The new‐generation, high‐energy, 595 nm, long pulse‐duration, pulsed‐dye laser effectively removes spider veins of the lower extremity
Authors: Bernstein Eric F.
Published: November 2006

Background and Objectives

Lower‐extremity spider veins are a cosmetic problem that poses formidable clinical difficulty for laser removal. They are significantly harder to remove than facial telangiectasias. A new‐generation, pulsed‐dye laser (PDL), capable of administering pulses that clinically behave like true 40‐millisecond pulses has been developed, by doubling the number of sub‐pulses comprising each laser pulse.

Study Design/Materials and Methods

Fifteen subjects with Fitzpatrick skin types I–III were enrolled in the study and treated to 35 sites. Subjects were treated three times at 6‐week intervals using an average fluence of 20.4 J/cm2, a 3×10 mm spot, and a dynamic cooling device to protect the epidermis. Digital photographs were taken before initiating treatment and 8 weeks following the final treatment.

Results

Mean improvement scores using a 4‐point scale as rated subjectively by the treating physician were 0.92 (<25%), 2.7 (∼40–50%), and 3.6 (∼65–75%), 6 weeks following 1st and 2nd treatments and 8 weeks following the 3rd and final treatment, respectively. Improvement was also determined by three physicians, rating digital photographs and blinded as to which photographs were pre‐ or post‐treatment. They rated improvement as mild (0–25%) in 10.5% of photographs, moderate (26–50%) in15.2%, marked (51–75%) in 38.1%, and excellent (76–100%) in 6.3%. There was no textural change in any treatment site.

Conclusions

The new‐generation, high‐energy, 595 nm, long pulse‐duration, PDL effectively removes lower‐extremity spider veins in subjects with skin types I–III. Lasers Surg. Med. 39:218–224, 2007. © 2006 Wiley‐Liss, Inc.
Determination of Intermolecular Acetyl Distribution of Cellulose Triacetate by Reversed Phase High Performance Liquid Chromatography
Authors: Asai Tanemi , Shimamoto Shu , Shibata Tohru , Kawai Tadatomo , Teramachi Shinya
Published: November 2006

The chromatographic method for the determination of the intermolecular acetyl distribution of cellulose triacetate (CTA) was established; the key point of the method is a gradient elution by gradually changing the solvent composition of the ternary mixture of chloroform, methanol, and water on a phenyl‐bonded silica gel stationary phase. A positive correlation between the retention time and the degree of acetyl substitution was observed under the established chromatographic conditions. The validity of the elution peak width as the measure of intermolecular acetyl distribution was confirmed by the co‐injection and fractionation experiments and the comparison of a peak width with a statistically estimated distribution.
New Evidence for the Mechanism of the Pore Formation in Polymerising High Internal Phase Emulsions or Why polyHIPEs Have an Interconnected Pore Network Structure
Authors: Menner Angelika , Bismarck Alexander
Published: November 2006

We present new evidence that the formation of pore throats (windows) or pore interconnects in polymerised High Internal Phase Emulsions (polyHIPEs) is most likely due to a mechanical action exerted during the post‐synthesis processing of the porous polymer monolith. We would like to invite researchers interested in this field to reopen the discussion on the mechanism which lead to the formation of pore throats during the polymerisation of concentrated emulsion templates.
Application of Modified Natural Oils as Reactive Diluents for Epoxy Resins
Authors: Czub Piotr
Published: November 2006

Bisphenol A based low‐molecular‐weight epoxy resin was modified with epoxidized soybean oil, which exhibit viscosity reducing ability comparable to commercial grade active diluents. The studied compositions showed a non‐Newtonian rheological behavior, typical for Bingham liquids. The values of the flow index (n) and the consistency index (k) for the compositions tested in the temperature range 25–65 °C were calculated from the Ostwald‐de Waele rheological model and were used to calculate the flow‐activation energy (Ea) using the Arhenius equation. Studies of co‐crosslinking of mixed oil‐resin compositions using isophorone diamine showed essential decrease of the reaction heat and peak maximum temperature. Mechanical properties, thermal stability, water absorption and chemical resistance of the epoxy resin modified with natural oil, were also investigated. Compositions of epoxy resin Ruetapox 0162, modified with the oil diluent, preserved very good mechanical properties of the epoxy resins and demonstrated relatively low water absorption as well as high chemical resistance. The compositions displayed even higher impact strength than pure epoxy resin due to plasticizing effect of the built‐in oil. Compositions with the high contents (up to 60 weight %) of the oil were flexible materials with fast elastic recovery.
Agarose Sols and Gels Revisited
Authors: Guenet Jean‐Michel , Rochas Cyrille
Published: November 2006

Agarose sols have been seen for long as solutions of flexible chains that, on cooling, produce thermoreversible gels through double‐helix formation. Investigations of the chain conformation in the sol state by small‐angle neutron scattering reveals instead a rigid chain with a very large persistence length (lp > 9 nm). The chain cross‐section radius and mass per unit length correspond to characteristics of helices as those described by Foord and Atkins. These results lead one to a reappraisal of the occurrence of double helices in the gelation process, as they rather suggest a transition of the type loose‐single helix⇒tight single helix. Studies of gels from agarose/water/cosolvent where the cosolvent is Dimethyl Sulfoxide (DMSO), Dimethyl Formamide (DMF), and Methyl Formamide (MF) have led one to conclude on the formation of agarose/water/ cosolvent ternary complexes. The contrast variation method by neutron scattering gives further support to this assumption. Finally, determination of the gel nanostructure allows one to account for the two regimes observed for the variation of the elastic modulus vs concentration.
Structural Phase Transitions of Aliphatic Nylons Viewed from the Simultaneous Measurements of WAXD and SAXS
Authors: Tashiro Kohji , Takeuchi Kazuhiro , Ohta Yasuaki , Hanesaka Makoto , Hashida Tomoko , Yoshioka Yayoi , Ramesh Chellaswami
Published: November 2006

Structural changes occurring in the high temperature region of doubly‐oriented nylon 10/10 sample have been investigated through the temperature‐dependent simultaneous measurements of wide‐angle and small‐angle X‐ray scatterings, and the results were compared with the infrared spectral data as well as the molecular dynamics simulation results. In the Brill transition region of 150–180 °C the methylene segments are conformationally disordered with keeping the intermolecular hydrogen bonds. During this phase transition the stacked lamellar structure did not change very much: the lamellae are tilted by ca. 34° from the draw axis and the long period is almost 160 Å. In the temperature region immediately below the melting point the molecular chains were found to be contracted by ca. 10% the original repeating period and the intermolecular hydrogen bonds were almost broken, causing the violent rotational and translational motions of the chains around the chain axis. At the same time the long period increased remarkably from 160 Å to 410 Å and the originally tilted lamellae stood up in parallel to the draw axis.
Polymers for Multifunctional Textiles
Authors: Visileanu Emilia , Ene Alexandra , Mihai Carmen , Kowalczuk Marek
Published: November 2006

Biodegradable P[(R,S)‐3HB‐co‐LA] and P[(R,S)‐3HB‐co‐CL] copolyesters for special medical application, i.e. as scaffolds for cartilage and soft tissue engineering, were synthesized by transesterification of the corresponding homopolymers, i.e. a‐PHB and poly(L‐lactide) or a‐PHB and poly(e‐caprolactone), respectively. The carried out biological studies emphasized the biocompatibility of the copolymer PHBV/a‐PHB, in for its using in the manufacturing of the haemostatical dressings.
Migration Study of Polypropylene (PP) Oil Blends in Food Simulants
Authors: Wang Qian , Storm Birgit K
Published: November 2006

Migration study in aqueous and olive oil food simulants was carried out on PP and its blend with oil mixture. It was found that after 10 days at 44 °C PP with oil content up to 0.83% had overall migration into olive oil less than 10 mg/dm2. However, under high temperature migration test (at 110–138 C for 4 hours), the overall migration into olive oil was large for both the virgin PP and all its blends. The overall migration in water, 10% ethanol, and 3% acetic acid was smaller than those in olive oil under both migration test conditions. DSC and density measurement showed that addition of oil in PP led to smaller spherulite size and increased degree of crystallinity in the pure PP part. Small decrease in tensile strength in the oil blends was also observed but there was no significant change in tensile strength after migration test.
Steady solutions of the Navier–Stokes equations with threshold slip boundary conditions
Authors: Roux C. Le , Tani A.
Published: November 2006

We establish the wellposedness of the time‐independent Navier–Stokes equations with threshold slip boundary conditions in bounded domains. The boundary condition is a generalization of Navier's slip condition and a restricted Coulomb‐type friction condition: for wall slip to occur the magnitude of the tangential traction must exceed a prescribed threshold, independent of the normal stress, and where slip occurs the tangential traction is equal to a prescribed, possibly nonlinear, function of the slip velocity. In addition, a Dirichlet condition is imposed on a component of the boundary if the domain is rotationally symmetric.

We formulate the boundary‐value problem as a variational inequality and then use the Galerkin method and fixed point arguments to prove the existence of a weak solution under suitable regularity assumptions and restrictions on the size of the data. We also prove the uniqueness of the solution and its continuous dependence on the data. Copyright © 2006 John Wiley & Sons, Ltd.
Intensity of CNS treatment for pediatric cancer: Prediction of social outcomes in survivors
Authors: Vannatta Kathryn , Gerhardt Cynthia A. , Wells Robert J. , Noll Robert B.
Published: November 2006

Purpose

To evaluate the association of central nervous system (CNS) treatment intensity and the social functioning of children who have completed treatment for leukemia, lymphoma, and solid tumors outside the CNS. Furthermore, we expected that these associations would be moderated by child age at diagnosis and gender.

Method

Peer, teacher, and self‐report data were obtained for 82 cancer survivors (age 9–17 years) using classroom rating and nomination procedures that are widely used in research on social development. Information regarding cranial radiation therapy (CRT), intrathecal chemotherapy (ITC), and systemic methotrexate were obtained from medical records and used to create a composite index of CNS treatment intensity.

Results

Higher scores on the index of CNS treatment intensity were associated with poorer peer acceptance, fewer friendships, greater social sensitivity‐isolation, and diminished leadership‐popularity based on peer‐report. These associations were stronger for boys and children who were younger (<10 years old) at diagnosis. In contrast, CNS treatment intensity was only predictive of teacher‐perceptions of aggressive–disruptive behavior and it was unrelated to social self‐perceptions.

Conclusion

These results suggest that children who receive CRT and ITC are at risk for problematic peer relations, particularly if they are male or younger at diagnosis. Given the stability of poor peer relationships and documented linkages between peer problems and subsequent academic and psychiatric difficulties, clinical services should address these issues. Research is needed to identify mechanisms that account for these outcomes and provide direction for prevention and treatment efforts. Pediatr Blood Cancer 2007;49:716–722. © 2006 Wiley‐Liss, Inc.