bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression: Protein Interaction Systems Network Modeling Identifies Transformation-Associated Molecules and Pathways in Ovarian Cancer
Authors: Bapat Sharmila A. , Krishnan Anagha , Ghanate Avinash D. , Kusumbe Anjali P. , Kalra Rajkumar S.
Published: June 2010

Multiple, dissimilar genetic defects in cancers of the same origin contribute to heterogeneity in tumor phenotypes and therapeutic responses of patients, yet the associated molecular mechanisms remain elusive. Here, we show at the systems level that serous ovarian carcinoma is marked by the activation of interconnected modules associated with a specific gene set that was derived from three independent tumor-specific gene expression data sets. Network prediction algorithms combined with preestablished protein interaction networks and known functionalities affirmed the importance of genes associated with ovarian cancer as predictive biomarkers, besides “discovering” novel ones purely on the basis of interconnectivity, whose precise involvement remains to be investigated. Copy number alterations and aberrant epigenetic regulation were identified and validated as significant influences on gene expression. More importantly, three functional modules centering on c-Myc activation, altered retinoblastoma signaling, and p53/cell cycle/DNA damage repair pathways have been identified for their involvement in transformation-associated events. Further studies will assign significance to and aid the design of a panel of specific markers predictive of individual- and tumor-specific pathways. In the parlance of this emerging field, such networks of gene-hub interactions may define personalized therapeutic decisions. Cancer Res; 70(12); 4809–19. ©2010 AACR.
Dexamethasone Destabilizes Nmyc to Inhibit the Growth of Hedgehog-Associated Medulloblastoma
Authors: Heine Vivi M. , Priller Markus , Ling Jason , Rowitch David H. , Schüller Ulrich
Published: June 2010

Mouse studies indicate that the synthetic glucocorticoid dexamethasone (Dex) impairs the proliferation of granule neuron precursors in the cerebellum, which are transformed to medulloblastoma by activation of Sonic hedgehog (Shh) signaling. Here, we show that Dex treatment also inhibits Shh-induced tumor growth, enhancing the survival of tumor-prone transgenic mice. We found that Nmyc was specifically required in granule cells for Shh-induced tumorigenesis and that Dex acted to reduce Nmyc protein levels. Moreover, we found that Dex-induced destabilization of Nmyc is mediated by activation of glycogen synthase kinase 3β, which targets Nmyc for proteasomal degradation. Together, our findings show that Dex antagonizes Shh signaling downstream of Smoothened in medulloblastoma. Cancer Res; 70(13); 5220–5. ©2010 AACR.
Serum Signature of Hypoxia-Regulated Factors Is Associated with Progression after Induction Therapy in Head and Neck Squamous Cell Cancer
Authors: Byers Lauren Averett , Holsinger F. Christopher , Kies Merrill S. , William William N. , El-Naggar Adel K. , Lee J. Jack , Hu Jianhua , Lopez Adriana , Tran Hai T. , Yan Shaoyu , Du Zhiqiang , Ang K. Kian , Glisson Bonnie S. , Raso Maria Gabriela , Wistuba Ignacio I. , Myers Jeffrey N. , Hong Waun-Ki , Papadimitrakopoulou Vali , Lippman Scott M. , Heymach John V.
Published: June 2010

Tumor hypoxia regulates many cytokines and angiogenic factors (CAF) and is associated with worse prognosis in head and neck squamous cell cancer (HNSCC). Serum CAF profiling may provide information regarding the biology of the host and tumor, prognosis, and response to therapy. We investigated 38 CAFs in HNSCC patients receiving induction therapy on a phase II trial of carboplatin, paclitaxel, and cetuximab. CAFs were measured by multiplex bead assay and enzyme-linked immunosorbent assay in 32 patients. Baseline and postinduction CAF levels were correlated with disease progression (PD) and human papilloma virus (HPV) status by Wilcoxon rank sum test. Baseline levels of eight hypoxia-regulated CAFs (the “high-risk signature” including vascular endothelial growth factor, interleukins 4 and 8, osteopontin, growth-related oncogene-α, eotaxin, granulocyte-colony stimulating factor, and stromal cell–derived factor-1α) were associated with subsequent PD. Elevation in ≥6 of 8 factors was strongly associated with shorter time to progression (P = 0.001) and was 73% specific and 100% sensitive for PD. Increasing growth-related oncogene-α from baseline to week 6 was also associated with PD. Progression-free and overall survival were shorter in patients with HPV-negative tumors (P = 0.012 and 0.046, respectively), but no individual CAF was associated with HPV status. However, among 14 HPV-negative patients, the high-risk CAF signature was seen in all 6 patients with PD, but only 2 of 14 without PD. In conclusion, serum CAF profiling, particularly in HPV-negative patients, may be useful for identifying those at highest risk for recurrence. Mol Cancer Ther; 9(6); 1755–63. ©2010 AACR.
High-Content Phenotypic Profiling of Drug Response Signatures across Distinct Cancer Cells
Authors: Caie Peter D. , Walls Rebecca E. , Ingleston-Orme Alexandra , Daya Sandeep , Houslay Tom , Eagle Rob , Roberts Mark E. , Carragher Neil O.
Published: June 2010

The application of high-content imaging in conjunction with multivariate clustering techniques has recently shown value in the confirmation of cellular activity and further characterization of drug mode of action following pharmacologic perturbation. However, such practical examples of phenotypic profiling of drug response published to date have largely been restricted to cell lines and phenotypic response markers that are amenable to basic cellular imaging. As such, these approaches preclude the analysis of both complex heterogeneous phenotypic responses and subtle changes in cell morphology across physiologically relevant cell panels. Here, we describe the application of a cell-based assay and custom designed image analysis algorithms designed to monitor morphologic phenotypic response in detail across distinct cancer cell types. We further describe the integration of these methods with automated data analysis workflows incorporating principal component analysis, Kohonen neural networking, and kNN classification to enable rapid and robust interrogation of such data sets. We show the utility of these approaches by providing novel insight into pharmacologic response across four cancer cell types, Ovcar3, MiaPaCa2, and MCF7 cells wild-type and mutant for p53. These methods have the potential to drive the development of a new generation of novel therapeutic classes encompassing pharmacologic compositions or polypharmacology in appropriate disease context. Mol Cancer Ther; 9(6); 1913–26. ©2010 AACR.
Enhanced Expression of PCAF Endows Apoptosis Resistance in Cisplatin-Resistant Cells
Authors: Hirano Gen , Izumi Hiroto , Kidani Akihiko , Yasuniwa Yoshihiro , Han Bin , Kusaba Hitoshi , Akashi Koichi , Kuwano Michihiko , Kohno Kimitoshi
Published: June 2010

Histone acetyltransferase (HAT) regulates transcription. We have previously shown that two HAT genes, Clock and Tip60, are overexpressed, and upregulate glutathione biosynthesis and the expression of DNA repair genes in cisplatin-resistant cells. To better understand the mechanism of HAT-related drug resistance, we investigated the role of another HAT gene, p300/CBP-associated factor (PCAF), and found that PCAF was also overexpressed in cisplatin-resistant cells and endowed an antiapoptotic phenotype through enhanced E2F1 expression. PCAF-overexpressing cells showed enhanced expression of E2F1 and conferred cell resistance to chemotherapeutic agents. Downregulation of PCAF decreased E2F1 expression and sensitized cells to chemotherapeutic agents. Moreover, knockdown of PCAF induced G1 arrest and apoptosis. These results suggest that PCAF is one of pleiotropic factors for drug resistance and seems to be critical for cancer cell growth. Mol Cancer Res; 8(6); 864–72. ©2010 AACR.
The Kingdoms of Nanzhong China's Southwest Border Region Prior to the Eighth Century
Authors: Herman John
Published: June 2010

This article utilizes recent ethno-historical scholarship and archaeological discoveries in southwest China to examine the accuracy of the earliest Chinese historical sources dealing with the peoples and cultures in Nanzhong, the most common name for the southwest region (Yunnan, Guizhou, and southern Sichuan) prior to the Tang dynasty. Archaeology makes clear that Nanzhong was a settled border region with several highly sophisticated and divergent cultures. Early Chinese incursions into Nanzhong left an indelible mark on the peoples living there, but these brief and generally unsuccessful forays also influenced the views of China's elites regarding China's relations with this region. Since at least the Qin and Han, China's scholar-officials considered Nanzhong not only as an inhospitable frontier populated with uncivilized barbarians (manyi), but also as a peripheral part of China where intrepid commanders such as Tang Meng in the second century BCE and Zhuge Liang at the beginning of the third century CE had staked China's claim. This article casts doubt on the historical fiction of a staked claim. Cet article s'appuie sur les recherches ethno-historiques et des découvertes archéologiques récentes pour vérifier l'exactitude des sources chinoises les plus anciennes concernant les peuples et les cultures du Nanzhong, comme était communément appelé le Sud-Ouest (le Yunnan, le Guizhou et le sud du Sichuan) avant la dynastie des Tang. L'archéologie montre à l'évidence que le Nanzhong était une région frontière habitée, siège de plusieurs cultures hautement sophistiquées et différenciées. Si les premières incursions chinoises dans le Nanzhong ont laissé une empreinte indélébile sur les populations locales, ces campagnes brèves et en général infructueuses ont également influencé l'opinion des élites chinoises concernant les relations de la Chine avec le Sud-Ouest. Depuis au moins les Qin et les Han les lettrés-fonctionnaires chinois considéraient le Nanzhong non seulement comme une frontière inhospitalière peuplée de barbares dénués de civilisation (manyi), mais aussi comme un territoire périphérique de la Chine où des généraux intrépides comme Tang Meng au iie siècle avant notre ère et Zhuge Liang au début du iiie siècle de notre ère avaient établi des droits pour la Chine. L'article met en doute cette fiction historique d'un droit établi.
Language Shift in Northern Pakistan: The Case of Domaakí and Pashto
Authors: Weinreich Matthias
Published: June 2010

The paper is devoted to the phenomenon of mother tongue change, which is known as the most common course of language death. The languages under consideration are Domaakí, with ca. 350 speakers in the Nager and Hunza Valleys, and Pashto, as spoken by permanent migrants in ca. 150 households scattered all over the Northern Areas. By analysing and comparing the social environment of both speech communities the author attempts to illustrate the importance of the speakers' attitude towards their own mother tongue in the process of language shift.
LFA-1 activity state on dendritic cells regulates contact duration with T cells and promotes T-cell priming
Authors: Balkow Sandra , Heinz Stefanie , Schmidbauer Patricia , Kolanus Waldemar , Holzmann Bernhard , Grabbe Stephan , Laschinger Melanie
Published: June 2010

A key event in the successful induction of adaptive immune responses is the antigen-specific activation of T cells by dendritic cells (DCs). Although LFA-1 (lymphocyte function–associated antigen 1) on T cells is considered to be important for antigen-specific T-cell activation, the role for LFA-1 on DCs remains elusive. Using 2 different approaches to activate LFA-1 on DCs, either by deletion of the αL-integrin cytoplasmic GFFKR sequence or by silencing cytohesin-1–interacting protein, we now provide evidence that DCs are able to make use of active LFA-1 and can thereby control the contact duration with naive T cells. Enhanced duration of DC/T-cell interaction correlates inversely with antigen-specific T-cell proliferation, generation of T-helper 1 cells, and immune responses leading to delayed-type hypersensitivity. We could revert normal interaction time and T-cell proliferation to wild-type levels by inhibition of active LFA-1 on DCs. Our data further suggest that cytohesin-1–interacting protein might be responsible for controlling LFA-1 deactivation on mature DCs. In summary, our findings indicate that LFA-1 on DCs needs to be in an inactive state to ensure optimal T-cell activation and suggest that regulation of LFA-1 activity allows DCs to actively control antigen-driven T-cell proliferation and effective immune responses.
Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods
Authors: Reese Jessica A. , Li Xiaoning , Hauben Manfred , Aster Richard H. , Bougie Daniel W. , Curtis Brian R. , George James N. , Vesely Sara K.
Published: June 2010

Drug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinical criteria, 87 (34%) were identified with evidence that the drug caused thrombocytopenia. (2) Serum samples from patients with suspected DITP were tested for 202 drugs; drug-dependent, platelet-reactive antibodies were identified for 67 drugs (33%). (3) The Food and Drug Administration's Adverse Event Reporting System database was searched for drugs associated with thrombocytopenia by use of data mining algorithms; 1444 drugs had at least 1 report associated with thrombocytopenia, and 573 (40%) drugs demonstrated a statistically distinctive reporting association with thrombocytopenia. Among 1468 drugs suspected of causing thrombocytopenia, 102 were evaluated by all 3 methods, and 23 of these 102 drugs had evidence for an association with thrombocytopenia by all 3 methods. Multiple methods, each with a distinct perspective, can contribute to the identification of drugs that can cause thrombocytopenia.
Matrix metalloproteinase-9gene polymorphisms in nasal polyposis
Authors: Wang Ling-Feng , Chien Chen-Yu , Tai Chih-Feng , Kuo Wen-Rei , Hsi Edward , Juo Suh-Hang Hank
Published: June 2010

Background

Matrix metalloproteinase (MMP) is involved in the upper airway remodeling process. We hypothesized that genetic variants of the MMP-9 gene are associated with cases of chronic rhinosinusitis with nasal polyposis.

Methods

We conducted a case-control study where 203 cases of chronic rhinosinusitis with nasal polyposis and 730 controls were enrolled. Three tagging single nucleotide polymorphisms (SNPs) and one promoter functional SNP rs3918242 were selected. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. Haplotype analysis was also performed. Permutation was used to adjust for multiple testing.

Results

All four SNPs were in HWE. The T allele of promoter SNP rs3918242 was associated with chronic rhinosinusitis with nasal polyposis under the dominant (nominal p = 0.023, empirical p = 0.022, OR = 1.62) and additive models (nominal p= 0.012, empirical p = 0.011, OR = 1.60). The A allele of rs2274756 has a nominal p value of 0.034 under the dominant model and 0.020 under the additive model. Haplotype analysis including the four SNPs showed a global p value of 0.015 and the most significant haplotype had a p value of 0.0045. We did not see any SNP that was more significant in the recurrent cases.

Conclusions

We concluded that MMP-9 gene polymorphisms may influence susceptibility to the development of chronic rhinosinusitis with nasal polyposis in Chinese population.
Differential expression of centrosomal proteins at different stages of human glioma
Authors: Loh Joon-Khim , Lieu Ann-Shung , Chou Chia-Hua , Lin Fang-Yi , Wu Chia-Hung , Howng Sheng-Long , Chio Chung-Ching , Hong Yi-Ren
Published: June 2010

Background

High-grade gliomas have poor prognosis, requiring aggressive treatment. The aim of this study is to explore mitotic and centrosomal dysregulation in gliomas, which may provide novel targets for treatment.

Methods

A case-control study was performed using 34 resected gliomas, which were separated into low- and high-grade groups. Normal human brain tissue was used as a control. Using immunohistochemical analysis, immunofluorescent microscopy, and RT-PCR, detection of centrins 1 and 2, γ-tubulin, hNinein, Aurora A, and Aurora B, expression was performed. Analysis of the GBM8401 glioma cell line was also undertaken to complement the in vivo studies.

Results

In high-grade gliomas, the cells had greater than two very brightly staining centrioles within large, atypical nuclei, and moderate-to-strong Aurora A staining. Comparing with normal human brain tissue, most of the mRNAs expression in gliomas for centrosomal structural proteins, including centrin 3, γ-tubulin, and hNinein isoforms 1, 2, 5 and 6, Aurora A and Aurora B were elevated. The significant different expression was observed between high- and low-grade glioma in both γ-tubulin and Aurora A mRNA s. In the high-grade glioma group, 78.6% of the samples had higher than normal expression of γ-tubulin mRNA, which was significantly higher than in the low-grade glioma group (18.2%, p < 0.05).

Conclusions

Markers for mitotic dysregulation, such as supernumerary centrosomes and altered expression of centrosome-related mRNA and proteins were more frequently detected in higher grade gliomas. Therefore, these results are clinically useful for glioma staging as well as the development of novel treatments strategies.
Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cells
Authors: Wu Xiang , Zhu Yu , Yan Huiqin , Liu Boning , Li Ying , Zhou Qinghua , Xu Ke
Published: June 2010

Background

Isothiocyanates are natural compounds found in consumable cruciferous vegetables. They have been shown to inhibit chemical carcinogenesis by a wide variety of chemical carcinogens in animal models. Recent studies have also shown that isothiocyanates have antitumor activity, inhibiting the growth of several types of cultured human cancer cells. Our previous study showed that PEITC inhibited human leukemia cells growth by inducing apoptosis. However, the effect of isothiocyanates on lung cancer cell metastasis has not been studied. In the present study, we investigated the inhibitory effects of BITC and PEITC on metastatic potential of highly metastatic human lung cancer L9981 cells.

Methods

Cell migration and invasion were measured by wound healing assay and transwell chemotaxis assay. Expression of metastasis-related genes was assessed by quantitative RT-PCR and Western blotting. The mechanisms of action were evaluated by flow cytometry, reporter assay and Western blotting.

Results

Our data showed that both BITC and PEITC inhibited L9981 cell growth in a dose-dependent manner, the IC50 values were 5.0 and 9.7 μM, respectively. Cell migrations were reduced to 8.1% and 16.5% of control, respectively; and cell invasions were reduced to 2.7% and 7.3% of control, respectively. Metastasis-related genes MMP-2, Twist and β-catenin were also modulated. BITC and PEITC inhibited cell survival signaling molecules Akt and NFκB activation. Moreover, BITC and PEITC increased ROS generation and caused GSH depletion. Pretreatment with NAC blocked BITC and PEITC induced ROS elevation and NFκB inhibition.

Conclusion

Our results indicated that BITC and PEITC suppress lung cancer cell metastasis potential by modulation of metastasis-related gene expression, inhibition of Akt/NFκB pathway. Induction of oxidative stress may play an important role.
Targeting melanoma growth and viability reveals dualistic functionality of the phosphonothionate analogue of carba cyclic phosphatidic acid
Authors: Altman Molly K , Gopal Vashisht , Jia Wei , Yu Shuangxing , Hall Hassan , Mills Gordon B , McGinnis A Cary , Bartlett Michael G , Jiang Guowei , Madan Damian , Prestwich Glenn D , Xu Yong , Davies Michael A , Murph Mandi M
Published: June 2010

Background

Although the incidence of melanoma in the U.S. is rising faster than any other cancer, the FDA-approved chemotherapies lack efficacy for advanced disease, which results in poor overall survival. Lysophosphatidic acid (LPA), autotaxin (ATX), the enzyme that produces LPA, and the LPA receptors represent an emerging group of therapeutic targets in cancer, although it is not known which of these is most effective.

Results

Herein we demonstrate that thio-ccPA 18:1, a stabilized phosphonothionate analogue of carba cyclic phosphatidic acid, ATX inhibitor and LPA1/3 receptor antagonist, induced a marked reduction in the viability of B16F10 metastatic melanoma cells compared with PBS-treated control by 80-100%. Exogenous LPA 18:1 or D-sn-1-O-oleoyl-2-O-methylglyceryl-3-phosphothioate did not reverse the effect of thio-ccPA 18:1. The reduction in viability mediated by thio-ccPA 18:1 was also observed in A375 and MeWo melanoma cell lines, suggesting that the effects are generalizable. Interestingly, siRNA to LPA3 (siLPA3) but not other LPA receptors recapitulated the effects of thio-ccPA 18:1 on viability, suggesting that inhibition of the LPA3 receptor is an important dualistic function of the compound. In addition, siLPA3 reduced proliferation, plasma membrane integrity and altered morphology of A375 cells. Another experimental compound designed to antagonize the LPA1/3 receptors significantly reduced viability in MeWo cells, which predominantly express the LPA3 receptor.

Conclusions

Thus the ability of thio-ccPA 18:1 to inhibit the LPA3 receptor and ATX are key to its molecular mechanism, particularly in melanoma cells that predominantly express the LPA3 receptor. These observations necessitate further exploration and exploitation of these targets in melanoma.
Enzymatic digestibility and ethanol fermentability of AFEX-treated starch-rich lignocellulosics such as corn silage and whole corn plant
Authors: Shao Qianjun , Chundawat Shishir PS , Krishnan Chandraraj , Bals Bryan , da Costa Sousa Leonardo , Thelen Kurt D , Dale Bruce E , Balan Venkatesh
Published: June 2010

Background

Corn grain is an important renewable source for bioethanol production in the USA. Corn ethanol is currently produced by steam liquefaction of starch-rich grains followed by enzymatic saccharification and fermentation. Corn stover (the non-grain parts of the plant) is a potential feedstock to produce cellulosic ethanol in second-generation biorefineries. At present, corn grain is harvested by removing the grain from the living plant while leaving the stover behind on the field. Alternatively, whole corn plants can be harvested to cohydrolyze both starch and cellulose after a suitable thermochemical pretreatment to produce fermentable monomeric sugars. In this study, we used physiologically immature corn silage (CS) and matured whole corn plants (WCP) as feedstocks to produce ethanol using ammonia fiber expansion (AFEX) pretreatment followed by enzymatic hydrolysis (at low enzyme loadings) and cofermentation (for both glucose and xylose) using a cellulase-amylase-based cocktail and a recombinant Saccharomyces cerevisiae 424A (LNH-ST) strain, respectively. The effect on hydrolysis yields of AFEX pretreatment conditions and a starch/cellulose-degrading enzyme addition sequence for both substrates was also studied.

Results

AFEX-pretreated starch-rich substrates (for example, corn grain, soluble starch) had a 1.5-3-fold higher enzymatic hydrolysis yield compared with the untreated substrates. Sequential addition of cellulases after hydrolysis of starch within WCP resulted in 15-20% higher hydrolysis yield compared with simultaneous addition of hydrolytic enzymes. AFEX-pretreated CS gave 70% glucan conversion after 72 h of hydrolysis for 6% glucan loading (at 8 mg total enzyme loading per gram glucan). Microbial inoculation of CS before ensilation yielded a 10-15% lower glucose hydrolysis yield for the pretreated substrate, due to loss in starch content. Ethanol fermentation of AFEX-treated (at 6% w/w glucan loading) CS hydrolyzate (resulting in 28 g/L ethanol at 93% metabolic yield) and WCP (resulting in 30 g/L ethanol at 89% metabolic yield) is reported in this work.

Conclusions

The current results indicate the feasibility of co-utilization of whole plants (that is, starchy grains plus cellulosic residues) using an ammonia-based (AFEX) pretreatment to increase bioethanol yield and reduce overall production cost.
Effect of thyroid statuses on sodium/iodide symporter (NIS) gene expression in the extrathyroidal tissues in mice
Authors: Harun-Or-Rashid Md , Asai Masato , Sun Xiao-yang , Hayashi Yoshitaka , Sakamoto Junichi , Murata Yoshiharu
Published: June 2010

Background

Iodide that is essential for thyroid hormone synthesis is actively transported into the thyroid follicular cells via sodium/iodide symporter (NIS) protein in vertebrates. It is well known that NIS expression in thyroid is regulated by the thyroid statuses mainly through thyroid stimulating hormone (TSH). AlthoughNISmRNA expressions in extrathyroidal tissues have been qualitatively reported, their regulation by thyroid statuses has not been well clarified.

Methods

Male ICR mice aged four weeks were assigned into three groups (control, hypothyroid, and hyperthyroid). Hypothyroid group of mice were treated with 0.02% methimazole in drinking water and hyperthyroid group of mice received intraperitoneal injection (4 μgL-T4twice a week) for four weeks.NISmRNA expression levels in the tissues were evaluated using Northern blot hybridization and quantitative real-time RTPCR (qPCR). Additionally, end-point RTPCR for the thyroid follicular cell-characteristic genes (TSH receptor,TSHR; thyroid transcription factor-1,TTF1; and paired box gene 8,Pax8) was carried out.

Results

By Northern blot analysis,NISmRNA was detected in thyroid and stomach. In addition to these organs, qPCR revealed the expression also in the submandibular gland, colon, testis, and lung. Expression ofNISmRNA in thyroid was significantly increased in hypothyroid and decreased in hyperthyroid group. Trends ofNISmRNA expression in extrathyroidal tissues were not in line with that in the thyroid gland in different thyroid statuses. Only in lung,NISmRNA was regulated by thyroid statuses but in opposite way compared to the manner in the thyroid gland. There were no extrathyroidal tissues that expressed all three characteristic genes of thyroid follicular cells.

Conclusions

NISmRNA expression in the thyroid gland was up-regulated in hypothyroid mice and was down-regulated in hyperthyroid mice, suggesting thatNISmRNA in the thyroid gland is regulated by thyroid statuses. In contrast,NISmRNA expression in extrathyroidal tissues was not altered by thyroid statuses although it was widely expressed. Lack of responsiveness ofNISmRNA expressions in extrathyroidal tissues reemphasizes additional functions of NIS protein in extrathyroidal tissues other than iodide trapping.
The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release
Authors: Prince Robin N. , Schreiter Eric R. , Zou Peng , Wiley H. Steven , Ting Alice Y. , Lee Richard T. , Lauffenburger Douglas A.
Published: June 2010

Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF is restricted by binding heparan-sulfate proteoglycans (HSPGs) in the extracellular matrix and/or cellular glycocalyx, ascertaining mechanisms governing non-released HB-EGF localization is also important for understanding its effects. We have employed a new method for independently tracking the localization of the extracellular EGF-like domain of HB-EGF and the cytoplasmic C-terminus. A striking observation was the absence of the HB-EGF transmembrane pro-form from the leading edge of COS-7 cells in a wound-closure assay; instead, this protein localized in regions of cell-cell contact. A battery of detailed experiments found that this localization derives from a trans interaction between extracellular HSPGs and the HB-EGF heparin-binding domain, and that disruption of this interaction leads to increased release of soluble ligand and a switch in cell phenotype from juxtacrine-induced growth inhibition to autocrine-induced proliferation. Our results indicate that extracellular HSPGs serve to sequester the transmembrane pro-form of HB-EGF at the point of cell-cell contact, and that this plays a role in governing the balance between juxtacrine versus autocrine and paracrine signaling.
AC. eleganseIF4E-family member upregulates translation at elevated temperatures of mRNAs encoding MSH-5 and other meiotic crossover proteins
Authors: Song Anren , Labella Sara , Korneeva Nadejda L. , Keiper Brett D. , Aamodt Eric J. , Zetka Monique , Rhoads Robert E.
Published: June 2010

Caenorhabditis elegans expresses five family members of the translation initiation factor eIF4E whose individual physiological roles are only partially understood. We report a specific role for IFE-2 in a conserved temperature-sensitive meiotic process. ife-2 deletion mutants have severe temperature-sensitive chromosome-segregation defects. Mutant germ cells contain the normal six bivalents at diakinesis at 20°C but 12 univalents at 25°C, indicating a defect in crossover formation. Analysis of chromosome pairing in ife-2 mutants at the permissive and restrictive temperatures reveals no defects. The presence of RAD-51-marked early recombination intermediates and 12 well condensed univalents indicate that IFE-2 is not essential for formation of meiotic double-strand breaks or their repair through homologous recombination but is required for crossover formation. However, RAD-51 foci in ife-2 mutants persist into inappropriately late stages of meiotic prophase at 25°C, similar to mutants defective in MSH-4/HIM-14 and MSH-5, which stabilize a critical intermediate in crossover formation. In wild-type worms, mRNAs for msh-4/him-14 and msh-5 shift from free messenger ribonucleoproteins to polysomes at 25°C but not in ife-2 mutants, suggesting that IFE-2 translationally upregulates synthesis of MSH-4/HIM-14 and MSH-5 at elevated temperatures to stabilize Holliday junctions. This is confirmed by an IFE-2-dependent increase in MSH-5 protein levels.
Using Spreadsheets to Enhance Learning in the Affective Domain for Undergraduate Statistics Students
Authors: Clayton Howard R. , Sankar Chetan S.
Published: June 2010

The Association to Advance Collegiate Schools of Business (AACSB) requires that undergraduate and graduate students exhibit proficiency in “statistical data analysis and management science as they support decision-making processes throughout an organization” [AACSB. 2008. Accreditation standards. Accessed October 20, 2008, http://www.aacsb.edu/accreditation/standards.asp ]. However, motivating business students to enjoy learning statistics has been a major challenge for decades in many American colleges and universities. This paper reports on the use of spreadsheets to teach an introductory statistics course with an emphasis on business applications. The results suggest that using spreadsheets as a teaching tool can effectively produce learning in the affective domain, which refers to the attitudes, beliefs, feelings, and motivations a student brings to a particular subject. This finding not only encourages business statistics instructors to continue to use spreadsheets in their classes, it also encourages other instructors to consider doing so in the future.
The clinical and occupational effectiveness of condition management for Incapacity Benefit recipients
Authors: Kellett Stephen , Bickerstaffe Darren , Purdie Fiona , Dyke Andrew , Filer Sarah , Lomax Victoria , Tomlinson Hayley
Published: June 2010

Objectives. The aim of the Condition Management Programme (CMP) is to help Incapacity Benefit recipients manage their health conditions more effectively and return to work. This paper seeks to examine the clinical and employment outcomes from a group‐based and mixed‐condition CMP.

Design. In a prospective cohort design, measures of employment status and psychological well‐being were taken at three time points; pre‐CMP, post‐CMP, and at 3‐month follow‐up.

Method. Participants (N= 2,064) with a variety of physical and mental health conditions voluntarily attended a seven session cognitive‐behaviourally informed psychoeducational group intervention. The psychological measures used were the Clinical Outcomes in Routine Evaluation – Outcome Measure, Work and Social Adjustment Scale, Self‐Efficacy Scale, and the Intrinsic Motivation Scale. The employment status of participants was also measured at the three time points of the evaluation.

Results. Following CMP, 50% of participants experienced a reliable improvement in psychological well‐being and 26% had either taken some steps towards work or returned to work at follow‐up. Participants with a mental health condition were more likely to experience a reliable improvement in psychological well‐being compared to those with physical health conditions.

Conclusions. The results suggest that participation in CMP may be helpful in facilitating more effective self‐management of the health conditions contributing to unemployment. The results have implications for whether formal employment assistance should be available in mental health services.
Nonlinear Contractions on Semimetric Spaces
Authors: Jachymski J. , Matkowski J. , Świa̧tkowski T.
Published: June 2010

Let (X, d) be a Hausdorff semimetric (d need not satisfy the triangle inequality) and d–Cauchy complete space. Let ƒ be a selfmap on X, for which d(ƒx, ƒy) ≤ φ(d(x, y)), (x, y ∈ X), where φ is a non– decreasing function from R
+, the nonnegative reals, into R
+ such that φn
(t) → 0, for all t ∈ R
+. We prove that ƒ has a unique fixed point if there exists an r > 0, for which the diameters of all balls in X with radius r are equi-bounded. Such a class of semimetric spaces includes the Frechet spaces with a regular ecart, for which the Contraction Principle was established earlier by M. Cicchese [Boll. Un. Mat. Ital 13–A: 175-179, 1976], however, with some further restrictions on a space and a map involved. We also demonstrate that for maps ƒ satisfying the condition d(ƒx, ƒy) ≤ φ(max{d(x, ƒx), d(y, ƒy)}), (x, y ∈ X) (the Bianchini [Boll. Un. Mat. Ital. 5: 103–108, 1972] type condition), a fixed point theorem holds under substantially weaker assumptions on a distance function d.
Domains of Attraction with Inner Norming on Sturm–Liouville Hypergroups
Authors: Zeuner H. M.
Published: June 2010

In this article we study the convergence of convolution powers of normalized measures (θCn
ν)*
n
on a Sturm–Liouville hypergroup (ℝ+,∗). It is shown that this sequence converges for a suitable choice of the normalizing constants cn
> 0 if and only if the usual regular variation conditions of the tail of ν are valid. The possible limit distributions are described in terms of their Fourier transform; they form a two dimensional family of probability measures on ℝ+.
A Result Related to the Problem CN of Fremlin
Authors: Kolman O. , Shelah S.
Published: June 2010

We show that the set of injective functions from any uncountable cardinal less than the continuum into the real numbers is of the second category in the box product topology.
Evidence for Vibrational Excitation of the Adlayer in Exoergic Processes at Metal Surfaces: H-atom Abstraction and Recombination and Adsorption-stimulated Desorption of CO
Authors: Molinari E. , Tomellini M.
Published: June 2010

The theoretical model presented in the previous paper predicts the possibility of vibrational excitation of the adlayer in exoergic process at metal surfaces to an extent determined by the interplay of reaction rates and energy dissipation into the metal. In the present paper this model will be employed for studying the following systems: a)The abstraction of Ds adspecies by Hgas and the accompanying H-atom recombination and b) the adsorption-stimulated desorption of COs in the presence of adsorbing COgas. Proper reduction of literature data provides the evidence for the existence of vibrational excitation of the H-Me and of the CO-Me adlayers, witnessed by desorption rates that are orders of magnitude larger than those expected for systems in Boltzmann equilibrium. Application of the model to Ds+Hgas relates the vibrational excitation of the adlayer and the corresponding non-Boltzmann desorption rates to the parameter Z/K and to the flux of adsorbing species. Rate coefficients K for vibrational relaxation of the H-Me bondare in the range 1013-1012 s−1 and decrease with increasing surface coverage σ. The analysis of COs desorption in the presence of adsorbing COgas confirms the dependence of desorption rates on Z/K, the coverage dependence of the rate coefficients K for energy relaxation of the CO-Me bond and brings out the predicted influence of gas pressure on the over-population of the vibrational levels of adsorbed CO. The decrease of K observed in both systems is discussed in terms of energy relaxation processes involving electron-hole pair excitation at the metal surface and it should be linked to the decrease of the surface electron density caused by the adsorbates.
The Combined Use of Nd:YAG Laser and Enamel Matrix Proteins in the Treatment of Periodontal Infrabony Defects
Authors: Dilsiz Alparslan , Canakci Varol , Aydin Tugba
Published: June 2010

Background: The objective of regenerative periodontal therapy is the reconstitution of lost periodontal structures, such as cementum, periodontal ligament, and alveolar bone. Enamel matrix proteins (EMP) are used as a local adjunct to periodontal surgery to stimulate regeneration of periodontal tissues lost to periodontal disease. The aim of this split‐mouth study evaluates and compares the healing of intrabony defects after treatment with an EMP with or without neodymium‐doped:yttrium‐aluminum‐garnet (Nd:YAG) laser application for root surface conditioning.

Methods: Forty‐two intrabony defects in 21 patients with chronic periodontitis were randomly assigned to an access flap surgery with application of Nd:YAG laser (1 W, 10 Hz, 100 mJ, 1064 nm) and EMP (test group), and on the contralateral defect to an access flap surgery with application of EDTA and EMP alone (control group). Clinical periodontal parameters were assessed at baseline and after 6 and 12 months.

Results: Both treatments yielded significant improvements in terms of decrease in probing depth (PD) and gain in clinical attachment level (CAL) compared to baseline values. At 12 months after therapy, in the test group, the mean PD value was reduced from 7.3 ± 0.6 to 3.3 ± 0.4 mm and the mean CAL value changed from 9.5 ± 0.7 to 6.9 ± 0.7 mm (P <0.001). The sites treated with EMP (control) showed a reduction in mean PD value from 7.3 ± 0.7 to 3 ± 0.4 mm and a change in mean CAL value from 9.3 ± 0.8 to 6.4 ± 0.5 mm (P <0.001). The control group showed a greater reduction in PD and gain in CAL compared to the test group (P <0.05).

Conclusion: Within the limits of the present study, it may be concluded that both therapies led to improvements of the clinical parameters, and Nd:YAG laser root conditioning as used in this study compared to EDTA root conditioning did not improve the outcome of EMP use.
Tillage and Straw Management Impacts on Soil Properties, Root Growth, and Grain Yield of Winter Wheat in Northwestern China
Authors: Feng F. X. , Huang G. B. , Chai Q. , Yu A. Z.
Published: June 2010

Studies on root development, soil physical properties, and yield are important for identifying suitable soil management practices for sustainable crop production. Field experiments with winter wheat (Triticum aestivum L.) were conducted in silt loam soil from 2005 through 2007 in arid northwestern China to determine the effects of five tillage systems on soil strength, soil moisture, crop root development, grain yield, and yield components. The five treatments were conventional tillage without wheat stubble (T), conventional tillage with wheat stubble incorporated (TSI), no‐tillage without wheat stubble mulching (NT), no‐tillage with wheat stubble standing (NTSS), and no‐tillage with wheat stubble mulching (NTS). Compared with the T treatment, the NTSS and NTS treatments improved soil water content in the 0‐ to 130‐cm soil depth by 10 to 17% and 15 to 25%, respectively (P < 0.05). The NTSS treatment also increased mean root length density (RLD) by 8 to 40% and crop yield by 13 to 24%, and NTS by 17 to 48% and 17 to 31%, compared with the T treatment. Yield components analysis indicated that thousand‐grain weight and spike density considerations helped explain the grain yield increases under conservation tillage systems (NT, NTSS, NTS), while spike length, number of grains per spike, and grain weight per spike failed to contribute to the model. Our results suggest that Chinese farmers should consider adopting conservation tillage practices in arid northwestern China because of benefits to soil strength, water storage, RLD, and wheat yield.
Genetic Diversity and Agronomic Improvement of North American Soybean Germplasm
Authors: Mikel Mark A. , Diers Brian W. , Nelson Randall L. , Smith Hebron H.
Published: June 2010

From 1970 to 2008 there were 2242 soybean [Glycine max (L.) Merr.] cultivars registered in North America through U.S. Plant Variety Protection (PVP), U.S. utility patent, and journal registration. Of these, 80% were developed through proprietary and 20% through public programs. Our objective was to characterize the development and genetic diversity of North American soybean cultivars. The most frequently used germplasm for cultivar development were the cultivars Williams (parent used in last cross before inbreeding in 70 cultivars), A3127 (63), Essex (45), Amsoy (38), Corsoy (33), Wayne (30), Forrest (27), Hutcheson (25), MO13404 (23), and Bedford (23). Genetic diversity (1 − coefficient of parentage), estimated from pedigree lineage, was 0.89 overall. Genetic diversity was the same within public (0.89) and proprietary (0.89) cultivars. The cultivar A3127 is a major progenitor of recently developed proprietary cultivars registered from 1999 to 2008. Of these 494 cultivars, 23% have a genetic contribution of at least 25% from A3127. New cultivars were predominantly developed from the following crosses: two‐parent (70% of cultivars developed), complex (12%), three‐parent (5%), one backcross (5%), multiple (two, three, or four) backcrosses (3%), and five or greater backcrosses (2%). In comparisons where both parent and progeny were evaluated together, seed yield increased 3.2% per breeding cycle. In these comparisons, seed yield had a correlation of 0.29 with parental diversity.
Determining the Pollen Parent of Field‐Grown Backcross Progenies of Wheat (Triticum aestivum L.) × Jointed Goatgrass (Aegilops cylindrica Host) Hybrids Using Genomic In Situ Hybridization (GISH)
Authors: Rehman M. , Hansen J. L. , Mallory‐Smith C. A. , Hang An , Burton C. , Zemetra R. S.
Published: June 2010

Jointed goatgrass (Aegilops cylindrica Host) with CCDD genomes is a noxious weed of winter wheat (Triticum aestivum L.). Wheat (BBAADD) and jointed goatgrass (JGG) can hybridize under natural conditions, leading to a possibility of gene flow between these two species. For a gene to move from herbicide‐resistant wheat to JGG, JGG must be the recurrent parent in a series (two) of backcrosses. One way of determining the pollen parent in the first backcross is to visualize C‐genome chromosomes using genomic in situ hybridization (GISH). By using GISH it was determined that 7 of 88 (8%) BC1 plants had more than seven C‐genome chromosomes, indicating that JGG was the pollen parent. By using wheat‐specific chloroplast simple sequence repeat marker (WCt‐3) analysis, 13.6% of the hybrids had wheat as the female parent, while the remaining plants had JGG as the female parent. This study presents a reliable way of determining the pollen parent of BC1 progeny and the hybridization dynamics between wheat and jointed goatgrass under natural field conditions. This information can be used to more accurately predict the risk for gene migration between wheat and jointed goatgrass.
Rapid Analysis of Nonstructural Carbohydrate Components in Grass Forage Using Microplate Enzymatic Assays
Authors: Zhao Duli , MacKown Charles T. , Starks Patrick J. , Kindiger Bryan K.
Published: June 2010

Measurements of nonstructural carbohydrates (NSC) in plant tissues are important to estimate plant organ resources available for plant growth and stress tolerance or for feed value to grazing animals. A popular commercially available assay kit used to detect glucose with a light‐sensitive dye reaction was recently discontinued and replaced by a test‐tube‐scale glucose kit (GAHK‐20) that assays glucose through enzymatic coupled reactions and the formation of reduced nicotinamide adenine dinucleotide. The objective of this study was to develop a microplate assay method that uses the GAHK‐20 to quantify forage NSC composition. A laboratory microplate enzymatic method was developed for the new glucose kit and evaluated for rapidly assaying NSC components, including glucose, fructose, sucrose, fructan, and starch in 11 species of cool‐season perennial grasses. By standard addition, dilution, and temporal tests of enzyme reactions, we found that this microplate enzymatic assay is a rapid and reliable method to quantify NSC composition in grass forage samples. The microplate method allows analysis of many samples per day and considerably improved time and reagent use efficiencies, especially for a large number of samples. In addition to forage, this method should be suitable for measuring NSC concentrations in fresh or dry tissues of a variety of other plant samples.
Status of the Global Cotton Germplasm Resources
Authors: Campbell B. T. , Saha S. , Percy R. , Frelichowski J. , Jenkins J. N. , Park W. , Mayee C. D. , Gotmare V. , Dessauw D. , Giband M. , Du X. , Jia Y. , Constable G. , Dillon S. , Abdurakhmonov I. Y. , Abdukarimov A. , Rizaeva S. M. , Abdullaev A. , Barroso P. A. V. , Pádua J. G. , Hoffmann L. V. , Podolnaya L.
Published: June 2010

The cultivated Gossypium spp. (cotton) represents the single most important, natural fiber crop in the world. In addition to its fiber, the oil and protein portion of the cottonseed also represents significant economic value. To protect the worldwide economic value of cotton fiber and cotton byproducts, coordinated efforts to collect and maintain cotton genetic resources have increased over the last 100 yr. The classified genetic resources of cotton are extensive and include five tetraploid species in the primary gene pool, 20 diploid species in the secondary gene pool, and 25 diploid species in the tertiary gene pool. This report provides information on the status and contents of eight major cotton germplasm collections present across the world. Based on the findings of this report, a number of classified Gossypium species are not maintained in these collections, and several are underrepresented and vulnerable to extinction. This report presents several critical challenges and opportunities facing international efforts to enhance and preserve the world's Gossypium genetic resources. Multinational communication and collaboration are essential to protect, secure, and evaluate the global cotton germplasm resources. Without global, collaborative efforts, the rarest and most unique cotton germplasm resources are vulnerable to extinction.