bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulators of the Cohesin Network
Authors: Xiong Bo , Gerton Jennifer L.
Published: June 2010

Chromosome cohesion is the term used to describe the cellular process in which sister chromatids are held together from the time of their replication until the time of separation at the metaphase to anaphase transition. In this capacity, chromosome cohesion, especially at centromeric regions, is essential for chromosome segregation. However, cohesion of noncentromeric DNA sequences has been shown to occur during double-strand break (DSB) repair and the transcriptional regulation of genes. Cohesion for the purposes of accurate chromosome segregation, DSB repair, and gene regulation are all achieved through a similar network of proteins, but cohesion for each purpose may be regulated differently. In this review, we focus on recent developments regarding the regulation of this multipurpose network for tying DNA sequences together. In particular, regulation via effectors and posttranslational modifications are reviewed. A picture is emerging in which complex regulatory networks are capable of differential regulation of cohesion in various contexts.
GLP-1 treatment reduces endogenous insulin resistance via activation of central GLP-1 receptors in mice fed a high-fat diet
Authors: Parlevliet Edwin T. , de Leeuw van Weenen Judith E. , Romijn Johannes A. , Pijl Hanno
Published: June 2010

Glucagon-like peptide-1 (GLP-1) improves insulin sensitivity in humans and rodents. It is currently unknown to what extent the (metabolic) effects of GLP-1 treatment are mediated by central GLP-1 receptors. We studied the impact of central GLP-1 receptor (GLP-1R) antagonism on the metabolic effects of peripheral GLP-1 administration in mice. High-fat-fed insulin-resistant C57Bl/6 mice were treated with continuous subcutaneous infusion of GLP-1 or saline (PBS) for 2 wk, whereas the GLP-1R antagonist exendin-9 (EX-9) and cerebrospinal fluid (CSF) were simultaneously infused in the left lateral cerebral ventricle (icv). Glucose and glycerol turnover were determined during a hyperinsulinemic euglycemic clamp. VLDL-triglyceride (VLDL-TG) production was determined in hyperinsulinemic conditions. Our data show that the rate of glucose infusion necessary to maintain euglycemia was significantly increased by GLP-1. Simultaneous icv infusion of EX-9 diminished this effect by 62%. The capacities of insulin to stimulate glucose disposal and inhibit glucose production were reinforced by GLP-1. Simultaneous icv infusion of EX-9 significantly diminished the latter effect. Central GLP-1R antagonism alone did not affect glucose metabolism. Also, GLP-1 treatment reinforced the inhibitory action of insulin on VLDL-TG production. In conclusion, peripheral administration of GLP-1 reinforces the ability of insulin to suppress endogenous glucose and VLDL-TG production (but not lipolysis) and boosts its capacity to stimulate glucose disposal in high-fat-fed C57Bl/6 mice. Activation of central GLP-1Rs contributes substantially to the inhibition of endogenous glucose production by GLP-1 treatment in this animal model.
Sustainable Algae Biodiesel Production in Cold Climates
Authors: Baliga Rudras , Powers Susan E.
Published: June 2010

This life cycle assessment aims to determine the most suitable operating conditions for algae biodiesel production in cold climates to minimize energy consumption and environmental impacts. Two hypothetical photobioreactor algae production and biodiesel plants located in Upstate New York (USA) are modeled. The photobioreactor is assumed to be housed within a greenhouse that is located adjacent to a fossil fuel or biomass power plant that can supply waste heat and flue gas containingCO2as a primary source of carbon. Model results show that the biodiesel areal productivity is high (19 to 25 L of BD/m2/yr). The total life cycle energy consumption was between 15 and 23 MJ/L of algae BD and 20 MJ/L of soy BD. Energy consumption and air emissions for algae biodiesel are substantially lower than soy biodiesel when waste heat was utilized. Algae's most substantial contribution is a significant decrease in the petroleum consumed to make the fuel.
Antioxidative Activity of Ferrocenes Bearing 2,6‐Di‐Tert‐Butylphenol Moieties
Authors: Milaeva E. R. , Filimonova S. I. , Meleshonkova N. N. , Dubova L. G. , Shevtsova E. F. , Bachurin S. O. , Zefirov N. S.
Published: June 2010

The antioxidative activity of ferrocenes bearing either 2,6‐di‐tert‐butylphenol or phenyl groups has been compared using DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) test and in the study of the in vitro impact on lipid peroxidation in rat brain homogenate and on some characteristics of rat liver mitochondria. The results of DPPH test at 20∘C show that the activity depends strongly upon the presence of phenolic group but is improved by the influence of ferrocenyl fragment. The activity of N‐(3,5‐di‐tert‐butyl‐4‐hydroxyphenyl)iminomethylferrocene (1), for instance, was 88.4%, which was higher than the activity of a known antioxidant 2,6‐di‐tert‐butyl‐4‐methylphenol (BHT) (48.5%), whereas the activity of N‐phenyl‐iminomethylferrocene 2 was almost negligible −2.9%. The data obtained demonstrate that the compounds with 2,6‐di‐tert‐butylphenol moiety are significantly more active than the corresponding phenyl analogues in the in vitro study of lipid peroxidation in rat brain homogenate. Ferrocene 1 performs a promising behavior as an antioxidant and inhibits the calcium‐dependent swelling of mitochondria. These results allow us to propose the potential cytoprotective (neuroprotective) effect of ditopic compounds containing antioxidant 2,6‐di‐tert‐butylphenol group and redox active ferrocene fragment.
Leiomyosarcoma Arising in the Pancreatic Duct: A Case Report and Review of the Current Literature
Authors: Riddle Nicole D. , Quigley Brian C. , Browarsky Irwin , Bui Marilyn M.
Published: June 2010

Context. Leiomyosarcomas are rare malignant smooth muscle tumors that may arise in any organ or tissue that contains smooth muscle, commonly within the gastrointestinal tract. They are most often found in the stomach, large and small intestines, and retroperitoneum. Primary pancreatic leiomyosarcoma is extremely rare, and to the best of our knowledge only 30 cases have been reported in the world literature since 1951. Our case represents the first to have a clear origin from the main pancreatic duct.Case Report. This case was diagnosed in a large, tertiary care center in Tampa, Florida. Pertinent information was obtained from chart review and interdepartmental collaboration. A mass in the tail of the pancreas was identified with large pleomorphic and spindle-shaped cells. Immunohistochemistry for vimentin, smooth muscle actin, and desmin was positive. All remaining immunohistochemical markers performed were negative. The tumor clearly originated from the pancreatic duct wall, filled and expanded the duct lumen, and was covered with a layer of benign biliary epithelium.Conclusion. Leiomyosarcoma of the pancreas is an extremely rare malignancy with few reported cases in the literature. The prognosis is poor, and treatment consists of alleviating symptoms and pain management. To our knowledge, this represents the first reported case demonstrating clear origin of a leiomyosarcoma from the pancreatic duct.
Detection of Fetomaternal Genotype Associations in Early-Onset Disorders: Evaluation of Different Methods and Their Application to Childhood Leukemia
Authors: Healy Jasmine , Bourgey Mathieu , Richer Chantal , Sinnett Daniel , Roy-Gagnon Marie-Helene
Published: June 2010

Several designs and analytical approaches have been proposed to dissect offspring from maternal genetic contributions to early-onset diseases. However, lack of parental controls halts the direct verification of the assumption of mating symmetry (MS) required to assess maternally-mediated effects. In this study, we used simulations to investigate the performance of existing methods under mating asymmetry (MA) when parents of controls are missing. Our results show that the log-linear, likelihood-based framework using a case-triad/case-control hybrid design provides valid tests for maternal genetic effects even under MA. Using this approach, we examined fetomaternal associations between 29 SNPs in 12 cell-cycle genes and childhood pre-B acute lymphoblastic leukemia (ALL). We identified putative fetomaternal effects at lociCDKN2Ars36228834 (P=.017) andCDKN2Brs36229158 (P=.022) that modulate the risk of childhood ALL. These data further corroborate the importance of the mother's genotype on the susceptibility to early-onset diseases.
Pricing and Unresponsive Flows Purging for Global Rate Enhancement
Authors: Abbas G. , Nagar A. K. , Tawfik H. , Goulermas J. Y.
Published: June 2010

Pricing‐based Active Queue Management (AQM), such as Random Exponential Marking (REM), outperforms other probabilistic counterpart techniques, like Random Early Detection (RED), in terms of both high utilization and negligible loss and delay. However, the pricing‐based protocols do not take account of unresponsive flows that can significantly alter the subsequent rate allocation. This letter presents Purge (Pricing and Un‐Responsive flows purging for Global rate Enhancement) that extends the REM framework to regulate unresponsive flows. We show that Purge is effective at providing fairness and requires small memory and low‐complexity operations.
Superficial Dsg2 Expression Limits Epidermal Blister Formation Mediated by Pemphigus Foliaceus Antibodies and Exfoliative Toxins
Authors: Brennan Donna , Hu Ying , Medhat Walid , Dowling Alicia , Mahoney Mỹ G.
Published: June 2010

Cell‐cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig. In response to PF Ig, we observed either a dramatic loss or a reorganization of Dsg1‐α, Dsg1‐β, and, to a lesser extent, Dsg1‐γ, in WT mice. The Inv‐Dsg2 Tg mice showed enhanced retention of Dsg1 at the cell‐cell border. Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister formation mediated by PF antibodies and exfoliative toxins.
Chickenpox at Ninety Four: A Case for Extending the Use of Varicella Vaccine in the UK
Authors: Bendig Justin , Sindall Fiona
Published: June 2010

A case of chickenpox in a 94-year-old female is described. Serological tests for Varicella zoster virus (VZV) performed on early and late serum samples confirmed primary VZV infection. The patient recovered but seventeen days after presentation she developed a stroke from which she subsequently died. Chickenpox in older people is relatively rare—this case may be the oldest case of laboratory-proven chickenpox described—but it is a life-threatening illness. The varicella vaccine is licensed for use in immunocompetent persons of 12 months of age or older but in the UK is only offered to susceptible healthcare workers and close contacts of immunocompromised patients. In the US, the vaccine is recommended for all susceptible adolescents and adults. The same recommendation should be made in the UK.
High-Throughput Sequencing of MicroRNAs in Adenovirus Type 3 Infected Human Laryngeal Epithelial Cells
Authors: Qi Yuhua , Tu Jing , Cui Lunbiao , Guo Xiling , Shi Zhiyang , Li Shuchun , Shi Wenting , Shan Yunfeng , Ge Yiyue , Shan Jun , Wang Hua , Lu Zuhong
Published: June 2010

Adenovirus infection can cause various illnesses depending on the infecting serotype, such as gastroenteritis, conjunctivitis, cystitis, and rash illness, but the infection mechanism is still unknown. MicroRNAs (miRNA) have been reported to play essential roles in cell proliferation, cell differentiation, and pathogenesis of human diseases including viral infections. We analyzed the miRNA expression profiles from adenovirus type 3 (AD3) infected Human laryngeal epithelial (Hep2) cells using a SOLiD deep sequencing. 492 precursor miRNAs were identified in the AD3 infected Hep2 cells, and 540 precursor miRNAs were identified in the control. A total of 44 miRNAs demonstrated high expression and 36 miRNAs showed lower expression in the AD3 infected cells than control. The biogenesis of miRNAs has been analyzed, and some of the SOLiD results were confirmed by Quantitative PCR analysis. The present studies may provide a useful clue for the biological function research into AD3 infection.
The Role of Tetrahydrobiopterin and Dihydrobiopterin in Ischemia/Reperfusion Injury When Given at Reperfusion
Authors: Chen Qian , Kim Elizabeth Eun Jung , Elio Katrina , Zambrano Christopher , Krass Samuel , Teng Jane Chun-wen , Kay Helen , Perkins Kerry-Anne , Pershad Sailesh , McGraw Sloane , Emrich Jeffrey , Adams Jovan S. , Young Lindon H.
Published: June 2010

Reduced nitric oxide (NO) bioavailability and increased oxidative stress are major factors mediating ischemia/reperfusion (I/R) injury. Tetrahydrobiopterin (BH4) is an essential cofactor of endothelial NO synthase (eNOS) to produce NO, whereas dihydrobiopterin (BH2) can shift the eNOS product profile from NO to superoxide, which is further converted to hydrogen peroxide (H2O2) and cause I/R injury. The effects ofBH4andBH2on oxidative stress and postreperfused cardiac functions were examined in ex vivo myocardial and in vivo femoral I (20 min)/R (45 min) models. In femoral I/R,BH4increased NO and decreasedH2O2releases relative to saline control, and these effects correlated with improved postreperfused cardiac function. By contrast,BH2decreased NO release relative to the saline control, but increasedH2O2release similar to the saline control, and these effects correlated with compromised postreperfused cardiac function. In conclusion, these results suggest that promoting eNOS coupling to produce NO and decreaseH2O2may be a key mechanism to restore postreperfused organ function during early reperfusion.
Interleukin-7 Permits Th1/Tc1 Maturation and PromotesEx vivoExpansion of Cord Blood T Cells: A Critical Step toward Adoptive Immunotherapy after Cord Blood Transplantation
Authors: Davis Craig C. , Marti Luciana C. , Sempowski Gregory D. , Jeyaraj Durairaj A. , Szabolcs Paul
Published: June 2010

Donor leukocyte infusions (DLI) in the allogeneic hematopoietic transplant setting can provide a clinically relevant boost of immunity to reduce opportunistic infections and to increase graft-versus-leukemia activity. Despite significant advances in applicability, DLI has not been available for single-unit recipients of unrelated cord blood transplant. Ex vivo expansion of cord blood T cells can be achieved with interleukin (IL)-2 and CD3/CD28 costimulatory beads. However, significant apoptosis occurs in proliferating T cells, diminishing the yield and skewing the CD4/CD8 ratio in the T-cell population, jeopardizing the potential efficacy of DLI. In this study, we show that interleukin (IL)-7 not only reduces apoptosis of activated T lymphocytes and enhances their proliferation but also promotes functional maturation, leading to secretion of IFN-γ and other key cytokines. Recognizing that infused T lymphocytes will need to meet microbial antigens in secondary lymphoid organs to generate effectors, we also show that expansion with IL-7 promotes the preservation of a polyclonal broad T-cell receptor repertoire and a surface phenotype that favors lymph node homing. Expanded lymphocytes lack alloreactivity against recipient and other allogeneic cells, indicating a favorable safety profile from graft-versus-host disease. Nevertheless, expanded T cells can be primed subsequently against lymphoid and myeloid leukemia cells to generate tumor-specific cytotoxic T cells. Taken together, our findings offer a major step in fulfilling critical numerical and biological requirements to quickly generate a DLI product ex vivo using a negligible fraction of a cord blood graft that provides a flexible adoptive immunotherapy platform for both children and adults. Cancer Res; 70(13); 5249–58. ©2010 AACR.
Angiopoietin-2 Regulates Gene Expression in TIE2-Expressing Monocytes and Augments Their Inherent Proangiogenic Functions
Authors: Coffelt Seth B. , Tal Andrea O. , Scholz Alexander , De Palma Michele , Patel Sunil , Urbich Carmen , Biswas Subhra K. , Murdoch Craig , Plate Karl H. , Reiss Yvonne , Lewis Claire E.
Published: June 2010

TIE2-expressing monocytes/macrophages (TEM) are a highly proangiogenic subset of myeloid cells in tumors. Here, we show that circulating human TEMs are already preprogrammed in the circulation to be more angiogenic and express higher levels of such proangiogenic genes as matrix metalloproteinase-9 (MMP-9), VEGFA, COX-2, and WNT5A than TIE2− monocytes. Additionally, angiopoietin-2 (ANG-2) markedly enhanced the proangiogenic activity of TEMs and increased their expression of two proangiogenic enzymes: thymidine phosphorylase (TP) and cathepsin B (CTSB). Three “alternatively activated” (or M2-like) macrophage markers were also upregulated by ANG-2 in TEMs: interleukin-10, mannose receptor (MRC1), and CCL17. To investigate the effects of ANG-2 on the phenotype and function of TEMs in tumors, we used a double-transgenic (DT) mouse model in which ANG-2 was specifically overexpressed by endothelial cells. Syngeneic tumors grown in these ANG-2 DT mice were more vascularized and contained greater numbers of TEMs than those in wild-type (WT) mice. In both tumor types, expression of MMP-9 and MRC1 was mainly restricted to tumor TEMs rather than TIE2− macrophages. Furthermore, tumor TEMs expressed higher levels of MRC1, TP, and CTSB in ANG-2 DT tumors than WT tumors. Taken together, our data show that although circulating TEMs are innately proangiogenic, exposure to tumor-derived ANG-2 stimulates these cells to exhibit a broader, tumor-promoting phenotype. As such, the ANG-2–TEM axis may represent a new target for antiangiogenic cancer therapies. Cancer Res; 70(13); 5270–80. ©2010 AACR.
Synergistic Activity of Sorafenib and Sulforaphane Abolishes Pancreatic Cancer Stem Cell Characteristics
Authors: Rausch Vanessa , Liu Li , Kallifatidis Georgios , Baumann Bernd , Mattern Jürgen , Gladkich Jury , Wirth Thomas , Schemmer Peter , Büchler Markus W. , Zöller Margot , Salnikov Alexei V. , Herr Ingrid
Published: June 2010

Recent evidence suggests that pancreatic cancer and other solid tumors contain a subset of tumorigenic cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. Sorafenib (SO) is a promising new multikinase inhibitor for treatment of advanced kidney and liver cancers. We report here targeting of pancreatic cancer stem cells (CSC) by SO and the development of a strategy to enhance this effect. Although SO administration diminished clonogenicity, spheroid formation, aldehyde dehydrogenase 1 (ALDH1) activity, growth on immunodeficient mice, proliferation, and angiogenesis and induced apoptosis, we observed SO-induced activation of NF-κB associated with survival and regrowth of spheroids. For enhanced elimination of CSC characteristics by SO, we cotreated cells with sulforaphane (SF). This broccoli isothiocyanate was recently described to eliminate pancreatic CSCs by downregulation of NF-κB activity without inducing toxic side effects. On combination treatment, SF completely eradicated SO-induced NF-κB binding, which was associated with abrogated clonogenicity, spheroid formation, ALDH1 activity, migratory capacity, and induction of apoptosis. In vivo, combination therapy reduced the tumor size in a synergistic manner. This was due to induction of apoptosis, inhibition of proliferation and angiogenesis, and downregulation of SO-induced expression of proteins involved in epithelial-mesenchymal transition. Our data suggest that SF may be suited to increase targeting of CSCs by SO. Cancer Res; 70(12); 5004–13. ©2010 AACR.
Traf2- and Nck-Interacting Kinase Is Essential for Wnt Signaling and Colorectal Cancer Growth
Authors: Shitashige Miki , Satow Reiko , Jigami Takafumi , Aoki Kazunori , Honda Kazufumi , Shibata Tatsuhiro , Ono Masaya , Hirohashi Setsuo , Yamada Tesshi
Published: June 2010

T-cell factor-4 (TCF4) is a transcription factor essential for maintaining the undifferentiated status and self-renewal of intestinal epithelial cells. It has therefore been considered that constitutive activation of TCF4 by aberrant Wnt signaling is a major force driving colorectal carcinogenesis. We previously identified Traf2- and Nck-interacting kinase (TNIK) as one of the proteins that interact with TCF4 in colorectal cancer cells, but its functional significance has not been elucidated. Here, we report that TNIK is an activating kinase for TCF4 and essential for colorectal cancer growth. TNIK, but not its catalytically inactive mutant, phosphorylated the conserved serine 154 residue of TCF4. Small interfering RNA targeting TNIK inhibited the proliferation of colorectal cancer cells and the growth of tumors produced by injecting colorectal cancer cells s.c. into immunodeficient mice. The growth inhibition was abolished by restoring the catalytic domain of TNIK, thus confirming that its enzyme activity is essential for the maintenance of colorectal cancer growth. Several ATP-competing kinase inhibitors have been applied to cancer treatment and have shown significant activity. Our findings suggest TNIK as a feasible target for pharmacologic intervention to ablate aberrant Wnt signaling in colorectal cancer. Cancer Res; 70(12); 5024–33. ©2010 AACR.
How to Train Your Biomarker
Authors: Yee Douglas
Published: June 2010

Type I insulin-like growth factor (IGF) receptor (IGF1R) inhibitors are new cancer therapies. Pitts and colleagues used in vitro data to “train” a predictive biomarker for an IGF1R tyrosine kinase inhibitor. Given the complexity of IGF signaling, additional layers of biomarker analysis will likely be needed to develop predictive factors. Clin Cancer Res; 16(12); 3091–3. ©2010 AACR.
Sensitization to Radiation and Alkylating Agents by Inhibitors of Poly(ADP-ribose) Polymerase Is Enhanced in Cells Deficient in DNA Double-Strand Break Repair
Authors: Löser Dana A. , Shibata Atsushi , Shibata Akiko K. , Woodbine Lisa J. , Jeggo Penny A. , Chalmers Anthony J.
Published: June 2010

As single agents, chemical inhibitors of poly(ADP-ribose) polymerase (PARP) are nontoxic and have clinical efficacy against BRCA1- and BRCA2-deficient tumors. PARP inhibitors also enhance the cytotoxicity of ionizing radiation and alkylating agents but will only improve clinical outcomes if tumor sensitization exceeds effects on normal tissues. It is unclear how tumor DNA repair proficiency affects the degree of sensitization. We have previously shown that the radiosensitizing effect of PARP inhibition requires DNA replication and will therefore affect rapidly proliferating tumors more than normal tissues. Because many tumors exhibit defective DNA repair, we investigated the impact of double-strand break (DSB) repair integrity on the sensitizing effects of the PARP inhibitor olaparib. Sensitization to ionizing radiation and the alkylating agent methylmethane sulfonate was enhanced in DSB repair–deficient cells. In Artemis−/− and ATM−/− mouse embryo fibroblasts, sensitization was replication dependent and associated with defective repair of replication-associated damage. Radiosensitization of Ligase IV−/− mouse embryo fibroblasts was independent of DNA replication and is explained by inhibition of "alternative" end joining. After methylmethane sulfonate treatment, PARP inhibition promoted replication-independent accumulation of DSB, repair of which required Ligase IV. Our findings predict that the sensitizing effects of PARP inhibitors will be more pronounced in rapidly dividing and/or DNA repair defective tumors than normal tissues and show their potential to enhance the therapeutic ratio achieved by conventional DNA-damaging agents. Mol Cancer Ther; 9(6); 1775–87. ©2010 AACR.
Artemin-Stimulated Progression of Human Non–Small Cell Lung Carcinoma Is Mediated by BCL2
Authors: Tang Jian-Zhong , Kong Xiang-Jun , Kang Jian , Fielder Graeme C. , Steiner Michael , Perry Jo K. , Wu Zheng-Sheng , Yin Zhinan , Zhu Tao , Liu Dong-Xu , Lobie Peter E.
Published: June 2010

We herein show that Artemin (ARTN), one of the glial cell line–derived neurotrophic factor family of ligands, promotes progression of human non–small cell lung carcinoma (NSCLC). Oncomine data indicate that expression of components of the ARTN signaling pathway (ARTN, GFRA3, and RET) is increased in neoplastic compared with normal lung tissues; increased expression of ARTN in NSCLC also predicted metastasis to lymph nodes and a higher grade in certain NSCLC subtypes. Forced expression of ARTN stimulated survival, anchorage-independent, and three-dimensional Matrigel growth of NSCLC cell lines. ARTN increased BCL2 expression by transcriptional upregulation, and inhibition of BCL2 abrogated the oncogenic properties of ARTN in NSCLC cells. Forced expression of ARTN also enhanced migration and invasion of NSCLC cells. Forced expression of ARTN in H1299 cells additionally resulted in larger xenograft tumors, which were highly proliferative, invasive, and metastatic. Concordantly, either small interfering RNA–mediated depletion or functional inhibition of endogenous ARTN with antibodies reduced oncogenicity and invasiveness of NSCLC cells. ARTN therefore mediates progression of NSCLC and may be a potential therapeutic target for NSCLC. Mol Cancer Ther; 9(6); 1697–708. ©2010 AACR.
A Novel Plant Homeodomain Finger 10–Mediated Antiapoptotic Mechanism Involving Repression of Caspase-3 in Gastric Cancer Cells
Authors: Wei Min , Liu Bingya , Su Liping , Li Jianfang , Zhang Jun , Yu Yingyan , Yan Min , Yang Zhongyin , Chen Xuehua , Liu Jiayun , Lv Xin , Nie Hui , Zhang Qing , Zheng Zhong , Yu Beiqin , Ji Jun , Zhang Jianian , Zhu Zhenggang , Gu Qinlong
Published: June 2010

The mechanisms governing tumorigenesis of gastric cancer have been an area of intense investigation. Currently, plant homeodomain (PHD) finger (PHF) proteins have been implicated in both tumor suppression and progression. However, the function of PHF10 has not been well characterized. Here, we show that various levels of PHF10 protein were observed in gastric cancer cell lines. Alteration of PHF10 expression, which is associated with tumor cell growth, may result in apoptosis in gastric cancer cells both in vitro and in vivo. Knockdown of PHF10 expression in gastric cancer cells led to significant induction of caspase-3 expression at both the RNA and protein levels and thus induced alteration of caspase-3 substrates in a time-dependent manner. Moreover, results from luciferase assays indicated that PHF10 acted as a transcriptional repressor when the two PHD domains contained in PHF10 were intact. Combined with previous findings, our data suggest that PHF10 transcriptionally regulates the expression of caspase-3. Finally, by using systematic reporter deletion and chromatin immunoprecipitation assays, we localized a region between nucleotides −270 and −170 in the caspase-3 promoter that was required for the efficient inhibition of caspase-3 promoter activity by PHF10. Collectively, our findings show that PHF10 repressed caspase-3 expression and impaired the programmed cell death pathway in human gastric cancer at the transcriptional level. Mol Cancer Ther; 9(6); 1764–74. ©2010 AACR.
XPB Induces C1D Expression to Counteract UV-Induced Apoptosis
Authors: Li Guang , Liu Juhong , Abu-Asab Mones , Masabumi Shibuya , Maru Yoshiro
Published: June 2010

Although C1D has been shown to be involved in DNA double-strand break repair, how C1D expression was induced and the mechanism(s) by which C1D facilitates DNA repair in mammalian cells remain poorly understood. We and others have previously shown that expression of xeroderma pigmentosum B (XPB) protein efficiently compensated the UV irradiation–sensitive phenotype of 27-1 cells, which lack functional XPB. To further explore XPB-regulated genes that could be involved in UV-induced DNA repair, differential display analysis of mRNA levels from CHO-9, 27-1, and 27-1 complemented with wild-type XPB was done and C1D gene was identified as one of the major genes whose expression was significantly upregulated by restoring XPB function. We found that XPB is essential to induce C1D transcription after UV irradiation. The increase in C1D expression effectively compensates for the UV-induced proteolysis of C1D and thus maintains cellular C1D level to cope with DNA damage inflicted by UV irradiation. We further showed that although insufficient to rescue 27-1 cells from UV-induced apoptosis by itself, C1D facilitates XPB DNA repair through direct interaction with XPB. Our findings provided direct evidence that C1D is associated with DNA repair complex and may promote repair of UV-induced DNA damage. Mol Cancer Res; 8(6); 885–95. ©2010 AACR.
PRDM1 Is Required for Mantle Cell Lymphoma Response to Bortezomib
Authors: Desai Shruti , Maurin Michelle , Smith Matthew A. , Bolick Sophia C.E. , Dessureault Sophie , Tao Jianguo , Sotomayor Eduardo , Wright Kenneth L.
Published: June 2010

Mantle cell lymphoma (MCL) is an aggressive form of B-cell lymphoma with a poor disease-free survival rate. The proteasome inhibitor bortezomib is approved for the treatment of relapsed and refractory MCL and has efficacy in about 30% of patients. However, the precise mechanism of action of bortezomib is not well understood. This report establishes a requirement for the transcription repressor PR domain zinc finger protein 1 (PRDM1, Blimp1) in the response to bortezomib. Bortezomib rapidly induces transcription of PRDM1 as part of the apoptotic response in both cell lines and primary MCL tumor cells. Knockdown of PRDM1 blocks activation of NOXA and inhibits apoptosis, whereas ectopic expression of PRDM1 alone leads to apoptosis in MCL. Two novel direct targets of PRDM1 were identified in MCL cells: MKI67 (Ki67) and proliferating cell nuclear antigen (PCNA). Both MKI67 and PCNA are required for proliferation and survival. Chromatin immunoprecipitation and knockdown studies reveal that specific repression of MKI67 and PCNA is mediated by PRDM1 in response to bortezomib. Furthermore, promoter studies and mutation/deletion analysis show that PRDM1 functions through specific sites in the PCNA proximal promoter and an MKI67 distal upstream repression domain. Together, these findings establish PRDM1 as a key mediator of bortezomib activity in MCL. Mol Cancer Res; 8(6); 907–18. ©2010 AACR.
Phylogenetic Origins of Early Alterations in Brain Region Proportions
Authors: Charvet Christine J. , Sandoval Alexis L. , Striedter Georg F.
Published: June 2010

Adult galliform birds (e.g. chickens) exhibit a relatively small telencephalon and a proportionately large optic tectum compared with parrots and songbirds. We previously examined the embryonic origins of these adult species differences and found that the optic tectum is larger in quail than in parakeets and songbirds at early stages of development, prior to tectal neurogenesis onset. The aim of this study was to determine whether a proportionately large presumptive tectum is a primitive condition within birds or a derived feature of quail and other galliform birds. To this end, we examined embryonic brains of several avian species (emus, parrots, songbirds, waterfowl, galliform birds), reptiles (3 lizard species, alligators, turtles) and a monotreme (platypuses). Brain region volumes were estimated from serial Nissl-stained sections. We found that the embryos of galliform birds and lizards exhibit a proportionally larger presumptive tectum than all the other examined species. The presumptive tectum of the platypus is unusually small. The most parsimonious interpretation of these data is that the expanded embryonic tectum of lizards and galliform birds is a derived feature in both of these taxonomic groups.
North-African Reference Values of Alveolar Membrane Diffusion Capacity and Pulmonary Capillary Blood Volume
Authors: Rouatbi Sonia , Ben Saad Helmi , Latiri Imed , Tabka Zouhair , Guénard Hervé
Published: June 2010

Background: In North-African adults, location-specific reference values for membrane diffusion capacity (Dm) and pulmonary capillary blood volume (Vc) were needed. Objectives: To verify the applicability of previously published reference equations for Dm and Vc in North-African healthy adults (age >18 years) and to determine specific reference equations for North Africa. Methods: The study was designed as a prospective cross-sectional study. Anthropometric data (age, height, weight and body mass index) and Dm and Vc were assessed in 85 healthy Tunisian adults. Univariate and multiple linear regression analyses were used to determine reference equations and to calculate the lower limit of the normal range (LLN). Results: The mean ages ± SD (minimum – maximum) for male and female adults were 53 ± 21 (21–85) and 42 ± 16 (18–72) years, respectively. Previously published reference equations did not reliably predict measured Dm and Vc. The reference equation (r2 = 47%) for Dm was –36.16 + 45.37 × height – 0.34 × age + 0.39 × weight + 7.41 × gender (0 = female and 1 = male). To calculate the Dm LLN subtract 24.36 from the reference value. The reference equation (r2 = 30%) for female Vc was 94.70 – 0.57 × age, and the reference equation (r2 = 52%) for male Vc was 0.82 – 0.48 × age + 52.47 × height + 0.16 × weight. To calculate the Vc LLN subtract 28.52 and 26.54 from these reference values for females and males, respectively. Conclusion: These Vc and Dm reference equations supplement the international World Bank of reference equations.
Cause-Specific Cardiovascular Risk Associated With Nonsteroidal Antiinflammatory Drugs Among Healthy Individuals
Authors: Fosbøl Emil Loldrup , Folke Fredrik , Jacobsen Søren , Rasmussen Jeppe N. , Sørensen Rikke , Schramm Tina Ken , Andersen Søren S. , Rasmussen Søren , Poulsen Henrik Enghusen , Køber Lars , Torp-Pedersen Christian , Gislason Gunnar H.
Published: June 2010

Background—

Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.

Methods and Results—

With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously. The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses. The entire Danish population age 10 years or more consisted of 4 614 807 individuals on January 1, 1997, of which 2 663 706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005. Of these; 1 028 437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy. Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63), but naproxen was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42).

Conclusions—

Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals, whereas our results suggest that naproxen has a safer cardiovascular risk-profile.
Traditional Economy of the Herder-Horticulturists of South Iran
Authors: Amanolahi Sekandar
Published: June 2010

The traditional ecological adaptation of the herder-horticulturists of South Iran represents a distinct pattern of subsistence and a different type of adaptation. Being neither pastoral nomads nor sedentary agriculturists, their economy is maintained by a combination of herding (mainly goats) and cultivation of semi-wild orchards and rose bushes on the high altitudes, without the use of irrigation. This study is predominantly based on the field-work materials recorded during several years in the late 1980s.
Genetic Affinity between the Armenian Yezidis and the Iraqi Kurds
Authors: Harutyunian Ashot , Khudoyan Armine , Andonian Laris , Margarian Ashot , Yepiskoposian Levon
Published: June 2010

The Yezidi community in Armenia has been formed during last two-three centuries as a consequence of several waves of migration. Due to the esoteric character of the community, the Yezidis have been reproductively isolated from neighbouring populations for centuries, which has left significant traces in their genetic structure. Our results based on the analysis of patrilineal genetic lineages demonstrate that the long-term isolation of the Yezidis has resulted in notable reduction of male sex chromosome variability compared to other populations and significant difference from the Kurds living in Iraq. However, the analysis of specific lineages provides evidence on similar genetic traits between the Armenian Yezidis and the Iraqi Kurds.
Age-related Changes in Tongue Pressure during Swallowing
Authors: Tamine K. , Ono T. , Hori K. , Kondoh J. , Hamanaka S. , Maeda Y.
Published: June 2010

Although swallowing movement is known to change with aging, age-related differences in the tongue pressure for propelling a bolus from the oral cavity into the pharynx have yet to be investigated in a physiological condition. We hypothesized that tongue pressure during swallowing changed with aging and, using a 0.1-mm-thick sensor sheet with 5 measuring points, measured it while a 15-mL quantity of water was swallowed by young and elderly dentate individuals. Both groups showed a similar order of tongue pressure production at each point. However, the elderly group showed longer duration at each point, lower maximal magnitude in the anterio-median part of the hard palate, and higher magnitude in the circumferential parts of the hard palate than the young group. These results provide the first quantitative evidence of the age-related changes in tongue movement during natural swallowing, which could be attributed to muscle weakening and morphological changes in the oropharynx.
Who Is Affected by Neighbourhood Income Mix? Gender, Age, Family, Employment and Income Differences
Authors: Galster George , Andersson Roger , Musterd Sako
Published: June 2010

This paper analyses the degree to which the mixture of low-, middle- and high-income males in the neighbourhood affects the subsequent earnings of individuals, and aims to test explicitly the degree to which these impacts vary across gender, age, presence of children, employment status or income at the start of the analysis period. An intertemporal differences specification of an econometric model is employed to eliminate the potential selection bias arising from unmeasured individual characteristics, utilising data on 1.67 million adults living in Swedish metropolitan areas 1991—99. It is found that there are important differences in the nature and magnitude of neighbourhood income mix effects in several dimensions, but many are statistically and economically significant. Neighbourhood mix effects are consistently stronger for parents and those who do not work full-time, independently of other individual dimensions, although a combination of personal attributes typically governs the vulnerability of the individual to the neighbourhood.
Attachment, relationship maintenance, and stress in long distance and geographically close romantic relationships
Authors: Pistole M. Carole , Roberts Amber , Chapman Marion L.
Published: June 2010

This study investigated attachment, maintenance behaviors, and stress in long distance (LDR) and geographically close (GCR) romantic relationships. Data was analyzed from participants (N = 473) who were in a serious romantic relationship and who completed two attachment measures, two maintenance behaviors measures, and a perceived global stress measure. A multivariate analysis of variance (MANOVA) revealed significant attachment style and significant LDR/GCR differences for some maintenance behaviors. Two hierarchical multiple regressions indicated that different attachment and maintenance behaviors contributed uniquely to perceived global stress in LDRs and in GCRs. Research and counseling implications are briefly discussed.
The 20-year trajectory of marital quality in enduring marriages: Does equity matter?
Authors: DeMaris Alfred
Published: June 2010

I examine the trajectory of marital quality as a function of relationship equity with data from a six-wave panel study of 704 married respondents between 1980 and 2000. Reporting that one “gives more” to the marriage (subjective underbenefit) is more likely for women than men at any given marital duration. Respondents’ relative contribution to income, paid labor, housework, and health (objective underbenefit) raises this probability for women of average religiosity. For the more religious, objective underbenefit has no effect on women’s sense of underbenefit, but reduces men’s sense of underbenefit. Objective underbenefit lowers women’s, but raises men’s, marital quality, at any marital duration. The relevance of equity was not diluted by the passage of time in marriage.
Authenticity with authority figures and peers: Girls’ friendships, self-esteem, and depressive symptomatology
Authors: Theran Sally A.
Published: June 2010

The current study examined authenticity in relationships as a predictor of quality of friendship and psychological well-being in an ethnically diverse sample (N = 108) of 14-year-old girls. Using structural equation modeling, and examining authenticity in relationships in multiple contexts, authenticity in relationships predicted the quality of friendships and psychological well-being (self-esteem and depressive symptomatology). Approval and emotional social support from family members moderated the relationship between authenticity in relationships with authority figures and depressive symptomatology. Specifically, at low levels of authenticity, those with greater social support from family members had fewer depressive symptoms than those with lower levels of social support. This study’s results contribute to an understanding of authenticity in relationships from a relational and contextual perspective.
Male same-sex couple dynamics and received social support for HIV medication adherence
Authors: Wrubel Judith , Stumbo Scott , Johnson Mallory O.
Published: June 2010

This qualitative study examines received social support by analyzing relationship dynamics concerning antiretroviral therapy adherence among HIV+ seroconcordant and serodiscordant male couples. Using narrative data from 40 participants (20 couples interviewed separately), we describe patterns of relationship dynamics and support preferences. One group viewed adherence as a Personal Responsibility. A second group viewed adherence as a Couple Responsibility and integrated support for medication adherence into the relationship. A third group was in the process of ending their relationships and adherence support was one-sided or withdrawn altogether. Examining support exchange contexts at cultural, situational, relational, and personal levels illuminated adherence processes. Qualitative methods provided a framework for investigating these complex relationships and their associations with HIV treatment adherence.
Does eccentric endurance training improve walking capacity in patients with coronary artery disease? A randomized controlled pilot study
Authors: Gremeaux V. , Duclay J. , Deley G. , Philipp JL , Laroche D. , Pousson M , Casillas JM
Published: June 2010

Objective: To examine the effect of eccentric endurance training on exercise capacities in patients with coronary artery disease.

Design: Randomized parallel group controlled study.

Setting: Cardiac rehabilitation unit, Dijon University Hospital.

Participants: Fourteen patients with stable coronary artery disease after percutaneous coronary intervention.

Intervention: Patients followed 15 sessions of training (1 session per day, 3 days a week), either in the concentric group, following a standard programme, or in the eccentric group, performing eccentric resistance exercises using both lower limbs on a specifically designed ergometer.

Main outcomes measured: Symptom-limited Vo2, peak workload, isometric strength of leg extensor and ankle plantar flexors, distance covered during the 6-minute walk test and time to perform the 200-m fast walk test in both groups, before and after the training period.

Results: Patients did not report any adverse effects and were highly compliant. All measured parameters improved in eccentric and concentric group, except for 200-m fast walk test: symptom-limited Vo2 (+14.2% versus +4.6%), peak workload (+30.8% versus +19.3%), 6-minute walk test distance walked (+12.6% versus +10.1%) and leg extensor strength (+7% versus +13%) improved to a similar degree in both groups (P<0.01); ankle plantar flexor strength improved in both groups with a significantly greater increase in the eccentric group (+17% versus +7%, P<0.05).

Conclusion: Patients with stable coronary artery disease can safely engage in eccentric endurance training, which appears to be as efficient as usual concentric training, with reduced oxygen consumption.