bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-expression of nuclear and cytoplasmic HMGB1 is inversely associated with infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer
Authors: Peng Rui-Qing , Wu Xiao-Jun , Ding Ya , Li Chun-Yan , Yu Xing-Juan , Zhang Xing , Pan Zhi-Zhong , Wan De-Sen , Zheng Li-Ming , Zeng Yi-Xin , Zhang Xiao-Shi
Published: September 2010

Background

The intratumoral infiltration of T cells, especially memory T cells, is associated with a favorable prognosis in early colorectal cancers. However, the mechanism underlying this process remains elusive. This study examined whether high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, is involved in the infiltration of T cells and disease progression in locally advanced colon cancer.

Methods

Seventy-two cases of pathologically-confirmed specimens were obtained from patients with stage IIIB (T3N1M0) colon cancer who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University. The density of tumor-infiltrating lymphocytes (TILs) within the tumor tissue and the expression of HMGB1 in the cancer cells were examined via immunohistochemical analysis. The phenotype of CD45RO+ cells was confirmed using a flow cytometric assay. The association between HMGB1 expression, the density of TILs, and the 5-year survival rate were analyzed.

Results

The density of CD45RO+ T cells within the tumor was independently prognostic, although a higher density of CD3+ T cells was also associated with a favorable prognosis. More importantly, the expression of HMGB1 was observed in both the nucleus and the cytoplasm (co-expression pattern) in a subset of colon cancer tissues, whereas nuclear-only expression of HMGB1 (nuclear expression pattern) existed in most of the cancer tissues and normal mucosa. The co-expression pattern of HMGB1 in colon cancer cells was inversely associated with the infiltration of both CD3+ and CD45RO+ T cells and 5-year survival rates.

Conclusions

This study revealed that the co-expression of HMGB1 is inversely associated with the infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer, indicating that the distribution patterns of HMGB1 might contribute to the progression of colon cancer via modulation of the local immune response.
Diabetes treatment patterns and goal achievement in primary diabetes care (DiaRegis) - study protocol and patient characteristics at baseline
Authors: Bramlage Peter , Binz Christiane , Gitt Anselm K , Krekler Michael , Plate Tanja , Deeg Evelin , Tschöpe Diethelm
Published: September 2010

Background

Patients with type 2 diabetes are at an increased risk for disease and treatment related complications after the initial approach of oral mono/dual antidiabetic therapy has failed. Data from clinical practice with respect to this patient group are however scarce. Therefore we set up a registry in primary care documenting the course and outcomes of this patient group.

Methods

Diabetes Treatment Patterns and Goal Achievement in Primary Diabetes Care (DiaRegis) is a prospective, observational, German, multicenter registry including patients with type-2 diabetes in which oral mono/dual antidiabetic therapy has failed. Data were recorded at baseline and will be prospectively documented during visits at 6 ± 1, 12 ± 2 and 24 ± 2 months. The primary objective is to estimate the proportion of patients with at least 1 episode of severe hypoglycemia within one year.

Results

313 primary care offices included 4,048 patients between June 2009 and March 2010 of which 3,810 patients fulfilled the in- and exclusion criteria. 46.7% of patients were female; patients had a median diabetes duration of 5.5 years and most were obese with respect to BMI or waist circumference. HbA1c at baseline was 7.4%, fasting plasma glucose 142 mg/dl and postprandial glucose 185 mg/dl. Co-morbidity in this patient population was substantial with 17.9% having coronary artery disease, 14.4% peripheral neuropathy, 9.9% heart failure and 6.0% peripheral arterial disease. 68.6% of patients received oral monotherapy, 31.4% dual oral combination therapy. The most frequent antidiabetic agent used as monotherapy was metformin (79.0%) followed by sulfonylureas (14.8%).

Conclusions

DiaRegis is a large, prospective registry in primary diabetes care to document the course and outcomes of patients with type-2 diabetes in which the initial approach of oral mono/dual antidiabetic therapy has failed. The two year follow-up will allow for a prospective evaluation of these patients during multiple adjustments of therapy.
Differential expression of DKK-1 binding receptors on stromal cells and myeloma cells results in their distinct response to secreted DKK-1 in myeloma
Authors: Dun Xiaoyi , Jiang Hua , Zou Jianfeng , Shi Jun , Zhou Lili , Zhu Rong , Hou Jian
Published: September 2010

Background

The canonical Wnt signaling is concurrently important for osteoblast differentiation and myeloma cell proliferation. Its activation in myeloma cells and its inhibition in osteoblasts and their progenitors have been identified in the previous studies. Osteoblast progenitors and myeloma cells from a myeloma patient share the same bone marrow (BM) microenvironment, but respond differently to DKK-1 secreted by myeloma cells. The mechanisms remain unclear.

Methods

Primary multiple myeloma (MM) cells were isolated from BM mononuclear cells of 12 MM patients. Human bone marrow stromal cells (SCs) were obtained from BM adherent cells of these MM patients and 10 healthy donors. The mRNA expression levels of DKK-1 binding receptor LRP5/6 and Kremen1/2 (Krm1/2) were analyzed by Real-time PCR in human myeloma cell line (HMCL) RPMI-8226, NCI-H929, U266, LP-1, CZ-1, KM-3, Sko-007, primary myeloma cells and SCs from 12 MM patients and SCs from 10 healthy donors. The binding capability of DKK-1 binding receptors to DKK-1 on primary myeloma cells and SCs was detected by flow cytometry assay.

Results

The mRNA expression levels of DKK-1 binding receptor LRP5/6 and Krm1/2 in SCs from patients with MM were significantly higher than those in myeloma cells and in SCs from healthy donors. The binding capability to DKK-1of DKK-1 binding receptors on SCs from MM patients was obviously higher than those on myeloma cells and SCs from healthy donors by flow cytometry assay. Similar to the effects of coculture with rhDKK1, coculture of SCs from healthy donors with myeloma cells in the presence or absence of a Transwell insert did up-regulate SCs' mRNA levels of LRP5/6 and Krm1/2, and down-regulate their mRNA levels of β-catenin.

Conclusion

Compared with myeloma cells, the SCs from MM patients overexpress DKK-1 binding receptors LRP5/6 and Krm1/2 in response to DKK-1 secreted by myeloma cells, which results in intracellular Wnt signaling inhibition. Our study provides a novel insight into mechanisms of myeloma associated osteolytic lesions.
Cisplatin sensitivity of testis tumour cells is due to deficiency in interstrand-crosslink repair and low ERCC1-XPF expression
Authors: Usanova Svetlana , Piée-Staffa Andrea , Sied Ulrike , Thomale Jürgen , Schneider Astrid , Kaina Bernd , Köberle Beate
Published: September 2010

Background

Cisplatin based chemotherapy cures over 80% of metastatic testicular germ cell tumours (TGCT). In contrast, almost all other solid cancers in adults are incurable once they have spread beyond the primary site. Cell lines derived from TGCTs are hypersensitive to cisplatin reflecting the clinical response. Earlier findings suggested that a reduced repair capacity might contribute to the cisplatin hypersensitivity of testis tumour cells (TTC), but the critical DNA damage has not been defined. This study was aimed at investigating the formation and repair of intrastrand and interstrand crosslinks (ICLs) induced by cisplatin in TTC and their contribution to TTC hypersensitivity.

Results

We observed that repair of intrastrand crosslinks is similar in cisplatin sensitive TTC and resistant bladder cancer cells, whereas repair of ICLs was significantly reduced in TTC. γH2AX formation, which serves as a marker of DNA breaks formed in response to ICLs, persisted in cisplatin-treated TTC and correlated with sustained phosphorylation of Chk2 and enhanced PARP-1 cleavage. Expression of the nucleotide excision repair factor ERCC1-XPF, which is implicated in the processing of ICLs, is reduced in TTC. To analyse the causal role of ERCC1-XPF for ICL repair and cisplatin sensitivity, we over-expressed ERCC1-XPF in TTC by transient transfection. Over-expression increased ICL repair and rendered TTC more resistant to cisplatin, which suggests that ERCC1-XPF is rate-limiting for repair of ICLs resulting in the observed cisplatin hypersensitivity of TTC.

Conclusion

Our data indicate for the first time that the exceptional sensitivity of TTC and, therefore, very likely the curability of TGCT rests on their limited ICL repair due to low level of expression of ERCC1-XPF.
Expression and localization of apolipoprotein M in human colorectal tissues
Authors: Luo Guanghua , Zhang Xiaoying , Mu Qinfeng , Chen Lujun , Zheng Lu , Wei Jiang , Berggren-Söderlund Maria , Nilsson-Ehle Peter , Xu Ning
Published: September 2010

Background

It has been well documented that apolipoprotein M (apoM) is principally expressed in the liver and kidney. However we found that there was weak apoM expression in other tissues or organs too, which could not be ignored. In the present study, we therefore examined apoM expression in human colorectal tissues including cancer tissues, cancer adjacent normal tissues, polyp tissues and normal mucosa as well as inflammatory mucosa.

Methods

Tissue samples were collected from patients who underwent surgical resection or endoscopic examination. ApoM mRNA levels were determined by the real-time RT-PCR and apoM protein mass were examined by the immunohistochemistry.

Results

ApoM protein can be detected in all colorectal tissues. However, apoM protein mass were significantly lower in the cancer tissues than its matched adjacent normal tissues, polyp tissues, normal mucosa and inflammatory mucosa. In parallel, apoM mRNA levels in the colorectal cancer tissues (0.0536 ± 0.0131) were also significantly lower than those in their adjacent normal tissues (0.1907 ± 0.0563) (P = 0.033). Interestingly, apoM mRNA levels in colorectal cancer tissues were statistic significant higher in the patients with lymph node metastasis than the patients without lymph node metastasis (P = 0.008). Patients under Dukes' C and D stages had much higher apoM mRNA levels than patients under Dukes' A and B stages (P = 0.034).

Conclusion

It is concluded that apoM could also be expressed in human colorectal tissues besides liver and kidney. ApoM mRNA levels in the colorectal cancer tissues were significantly increased in the patients with lymph node metastasis. Whether increased apoM expression in the patients with lymph node metastasis being related to patients' prognosis and the physiopathological importance of apoM expression in colorectal tissues need further investigation.
Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers
Authors: Bøhn Siv K , Myhrstad Mari C , Thoresen Magne , Holden Marit , Karlsen Anette , Tunheim Siv Haugen , Erlund Iris , Svendsen Mette , Seljeflot Ingebjørg , Moskaug Jan Ø , Duttaroy Asim K , Laake Petter , Arnesen Harald , Tonstad Serena , Collins Andrew , Drevon Christan A , Blomhoff Rune
Published: September 2010

Background

Plant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases. However, the mechanisms behind this protective effect are not elucidated. We have tested the hypothesis that intake of antioxidant-rich foods can affect groups of genes associated with cellular stress defence in human blood cells. Trial registration number: NCT00520819http://clinicaltrials.gov.

Methods

In an 8-week dietary intervention study, 102 healthy male smokers were randomised to either a diet rich in various antioxidant-rich foods, a kiwifruit diet (three kiwifruits/d added to the regular diet) or a control group. Blood cell gene expression profiles were obtained from 10 randomly selected individuals of each group. Diet-induced changes on gene expression were compared to controls using a novel application of the gene set enrichment analysis (GSEA) on transcription profiles obtained using Affymetrix HG-U133-Plus 2.0 whole genome arrays.

Results

Changes were observed in the blood cell gene expression profiles in both intervention groups when compared to the control group. Groups of genes involved in regulation of cellular stress defence, such as DNA repair, apoptosis and hypoxia, were significantly upregulated (GSEA, FDR q-values < 5%) by both diets compared to the control group. Genes with common regulatory motifs for aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (AhR/ARNT) were upregulated by both interventions (FDR q-values < 5%). Plasma antioxidant biomarkers (polyphenols/carotenoids) increased in both groups.

Conclusions

The observed changes in the blood cell gene expression profiles suggest that the beneficial effects of a plant-based diet on human health may be mediated through optimization of defence processes.
Transcription phase, protein characteristics of DEV UL45 and prokaryotic expression, antibody preparation of the UL45 des-transmembrane domain
Authors: Shen Ai-Mei , Ma Guang-Peng , Cheng An-Chun , Wang Ming-Shu , Luo Dan-Dan , Lu Li-Ting , Zhou Tao , Zhu De-Kang , Luo Qi-Hui , Jia Ren-Yong , Chen Zheng-Li , Zhou Yi , Chen Xiao-Yue
Published: September 2010

Background

Some UL45 gene function of Herpesvirus was reported. While there was no any report of the duck enteritis virus (DEV) UL45 protein as yet.

Results

The UL45 gene and des-transmembrane domain of UL45 (named UL45Δ gene, 295-675bp of UL45) of DEV were amplified by PCR and subcloned into the prokaryotic expression vector pET-32a(+). The constructed recombinant plasmids were transformed into the host strain BL21(DE3) PLysS and induced by IPTG. SDS-PAGE analysis showed the UL45 gene couldn't express while UL45Δ gene was highly expressed. His Purify Kit or salting-out could purify the protein effectively. Using the purified protein to immunize New-Zealand rabbits and produce polyclonal antibody. The agar diffusion reaction showed the titer of antibody was 1:32. Western blot analysis indicated the purified rabbit anti-UL45Δ IgG had a high level of specificity and the UL45 gene was a part of DEV genome. The transcription phase study of UL45 gene showed that expression of UL45 mRNA was at a low level from 0 to 18 h post-infection (pi), then accumulated quickly at 24 h pi and peaked at 42 h pi. It can be detected till 72 h pi. Besides, western blot analysis of purified virion and different viral ingredients showed that the UL45 protein resided in the purified virion and the viral envelope.

Conclusions

The rabbit anti-UL45Δ IgG was produced successfully and it can serve as a good tool for penetrating studies of the function of DEV UL45 protein. The transcription phase and protein characteristics analysis indicated that DEV UL45 gene was a late gene and UL45 protein may be a viral envelope protein.
Two initial vaccinations with the Bm86-based Gavacplus vaccine against Rhipicephalus (Boophilus) microplusinduce similar reproductive suppression to three initial vaccinations under production conditions
Authors: Vargas Milagros , Montero Carlos , Sánchez Dunia , Pérez Danny , Valdés Mario , Alfonso Aymé , Joglar Marisdania , Machado Héctor , Rodríguez Elsa , Méndez Luis , Lleonart Ricardo , Suárez Marisela , Fernández Erlinda , Estrada Mario P , Rodríguez-Mallón Alina , Farnós Omar
Published: September 2010

Background

The cattle tick, Rhipicephalus (Boophilus) microplus, affects livestock production in many regions of the world. Up to now, the widespread use of chemical acaricides has led to the selection of acaricide-resistant ticks and to environmental contamination. Gavacplus is a subunit vaccine based on the recombinant Bm86 tick antigen expressed in yeast, capable to control infestations of R. microplus under controlled and production conditions. The vaccine constitutes the core element of broad control programs against this ectoparasite, in which acquired immunity in cattle to Bm86 is combined with a rational use of acaricides. At present, the conventional vaccine scheme consists of three doses that should be administered at weeks 0, 4 and 7, followed by a booster every six months.

Results

In this study we assayed a reduction in the number of the initial doses of Gavacplus, evaluated the time course and the level of bovine anti-Bm86 antibodies elicited, and analyzed the vaccine effect on ticks engorging on immunized cattle under production conditions. Following three different immunization schemes, the bovines developed a strong and specific immune response characterized by elevated anti-Bm86 IgG titers. A reduction in the weight of engorging female ticks, in the weight of the eggs laid and also in R. microplus viable eggs percentage was obtained by using only two doses of Gavacplus administered at weeks 0 and 4, followed by a booster six months later. This reduction did not differ from the results obtained on ticks engorging on cattle immunized at weeks 0, 4 and 7. It was also demonstrated that anti-Bm86 antibody titers over 1:640, measured in bovines immunized at weeks 0 and 4, were sufficient to affect weight and reproductive potential of female ticks as compared with ticks engorging on unvaccinated animals. In addition, no statistically significant differences were detected in the average weight of eggs laid by ticks engorged on immunized cattle that showed anti-Bm86 specific titers in the range of 1:640 to 1:81920.

Conclusion

The administration of two initial doses of Gavacplus containing 100 μg of Bm86 antigen to non-immunized cattle under production conditions is sufficient to affect the weight and the reproductive capacity of R. microplus engorging females. According to these results, cattle herds' manipulation and vaccine costs could be potentially reduced with a positive impact on the implementation of integrated control programs against R. microplus.
A genetic screen for replication initiation defective (rid) mutants in Schizosaccharomyces pombe
Authors: Locovei Alexandra M , Yin Ling , D'Urso Gennaro
Published: September 2010

In fission yeast the intra-S phase and DNA damage checkpoints are activated in response to inhibition of DNA replication or DNA damage, respectively. The intra-S phase checkpoint responds to stalled replication forks leading to the activation of the Cds1 kinase that both delays cell cycle progression and stabilizes DNA replication forks. The DNA damage checkpoint, that operates during the G2 phase of the cell cycle delays mitotic progression through activation of the checkpoint kinase, Chk1. Delay of the cell cycle is believed to be essential to allow time for either replication restart (in S phase) or DNA damage repair (in G2). Previously, our laboratory showed that fission yeast cells deleted for the N-terminal half of DNA polymerase ε (Cdc20) are delayed in S phase, but surprisingly require Chk1 rather than Cds1 to maintain cell viability. Several additional DNA replication mutants were then tested for their dependency on Chk1 or Cds1 when grown under semi-permissive temperatures. We discovered that mutants defective in DNA replication initiation are sensitive only to loss of Chk1, whilst mutations that inhibit DNA replication elongation are sensitive to loss of both Cds1 and Chk1. To confirm that the Chk1-sensitive, Cds1-insensitive phenotype (rid phenotype) is specific to mutants defective in DNA replication initiation, we completed a genetic screen for cell cycle mutants that require Chk1, but not Cds1 to maintain cell viability when grown at semi-permissive temperatures. Our screen identified two mutants, rid1-1 and rid2-1, that are defective in Orc1 and Mcm4, respectively. Both mutants show defects in DNA replication initiation consistent with our hypothesis that the rid phenotype is replication initiation specific. In the case of Mcm4, the mutation has been mapped to a highly conserved region of the protein that appears to be required for DNA replication initiation, but not elongation. Therefore, we conclude that the cellular response to inhibition of DNA replication initiation is distinct from blocking DNA replication elongation, and this difference can be exploited to identify mutants specifically defective in DNA replication initiation.
Protein complex prediction based on k-connected subgraphs in protein interaction network
Authors: Habibi Mahnaz , Eslahchi Changiz , Wong Limsoon
Published: September 2010

Background

Protein complexes play an important role in cellular mechanisms. Recently, several methods have been presented to predict protein complexes in a protein interaction network. In these methods, a protein complex is predicted as a dense subgraph of protein interactions. However, interactions data are incomplete and a protein complex does not have to be a complete or dense subgraph.

Results

We propose a more appropriate protein complex prediction method, CFA, that is based on connectivity number on subgraphs. We evaluate CFA using several protein interaction networks on reference protein complexes in two benchmark data sets (MIPS and Aloy), containing 1142 and 61 known complexes respectively. We compare CFA to some existing protein complex prediction methods (CMC, MCL, PCP and RNSC) in terms of recall and precision. We show that CFA predicts more complexes correctly at a competitive level of precision.

Conclusions

Many real complexes with different connectivity level in protein interaction network can be predicted based on connectivity number. Our CFA program and results are freely available from http://www.bioinf.cs.ipm.ir/softwares/cfa/CFA.rar.
Cross-reactions between engineered xylose and galactose pathways in recombinant Saccharomyces cerevisiae
Authors: Garcia Sanchez Rosa , Hahn-Hägerdal Bärbel , Gorwa-Grauslund Marie F
Published: September 2010

Background

Overexpression of the PGM2 gene encoding phosphoglucomutase (Pgm2p) has been shown to improve galactose utilization both under aerobic and under anaerobic conditions. Similarly, xylose utilization has been improved by overexpression of genes encoding xylulokinase (XK), enzymes from the non-oxidative pentose phosphate pathway (non-ox PPP) and deletion of the endogenous aldose reductase GRE3 gene in engineered Saccharomyces cerevisiae strains carrying either fungal or bacterial xylose pathways. In the present study, we investigated how the combination of these traits affect xylose and galactose utilization in the presence or absence of glucose in S. cerevisiae strains engineered with the xylose reductase (XR)-xylitol dehydrogenase (XDH) pathway.

Results

In the absence of PGM2 overexpression, the combined overexpression of XK, the non-ox PPP and deletion of the GRE3 gene significantly delayed aerobic growth on galactose, whereas no difference was observed between the control strain and the xylose-engineered strain when the PGM2 gene was overexpressed. Under anaerobic conditions, the overexpression of the PGM2 gene increased the ethanol yield and the xylose consumption rate in medium containing xylose as the only carbon source. The possibility of Pgm2p acting as a xylose isomerase (XI) could be excluded by measuring the XI activity in both strains. The additional copy of the PGM2 gene also resulted in a shorter fermentation time during the co-consumption of galactose and xylose. However, the effect was lost upon addition of glucose to the growth medium.

Conclusions

PGM2 overexpression was shown to benefit xylose and galactose fermentation, alone and in combination. In contrast, galactose fermentation was impaired in the engineered xylose-utilizing strain harbouring extra copies of the non-ox PPP genes and a deletion of the GRE3 gene, unless PGM2 was overexpressed. These cross-reactions are of particular relevance for the fermentation of mixed sugars from lignocellulosic feedstock.
Thyroid Cancer Recurrence in Patients Clinically Free of Disease with Undetectable or Very Low Serum Thyroglobulin Values
Authors: Kloos Richard T.
Published: September 2010

Design: This was a retrospective clinical study.

Setting: The study was conducted at a university-based tertiary cancer hospital.

Patients: One hundred seven patients had initial thyroid cancer surgery and subsequent remnant radioiodine ablation. Patients underwent recombinant human TSH (rhTSH)-mediated diagnostic whole-body scan and rhTSH-stimulated thyroglobulin (Tg) measurement before April 2001 if they had no antithyroglobulin antibodies, were clinically free of disease, and had one or more undetectable (≤0.5 ng/ml) or low (0.6–1 ng/ml) basal Tg measurements on levothyroxine. Patients were stratified according to their rhTSH-Tg responses: group 1, Tg 0.5 ng/ml or less (68 patients); group 2, Tg from 0.6 to 2.0 ng/ml (19 patients); and group 3, Tg greater than 2 ng/ml (20 patients).

Main Outcome Measures: Tumor recurrence was measured.

Results: In group 1, two of 62 patients (3%) with follow-up recurred. In group 2, 63% converted to group 1, whereas two of 19 (11%) converted to group 3 and then recurred. Sixteen of the initial 20 group 3 patients (80%) recurred, including recurrence rates of 69 and 100% for those with an initial rhTSH-Tg greater than 2.0 ng/ml but 5.0 ng/ml or less, and 4.6 ng/ml or greater, respectively. One group 3 patient died of distant metastases. rhTSH-Tg more accurately predicted tumor recurrence than basal Tg. An rhTSH-Tg threshold of 2.5 ng/ml or greater optimally predicted future recurrence with sensitivity, specificity, and negative and positive predictive values of 80, 97, 95, and 84%, respectively.

Conclusions: The prevalence of postablation thyroid cancer recurrence is predicted by the rhTSH-Tg response with an optimal Tg threshold of 2.5 ng/ml. Still, recurrent disease occurs in some patients with an initial rhTSH-Tg of 0.5 ng/ml or less.
Effects of Medroxyprogesterone Acetate on Gene Expression in Myometrial Explants from Pregnant Women
Authors: Cordeaux Yolande , Tattersall Mark , Charnock-Jones D. Stephen , Smith Gordon C. S.
Published: September 2010

Context: Progesterone is important physiologically and therapeutically to maintain uterine quiescence during pregnancy, in part through controlling myometrial gene expression.

Objective: The objective of the study was to use expression microarray and quantitative reverse transcriptase-PCR (qRT-PCR) validation to determine the changes in gene expression induced by prolonged exposure of human myometrium to a synthetic progestogen.

Design: Myometrial explants, obtained at elective cesarean section (n = 9), were maintained in culture, under 0.6 g tension, for 65 h in the presence of medroxyprogesterone acetate (100 nm) or vehicle. Expression array was performed using Illumina beadchip arrays. Approximately 30% of differentially expressed transcripts were validated in biological replicates (n = 10) by qRT-PCR.

Results: The 114 significantly regulated transcripts were significantly enriched in inflammatory response (P = 0.00001), growth factor activity (P = 0.0004), and cytokine activity genes (P = 0.008). Thirty-four transcripts were validated using qRT-PCR in explants obtained from 10 further women. There was very close agreement in the fold changes obtained by array and qRT-PCR (r2 = 0.9, P < 0.0001). We confirmed significant down-regulation of a number of genes that have been well characterized as progesterone sensitive (IL-1B, IL-6, PTGS2, and GJA1). However, the top and sixth most down-regulated transcripts encoded two cytokines, IL-11 and IL-24, respectively, not previously implicated in mediating the effects of progesterone in myometrium. Both were validated by qRT-PCR (4.3- and 2.2-fold down-regulated, both P < 0.001).

Conclusions: Medroxyprogesterone acetate controls expression of multiple genes in myometrium, including many that have not previously been characterized as progestogen regulated in this tissue, including IL-11 and IL-24. It is plausible that proteins encoded by some of these genes may have important but as yet uncharacterized effects in controlling human parturition.
Building the Mosaic of Mediterranean Integration
Authors: Frendo Michael
Published: September 2010

Drawing on his personal experience as Malta's foreign minister from 2004 to 2008, the author argues that the process of Mediterranean integration should be viewed as building a mosaic block by block, with each tile being important to the whole. The original idea for a Union of the Mediterranean is depicted as being superior to its successor, the Union for the Mediterranean The aim should have been to establish a council of the Mediterranean along the lines of the Council of the Baltic States. The political architecture of the Mediterranean is composed of a variable geometry and concentric circles, in which the Olive Group is a “soft” landing place for informal dialogue among the group members and other non-EU states on the Mediterranean littoral.
Turkey's Path to Europe: Defense of Human Rights and Respect for International Obligations
Authors: Payne Donald M.
Published: September 2010

The author, a US representative (Dem., N.J.), outlines the obstacles to Turkey's path to membership in the European Union. They are of Turkey's creation, centered around human rights and freedoms of ethnic and religious minorities.
Why the Islamic Revolution Ended: The Regional Politics of Sudan Since 1989
Authors: Mantzikos Ioannis
Published: September 2010

This essay examines the Islamic movement's role in shaping Sudan's regional relations and politics, particularly in the greater Horn of Africa. The focus is on the competing foreign policies adopted by the Islamic regime in Khartoum in 1989 and the extent to which the radical Islamic or the national interest agenda prevailed. Moreover, the essay emphasizes the extent to which the internal power struggle between Sudan's most powerful men, Omar al-Bashir and Hassan al-Turabi, determined the country's foreign policy rationale. Since 1996, Turabi's international Islamist goals have clashed with Bashir's domestic objectives, leading to a split within the Islamic movement in Sudan.
Fyrom: Searching for a Name, and Problems with the Expropriation of History
Authors: Papavizas George C.
Published: September 2010

Known as Paionia in antiquity, Vardarska Banovina from 1929 through 1944, and the Socialist Republic of Macedonia in Josip Broz Tito's time, this small Yugoslav province seceded from Yugoslavia to become the “Republic of Macedonia.” Accepted by the United Nations as the “Former Yugoslav Republic of Macedonia” (FYROM), it revealed its irredentist aspirations and a furious wave of hatred against Greece (which owns 75 percent of King Philip's Macedonia). Claiming that its Slavic inhabitants are “Macedonians,” FYROM's ultranationalist administration is determined to continue stirring political, demographic, and territorial problems, paying Greece back for its financial generosity with a constant barrage of anti-Hellenic propaganda, provocations in the media and on the Internet, and distortions of history. It also struggles to establish kinship between ancient Macedonians and the FYROM Slavs while discrediting Macedonian Hellenism, and to apprehend the Macedonian patrimony all the way back to the fifth century BC. If it desires to succeed in its ongoing misguided journey to integration with the North Atlantic Treaty Organization and the European Union, FYROM must abandon the mentality of the communist past, which had produced hostile irredentist dogma.
How Europeanized Has Maltese Foreign Policy Become?
Authors: Fiott Daniel
Published: September 2010

This essay focuses on the degree to which Maltese foreign policy has become Europeanized because of its membership in the European Union. The author focuses on three trends resulting from the Europeanization process: first, the ways in which Malta's national policies and political structures have become altered to meet the demands of EU membership; second, the manner in which Malta projects its own interests at the EU level; and third, the degree to which Maltese national identity has transformed since becoming an EU member state in 2004. The author then provides a brief overview of the particular national characteristics of Maltese politics.
Integrin αV is necessary for gastrulation movements that regulate vertebrate body asymmetry
Authors: Ablooglu Ararat J. , Tkachenko Eugene , Kang Jian , Shattil Sanford J.
Published: September 2010

Integrin αV can form heterodimers with several β subunits to mediate cell-cell and cell-extracellular matrix interactions. During zebrafish gastrulation, αV is expressed maternally and zygotically. Here, we used a morpholino-mediated αV knockdown strategy to study αV function. Although αV morphants displayed vascular defects, they also exhibited left-right body asymmetry defects affecting multiple visceral organs. This was preceded by mislocalization of dorsal forerunner cells (DFCs) and malformation of the Kupffer's vesicle (KV) laterality organ. These defects were rescued with morpholino-resistant αV mRNA. Like αV, integrin β1b was expressed in DFCs, and β1b knockdown largely recapitulated the laterality phenotype of αV morphants. When tracked in real-time, individual DFCs of both morphants showed defects in DFC migration, preventing them from organizing into a KV of normal shape and size. Thus, we propose that αVβ1b mediates cellular interactions that are necessary for DFC clustering and movements necessary for Kupffer's vesicle formation, uncovering an early contribution of integrins to the regulation of vertebrate laterality.
Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ
Authors: Oteiza Pablo , Köppen Mathias , Krieg Michael , Pulgar Eduardo , Farias Cecilia , Melo Cristina , Preibisch Stephan , Müller Daniel , Tada Masazumi , Hartel Steffen , Heisenberg Carl-Philipp , Concha Miguel L.
Published: September 2010

Organ formation requires the precise assembly of progenitor cells into a functional multicellular structure. Mechanical forces probably participate in this process but how they influence organ morphogenesis is still unclear. Here, we show that Wnt11- and Prickle1a-mediated planar cell polarity (PCP) signalling coordinates the formation of the zebrafish ciliated laterality organ (Kupffer's vesicle) by regulating adhesion properties between organ progenitor cells (the dorsal forerunner cells, DFCs). Combined inhibition of Wnt11 and Prickle1a reduces DFC cell-cell adhesion and impairs their compaction and arrangement during vesicle lumen formation. This leads to the formation of a mis-shapen vesicle with small fragmented lumina and shortened cilia, resulting in severely impaired organ function and, as a consequence, randomised laterality of both molecular and visceral asymmetries. Our results reveal a novel role for PCP-dependent cell adhesion in coordinating the supracellular organisation of progenitor cells during vertebrate laterality organ formation.
Wage Risk and Employment Risk over the Life Cycle
Authors: Low Hamish , Meghir Costas , Pistaferri Luigi
Published: September 2010

We specify a life-cycle model of consumption, labor supply and job mobility in an economy with search frictions. We distinguish different sources of risk, including shocks to productivity, job arrival, and job destruction. Allowing for job mobility has a large effect on the estimate of productivity risk. Increases in the latter impose a considerable welfare loss. Increases in employment risk have large effects on output and, primarily through this channel, affect welfare. The welfare value of programs such as Food Stamps, partially insuring productivity risk, is greater than the value of unemployment insurance which provides (partial) insurance against employment risk. (JEL D91, J22, J31, J61, J64, J65)
The Law of the Few
Authors: Galeotti Andrea , Goyal Sanjeev
Published: September 2010

Empirical work shows that a large majority of individuals get most of their information from a very small subset of the group, viz., the influencers; moreover, there exist only minor differences between the observable characteristics of the influencers and the others. We refer to these empirical findings as the Law of the Few. This paper develops a model where players personally acquire information and form connections with others to access their information. Every (robust) equilibrium of this model exhibits the law of the few. (JEL D83, D85, Z13)
Sovereign Risk and Secondary Markets
Authors: Broner Fernando , Martin Alberto , Ventura Jaume
Published: September 2010

Conventional wisdom says that, in the absence of default penalties, sovereign risk destroys all foreign asset trade. We show that this conventional wisdom rests on one implicit assumption: that assets cannot be retraded in secondary markets. Without this assumption, foreign asset trade is possible even in the absence of default penalties. This result suggests a broader perspective regarding the origins of sovereign risk and its remedies. Sovereign risk affects foreign asset trade only if default penalties are insufficient and secondary markets work imperfectly. To reduce its effects, one can either increase default penalties or improve the working of secondary markets. (JEL F34, G12, G15)
A Price Theory of Multi-Sided Platforms
Authors: Weyl E. Glen
Published: September 2010

I develop a general theory of monopoly pricing of networks. Platforms use insulating tariffs to avoid coordination failure, implementing any desired allocation. Profit maximization distorts in the spirit of A. Michael Spence (1975) by internalizing only network externalities to marginal users. Thus the empirical and prescriptive content of the popular Jean-Charles Rochet and Jean Tirole (2006) model of two-sided markets turns on the nature of user heterogeneity. I propose a more plausible, yet equally tractable, model of heterogeneity in which users differ in their income or scale. My approach provides a general measure of market power and helps predict the effects of price regulation and mergers. (JEL D42, D85, L14)
Consumption Taxes and Redistribution
Authors: Correia Isabel
Published: September 2010

This study considers replacing the current US tax system with only a flat tax consumption tax, showing, in contrast to the literature, that such a reform leads to a decline in inequality and increase in welfare for the welfare-poor. The results are obtained from a simple model that identifies the main channels through which the reform affects the economy. It is shown also that these novel results depend on the distribution of wealth and earnings, and that they hold for the relevant empirical distributions. (JEL D31, H23, H25)
Elections, Capital Flows, and Politico-Economic Equilibria
Authors: Chang Roberto
Published: September 2010

We study an open economy where a pro-labor and a pro-business candidate compete in an election. The winner chooses taxes, which affect investment returns. Electoral outcomes depend on the size of the foreign debt, but the debt itself reflects expectations about the election. The resulting interaction is novel and has several implications. Elections are associated with increased volatility. Politico-economic crises can occur. Inefficiencies vanish if the candidates commit to an appropriate tax policy, but such commitments have predictable effects on the election. Empirical evidence supporting the theory is discussed. (JEL D72, F34, O17, O19)
Watta Satta: Bride Exchange and Women's Welfare in Rural Pakistan
Authors: Jacoby Hanan G , Mansuri Ghazala
Published: September 2010

Can marriage institutions limit marital inefficiency? We study the pervasive custom of watta satta in rural Pakistan, a bride exchange between families coupled with a mutual threat of retaliation. Watta satta can be seen as a mechanism for coordinating the actions of two sets of parents, each wishing to restrain their son-in-law. We find that marital discord, as measured by estrangement, domestic abuse, and wife's mental health, is indeed significantly lower in watta satta versus “conventional” marriage, but only after accounting for selection bias. These benefits cannot be explained by endogamy, a marriage pattern associated with watta satta. (JEL J12, J16, O15, O18, Z13)
The Gender Wage Gap and Domestic Violence
Authors: Aizer Anna
Published: September 2010

Three quarters of all violence against women is perpetrated by domestic partners. This study exploits exogenous changes in the demand for labor in female-dominated industries to estimate the impact of the male-female wage gap on domestic violence. Decreases in the wage gap reduce violence against women, consistent with a household bargaining model. These findings shed new light on the health production process as well as observed income gradients in health and suggest that in addition to addressing concerns of equity and efficiency, pay parity can also improve the health of American women via reductions in violence. (JEL D13, I12, J16, J23, J31)
Bidding with Securities: Comment
Authors: Che Yeon-Koo , Kim Jinwoo
Published: September 2010

Peter DeMarzo, Ilan Kremer, and Andrzej Skrzypacz (2005) analyzed auctions in which bidders compete in securities. They show that a steeper security leads to a higher expected revenue for the seller, and also use this to establish the revenue ranking between standard auctions. In this comment, we obtain the opposite results to DKS's by assuming that a higher return requires a higher investment cost. Given this latter assumption, steeper securities are more vulnerable to adverse selection, and may yield lower expected revenue, than flatter ones. (JEL D44)
Health Services Research: Rethinking the Quest to be Useful
Authors: Lewis Steven
Published: September 2010

Health services research (HSR) is conceived as an applied discipline and studies are expected to be useful. Yet some of the most justly famous and important HSR has no tangible short-term impact. This raises the question of what constitutes ‘useful’ and whether it is possible to predict which studies will influence policy or practice. Attribution is also a constant issue: elements of health care systems change all the time and changes consistent with research findings may not signal causation but mere correlation. It is possible to make good changes in the absence of solid research evidence and it is also possible to make good changes while unaware of supportive research. Given these contingencies, it is worthwhile reflecting on the extent to which it is reasonable to expect HSR to affect policy or practice. Herein lies a paradox: the easier it is to act on research evidence, the more likely the change may have taken place regardless, while the more original and potentially game-changing the research, the greater the challenge of responding to it. It is nonetheless possible to design health services research more effectively to increase the likelihood of applicability (usually by broadening its scope and examining contextual issues that decision-makers must take into account). For their part, funders of HSR should take note of the historical fact that uptake of the most important work may take decades and may manifest in unforeseeable ways.
When Employees Do Bad Things for Good Reasons: Examining Unethical Pro-Organizational Behaviors
Authors: Umphress Elizabeth E. , Bingham John B.
Published: September 2010

We propose that employees sometimes engage in unethical acts with the intent to benefit their organization, its members, or both—a construct we term unethical pro-organizational behavior. We suggest that positive social exchange relationships and organizational identification may lead to unethical pro-organizational behavior indirectly via neutralization, the process by which the moral content of unethical actions is overlooked. We incorporate situational and individual-level constructs as moderators of these relationships and consider managerial implications and future research.
The Missing Link: The Effect of Customers on the Formation of Relationships Among Producers in the Multiplex Triads
Authors: Shipilov Andrew V. , Li Stan Xiao
Published: September 2010

This paper develops a concept of a “multiplex triad,” i.e., a triplet composed of actors playing different roles and interconnected by different kinds of relationships. An example of such triad is a social structure comprising two producers connected via horizontal relationships and a customer connected to producers via vertical ties. Multiplex triads are important drivers of network evolution, but their dynamics remains poorly understood. Although conventional wisdom suggests that horizontal ties between producers are driven solely by their prior interactions, we find that vertical ties drive the formation of horizontal relationships in a multiplex triad. We also find that these triads are affected by the agency of the customers who (a) force producers into horizontal relationships with those producers that have protected the customers' interests in the past and (b) prevent closure in triads containing strong horizontal relationships because of the divergent objectives of these triads' members. By drawing attention to the existence of multiplex triads and their underlying dynamics, this paper advances a novel view on transitivity incorporating conflicting interests and agencies of actors within social systems.
Comparing booking systems for elective orthopaedic surgery: partial booking reduced cancellation from 56% to 8%
Authors: McNally SA , Alsousou J , Sinha A
Published: September 2010

There have been many recent targets aimed at improving surgical services in the UK. Some of these have not been tested. The government's NHS Plan declared that by 2005, waiting lists will have been abolished. There are three ways of booking patients onto operating lists:
Anatomy Teaching – The Cruellest Cut of All
Authors: Rainsbury Dick , Barbour Alex , Mahadevan Vishy
Published: September 2010

The conference, Anatomy Teaching – the Cruellest Cut of All, was attended by 160 delegates representing a wide range of professions. The aim was to highlight the key issues surrounding the teaching of anatomy today and to reach a consensus on how to make teaching fit for purpose in the future. Andrew Raftery, chair of the College's anatomy steering group and the vocal champion for anatomy on the College Council, eloquently set the scene for the day. He reminded the audience that anatomy remained the basic language of medicine, which through dissection as well as illustrating biological variations and common pathological conditions also promoted teamwork, communication skills, the reality of death and a respect for the human body.
Digital terrestrial television roll-out policies in Spain and the changing television scene in the context of analogue switch-off
Authors: Alonso Isabel Fernndez , Daz-Gonzlez Mara-Jess
Published: September 2010

This article describes and analyses the digital terrestrial television roll-out polices developed and applied in Spain by conservative and socialist governments (Partido Popular [19962004] and Partido Socialista Obrero Espaol [20042010], respectively) from the end of the 1990s until
the analogue switch-off in April 2010. It also considers, from national, regional and local perspectives, the implications of this digitalization process for the terrestrial television scene in Spain. Finally, it points to a number of pending public policy issues and potential market trends.
As a result of this process, Spain has become one of the first large Western European countries with a predominantly terrestrial television model to switch off analogue broadcasts.