bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling opportunity in health under partial observability of circumstances
Authors: Rosa Dias Pedro
Published: January 2010

This paper proposes a behavioural model of inequality of opportunity in health that integrates John Roemer's framework of inequality of opportunity with the Grossman model of health capital and demand for health. The model generates a recursive system of equations for health and lifestyles, which is then jointly estimated by full information maximum likelihood with freely correlated error terms. The analysis innovates by accounting for the presence of unobserved heterogeneity, therefore addressing the partial‐circumstance problem, and by extending the examination of inequality of opportunity to health outcomes other than self‐assessed health, such as long‐standing illness, disability and mental health. The results provide evidence for the existence of third factors that simultaneously influence health outcomes and lifestyle choices, supporting the empirical relevance of the partial‐circumstance problem. Accounting for these factors, the paper corroborates that the effect of parental and early circumstances on adult health disparities is paramount. However, the particular set of circumstances that affect each of the analysed health outcomes differs substantially. The results also show that differences in educational opportunities, and in social development in childhood, are crucial determinants of lifestyles in adulthood, which, in turn, shape the observed health inequalities. Copyright © 2010 John Wiley & Sons, Ltd.
Entecavir Treatment for Up to 5 Years in Patients With Hepatitis B E Antigen–Positive Chronic Hepatitis B
Authors: Chang Ting-Tsung , Lai Ching-Lung , Yoon Seung Kew , Lee Samuel S. , Coelho Henrique Sergio M. , Carrilho Flair Jose , Poordad Fred , Halota Waldemar , Horsmans Yves , Tsai Naoky , Zhang Hui , Tenney Daniel J. , Tamez Ricardo , Iloeje Uchenna
Published: January 2010

Sustained virologic suppression is a primary goal of therapy for chronic hepatitis B (CHB). In study entecavir (ETV)-022, 48 weeks of entecavir 0.5 mg was superior to lamivudine for virologic suppression for hepatitis B e antigen (HBeAg)-positive CHB. A total of 183 entecavir-treated patients from ETV-022 subsequently enrolled in study ETV-901. We present the results after up to 5 years (240 weeks) of continuous entecavir therapy. The entecavir long-term cohort consists of patients who received ≥1 year of entecavir 0.5 mg in ETV-022 and then entered ETV-901 with a treatment gap ≤35 days. In ETV-901 the entecavir dose was 1.0 mg daily. For patients with samples available at Year 5, proportions with hepatitis B virus (HBV) DNA <300 copies/mL, normal alanine aminotransferase (ALT) levels, HBeAg loss, and HBeAg seroconversion were determined. In all, 146 patients met criteria for inclusion in the entecavir long-term cohort. At Year 5, 94% (88/94) had HBV DNA <300 copies/mL and 80% (78/98) had normal ALT levels. In addition to patients who achieved serologic responses during study ETV-022, 23% (33/141) achieved HBeAg seroconversion and 1.4% (2/145) lost hepatitis B surface antigen (HBsAg) during study ETV-901. Through 5 years, entecavir resistance emerged in one patient. The safety profile of entecavir was consistent with previous reports.

Conclusion:

Extended therapy with entecavir through 5 years maintained or increased rates of HBV DNA suppression and ALT normalization. Additional patients also achieved HBeAg loss and seroconversion. Entecavir provides sustained viral suppression with minimal resistance during long-term treatment of HBeAg-positive CHB. (Hepatology 2010.)
Allogeneic hematopoietic stem cell transplantation in ovarian cancer—the EBMT experience
Authors: Bay Jacques‐Olivier , Cabrespine‐Faugeras Aurélie , Tabrizi Reza , Blaise Didier , Viens Patrice , Ehninger Gerhard , Bornhauser Martin , Slavin Shimon , Rosti Giovanni , Peccatori Jacopo , Demirer Taner , Bregni Marco
Published: January 2010

Although preliminary results suggest that allogeneic hematopoietic stem cell transplantation (allo HCT) for ovarian cancer (OC) is a feasible procedure, the low patient number in previous studies had limited ability to evaluate the true benefit of allo HCT in OC. This retrospective multicenter study included 30 patients with OC allografted between 1995 and 2005 to determine the outcome of patients with OC treated with allo HCT. Prior to allo HCT, patients were in complete response (n = 1), partial response (n = 7), stable disease (n = 11) or had progressive disease (n = 13). An objective response (OR) was observed in 50% (95% CI, 33–67) of patients. Three patients of responding patients had an objective response following the development of acute graft‐versus‐host disease (aGvHD). The cumulative incidence of chronic GvHD (cGVHD) was 34% (95% CI, 18–50). Transplant relative mortality rates were 7 and 20% on day 100 and 1 year, respectively. With a median follow‐up of 74.5 months (range 16–148), median progression free survival (PFS) was 6 months and median overall survival (OS) was 10.4 months. Patients who developed cGvHD following allo HCT had a significant OS improvement compared to those who did not (17.6 months vs. 6.5 months, p = 0.042). However, PFS was not similarly significantly improved in patients who developed cGvHD (12 months versus 3.7 months, p = 0.81). Allo HCT in OC may lead to graft‐versus‐OC effects. Their clinical relevance remains to be shown.
Harm reduction therapy: a practice‐friendly review of research
Authors: Logan Diane E. , Marlatt G. Alan
Published: January 2010

Harm reduction is an umbrella term for interventions aiming to reduce the problematic effects of behaviors. Although harm reduction was originally and most frequently associated with substance use, it is increasingly being applied to a multitude of other behavioral disorders. This article reviews the state of empirical research on harm reduction practices including alcohol interventions for youth, college students, and a variety of other adult interventions. We also review nicotine replacement and opioid substitution, as well as needle exchanges and safe injection sites for intravenous drug users. Dozens of peer‐reviewed controlled trial publications provide support for the effectiveness of harm reduction for a multitude of clients and disorders without indications of iatrogenic effects. Harm reduction interventions provide additional tools for clinicians working with clients who, for whatever reason, may not be ready, willing, or able to pursue full abstinence as a goal. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66: 1–14, 2010.
Ion transport in a human lens epithelial cell line exposed to hyposmotic and apoptotic stress
Authors: Chimote Ameet A. , Adragna Norma C. , Lauf Peter K.
Published: January 2010

Membrane transport changes in human lens epithelial (HLE‐B3) cells under hyposmotic and apoptotic stress were compared. Cell potassium content, Ki, uptake of the K congener rubidium, Rbi, and water content were measured after hyposmotic stress induced by hypotonicity, and apoptotic stress by the protein‐kinase inhibitor staurosporine (STP). Cell water increased in hyposmotic (150 mOsm) as compared to isosmotic (300 mOsm) balanced salt solution (BSS) by >2‐fold at 5 min and decreased within 15 min to baseline values accompanied by a 40% Ki loss commensurate with cell swelling and subsequent cell shrinkage likely due to regulatory volume decrease (RVD). Loss of Ki, and accompanying water, and Rbi uptake in hyposmotic BSS were prevented by clotrimazole (CTZ) suggesting water shifts associated with K and Rb flux via intermediate conductance K (IK) channels, also detected at the mRNA and protein level. In contrast, 2 h after 2 µM STP exposure, the cells lost ∼40% water and ∼60% Ki, respectively, consistent with apoptotic volume decrease (AVD). Indeed, water and Ki loss was at least fivefold greater after hyposmotic than after apoptotic stress. High extracellular K and 2 mM 4‐aminopyridine (4‐AP) but not CTZ significantly reduced apoptosis. Annexin labeling phosphatidylserine (PS) at 15 min suggested loss of lipid asymmetry. Quantitative PCR revealed significant IK channel expression during prolonged hyposmotic stress. Results suggest in HLE‐B3 cells, IK channels likely partook in and were down regulated after RVD, whereas pro‐apoptotic STP‐activation of 4‐AP‐sensitive voltage‐gated K channels preceded or accompanied PS externalization before subsequent apoptosis. J. Cell. Physiol. 223: 110–122, 2010. © 2009 Wiley‐Liss, Inc.
Cyclophilin C‐associated protein/Mac‐2 binding protein colocalizes with calnexin and regulates the expression of tissue transglutaminase
Authors: Kong Wuyi , Lin Bryan W. , Li Shaowei , Longaker Michael T. , Lorenz H. Peter
Published: January 2010

Cyclophilin C‐associated protein (CyCAP) or Mac‐2 binding protein has been identified as a binding protein for cyclophilin C in mice and for Mac‐2 (galectin‐3) in human, suggesting its multiple binding activity to proteins. In the present study, using specific anti‐rat‐CyCAP antibody, we found that CyCAP colocalizes with calnexin at the location near the nuclear envelope, however CyCAP does not have colocalization with calreticulin. In senescent fibroblasts and interferon‐gamma (IFNγ) treated fibroblasts, both calnexin and CyCAP form larger polymers and are released from the endoplasmic reticulum (ER) through the cellular membrane to the extracellular area. Immunoprecipitation studies further confirm that the release of calnexin is through binding to CyCAP. Further, we found that tissue transglutaminase (tTG) protein is decreased, however not at the RNA level, in CyCAP null fibroblasts, which suggests that CyCAP is involved in tTG post‐translational modification. Our data give novel evidence that CyCAP regulates the post‐translational modification of tTG through its colocalization with calnexin in ER. J. Cell. Physiol. 223: 151–157, 2010. © 2009 Wiley‐Liss, Inc.
Regulation of ATPase activity of transglutaminase 2 by MT1‐MMP: Implications for mineralization of MC3T3‐E1 osteoblast cultures
Authors: Nakano Yukiko , Forsprecher Jennifer , Kaartinen Mari T.
Published: January 2010

A pro‐mineralization function for transglutaminase 2 (TG2) has been suggested in numerous studies related to bone, cartilage, and vascular calcification. TG2 is an enzyme which can perform protein crosslinking functions, or act as a GTPase/ATPase depending upon different stimuli. We have previously demonstrated that TG2 can act as an ATPase in a Ca2+‐rich environment and that it can regulate phosphate levels in osteoblast cultures. In this study, we investigate the role MT1‐MMP in regulating the ATPase activity of TG2. We report that proteolytic cleavage of TG2 by MT1‐MMP in vitro results in nearly a 3‐fold increase in the ATPase activity of TG2 with a concomitant reduction in its protein‐crosslinking activity. We show that MC3T3‐E1 osteoblasts secreted full‐length TG2 and major smaller fragments of 66 and 56 kDa, the latter having ATP‐binding abilities. MT1‐MMP inhibition by a neutralizing antibody suppressed mineralization of osteoblast cultures to 35% of control, and significantly reduced phosphate levels in conditioned medium (CM). Furthermore, MT1‐MMP inhibition abolished two of TG2 fragments in the cultures, one of which, the 56‐kDa fragment, has ATPase activity. Neutralization of MT1‐MMP at early phases of mineralization significantly reduced mineral deposition, but had no effect in later phases implying MT1‐MMP and TG2 might contribute to the initiation of mineralization. The cleavage of TG2 by MT1‐MMP likely occurs on the cell surface/pericellular matrix where MT1‐MMP and TG2 were co‐localized. Based on these data, we propose that MT1‐MMP modulates the extracellular function TG2 as part of a regulatory mechanism activates the pro‐mineralization function of TG2. J. Cell. Physiol. 223: 260–269, 2010. © 2009 Wiley‐Liss, Inc.
Decomposition of 1,1‐dimethyl‐1‐silacyclobutane on a tungsten filament—evidence of both ring CC and ring SiC bond cleavages
Authors: Tong L. , Shi Y. J.
Published: January 2010

The decomposition of 1,1‐dimethyl‐1‐silacyclobutane (DMSCB) on a heated tungsten filament has been studied using vacuum ultraviolet laser single photon ionization time‐of‐flight mass spectrometry. It is found that the decomposition of DMSCB on the W filament to form ethene and 1,1‐dimethylsilene is a catalytic process. In addition, two other decomposition channels exist to produce methyl radicals via the SiCH3 bond cleavage and to form propene (or cyclopropane)/dimethylsilylene. It has been demonstrated that both the formation of ethene and that of propene are stepwise processes initiated by the cleavage of a ring CC bond and a ring SiC bond, respectively, to form diradical intermediates, followed by the breaking of the remaining central bonds in the diradicals. The formation of ethene via an initial cleavage of a ring CC bond is dominant over that of propene via an initial cleavage of a ring SiC bond. When the collision‐free condition is voided, secondary reactions in the gas‐phase produce various methyl‐substituted 1,3‐disilacyclobutane molecules. The dominant of all is found to be 1,1,3,3‐tetramethyl‐1,3‐disilacyclobutane originated from the dimerization of 1,1‐dimethylsilene. Copyright © 2010 John Wiley & Sons, Ltd.
Femtosecond vs. Picosecond Laser Material Processing
Authors: Tuennermann Andreas , Nolte Stefan , Limpert Jens
Published: January 2010

Laser materials processing has been an intensive research topic since the invention of the laser. nowadays, lasers are used as efficient and qualified tools in many industrial processes, like heavy industrial cutting, hardening, and welding. however, as the miniaturization of components and devices is progressing, finer structures are required. here, the flexible laser processing with conventional laser sources is typically limited by thermal or mechanical damage (melting, formation of burr and cracks, changes in the morphology etc.), which is especially true if metals have to be processed. In order to overcome these limitations and to minimize collateral damage various research activities based on the use of ultrashort laser pulses with picosecond or femtosecond duration have been started in the early 1990s (e.g. [1–8]).
Adaptation of the curve number approach to runoff estimation for loamy soils over a growing season for winter wheat: Comparison with the STREAM approach
Authors: Martin P. , Ouvry J. F. , Bockstaller C.
Published: December 2009

This paper proposes an adaptation of the curve number (CN) approach to runoff estimation in an agricultural context. The approach is proposed for the north‐western European loess belt regions whose soils are very sensitive to surface crusting which can lead to runoff, soil erosion and muddy flows. The likelihood of runoff is assessed from the sequence of soil surface states generated by cultivation practices. The new approach is based on the calculation of CN values for each stage of the soil‐surface‐state sequence. The approach is described for winter‐sown wheat, which is the main crop of the European loess belt. The authors define a sequence made up of six stages from wheat sowing to sowing of a green manure (mustard) after wheat harvest. Use of a long‐term network of experimental plots set up in Upper Normandy enables protocols to be defined for calculating runoff for each of these stages. Results were compared to those obtained with the STREAM model. Runoff calculated from the CNs appeared to agree with the measured values, whereas results obtained with the STREAM model are less accurate. Starting from there, the authors provide the basis of a diagnostic tool based on the new CN approach using the soil surface conditions characterisation for adjusting CN data for cultivation practices not yet tested on experimental plots. Copyright © 2009 John Wiley & Sons, Ltd.
Eugenol precludes cutaneous chemical carcinogenesis in mouse by preventing oxidative stress and inflammation and by inducing apoptosis
Authors: Kaur Gurpreet , Athar Mohammad , Alam M. Sarwar
Published: December 2009

The present study was designed to investigate the protective efficacy of eugenol against skin cancer and probe into the mechanistic aspects. Skin tumors were initiated by applying 160 nmol DMBA and promoted by twice weekly applications of 8.5 nmol TPA for 28 wk. All mice developed tumors by 13 wk of promotion. However, in mice pretreated with 30 µL eugenol, no tumors were detected until 8 wk (following anti‐initiation protocol) and until 14 wk (following antipromotion protocol) of tumor promotion. PCNA and TUNEL immunohistochemistry of tumors revealed eugenol to ameliorate cell proliferation and elevate apoptosis respectively. The effect of eugenol was assessed on specific stages of carcinogenesis. Initiation with DMBA led to a significant upregulation of p53 expression with a concomitant increase in p21WAF1 levels in epidermal cells indicating induction of damage to the DNA. However, pretreatment with eugenol led to overexpression of these genes, which probably helped stimulate apoptosis of the initiated cells. To ascertain the molecular mechanisms implicated in the antitumor promoting activity of eugenol, its effect was investigated on markers of tumor promotion and inflammation: ODC activity and iNOS and COX‐2 expression, and on levels of proinflammatory cytokines (IL‐6, TNF‐α, and PGE2). Eugenol markedly inhibited all. Eugenol also inhibited the upstream signaling molecule: NF‐κB, which regulates the expression of these genes. TPA‐induced depletion of cutaneous GSH and antioxidant enzymes armory was also precluded by eugenol. From these results, it could be concluded that eugenol markedly protects against chemically induced skin cancer and acts possibly by virtue of its antiproliferative, anti‐inflammatory, and antioxidant activities. © 2009 Wiley‐Liss, Inc.
Vitamin D receptor ligands, adenomatous polyposis coli, and the vitamin D receptor FokI polymorphism collectively modulate β‐catenin activity in colon cancer cells
Authors: Egan Jan B. , Thompson Patricia A. , Vitanov Milen V. , Bartik Leonid , Jacobs Elizabeth T. , Haussler Mark R. , Gerner Eugene W. , Jurutka Peter W.
Published: December 2009

The activity of β‐catenin, commonly dysregulated in human colon cancers, is inhibited by the vitamin D receptor (VDR), and this mechanism is postulated to explain the putative anti‐cancer activity of vitamin D metabolites in the colon. We investigated the effect of a common FokI restriction site polymorphism (F/f) in the human VDR gene as well as the effect of anti‐tumorigenic 1,25‐dihydroxyvitamin D3 (1,25D) and pro‐tumorigenic lithocholic acid (LCA) VDR ligands on β‐catenin transcriptional activity. Furthermore, the influence of a major regulatory protein of β‐catenin, the APC tumor suppressor gene, on VDR‐dependent inhibition of β‐catenin activity was examined. We report herein that β‐catenin‐mediated transcription is most effectively suppressed by the VDR FokI variant F/M4 when 1,25D is limiting. Using Caco‐2 colorectal cancer (CRC) cells, it was observed that VDR ligands, 1,25D and LCA, both suppress β‐catenin transcriptional activity, though 1,25D exhibited significantly greater inhibition. Moreover, 1,25D, but not LCA, suppressed endogenous expression of the β‐catenin target gene DKK‐4 independent of VDR DNA‐binding activity. These results support β‐catenin sequestration away from endogenous gene targets by 1,25D–VDR. This activity is most efficiently mediated by the FokI gene variant F/M4, a VDR allele previously associated with protection against CRC. Interestingly, we found the inhibition of β‐catenin activity by 1,25D–VDR was significantly enhanced by wild‐type APC. These results reveal a previously unrecognized role for 1,25D–VDR in APC/β‐catenin cross talk. Collectively, these findings strengthen evidence favoring a direct effect on the Wnt‐signaling molecule β‐catenin as one anti‐cancer target of 1,25D–VDR action in the colorectum. © 2009 Wiley‐Liss, Inc.
Total obstetric brachial plexus palsy: Results and strategy of microsurgical reconstruction
Authors: El‐gammal Tarek A. , El‐Sayed Amr , Kotb Mohamed M. , Ragheb Yasser Farouk , Saleh Waleed Riad , Elnakeeb Ramy Mohamed , El‐Sayed Semaya Ahmad
Published: January 2010

From 2000 to 2006, 35 infants with total obstetric brachial plexus palsy underwent brachial plexus exploration and reconstruction. The mean age at surgery was 10.8 months (range 3–60 months), and the median age was 8 months. All infants were followed for at least 2.5 years (range 2.5–7.3 years) with an average follow‐up of 4.2 years. Assessment was performed using the Toronto Active Movement scale. Surgical procedures included neurolysis, neuroma excision and interposition nerve grafting and neurotization, using spinal accessory nerve, intercostals and contralateral C7 root. Satisfactory recovery was obtained in 37.1% of cases for shoulder abduction; 54.3% for shoulder external rotation; 75.1% for elbow flexion; 77.1% for elbow extension; 61.1% for finger flexion, 31.4% for wrist extension and 45.8% for fingers extension. Using the Raimondi score, 18 cases (53%) achieved a score of three or more (functional hand). The mean Raimondi score significantly improved postoperatively as compared to the preoperative mean: 2.73 versus 1, and showed negative significant correlation with age at surgery. In total, obstetrical brachial plexus palsy, early intervention is recommended. Intercostal neurotization is preferred for restoration of elbow flexion. Tendon transfer may be required to improve external rotation in selected cases. Apparently, intact C8 and T1 roots should be left alone if the patient has partial hand recovery, no Horner syndrome, and was operated early (3‐ or 4‐months old). Apparently, intact nonfunctioning lower roots with no response to electrical stimulation, especially in the presence of Horner syndrome, should be neurotized with the best available intraplexal donor. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.
Complete free flap loss due to extensive hemodilution
Authors: Namdar Thomas , Bartscher Tanja , Stollwerck Peter L. , Mailänder Peter , Lange Thomas
Published: January 2010

Background: Free tissue transfer in reconstruction of lower extremity wounds is well established. Controversy surrounds type and regimen of intravenous fluid application during microsurgery. Hemodilution is supposed to influence haemostatic process. Patients and Methods: We performed an analysis of 48 patients treated with a free latissimus dorsi muscle flap to the lower leg for posttraumatic soft‐tissue coverage. Postoperative latissimus dorsi muscle flap perfusion was controlled by clinical monitoring. Intraoperative infusion management was evlatuated retrospectively. Results: In 4 of 48 included patients, a complete loss of free latissimus dorsi muscle flap was registered. Concomitant increased saline infusion was detected (4,534 ml versus. 6,125 ml; P = 0.048). Similar findings for relation of total infusion volume to body weight were seen (44 ml/kg versus 69 ml/kg; P = 0.01). No significant colloid infusion was detected. Conclusions: We demonstrate the clinical relevance of extensive intraoperative hyperhydration, which can provoke a complete free flap loss. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.
Surgical complications in kidney transplantation in nonhuman primates
Authors: Song Lijun , Qi Shijie , Dun Hao , Hu Yanxin , Ma Anlun , Yu Guang , Xiong Zuquan , Zhu Shenyun , Wang Xiang , Xu Dasheng , Li Gang , Shang Yupu , Kinugasa Fumitaka , Sudo Yuji , Bai Jieying , Zeng Lin , Daloze Pierre , Chen Huifang
Published: January 2010

Surgical complications are important causes of graft loss in the nonhuman primate kidney transplantation model. We reviewed the incidence and intervention methods in 182 kidney transplantations performed in our lab recently 2 years in Cynomolgus monkeys. There were six renal artery thromboses (3.3%), eight urine leakages (4.4%), and five ureteral stenoses (2.7%). All renal artery thrombosis cases were found within 3 days after surgery. Urine leakage appeared from the 5th to 12th day after surgery and all cases were caused by ureter rupture. Reexploration was performed in five cases to reanastomose ureter with stent. Four cases reached long‐term survival. The rest one died of graft rejection. Ureteral stenoses were found in long‐term survival cases. Ureter reanastomoses with stent were performed in two cases. The postoperative renal functions of these two monkeys recovered to normal and they survived until study termination. From this large number of study, our experience indicated that kidney transplantation in the nonhuman primate is a safe procedure with low complications. Reexploration is recommended for salvage of the graft with urine leakage and ureteral stenosis. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.
Expression pattern of acetylated α‐tubulin in porcine spermatogonia
Authors: Luo Jinping , Rodriguez‐Sosa Jose Rafael , Tang Lin , Bondareva Alla , Megee Susan , Dobrinski Ina
Published: December 2009

Mammalian spermatogonial stem cells reside on the basement membrane of the seminiferous tubules. The mechanisms responsible for maintenance of spermatogonia at the basement membrane are unclear. Since acetylated α‐tubulin (Ac‐α‐Tu) is a component of long‐lived, stable microtubules and deacetylation of α‐tubulin enhances cell motility, we hypothesized that acetylation of α‐tubulin might be associated with positioning of spermatogonia at the basement membrane. The expression pattern of Ac‐α‐Tu at different stages of testis development was characterized by immunohistochemistry for Ac‐α‐Tu and spermatogonia‐specific proteins (PGP 9.5, DAZL). In immature pig testes, Ac‐α‐Tu was present exclusively in gonocytes at 1 week of age, and in a subset of spermatogonia at 10 weeks of age. At this age, spermatogonia are migrating toward the tubule periphery and Ac‐α‐Tu appeared polarized toward the basement membrane. In adult pig testes, Ac‐α‐Tu was detected in few single or paired spermatogonia at the basement membrane as well as in spermatids and spermatozoa. Only undifferentiated (DAZL−), proliferating (determined by BrdU incorporation) spermatogonia expressed high levels of Ac‐α‐Tu. Comparison with the expression pattern of β‐tubulin and tyrosinated α‐tubulin confirmed that only Ac‐α‐Tu is specific to germ cells. The unique pattern of Ac‐α‐Tu in undifferentiated germ cells during postnatal development suggests that posttranslational modifications of microtubules may play an important role in recruiting and anchoring spermatogonia at the basement membrane. Mol. Reprod. Dev. 77: 348–352, 2010. © 2009 Wiley‐Liss, Inc.
Purposeful commingling of adult and child cranial elements from the Chelechol ra Orrak Cemetery, Palau
Authors: Fitzpatrick S. M. , Nelson G. C.
Published: December 2009

Continued excavation in 2007 of the early (ca. 2000–3000 calBP) cemetery at Chelechol ra Orrak in Palau, Micronesia revealed the remains of at least six individuals, adding to a minimum number of at least 25 other mostly fragmented individuals recovered in previous years. Of particular interest was the discovery of two isolated adult partial crania one of which, when emptied of sandy matrix, was found to contain a complete child's frontal bone. Here we explore the possibility that the placement of the skulls, particularly the commingling of the adult and child cranial elements, was done purposefully and discuss its significance for early Pacific mortuary behaviours. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis and characterization of novel h‐HTBN/PEG PU copolymers for tissue engineering: degradation, phase behavior, and mechanical properties
Authors: Luo Yan‐Ling , Nan Yun‐Fei , Xu Feng , Chen Ya‐Shao , Di Hong‐Wei
Published: December 2009

The phase behavior of the as‐prepared polyether polyurethane (PU) elastomers was investigated by dynamic mechanical analysis (DMA), polarized optical microscope (POM), and atomic force microscopy (AFM). This PU copolymers were composed of different compositions of two soft segments, poly(ethylene glycol) (PEG) and hydrolytically modified hydroxyl‐terminated poly(butadiene‐co‐acrylonitrile) (h‐HTBN) oligomers. The microphase separation behavior is confirmed to occur between soft and hard segments as well as soft and soft segments as the h‐HTBN is incorporated into the PU system, depending on soft‐soft and/or soft‐hard microdomain composition, molecular weight (MW) of PEG, and hydrolysis time of HTBN. The driving force for this phase separation is mainly due to the formation of inter‐ and intramolecular hydrogen bonding interaction. The PU‐70, PU‐50 samples with non‐reciprocal composition seem to exhibit larger microphase separation than any other PU ones. The hydrolysis degradation, thermal stability, and mechanical properties of the copolymers were assessed by gravimetry, scanning electron microscope (SEM), thermal gravity analysis (TGA), and tensile test, respectively. The experimental results indicated that the incorporation of h‐HTBN soft segment into PEG as well as low MW of PEG leads to increased thermal and degradable stability based on the intermolecular hydrogen bond interaction. The PU‐70 and PU‐50 copolymers exhibit better mechanical properties such as high flexibility and high ductility because of their larger microphase separation architecture with the hard domains acting as reinforcing fillers and/or physical crosslinking agents dispersed in the soft segment matrix. Copyright © 2009 John Wiley & Sons, Ltd.
Functional proteomic and structural insights into molecular targets related to the growth inhibitory effect of tanshinone IIA on HeLa cells
Authors: Pan Tai‐Long , Hung Yu‐Chiang , Wang Pei‐Wen , Chen Shui‐Ten , Hsu Teng‐Kuei , Sintupisut Nardnisa , Cheng Chao‐Sheng , Lyu Ping‐Chiang
Published: January 2010

Certain antitumor agents have recently been extracted from the roots of Salvia miltiorrhiza Bunge. The diterpene derivative, tanshinone IIA, possesses cytotoxic activity against several human carcinoma cell lines. It also inhibits invasion and metastasis of cancer cells. In the present study, we isolated tanshinone IIA from S. miltiorrhiza, and it exhibited strong growth inhibition against human cervical cancer cells in dose‐ and time‐dependent manners with a 50% cell growth inhibition value of 2.5 μg/mL (8.49 μM). Flow cytometric analysis of cell cycle progression revealed that G2/M arrest was initiated after a 24 h exposure to the drug. It also resulted in DNA fragmentation and degradation of poly (ADP‐ribose) polymerase indicating that tanshinone IIA may be a potential antitumor agent. Furthermore, we performed a comprehensive proteomic analysis to survey global protein changes induced by tanshinone IIA treatment on HeLa cells. Significant changes in the levels of cytoskeleton proteins as well as stress‐associated proteins were observed. Immunoblot analysis and immunofluorescence staining were used to confirm the levels of protein expression. Overexpression of the vimentin rescued these tanshinone IIA‐induced events. Computational docking methods indicated that tanshinone IIA could stably bind to the β‐subunit of the microtubule protein. An interaction network analysis of these 12 proteins using MetaCore™ software suggested that tanshinone IIA treatment regulated the expressions of proteins involved in apoptotic processes, spindle assembly, and p53 activation, including vimentin, Maspin, α‐ and β‐tubulin, and GRP75. Taken together, our results suggest that tanshinone IIA strongly inhibited the growth of cervical cancer cells through interfering in the process of microtubule assembly, leading to G2/M phase arrest and sequent apoptosis. The success of this large‐scale effort was assessed by a bioinformatics analysis of proteins through predictions of protein domains and possible functional roles. The possible contributions of these proteins to the cytotoxicity of tanshinone IIA provide potential opportunities for the development of cancer therapeutics.
Proteomic analysis of symbiosome membranes in Cnidaria–dinoflagellate endosymbiosis
Authors: Peng Shao‐En , Wang Yu‐Bao , Wang Li‐Hsueh , Chen Wan‐Nan Uang , Lu Chi‐Yu , Fang Lee‐Shing , Chen Chii‐Shiarng
Published: January 2010

Symbiosomes are specific intracellular membrane‐bound vacuoles containing microalgae in a mutualistic Cnidaria (host)–dinoflagellate (symbiont) association. The symbiosome membrane is originally derived from host plasma membranes during phagocytosis of the symbiont; however, its molecular components and functions are not clear. In order to investigate the protein components of the symbiosome membranes, homogenous symbiosomes were isolated from the sea anemone Aiptasia pulchella and their purities and membrane intactness examined by Western blot analysis for host contaminants and microscopic analysis using various fluorescent probes, respectively. Pure and intact symbiosomes were then subjected to biotinylation by a cell impermeant agent (Biotin‐XX sulfosuccinimidyl ester) to label membrane surface proteins. The biotinylated proteins, both Triton X‐100 soluble and insoluble fractions, were subjected to 2‐D SDS‐PAGE and identified by MS using an LC‐nano‐ESI‐MS/MS. A total of 17 proteins were identified. Based on their different subcellular origins and functional categories, it indicates that symbiosome membranes serve as the interface for interaction between host and symbiont by fulfilling several crucial cellular functions such as those of membrane receptors/cell recognition, cytoskeletal remodeling, ATP synthesis/proton homeostasis, transporters, stress responses/chaperones, and anti‐apoptosis. The results of proteomic analysis not only indicate the molecular identity of the symbiosome membrane, but also provide insight into the possible role of symbiosome membranes during the endosymbiotic association.
Screening for therapeutic targets of vorinostat by SILAC‐based proteomic analysis in human breast cancer cells
Authors: Zhou Qun , Chaerkady Raghothama , Shaw Patrick G. , Kensler Thomas W. , Pandey Akhilesh , Davidson Nancy E.
Published: January 2010

Histone deacetylases (HDACs) play critical roles in silencing tumor suppressor genes. HDAC inhibitors reactivate tumor suppressor genes and inhibit tumor cell growth in vitro and in vivo, and several HDAC inhibitors are currently being evaluated in clinical trials for cancer therapy. A comprehensive analysis of proteins regulated by HDAC inhibitors would enhance our ability to define and characterize their essential therapeutic targets. Here, we employed stable isotope labeling with amino acids in cell culture‐based quantitative proteomics to identify acetylated proteins in human breast cancer cells. Treatment with the clinically relevant HDAC inhibitor, suberoylanilide hydroxamic acid (vorinostat), induces lysine acetylation of 61 proteins in MDA‐MB‐231 human breast cancer cells. Suberoylanilide hydroxamic acid not only induces lysine acetylation in chromatin‐associated proteins, but also acetylates previously unrecognized nonhistone proteins, including transcriptional factors and regulators, chaperones, cell structure proteins, and glycolytic enzymes in a time‐dependent manner. Knowledge of the full repertoire of acetylated proteins will provide a foundation for further defining the functions of HDACs in cancer cells.
Telomerase enzyme inhibition (TEI) and cytolytic therapy in the management of androgen independent osseous metastatic prostate cancer
Authors: Li Yingming , Malaeb Bahaa S. , Li Zhong‐ze , Thompson Melissa G. , Chen Zhi , Corey David R. , Hsieh Jer‐Tsong , Shay Jerry W. , Koeneman Kenneth S.
Published: December 2009

BACKGROUND

Recurrent prostate cancer can be osseous, androgen independent and lethal. The purpose is to discern the efficacy of synthetic small molecule telomerase enzyme inhibitors (TEI) alone or in combination with other cytotoxic therapies in controlling metastatic osseous prostate cancer.

METHODS

C4‐2B was pre‐treated with a match or mismatch TEI for 6 weeks and then inoculated into nude mice subcutaneously or intraosseously. In a separate experiment, untreated C4‐2B was injected into femur of nude mice. The mice were divided into seven systemic “combination” treatment groups of control, Ad‐BSP‐E1a virus, docetaxel, mismatch and match TEI. Serum PSA was followed longitudinally. Histology analyses and histomorphometry were performed. Repeated measure analysis was applied for statistical analysis and Bonferroni method was used in multiple comparisons.

RESULTS

In the pre‐treated study, the PSA of match treated cells in subcutaneous or intraosseous model was significantly lower than mismatch TEI or PBS treated group (P < 0.05). Histology revealed increased fibrosis, apoptosis and decreased PSA staining in the match TEI treated subcutaneous xenografts. In the combination treatment study, the PSA was significantly lower in single/double treatment and triple treatment than control (P < 0.05). Histology revealed that triple therapy mice had normal femur architecture. Histomorphometrics revealed that the area of femur tumor and woven bone was significantly positively correlated (P = 0.007).

CONCLUSIONS

Multiple lines of data point toward the efficacy of systemically administered telomerase inhibitors. Combining cytotoxic regimens with telomerase inhibitors could be beneficial in controlling prostate cancer. Clinical trials are warranted to explore the efficacy of TEI in prostate cancer. Prostate 70: 616–629, 2010. © 2009 Wiley‐Liss, Inc.
ESIprot: a universal tool for charge state determination and molecular weight calculation of proteins from electrospray ionization mass spectrometry data
Authors: Winkler Robert
Published: January 2010

Electrospray ionization (ESI) ion trap mass spectrometers with relatively low resolution are frequently used for the analysis of natural products and peptides. Although ESI spectra of multiply charged protein molecules also can be measured on this type of devices, only average spectra are produced for the majority of naturally occurring proteins. Evaluating such ESI protein spectra would provide valuable information about the native state of investigated proteins. However, no suitable and freely available software could be found which allows the charge state determination and molecular weight calculation of single proteins from average ESI‐MS data. Therefore, an algorithm based on standard deviation optimization (scatter minimization) was implemented for the analysis of protein ESI‐MS data. The resulting software ESIprot was tested with ESI‐MS data of six intact reference proteins between 12.4 and 66.7 kDa. In all cases, the correct charge states could be determined. The obtained absolute mass errors were in a range between −0.2 and 1.2 Da, the relative errors below 30 ppm. The possible mass accuracy allows for valid conclusions about the actual condition of proteins. Moreover, the ESIprot algorithm demonstrates an extraordinary robustness and allows spectral interpretation from as little as two peaks, given sufficient quality of the provided m/z data, without the necessity for peak intensity data. ESIprot is independent from the raw data format and the computer platform, making it a versatile tool for mass spectrometrists. The program code was released under the open‐source GPLv3 license to support future developments of mass spectrometry software. Copyright © 2010 John Wiley & Sons, Ltd.
Application of matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry for the study of Helicobacter pylori
Authors: Ilina Elena N. , Borovskaya Alexandra D. , Serebryakova Marina V. , Chelysheva Vera V. , Momynaliev Kuvat T. , Maier Thomas , Kostrzewa Markus , Govorun Vadim M.
Published: January 2010

The characteristics of matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectrometry based investigation of extremely variable bacteria such as Helicobacter pylori were studied. H. pylori possesses a very high natural variability. Accurate tools for species identification and epidemiological characterization could help the scientific community to better understand the transmission pathways and virulence mechanisms of these bacteria. Seventeen clinical as well as two laboratory strains of H. pylori were analyzed by the MALDI Biotyper method for rapid species identification. Mass spectra collected were found containing 7–13 significant peaks per sample, and only six protein signals were identical for more than half of the strains. Four of them could be assigned to ribosomal proteins RL32, RL33, RL34, and RL36. The reproducible peak with m/z 6948 was identified as a histidine‐rich metal‐binding polypeptide by tandem mass spectrometry (MS/MS). In spite of the evident protein heterogeneity of H. pylori the mass spectra collected for a particular strain under several cultivations were highly reproducible. Moreover, all clinical strains were perfectly identified as H. pylori species through comparative analysis using the MALDI Biotyper software (Bruker Daltonics, Germany) by pattern matching against a database containing mass spectra from different microbial strains (n = 3287) including H. pylori 26695 and J99. The results of this study allow the conclusion that the MALDI‐TOF direct bacterial profiling is suited for H. pylori identification and could be supported by mass spectra fragmentation of the observed polypeptide if necessary. Copyright © 2010 John Wiley & Sons, Ltd.
A parametric mixture model for clustering multivariate binary data
Authors: Tamhane Ajit C. , Qiu Dingxi , Ankenman Bruce E
Published: December 2009

The traditional latent class analysis (LCA) uses a mixture model with binary responses on each subject that are independent conditional on cluster membership. However, in many practical applications, the responses are correlated because they are observed on the same subject; this is known as local dependence. In this paper, we extend the LCA model to allow for local dependence in each cluster to improve clustering accuracy. The clustering problem is hard because of its unsupervised learning nature (the true cluster memberships and even the true number of clusters are unknown), the difficulty of estimating a correlation matrix for each cluster and the paucity of information in binary data. Therefore, we follow a parametric approach in which we fit a mixture model whose components follow multivariate Bernoulli distributions (one for each cluster). An extension of a family of parametric models by Oman and Zucker1is adopted for this purpose and the maximum likelihood estimation method is used for fitting. The Bayesian information criterion (BIC) due to Schwarz2is employed to select the number of clusters. Subjects are classified to clusters using the maximum posterior rule. The proposed method is tested and compared with the LCA method via simulation and by applying both methods to two real data sets. Significant improvement is demonstrated relative to the LCA method. Copyright © 2009 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 3: 3‐19, 2010
Co‐clustering numerical data under user‐defined constraints
Authors: Pensa Ruggero G. , Boulicaut Jean‐Francois , Cordero Francesca , Atzori Maurizio
Published: December 2009

In the generic setting of objects × attributes matrix data analysis, co‐clustering appears as an interesting unsupervised data mining method. A co‐clustering task provides a bi‐partition made of co‐clusters: each co‐cluster is a group of objects associated to a group of attributes and these associations can support expert interpretations. Many constrained clustering algorithms have been proposed to exploit the domain knowledge and to improve partition relevancy in the mono‐dimensional clustering case (e.g. using the must‐link and cannot‐link constraints on one of the two dimensions). Here, we consider constrained co‐clustering not only for extended must‐link and cannot‐link constraints (i.e. both objects and attributes can be involved), but also for interval constraints that enforce properties of co‐clusters when considering ordered domains. We describe an iterative co‐clustering algorithm which exploits user‐defined constraints while minimizing a given objective function. Thanks to a generic setting, we emphasize that different objective functions can be used. The added value of our approach is demonstrated on both synthetic and real data. Among others, several experiments illustrate the practical impact of this original co‐clustering setting in the context of gene expression data analysis, and in an original application to a protein motif discovery problem. Copyright © 2009 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 3: 38‐55, 2010
Constrained overlapping clusters: minimizing the negative effects of bridge‐nodes
Authors: Scripps Jerry , Tan Pang‐Ning
Published: December 2009

This paper presents a new approach to form overlapping clusters of objects by balancing the effects of incompleteness, impurity, and overlap. Incompleteness results from similar objects separated into different clusters while impurity arises when a cluster contains dissimilar objects. Overlap is caused by nodes that appear in more than one cluster. The key to balancing these effects is the identification of bridge‐nodes. We show the limitations of traditional clustering algorithms in handling bridge‐nodes and demonstrate the intractability of minimizing all three effects. Approximation algorithms based on graph mincut and genetic algorithm are proposed to minimize these effects. Our results with real data sets show significant improvement over traditional methods with regard to incompleteness, impurity, and overlap. Copyright © 2009 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 3: 20‐37, 2010
Life-Sparing Effect of Human Cord Blood-Mesenchymal Stem Cells in Experimental Acute Kidney Injury
Authors: Morigi Marina , Rota Cinzia , Montemurro Tiziana , Montelatici Elisa , Lo Cicero Viviana , Imberti Barbara , Abbate Mauro , Zoja Carla , Cassis Paola , Longaretti Lorena , Rebulla Paolo , Introna Martino , Capelli Chiara , Benigni Ariela , Remuzzi Giuseppe , Lazzari Lorenza
Published: January 2010

In search for new sources of mesenchymal stem cells (MSCs) for renal repair in acute kidney injury (AKI), we investigated the potential of human cord blood (CB)-MSCs to cure mice with AKI. Infusion of CB-MSCs in immunodeficient mice with cisplatin-induced AKI ameliorated both renal function and tubular cell injury, and prolonged survival. Transplanted CB-MSCs localized in peritubular areas, limited capillary alterations and neutrophil infiltration. Apoptosis reduced and tubular cell proliferation increased by virtue of stem cell capacity to produce growth factors. The reno-protective effect of CB-MSCs was further confirmed by their ability to inhibit oxidative damage and to induce the prosurvival factor Akt in tubular cells. The evidence that CB-MSCs in vitro increased the production of growth factors and inhibited IL-1β and TNFα synthesis when cocultured with damaged proximal tubular cells indicates a regenerative and anti-inflammatory action of stem cell treatment. Altogether these results highlight the potential of human CB-MSCs as future cell therapy for testing in human AKI.
Covalently linked wall proteins in ascomycetous fungi
Authors: Klis Frans M. , Brul Stanley , De Groot Piet W. J.
Published: December 2009

The covalently linked wall proteins of Saccharomyces cerevisiae and Candida albicans and to a lesser extent of Candida glabrata have been extensively studied. Here we describe some of their main structural features and discuss their conservation in other ascomycetous fungi. We also discuss the hybrid nature of many wall proteins and the frequent occurrence of families of wall proteins with a common multi‐domain structure. Finally, some quantitative data regarding wall proteins are presented. Copyright © 2009 John Wiley & Sons, Ltd.