bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refusing to apologize can have psychological benefits (and we issue no mea culpa for this research finding)
Authors: Okimoto Tyler G. , Wenzel Michael , Hedrick Kyli 
Published: November 2012

AbstractDespite an understanding of the perception and consequences of apologies for their recipients, little is known about the consequences of interpersonal apologies, or their denial, for the offending actor. In two empirical studies, we examined the unexplored psychological consequences that follow from a harm‐doer's explicit refusal to apologize. Results showed that the act of refusing to apologize resulted in greater self‐esteem than not refusing to apologize. Moreover, apology refusal also resulted in increased feelings of power/control and value integrity, both of which mediated the effect of refusal on self‐esteem. These findings point to potential barriers to victim–offender reconciliation after an interpersonal harm, highlighting the need to better understand the psychology of harm‐doers and their defensive behavior for self‐focused motives. Copyright © 2012 John Wiley & Sons, Ltd.
Intrinsic connectivity between the hippocampus, nucleus accumbens, and ventral tegmental area in humans
Authors: Kahn I. , Shohamy D. 
Published: November 2012

AbstractRecent studies suggest that memory formation in the hippocampus is modulated by the motivational significance of events, allowing past experience to adaptively guide behavior. The effects of motivation on memory are thought to depend on interactions between the hippocampus, the ventral tegmental area (VTA), and the nucleus accumbens (NAcc). Indeed, animal studies reveal anatomical pathways for circuit‐level interaction between these regions. However, a homologue circuit connectivity in humans remains to be shown. We characterized this circuitry in humans by exploiting spontaneous low‐frequency modulations in the fMRI signal (termed resting‐state functional connectivity), which are thought to reflect functionally related regions and their organization into functional networks in the brain. We examined connectivity in this network across two datasets (hi‐resolution, n = 100; standard resolution, n = 894). Results reveal convergent connectivity between the hippocampus, and both the NAcc and the VTA centered on ventral regions in the body of the hippocampus. Additionally, we found individual differences in the strength of connectivity within this network. Together, these results provide a novel task‐independent characterization of circuitry underlying interactions between the hippocampus, NAcc, and VTA and provide a framework with which to understand how connectivity might reflect and constrain the effects of motivation on memory. © 2012 Wiley Periodicals, Inc.
Diabetes in Kyrgyzstan: changes between 2002 and 2009
Authors: Beran David , Abdraimova Aida , Akkazieva Baktygul , McKee Martin , Balabanova Dina , Yudkin John S 
Published: November 2012

ABSTRACTHealth system reform in Kyrgyzstan is seen as a relative success story in central Asia. Initially, most attention focused on structural changes, and it is only since 2006 that the delivery of care and the experience of health service users have risen on the agenda. One exception from the earlier period was a rapid appraisal of the management of diabetes, undertaken in 2002. Using that study as a baseline, we describe the findings of a new evaluation of diabetes management, undertaken in 2009, using the Rapid Assessment Protocol for Insulin Access, now implemented in seven countries. Access to care has improved through the creation of the Family Medical Centres and the deployment of endocrinologists to them. Another improvement is the access to insulin and related medicines, although assessment of the procurement system reveals that the government is getting very poor value for money. Looking ahead, there are grounds for optimism that the passage of the law on diabetes may progressively have a greater impact. Although the law is not yet fully implemented, it has enabled the diabetes associations to defend the rights of their members. This increased capacity is credited with some improvements in diabetes care.Copyright © 2012 John Wiley & Sons, Ltd.
MAGE‐A10 cancer/testis antigen is highly expressed in high‐grade non‐muscle‐invasive bladder carcinomas
Authors: Mengus Chantal , Schultz‐Thater Elke , Coulot Julie , Kastelan Zeljko , Goluza Eleonora , Coric Marijana , Spagnoli Giulio C. , Hudolin Tvrtko 
Published: November 2012

AbstractBladder cancer is a common urinary malignancy and a prevalent cause of cancer‐related death. Current therapies of early stage non‐muscle‐invasive bladder cancer (NMIBC) are frequently associated with undesirable toxicities and recurrence. Active antigen‐specific immunotherapy may provide a valid therapeutic option for patients with NMIBC. Cancer‐testis antigens (CTA) expressed in various tumour types and in a limited range of healthy tissues may represent potential targets for specific immunotherapy. MAGE‐A10 is probably the most immunogenic antigen of the MAGE‐A family. We evaluated the expression of MAGE‐A10 in NMIBC. Seventy‐nine patients undergoing surgical treatment for NMIBC were enrolled in the study. MAGE‐A10 gene expression was assessed by quantitative real‐time polymerase chain reaction. Immunohistochemistry was performed on paraffin‐embedded sections. MAGE‐A10 gene was specifically expressed in one‐third of NMIBC (n = 24: 32.43%). Gene expression was correlated with high tumour grade. MAGE‐A10 protein was exclusively detectable in nuclei of tumour cells. More importantly, MAGE‐A10 protein was also more frequently detectable in high‐grade tumours (p = 0.0001) and in stage T1 tumours invading subepithelial tissue or lamina propria (p = 0.01). A strong correlation between MAGE‐A10 staining score and tumour grade and stage could accordingly be observed. These data indicate that MAGE‐A10 expression is a feature of aggressive NMIBC and might be used as a novel target for specific immunotherapy of these cancers.
Inhibition of leydig tumor growth by farnesoid X receptor activation: The in vitro and in vivo basis for a novel therapeutic strategy
Authors: Catalano Stefania , Panza Salvatore , Malivindi Rocco , Giordano Cinzia , Barone Ines , Bossi Gianluca , Lanzino Marilena , Sirianni Rosa , Mauro Loredana , Sisci Diego , Bonofiglio Daniela , Andò Sebastiano 
Published: November 2012

AbstractLeydig cell tumors (LCTs) are the most common tumors of the gonadal stroma and represent about 3% of all testicular neoplasms. In most cases, LCTs are benign; however, if the tumor is malignant, no effective treatments are currently available. We have recently reported that farnesoid X receptor (FXR) is expressed in R2C Leydig tumor cells, and it reduces the estrogen‐dependent cell proliferation by negatively regulating aromatase expression. Here, we demonstrated that treatment with GW4064, a specific FXR agonist, markedly reduced Leydig tumor growth in vivo by inhibiting proliferation and inducing apoptosis. Indeed, the tumors from GW4064‐treated mice exhibited a decrease in the expression of the proliferation marker Ki‐67 and aromatase along with an increase in the apoptotic nuclei. FXR activation induced an enhanced poly(ADP‐ribose) polymerase cleavage, a marked DNA fragmentation and a strong increase in TUNEL‐positive R2C cells also in vitro. Moreover, in both in vivo and in vitro models, FXR ligands upregulated mRNA and protein levels of p53 and of its downstream effector p21WAF1/Cip1. Functional experiments showed that FXR ligands upregulated p53 promoter activity and this occurred through an increased binding of FXR/nuclear factor‐kB (NF‐kB) complex to the NF‐kB site located within p53 promoter region as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation analysis. Taken together, results from our study show, for the first time, that treatment with FXR ligands induces Leydig tumor regression in vivo, suggesting that activation of FXR may represent a promising therapeutic strategy for LCTs.
Cancer cells preferentially lose small chromosomes
Authors: Duijf Pascal H.G. , Schultz Nikolaus , Benezra Robert 
Published: November 2012

AbstractGenetic and genomic aberrations are the primary cause of cancer. Chromosome missegregation leads to aneuploidy and provides cancer cells with a mechanism to lose tumor suppressor loci and gain extra copies of oncogenes. Using cytogenetic and array‐based comparative genomic hybridization data, we analyzed numerical chromosome aneuploidy in 43,205 human tumors and found that 68% of solid tumors are aneuploid. In solid tumors, almost all chromosomes are more frequently lost than gained with chromosomes 7, 12 and 20 being the only exceptions with more frequent gains. Strikingly, small chromosomes are lost more readily than large ones, but no such inverse size correlation is observed with chromosome gains. Because of increasing levels of proteotoxic stress, chromosome gains have been shown to slow cell proliferation in a manner proportional to the number of extra gene copies gained. However, we find that the extra chromosome in trisomic tumors does not preferentially have a low gene copy number, suggesting that a proteotoxicity‐mediated proliferation barrier is not sustained during tumor progression. Paradoxically, despite a bias toward chromosome loss, gains of chromosomes are a poor prognostic marker in ovarian adenocarcinomas. In addition, we find that solid and non‐solid cancers have markedly distinct whole‐chromosome aneuploidy signatures, which may underlie their fundamentally different etiologies. Finally, preferential chromosome loss is observed in both early and late stages of astrocytoma. Our results open up new avenues of enquiry into the role and nature of whole‐chromosome aneuploidy in human tumors and will redirect modeling and genetic targeting efforts in patients.
Enzymatic processing by MMP‐2 and MMP‐9 of wild‐type and mutated mouse β‐dystroglycan
Authors: Sbardella Diego , Inzitari Rosanna , Iavarone Federica , Gioia Magda , Marini Stefano , Sciandra Francesca , Castagnola Massimo , Van den Steen Philippe E. , Opdenakker Ghislain , Giardina Bruno , Brancaccio Andrea , Coletta Massimo , Bozzi Manuela 
Published: November 2012

AbstractDystroglycan (DG) is a membrane‐associated protein complex formed by two noncovalently linked subunits, α‐DG, a highly glycosylated extracellular protein, and β‐DG, a transmembrane protein. The interface between the two DG subunits, which is crucial to maintain the integrity of the plasma membrane, involves the C‐terminal domain of α‐DG and the N‐terminal extracellular domain of β‐DG. It is well known that under both, physiological and pathological conditions, gelatinases (i.e. MMP‐9 and/or MMP‐2) can degrade DG, disrupting the connection between the extracellular matrix and the cytoskeleton. However, the molecular mechanisms and the exact cleavage sites underlying these events are still largely unknown. In a previous study, we have characterized the enzymatic digestion of the murine β‐DG ectodomain by gelatinases, identifying a main cleavage site on the β‐DG ectodomain produced by MMP‐9. In this article, we have deepened the pattern of the β‐DG ectodomain digestion by MMP‐2 by using a combined approach based on SDS‐PAGE, Orbitrap, and HPLC‐ESI‐IT mass spectrometry. Furthermore, we have characterized the kineticparameters of the digestion of some β‐DG ectodomain mutants by gelatinases. © 2012 IUBMB IUBMB Life, 64(12): 988–994, 2012
Longitudinal differences in the mechanical properties of the thoracic aorta depend on circumferential regions
Authors: Kim Jungsil , Hong Jung‐Wuk , Baek Seungik 
Published: November 2012

AbstractUnderstanding the mechanical behavior of the arterial wall and its spatial variations is essential for the study of vascular physiopathology and the design of biomedical devices that interact with the arterial wall. Although it is generally accepted that the aortic wall gets stiffer along its length, the spatial variations in the mechanical behavior of the thoracic aorta are not well understood. In this study, therefore, we investigate both longitudinal and circumferential variations in the mechanical properties of the porcine descending thoracic aorta. Using a previously developed experimental method and stress–strain analysis, the stress, stretch, tangent modulus (TM), and pressure–strain elastic modulus (PSEM) are estimated in the range of in vivo pressure. The results show that the longitudinal differences of both TM and PSEM are statistically significant in the posterior region but not in the anterior region. Both moduli are greater in the posterior distal region when compared with the other test regions. The findings of this study meet a need for clarifying the region investigated, especially in circumferential region, to study the regional variations in biomechanics of blood vessels. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Characterization of hyaluronan–methylcellulose hydrogels for cell delivery to the injured spinal cord
Authors: Caicco Matthew J. , Zahir Tasneem , Mothe Andrea J. , Ballios Brian G. , Kihm Anthony J. , Tator Charles H. , Shoichet Molly S. 
Published: November 2012

AbstractNo effective clinical treatment currently exists for traumatic spinal cord injury. Cell replacement therapy holds promise for attaining functional repair. Cells may be delivered directly or near the injury site; however, this strategy requires a delivery vehicle to maintain cell viability. We have identified an injectable, biocompatible, and biodegradable hydrogel scaffold composed of hyaluronan (HA) and methylcellulose (MC) that may be an effective scaffold for therapeutic cell delivery. The purpose of the present study was to determine the effects of polymer concentration on HAMC mechanical strength, gelation time, and cell viability. The yield stress of HAMC, a measure of mechanical stiffness, was tunable via manipulation of MC and HA content. Measurement of the elastic and storage moduli as functions of time revealed that HAMC gels in less than 5 min at physiological temperatures. Human umbilical tissue‐derived cells encapsulated in HAMC were homogenously and stably distributed over 3 days in culture and extended processes into the scaffold. Cell viability was stable over this period in all but the most concentrated HAMC formulation. Because of its strength‐tunability, rapid gelation, and ability to maintain cell viability, HAMC is a promising vehicle for cell delivery and is being tested in ongoing in vivo studies. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets
Authors: Wöhrle Simon , Henninger Christine , Bonny Olivier , Thuery Anne , Beluch Noemie , Hynes Nancy E , Guagnano Vito , Sellers William R , Hofmann Francesco , Kneissel Michaela , Graus Porta Diana 
Published: November 2012

Abstract
Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by osteocytes that is essential for phosphate homeostasis. In kidney proximal tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Excess levels of FGF23 cause renal phosphate wasting and suppression of circulating 1,25(OH)2D3 levels and are associated with several hereditary hypophosphatemic disorders with skeletal abnormalities, including X-linked hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets (ARHR). Currently, therapeutic approaches to these diseases are limited to treatment with activated vitamin D analogues and phosphate supplementation, often merely resulting in partial correction of the skeletal aberrations. In this study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR inhibitor currently in Phase I clinical trials for cancer therapy. In two different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs efficiently abrogates aberrant FGF23 signaling and normalizes the hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long-term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased mineralization, and reorganization of the disturbed growth plate structure. We therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of FGF23-mediated hypophosphatemic diseases. © 2013 American Society for Bone and Mineral Research.
Delphinidin Induces Autolysosome as well as Autophagosome Formation and Delphinidin‐Induced Autophagy Exerts a Cell Protective Role
Authors: Tsuyuki Satoshi , Fukui Sayuri , Watanabe Akari , Akune Satoshi , Tanabe Mizuki , Yoshida Kenichi 
Published: November 2012

ABSTRACTAnthocyanidins, which are polyphenols that are believed to be effective for preventing cancer, are composed of a basic structure of the plant pigment anthocyanin. In this study, we investigated the biological activity of anthocyanidins, including delphinidin, against HeLa cells. The cytotoxicity observed in the anthocyanidins‐treated cells was well correlated with the inhibitory effects of anthocyanidins on c‐Jun‐dependent transcriptional activity. Remarkably, anthocyanidin induced autophagosome formation but lacked the ability to induce apoptosis. Notably, delphinidin enhanced autolysosome formation as well as autophagosome formation. Delphinidin treatment resulted in the accumulation of the lipidated form of Map1lc3b protein in an Atg5‐dependent manner in mouse embryonic fibroblasts. Finally, we revealed that the cytotoxicity induced by delphinidin was more severe in Atg5‐deficient mouse embryonic fibroblasts than in wild‐type cells. Taken together, these results indicate that the cytotoxicity induced by delphinidin was accompanied by autophagy and delphinidin‐induced autophagy exerted a cell protective role. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:445‐453, 2012; View this article online at wileyonlinelibrary.com. DOI 10:1002/jbt.21443
Luteolin inhibition of V‐ATPase a3–d2 interaction decreases osteoclast resorptive activity
Authors: Crasto Gazelle J. , Kartner Norbert , Yao Yeqi , Li Keying , Bullock Liv , Datti Alessandro , Manolson Morris F. 
Published: November 2012

AbstractV‐ATPase‐mediated acid secretion is required for osteoclast bone resorption. Osteoclasts are enriched in V‐ATPase a3 and d2 subunit isoforms, and disruption of either of their genes impairs bone resorption. Using purified fusion proteins of a3 N‐terminal domain (NTa3) and full‐length d subunits we determined in a solid‐phase binding assay that half‐maximal binding of d1 or d2 to immobilized NTa3 occurs at 3.1 ± 0.4 or 3.6 ± 0.6 nM, respectively, suggesting equally high‐affinity interactions. A high‐throughput modification of this assay was then used to screen chemical libraries for a3–d2 interaction inhibitors, and luteolin, a naturally occurring flavonoid, was identified, with half‐maximal inhibition at 2.4 ± 0.9 µM. Luteolin did not significantly affect NIH/3T3 or RAW 264.7 cell viability, nor did it affect cytokine‐induced osteoclastogenesis of RAW 264.7 cells or bone marrow mononuclear cells at concentrations ≤40 µM. Luteolin inhibited osteoclast bone resorption with an EC50 of approximately 2.5 µM, without affecting osteoclast actin ring formation. Luteolin‐treated osteoclasts produced deeper resorption pits, but with decreased surface area, resulting in overall decreased pit volume. Luteolin did not affect transcription, or protein levels, of V‐ATPase subunits a3, d2, and E, or V1V0 assembly. Previous work has shown that luteolin can be effective in reducing bone resorption, and our studies suggest that this effect of luteolin may be through disruption of osteoclast V‐ATPase a3–d2 interaction. We conclude that the V‐ATPase a3–d2 interaction is a viable target for novel anti‐resorptive therapeutics that potentially preserve osteoclast–osteoblast signaling important for bone remodeling. J. Cell. Biochem. 114: 929–941, 2013. © 2012 Wiley Periodicals, Inc.
Kallikrein‐binding protein inhibits LPS‐induced TNF‐α by upregulating SOCS3 expression
Authors: Dai Zhiyu , Lu Lei , Yang Zhonghan , Mao Yuling , Lu Juling , Li Cen , Qi Weiwei , Chen Yifei , Yao Yachao , Li Lei , Chen Shaobo , Zhang Yang , Cai Weibin , Yang Xia , Gao Guoquan 
Published: November 2012

AbstractKallikrein‐binding protein (KBP) was previously identified as a serpin family member with specific inhibitory effect on tissue kallikrein and angiogenesis, while there is little knowledge about the effects on inflammation. The aim of this study is to investigate whether KBP can suppress LPS‐induced inflammatory process. Our results showed that both recombinant KBP and KBP overexpression inhibited LPS‐stimulated TNF‐α transcription and translation in macrophage cell line RAW264.7 and primary macrophages. Furthermore, KBP treatment protected mice from endotoxin shock and repressed serum TNF‐α production, increasing survival rate of mice from 10% to 50% when compared to LPS alone. Moreover, qPCR and Western blot analysis demonstrated that both suppressor of cytokine signaling 3 (SOCS3) transcription and translation were induced by KBP treatment in the present of LPS. RNA interference assay and luciferase assay showed that SOCS3 was responsible for the down‐regulation of TNF‐α by KBP, rather than NF‐κB subunit p65 and β‐catenin. Therefore, we demonstrated that KBP suppressed LPS‐induced TNF‐α production via upregulating SOCS3 expression. These results present the protective effects of KBP on LPS‐induced inflammation and provide novel information for the anti‐inflammation mechanism. J. Cell. Biochem. 114: 1020–1028, 2013. © 2012 Wiley Periodicals, Inc.
Notch pathway is involved in high glucose‐induced apoptosis in podocytes via Bcl‐2 and p53 pathways
Authors: Gao Feng , Yao Min , Shi Yonghong , Hao Jun , Ren Yunzhuo , Liu Qingjuan , Wang Xiaomeng , Duan Huijun 
Published: November 2012

AbstractRecent studies have shown that Notch pathway plays a key role in the pathogenesis of diabetic nephropathy (DN), however, the exact mechanisms remain elusive. Here we demonstrated that high glucose (HG) upregulated Notch pathway in podocytes accompanied with the alteration of Bcl‐2 and p53 pathways, subsequently leading to podocytes apoptosis. Inhibition of Notch pathway by chemical inhibitor or specific short hairpin RNA (shRNA) vector in podocytes prevented Bcl‐2‐ and p53‐dependent cell apoptosis. These findings suggest that Notch pathway mediates HG‐induced podocytes apoptosis via Bcl‐2 and p53 pathways. J. Cell. Biochem. 114: 1029–1038, 2013. © 2012 Wiley Periodicals, Inc.