bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling
Authors: Wachter Franziska , Grunert Michaela , Blaj Cristina , Weinstock David M , Jeremias Irmela , Ehrhardt Harald 
Published: April 2013

Abstract

Background
The p53 protein is the best studied target in human cancer. For decades, p53 has been believed to act mainly as a tumor suppressor and by transcriptional regulation. Only recently, the complex and diverse function of p53 has attracted more attention. Using several molecular approaches, we studied the impact of different p53 variants on extrinsic and intrinsic apoptosis signaling.

Results
We reproduced the previously published results within intrinsic apoptosis induction: while wild-type p53 promoted cell death, different p53 mutations reduced apoptosis sensitivity. The prediction of the impact of the p53 status on the extrinsic cell death induction was much more complex. The presence of p53 in tumor cell lines and primary xenograft tumor cells resulted in either augmented, unchanged or reduced cell death. The substitution of wild-type p53 by mutant p53 did not affect the extrinsic apoptosis inducing capacity.

Conclusions
In summary, we have identified a non-expected impact of p53 on extrinsic cell death induction. We suggest that the impact of the p53 status of tumor cells on extrinsic apoptosis signaling should be studied in detail especially in the context of therapeutic approaches that aim to restore p53 function to facilitate cell death via the extrinsic apoptosis pathway.
Solutions for a class of nonlinear Volterra integral and integro-differential equation using cyclic "Equation missing" -contraction
Authors: Nashine Hemant Kumar , Pathak RP , Somvanshi Piyusha S , Pantelic Slavisa , Kumam Poom 
Published: April 2013

Abstract
We establish the existence and uniqueness of solutions for a class of nonlinear Volterra integral and integro-differential equations using fixed-point theorems for a new variant of cyclic

(
φ
,
ψ
,
θ
)

-contractive mappings. Nontrivial examples are given to support the usability of our results.

MSC:47H10, 54H25.
Analyzing the sources and nature of influence: how the Avahan program used evidence to influence HIV/AIDS prevention policy in India
Authors: Tran Nhan T , Bennett Sara C , Bishnu Rituparna , Singh Suneeta 
Published: April 2013

Abstract

Background
Major investments by development partners in low- and middle-income countries (LMICs) often seek to develop a supportive policy environment. There is limited knowledge about the mechanisms that development partners use to influence government policy, or which mechanisms are effective. This study assessed the influence of Avahan, a large HIV/AIDS prevention program in India supported by the Bill and Melinda Gates Foundation, on the development of HIV/AIDS policies in India, particularly the National AIDS Control Program III (NACP III).

Methods
A retrospective assessment of the contributions of Avahan to the development of NACP III was conducted based upon document review and in-depth interviews with key informants, including Avahan staff and staff of implementing partners. This assessment was carried out within a framework centered on three domains: evidence considered by policy and decision-makers; the channel through which influence is exerted; and the target audience for influence.

Results
Respondents identified a number of respects in which Avahan influenced NACP III policy, notably, Avahan influenced perception of the feasibility of scaling up services (through a demonstration effect) and Avahan, along with others, helped ensure a strong focus on targeted interventions. Overall Avahan’s influence was greatest during policy implementation. While the extent to which research evidence generated by Avahan influenced NACP III was limited, best practice evidence generated by Avahan, including the lessons learned from routine implementation and management, contributed significantly to NACP III. This was largely due to the credibility Avahan had established and strategic ‘inside track’ communications.

Conclusion
While studies of knowledge translation typically focus primarily on scientific evidence, this study suggests that other forms of evidence, notably best practice evidence derived from program experience, and disseminated through personal communication, were particularly influential. The framework developed for the paper provides a useful tool to analyze how evidence-based influence is exerted.
The characteristics of short- and long-term surviving Shiba dogs with chronic enteropathies and the risk factors for poor outcome
Authors: Okanishi Hiroki , Sano Tadashi , Yamaya Yoshiki , Kagawa Yumiko , Watari Toshihiro 
Published: April 2013

AbstractBackgroundThe objectives of this study were to investigate the differences in the characteristics of short- and long-term surviving dogs, and the factors that predict poor outcome in Shiba dogs with chronic enteropathies (CE).MethodsA total of 25 Shiba dogs were included in this study, and classified as either short-term (≤6 months) survivors (Ss; n=16) or long-term (>6 months) survivors (Ls; n=9). The clinical and clinicopathological variables, histopathology, response to therapy, and outcomes were investigated between groups. Furthermore, these factors were tested for their ability to predict poor outcome.ResultsAll CE dogs were diagnosed as having inflammatory bowel disease (IBD) with lymphocytic-plasmacytic enteritis (LPE). Age and canine inflammatory bowel disease activity index (CIBDAI) were significantly higher in the Ss group than in the Ls group (age:p= 0.035, CIBDAI:p= 0.018), as determined via univariate logistic regression analysis. According to receiver operator characteristic (ROC) curve analysis, the best predictors of poor outcome were age and CIBDAI, with the cutoffs determined as 7 years and 9 points, respectively. The majority of the cases (84%) responded to initial treatment; in particular, 75% of dogs in Ss group responded to therapy. The time to response (days) to the initial treatment in the Ss group (median 42.5 days, range: 20-91 days) was significantly shorter than that of the Ls group (median 285 days, range: 196-1026 days). Approximately half (55.5%) of the dogs in the Ls group died due to relapse of CE.ConclusionsThis study suggested that there is a high risk of early mortality in Shiba dogs with CE, particularly if the dogs are older (>7 years) and have a high CIBDAI score (>9 points). There appears to be a possibility of early mortality even if the initial treatment was efficacious. Furthermore, Shiba dogs with CE that become less responsive to initial therapy in the short-term (approximately 3 months) are more likely to have an early mortality. Thus, it is necessary to follow-up Shiba dogs with CE in the long-term, as approximately half of the long-term survivors eventually died due to a relapse of the signs.
Serum folate receptor alpha, mesothelin and megakaryocyte potentiating factor in ovarian cancer: association to disease stage and grade and comparison to CA125 and HE4
Authors: O’Shannessy Daniel J , Somers Elizabeth B , Palmer Leslie M , Thiel Robert P , Oberoi Pankaj , Heath Ryan , Marcucci Lisa 
Published: April 2013

Abstract

Background
Evaluate and compare the utility of serum folate receptor alpha (FRA) and megakaryocyte potentiating factor (MPF) determinations relative to serum CA125, mesothelin (MSLN) and HE4 for the diagnosis of epithelial ovarian cancer (EOC).

Methods
Electrochemiluminescent assays were developed for FRA, MSLN and MPF and used to assess the levels of these biomarkers in 258 serum samples from ovarian cancer patients. Commercial assays for CA125 and HE4 were run on a subset of 176 of these samples representing the serous histology. Data was analyzed by histotype, stage and grade of disease. A comparison of the levels of the FRA, MSLN and MPF biomarkers in serum, plasma and urine was also performed in a subset of 57 patients.

Results
Serum and plasma levels of FRA, MSLN and MPF were shown to be highly correlated between the two matrices. Correlations between all pairs of markers in 318 serum samples were calculated and demonstrated the highest correlation between HE4 and MPF, and the lowest between FRA and MPF. Serum levels of all markers showed a dependence on both stage and grade of disease. A multi-marker logistic regression model was developed resulting in an AUC=0.91 for diagnosis of serous ovarian cancer, a significant improvement over the AUC for any of the individual markers, including CA125 (AUC=0.84).

Conclusions
FRA has significant potential as a biomarker for ovarian cancer, both as a stand-alone marker and in combination with other known markers for EOC. The lack of correlation between the various markers analyzed in the present study suggests that a panel of markers can aid in the detection and/or monitoring of this disease.
Three are better than one: plasminogen receptors as cancer theranostic targets
Authors: Ceruti Patrizia , Principe Moitza , Capello Michela , Cappello Paola , Novelli Francesco 
Published: April 2013

AbstractActivation of plasminogen on the cell surface initiates a cascade of protease activity with important implications for several physiological and pathological events. In particular, components of the plasminogen system participate in tumor growth, invasion and metastasis. Plasminogen receptors are in fact expressed on the cell surface of most tumors, and their expression frequently correlates with cancer diagnosis, survival and prognosis. Notably, they can trigger multiple specific immune responses in cancer patients, highlighting their role as tumor-associated antigens. In this review, three of the most characterized plasminogen receptors involved in tumorigenesis, namely Annexin 2 (ANX2), Cytokeratin 8 (CK8) and alpha-Enolase (ENOA), are analyzed to ascertain an overall view of their role in the most common cancers. This analysis emphasizes the possibility of delineating new personalized therapeutic strategies to counteract tumor growth and metastasis by targeting plasminogen receptors, as well as their potential application as cancer predictors.
Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity
Authors: Sasagawa Yohei , Nikaido Itoshi , Hayashi Tetsutaro , Danno Hiroki , Uno Kenichiro D , Imai Takeshi , Ueda Hiroki R 
Published: April 2013

AbstractDevelopment of a highly reproducible and sensitive single-cell RNA sequencing (RNA-seq) method would facilitate the understanding of the biological roles and underlying mechanisms of non-genetic cellular heterogeneity. In this study, we report a novel single-cell RNA-seq method called Quartz-Seq that has a simpler protocol and higher reproducibility and sensitivity than existing methods. We show that single-cell Quartz-Seq can quantitatively detect various kinds of non-genetic cellular heterogeneity, and can detect different cell types and different cell-cycle phases of a single cell type. Moreover, this method can comprehensively reveal gene-expression heterogeneity between single cells of the same cell type in the same cell-cycle phase.
A Surgical Model in Male Obese Rats Uncovers Protective Effects of Bile Acids Post-Bariatric Surgery
Authors: Kohli Rohit , Setchell Kenneth DR , Kirby Michelle , Myronovych Andriy , Ryan Karen K. , Ibrahim Samar H. , Berger Jose , Smith Kathi , Toure Mouhamadoul , Woods Stephen C. , Seeley Randy J. 
Published: April 2013

AbstractBariatric surgery elevates serum bile acids. Conjugated bile acid administration, such as tauroursodeoxycholic acid (TUDCA), improves insulin sensitivity, whereas short-circuiting bile acid circulation through ileal interposition surgery in rats raises TUDCA levels. We hypothesized that bariatric surgery outcomes could be recapitulated by short circuiting the normal enterohepatic bile circulation. We established a model wherein male obese rats underwent either bile diversion (BD) or Sham (SH) surgery. The BD group had a catheter inserted into the common bile duct and its distal end anchored into the middistal jejunum for 4–5 weeks. Glucose tolerance, insulin and glucagon-like peptide-1 (GLP-1) response, hepatic steatosis, and endoplasmic reticulum (ER) stress were measured. Rats post-BD lost significantly more weight than the SH rats. BD rats gained less fat mass after surgery. BD rats had improved glucose tolerance, increased higher postprandial glucagon-like peptide-1 response and serum bile acids but less liver steatosis. Serum bile acid levels including TUDCA concentrations were higher in BD compared to SH pair-fed rats. Fecal bile acid levels were not different. Liver ER stress (C/EBP homologous protein mRNA and pJNK protein) was decreased in BD rats. Bile acid gavage (TUDCA/ursodeoxycholic acid [UDCA]) in diet-induced obese rats, elevated serum TUDCA and concomitantly reduced hepatic steatosis and ER stress (C/EBP homologous protein mRNA). These data demonstrate the ability of alterations in bile acids to recapitulate important metabolic improvements seen after bariatric surgery. Further, our work establishes a model for focused study of bile acids in the context of bariatric surgery that may lead to the identification of therapeutics for metabolic disease.
Histidines in Potential Substrate Recognition Sites Affect Thyroid Hormone Transport by Monocarboxylate Transporter 8 (MCT8)
Authors: Braun Doreen , Lelios Iva , Krause Gerd , Schweizer Ulrich 
Published: April 2013

Abstract
Mutations in monocarboxylate transporter 8 (MCT8; SLC16A2) cause the Allan-Herndon-Dudley syndrome, a severe X-linked psychomotor retardation syndrome. MCT8 belongs to the major facilitator superfamily of 12 transmembrane-spanning proteins and transports thyroid hormones across the blood-brain barrier and into neurons. How MCT8 distinguishes thyroid hormone substrates from structurally closely related compounds is not known. The goal of this study was to identify critical amino acids along the transport channel cavity, which participate in thyroid hormone recognition. The fact that T3 is bound between a His-Arg clamp in the crystal structure of the T3 receptor/T3 complex prompted us to investigate whether such a motif might potentially be relevant for T3 recognition in MCT8. We therefore replaced candidate histidines and arginines by site-directed mutagenesis and performed activity assays in MDCK-1 cells and Xenopus oocytes. Histidines were replaced by alanine, phenylalanine, and glutamine to probe for molecular properties like aromatic ring structure and H-bonding properties. It was found that some mutations in His192 and His415 significantly changed substrate transport kinetics. Arg301 at the intracellular end of the substrate channel is at an ideal distance to His415 to participate in a His-Arg clamp and mutation to alanine-abrogated hormone transport. Molecular modeling demonstrates a perfect fit of T3 poised into the substrate channel between His415 and Arg301 and observing the same geometry as in the T3 receptor.
The effect of hypoxia on facial shape variation and disease phenotypes in chicken embryos
Authors: Smith Francis , Hu Diane , Young Nathan M. , Lainoff Alexis J. , Jamniczky Heather A. , Maltepe Emin , Hallgrimsson Benedikt , Marcucio Ralph S. 
Published: April 2013

SummaryCraniofacial anomalies can arise from both genetic and environmental factors, including prenatal hypoxia. Recent clinical evidence correlates hypoxia to craniofacial malformations. However, the mechanisms by which hypoxia mediates these defects are not yet understood. We examined the cellular mechanisms underlying malformations induced by hypoxia using a chicken (Gallus gallus) embryo model. Eggs were incubated in either hypoxic (7, 9, 11, 13, 15, 17 or 19% O2) or normoxic (21% O2) conditions. Embryos were photographed for morphological analysis at days 3-6. For analysis of skeletal development, 13-day embryos were cleared and stained with alcian blue and alizarin red for cartilage and bone, respectively. Quantitative analysis of facial shape variation was performed on images of embryos via geometric morphometrics. Early-stage embryos (day 2) were analyzed for apoptosis via whole-mount and section TUNEL staining and immunostaining for cleaved caspase-3, whereas later-stage embryos (days 4-6) were sectioned in paraffin for analysis of cell proliferation (BrdU), apoptosis (TUNEL) and metabolic stress (phospho-AMPK). Results demonstrate that survival is reduced in a dose-dependent manner. Hypoxic embryos displayed a spectrum of craniofacial anomalies, from mild asymmetry and eye defects to more severe frontonasal and cephalic anomalies. Skull bone development was delayed in hypoxic embryos, with some skeletal defects observed. Morphometric analysis showed facial shape variation relative to centroid size and age in hypoxic groups. Hypoxia disrupted cell proliferation and, in early-stage embryos, caused apoptosis of neural crest progenitor cells. Hypoxic embryos also displayed an increased metabolic stress response. These results indicate that hypoxia during early embryonic craniofacial development might induce cellular oxidative stress, leading to apoptosis of the neural crest progenitor cells that are crucial to normal craniofacial morphogenesis.
Improved Detection Rate of Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia and Other Mature B-Cell Neoplasms With Use of CpG-Oligonucleotide DSP30 and Interleukin 2 Stimulation
Authors: Shi Min , Cipollini Matthew J. , Crowley-Bish Patricia A. , Higgins Anne W. , Yu Hongbo , Miron Patricia M. 
Published: April 2013

Abstract
Detection of cytogenetic abnormalities requires successful culture of the clonal population to obtain metaphase chromosomes for study, and as such, has been hampered by low mitotic indices of mature B cells in culture. Our study presents data on the improved abnormality detection rate with the use of a CpG-oligonucleotide/interleukin 2 (OL/IL-2) culture protocol for mature B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and non-CLL specimens. The increased detection rate of abnormalities, compared with unstimulated culture and traditional pokeweed mitogen culture, was statistically significant for both CLL and non-CLL neoplasms. For CLL specimens, our data also showed that for cytogenetically visible aberrations, OL/IL-2 was as, if not more, sensitive than detection with interphase fluorescence in situ hybridization (iFISH). Use of OL/IL-2 allowed a number of abnormalities to be detected, which were not covered by specific iFISH panels, especially balanced translocations. Therefore, OL/IL-2 stimulation improves diagnostic sensitivity and increases discovery rate of novel prognostic findings.
Nonmucinous Cystadenomas of the Pancreas With Pancreatobiliary Phenotype and Ovarian-Like Stroma
Authors: Albores-Saavedra Jorge , Manivel Carlos , Dorantes-Heredia Rita , Chablé-Montero Fredy , Godoy-Valdés César , Chan-Nuñez Carlos , Henson Donald E. 
Published: April 2013

Abstract
Among 31 benign cystic neoplasms of the pancreas diagnosed as mucinous cystadenomas, we identified 9 (29%) cases of nonmucinous cystadenomas with a pancreatobiliary phenotype and an ovarian-like stroma. Although both cystic tumors belong to the same family, they should be separated because their epithelial lining and cyst fluid are different. The lining cells of the nonmucinous cystadenomas consisted of a single layer of cuboidal cells, similar to the epithelial cells of the normal pancreatic ducts, and were not dysplastic (90%–100% of the lining cells). The cyst fluid was described as serous or clear. The remaining 22 classical mucinous cystadenomas, lined predominantly by mucinous and foveolar epithelium, revealed focal pancreatobiliary epithelium in 86% of the cases, and 6 pancreatic invasive mucinous cystadenocarcinomas failed to show pancreatobiliary differentiation. We believe that these nonmucinous cystadenomas of the pancreas represent a distinctive subset of cystic neoplasms of the pancreas that probably have no malignant potential.
Bone Marrow Findings in HIV-Positive Patients With Kaposi Sarcoma Herpesvirus–Associated Multicentric Castleman Disease
Authors: Venkataraman Girish , Uldrick Thomas S. , Aleman Karen , O’Mahony Deirdre , Karcher Donald S. , Steinberg Seth M. , Raffeld Mark A. , Marshall Vickie , Whitby Denise , Little Richard F. , Yarchoan Robert , Pittaluga Stefania , Maric Irina 
Published: April 2013

Abstract
Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus-8, is associated with 1 form of multicentric Castleman disease (MCD) and is the etiologic agent for most MCD in human immunodeficiency virus (HIV)–infected patients. Diagnosis is usually determined by lymph node biopsy. Bone marrow findings in KSHV-MCD are not well characterized. We conducted histomorphologic and immunohistochemical evaluation of bone marrow biopsy specimens in HIV-infected patients with KSHV-MCD, including evaluation for KSHV latency-associated nuclear antigen. Findings were correlated with clinical features and KSHV viral load. Reactive plasmacytosis was the predominant feature. Lymphoid aggregates were less common and not diagnostic of KSHV-MCD. Forty-eight percent of cases contained scattered KSHV-infected mononuclear cells. Although patients were generally cytopenic, bone marrow biopsy specimens were normocellular to hypercellular except in patients receiving hematotoxic therapy. Bone marrow biopsy specimens in KSHV-MCD patients recapitulate findings of interleukin-6 excess. In patients with HIV, unexplained cytopenias, and bone marrow plasmacytosis, evaluation for KSHV-MCD is warranted.
Papillary Thyroid Carcinoma With Heterotopic Ossification Is a Special Subtype With Extensive Progression
Authors: Takeda Masahiko , Mikami Tetuo , Numata Yoshiko , Okamoto Makito , Okayasu Isao 
Published: April 2013

Abstract
An immunohistochemical study was conducted of 108 papillary carcinoma cases, including 48 cases with intratumoral heterotopic ossification (IHO). In 48 cases, papillary carcinoma with IHO was accompanied by nodular fibrosis. Cases of papillary carcinoma with IHO or nodular fibrosis showed higher incidences of lymph node metastasis, multifocal lesions, and extrathyroidal invasion than those without IHO and nodular fibrosis. A higher number of stromal myofibroblasts was observed in papillary carcinoma with IHO or nodular fibrosis than in that without fibrosis. Expression of both basic fibroblast growth factor (bFGF) and bone morphogenetic protein (BMP)–2 was the highest in papillary carcinoma with IHO. Papillary carcinoma with IHO showed higher vascular invasion and higher numbers of capillaries expressing nestin, which is associated with high expression of vascular endothelial growth factor (VEGF). Papillary carcinoma with IHO is a unique subtype with extensive progression including frequent lymph node metastasis, multifocality, and invasive behavior. Papillary carcinoma with IHO was correlated with expression of bFGF, BMP-2, and VEGF in the carcinoma cells, leading to neovascularization.