bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis
Authors: Neklason Deborah W. , Kerber Richard A. , Nilson David B. , Anton-Culver Hoda , Schwartz Ann G. , Griffin Constance A. , Lowery Jan T. , Schildkraut Joellen M. , Evans James P. , Tomlinson Gail E. , Strong Louise C. , Miller Alexander R. , Stopfer Jill E. , Finkelstein Dianne M. , Nadkarni Prakash M. , Kasten Carol H. , Mineau Geraldine P. , Burt Randall W. 
Published: October 2008

Abstract
Present investigations suggest that ∼30% of colorectal cancer cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with colorectal cancer. Individuals from families with at least two siblings diagnosed with colorectal adenocarcinoma or high-grade dysplasia were enrolled. Known familial colorectal cancer syndromes were excluded. A genome-wide scan on 151 DNA samples from 70 kindreds was completed using deCODE 1100 short tandem repeat marker set at an average 4-cM density. Fine mapping on a total of 184 DNAs from 83 kindreds was done in regions suggesting linkage. Linkage analysis was accomplished with Merlin analysis package. Nonparametric linkage analysis revealed three genetic regions with logarithm of the odds (LOD) scores ≥2.0: Ch. 3q29, LOD 2.61 (P = 0.0003); Ch. 4q31.3, LOD 2.13 (P = 0.0009); and Ch. 7q31.31, LOD 3.08 (P = 0.00008). Affected siblings with increased sharing at the 7q31 locus have a 3.8-year (± 3.5) earlier age of colorectal cancer onset although this is not statistically significant (P = 0.11). No significant linkage was found near genes causing known syndromes or regions previously reported (8q24, 9q22, and 11q23). The chromosome 3q21–q24 region reported to be linked in colorectal cancer relative pairs is supported by our study, albeit a minor peak (LOD 0.9; P = 0.02). No known familial cancer genes reside in the 7q31 locus, and thus the identified region may contain a novel susceptibility gene responsible for common familial colorectal cancer. [Cancer Res 2008;68(21):8993–7]
The Chemokine Receptor CX3CR1 Is Involved in the Neural Tropism and Malignant Behavior of Pancreatic Ductal Adenocarcinoma
Authors: Marchesi Federica , Piemonti Lorenzo , Fedele Giuseppe , Destro Annarita , Roncalli Massimo , Albarello Luca , Doglioni Claudio , Anselmo Achille , Doni Andrea , Bianchi Paolo , Laghi Luigi , Malesci Alberto , Cervo Luigi , Malosio MariaLuisa , Reni Michele , Zerbi Alessandro , Di Carlo Valerio , Mantovani Alberto , Allavena Paola 
Published: October 2008

Abstract
Tumor perineural dissemination is a hallmark of human pancreatic ductal adenocarcinoma (PDAC) and represents a major source of local tumor recurrence after surgery. In this study, we provide in vitro and in vivo evidence that the chemokine receptor CX3CR1 may be involved in the neurotropism of PDAC cells to local peripheral nerves. Neoplastic cells from PDAC cell lines and surgical specimens express the chemokine receptor CX3CR1, absent in normal pancreatic ducts. Its unique ligand, the transmembrane chemokine CX3CL1, is expressed by neurons and nerve fibers. CX3CR1 + PDAC cell lines migrated in response to human recombinant CX3CL1 and specifically adhered to CX3CL1-expressing cells of neural origin via mechanisms involving activation of G proteins, β1 integrins, and focal adhesion kinase. In vivo experiments with transplanted PDAC showed that only CX3CR1-transfected tumor cells infiltrated the local peripheral nerves. Immunohistochemistry of CX3CR1 in PDAC specimens revealed that 90% of the samples were positive with a heterogeneous pattern of expression. High receptor score was significantly associated with more prominent tumor perineural infiltration evaluated histologically (P = 0.026). Regression analyses (univariate and multivariate) showed that high CX3CR1 expression and perineural invasion were strongly associated with local and earlier tumor recurrence (P = 0.007). Collectively, this study shows that the CX3CR1 receptor may be involved in PDAC tumor neurotropism and is a relevant and independent risk factor to predict an early local tumor relapse in resected patients. Thus, the CX3CR1-CX3CL1 axis could represent a valuable therapeutic target to prevent tumor perineural dissemination in pancreatic cancer. [Cancer Res 2008;68(21):9060–9]
The Taccalonolides: Microtubule Stabilizers That Circumvent Clinically Relevant Taxane Resistance Mechanisms
Authors: Risinger April L. , Jackson Evelyn M. , Polin Lisa A. , Helms Gregory L. , LeBoeuf Desiree A. , Joe Patrick A. , Hopper-Borge Elizabeth , Ludueña Richard F. , Kruh Gary D. , Mooberry Susan L. 
Published: October 2008

AbstractThe taccalonolides are a class of structurally and mechanistically distinct microtubule-stabilizing agents isolated from Tacca chantrieri. A crucial feature of the taxane family of microtubule stabilizers is their susceptibility to cellular resistance mechanisms including overexpression of P-glycoprotein (Pgp), multidrug resistance protein 7 (MRP7), and the βIII isotype of tubulin. The ability of four taccalonolides, A, E, B, and N, to circumvent these multidrug resistance mechanisms was studied. Taccalonolides A, E, B, and N were effective in vitro against cell lines that overexpress Pgp and MRP7. In addition, taccalonolides A and E were highly active in vivo against a doxorubicin- and paclitaxel-resistant Pgp-expressing tumor, Mam17/ADR. An isogenic HeLa-derived cell line that expresses the βIII isotype of tubulin was generated to evaluate the effect of βIII-tubulin on drug sensitivity. When compared with parental HeLa cells, the βIII-tubulin–overexpressing cell line was less sensitive to paclitaxel, docetaxel, epothilone B, and vinblastine. In striking contrast, the βIII-tubulin–overexpressing cell line showed greater sensitivity to all four taccalonolides. These data cumulatively suggest that the taccalonolides have advantages over the taxanes in their ability to circumvent multiple drug resistance mechanisms. The ability of the taccalonolides to overcome clinically relevant mechanisms of drug resistance in vitro and in vivo confirms that the taccalonolides represent a valuable addition to the family of microtubule-stabilizing compounds with clinical potential. [Cancer Res 2008;68(21):8881–8]
Insulin-like Growth Factor 2 Is Required for Progression to Advanced Medulloblastoma in patched1 Heterozygous Mice
Authors: Corcoran Ryan B. , Bachar Raveh Tal , Barakat Monique T. , Lee Eunice Y. , Scott Matthew P. 
Published: October 2008

Abstract
Medulloblastoma (MB) can arise in the cerebellum due to genetic activation of the Sonic Hedgehog (Shh) signaling pathway. During normal cerebellum development, Shh spurs the proliferation of granule neuron precursors (GNP), the precursor cells of MB. Mutations in the Shh receptor gene patched1 (ptc1+/−) lead to increased MB incidence in humans and mice. MB tumorigenesis in mice heterozygous for ptc1+/− shows distinct steps of progression. Most ptc1+/− mice form clusters of preneoplastic cells on the surface of the mature cerebellum that actively transcribe Shh target genes. In ∼15% of mice, these preneoplastic cells will become fast-growing, lethal tumors. It was previously shown that the loss of function of insulin-like growth factor 2 (igf2) suppresses MB formation in ptc1+/− mice. We found that igf2 is not expressed in preneoplastic lesions but is induced as these lesions progress to more advanced MB tumors. Igf2 is not required for formation of preneoplastic lesions but is necessary for progression to advanced tumors. Exogenous Igf2 protein promoted proliferation of MB precursor cells (GNP) and a MB cell line, PZp53MED. Blocking igf2 signaling inhibited growth of PZp53MED cells, implicating igf2 as a potential clinical target. [Cancer Res 2008;68(21):8788–95]
Neuropilin-1 Upholds Dedifferentiation and Propagation Phenotypes of Renal Cell Carcinoma Cells by Activating Akt and Sonic Hedgehog Axes
Authors: Cao Ying , Wang Ling , Nandy Debashis , Zhang Ying , Basu Ananda , Radisky Derek , Mukhopadhyay Debabrata 
Published: October 2008

Abstract
Expression of neuropilin-1 (NRP-1) has been shown in many cancer cells, but its molecular effect on tumorigenesis is largely unknown. In this report, we show that in aggressive types of renal cell carcinoma (RCC), NRP-1 is expressed at a high level. We show that after knockdown of NRP-1 by short hairpin RNA, RCC cells express significantly lower levels of MDM-2 and p63 proteins but higher levels of p53, and exhibit reduced migration and invasion. When implanted in mice, RCC cells with a reduced NRP-1 level have a statistically significant smaller tumor-forming ability than control cells. Also, NRP-1 knockdown RCC cells exhibit a more differentiated phenotype, as evidenced by the expression of epithelial-specific and kidney-specific cadherins, and the inhibition of sonic hedgehog expression participated in this effect. Inhibition of sonic hedgehog expression can be reversed by ΔNp63α overexpression. Our study reveals that NRP-1 helps maintain an undifferentiated phenotype in cancer cells. [Cancer Res 2008;68(21):8667–72]
Genetic uniformity of Rana pyrenaica Serra-Cobo, 1993 across its distribution range: a preliminary study with mtDNA sequences
Authors: Carranza Salvador , Arribas Oscar 
Published: October 2008

AbstractThe genetic variability of the Pyrenean frog Rana pyrenaica was assessed using DNA sequences of the cytochrome b, COI and 12S rRNA mitochondrial genes. The results show that, despite inhabiting an area of mountainous terrain with high mountain peaks and deep isolated valleys, R. pyrenaica is genetically very homogeneous. The extremely low level of genetic variability observed, even in the fast evolving cytochrome b and COI genes, suggests that R. pyrenaica may have colonized most of its present range very rapidly after the last Würm glaciation from a refuge area in the Prepyrenees. This is the first attempt to establish the level of genetic variability of this endangered Pyrenean endemism and, as a result, it has major implications for its conservation.
Hybrids of Darevskia valentini, D. armeniaca and D. unisexualis from a sympatric population in Armenia
Authors: Arakelyan Marine , Danielyan Felix , Stepanyan Ilona 
Published: October 2008

AbstractA unique hybridization zone of rock lizard species of genus Darevskia, with diploid (2n), triploid (3n) and tetraploid (4n) individuals, occurs in the mountain steppe of central Armenia. Our long-term monitoring has showed an increasing birth rate of triploid hybrids in this mixed population. Among these hybrids, the frequency of captured males with fully developed reproductive systems and presumably fertile females also increased significantly. Consequently, intensive microevolution has taken place in this sympatric population. The morphological, ecological, cytological, histological, and parasitological characteristics of the hybrid Darevskia are presented here and compared with parental species.
Density, population structure and activity pattern of Hydromedusa tectifera (Testudines-Chelidae) in a mountain stream of Córdoba province, Argentina
Authors: Bonino Marcelo , Leynaud Gerardo , Lescano Julián 
Published: October 2008

AbstractThe Snake-necked Turtle (Hydromedusa tectifera) is mainly distributed in the northeastern provinces of Argentina; however, some isolated populations occur in central Córdoba. This is the first report on some ecological aspects of one of these populations. Population density and annual activity pattern were characterized at Toro Muerto Stream in the Sierras region of the Córdoba province, central Argentina. Turtles were hand-captured and sex and carapace length were determined for each individual. Mark-recapture data were used to estimate population density, variation in monthly capture rates, and sex ratios throughout the sampling months. A total of 96 turtles were captured and density was estimated at 218 individuals ha−1. Individuals were captured all year round, but showed activity peaks in spring and summer. This seasonal pattern has also been observed in other freshwater turtles. During the mating season a higher number of males were captured, which suggested a seasonal difference in activity patterns between sexes.
Social Adversities in First-Time and Repeat Prisoners
Authors: Kjelsberg Ellen , Friestad Christine 
Published: October 2008

Aims: To explore possible systematic differences between prison inmates serving their first sentence and inmates having experienced previous incarcerations. It is hoped that a better knowledge of these issues will make us better equipped to meet the rehabilitation needs of our prisoners and decrease their risk of reoffending and reincarceration. Methods: In this cross-sectional study a randomly selected and nationally representative sample of 260 Norwegian prisoners, 100 serving their first sentence and 160 recidivists, was interviewed with special focus on childhood circumstances, education, work experience, and present social and economic situation. In addition their criminal records were collected from the National Crime Registry. Results: In males multivariate analyses identified a number of variables independently and significantly associated with being a repeat offender. The odds for reincarceration increased significantly if the person fulfilled any one of the following criteria: having experienced the incarceration of a family member during childhood ( OR = 3.6); having experienced childcare interventions during childhood ( OR = 3.2); current drug abuse ( OR = 2.6); current housing problems ( OR = 2.3). In females only one strong correlation emerged: if the person had current drug problems the odds for being a recidivist increased substantially ( OR = 10.9). Conclusions: While criminal reoffending and reincarceration seemed to be primarily associated with drug abuse in females, the childhood problems of male repeat offenders, compared with males serving their first sentence, indicate that these individuals' current multiple social and economic disadvantages were complex in origin and of long standing. Interventions aimed at preventing reoffending must take into account the gender differences demonstrated. Aiming at primary prevention, the negative effects associated with parental incarceration are crucial: how can one prevent the perpetuation of these problems from one generation to the next?
Rituximab levels in cerebrospinal fluid of patients with neurological autoimmune disorders
Authors: Petereit HF , Rubbert-Roth A 
Published: October 2008

Background Rituximab, a monoclonal antibody against the B-cell-specific surface protein CD20, is being evaluated for treatment of multiple sclerosis and neuromyelitis optica. Both diseases are restricted to the brain and cerebrospinal fluid (CSF). Whereas the ability of rituximab to deplete B cells in peripheral blood and tissue is well known, little information is available about the ability of rituximab to penetrate the barriers separating brain and CSF from the serum compartment. Objective To measure rituximab levels in serum and CSF of rituximab-treated patients and correlate them with CSF and response markers. Methods Fourteen paired serum/CSF samples of patients with autoimmune nervous system disorder were analyzed for up to 43 weeks after rituximab application. Results Rituximab remains detectable within the CSF after i.v. application for up to 24 weeks. Furthermore, levels of rituximab in CSF correlate significantly with the integrity of the blood CSF barrier.
Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems
Authors: Levi Boaz P. , Yilmaz Ömer H. , Duester Gregg , Morrison Sean J. 
Published: October 2008

Abstract
High levels of aldehyde dehydrogenase (ALDH) activity have been proposed to be a common feature of stem cells. Adult hematopoietic, neural, and cancer stem cells have all been reported to have high ALDH activity, detected using Aldefluor, a fluorogenic substrate for ALDH. This activity has been attributed to Aldh1a1, an enzyme that is expressed at high levels in stem cells and that has been suggested to regulate stem cell function. Nonetheless, Aldh1a1 function in stem cells has never been tested genetically. We observed that Aldh1a1 was preferentially expressed in mouse hematopoietic stem cells (HSCs) and expression increased with age. Hematopoietic cells from Aldh1a1-deficient mice exhibited increased sensitivity to cyclophosphamide in a non–cell-autonomous manner, consistent with its role in cyclophosphamide metabolism in the liver. However, Aldh1a1 deficiency did not affect hematopoiesis, HSC function, or the capacity to reconstitute irradiated recipients in young or old adult mice. Aldh1a1 deficiency also did not affect Aldefluor staining of hematopoietic cells. Finally, Aldh1a1 deficiency did not affect the function of stem cells from the adult central or peripheral nervous systems. Aldh1a1 is not a critical regulator of adult stem cell function or Aldefluor staining in mice.
Neutral network sizes of biological RNA molecules can be computed and are not atypically small
Authors: Jörg Thomas , Martin Olivier C , Wagner Andreas 
Published: October 2008

Abstract

Background
Neutral networks or sets consist of all genotypes with a given phenotype. The size and structure of these sets has a strong influence on a biological system's robustness to mutations, and on its evolvability, the ability to produce phenotypic variation; in the few studied cases of molecular phenotypes, the larger this set, the greater both robustness and evolvability of phenotypes. Unfortunately, any one neutral set contains generally only a tiny fraction of genotype space. Thus, current methods cannot measure neutral set sizes accurately, except in the smallest genotype spaces.

Results
Here we introduce a generalized Monte Carlo approach that can measure neutral set sizes in larger spaces. We apply our method to the genotype-to-phenotype mapping of RNA molecules, and show that it can reliably measure neutral set sizes for molecules up to 100 bases. We also study neutral set sizes of RNA structures in a publicly available database of functional, noncoding RNAs up to a length of 50 bases. We find that these neutral sets are larger than the neutral sets in 99.99% of random phenotypes. Software to estimate neutral network sizes is available at http://www.bioc.uzh.ch/wagner/publications-software.html.

Conclusion
The biological RNA structures we examined are more abundant than random structures. This indicates that their robustness and their ability to produce new phenotypic variants may also be high.
Social and cultural aspects of 'malaria' and its control in central Côte d'Ivoire
Authors: Essé Clémence , Utzinger Jürg , Tschannen Andres B , Raso Giovanna , Pfeiffer Constanze , Granado Stefanie , Koudou Benjamin G , N'Goran Eliézer K , Cissé Guéladio , Girardin Olivier , Tanner Marcel , Obrist Brigit 
Published: October 2008

Abstract

Background
A sound local understanding of preventive measures and health-seeking behaviour is important for the effective control of malaria. The purpose of this study was to assess the knowledge, attitudes, practices and beliefs of 'malaria' and its control in two rural communities of central Côte d'Ivoire, and to examine associations between 'malaria' and the households' socioeconomic status.

Methods
A cross-sectional household survey was carried out, using a combination of qualitative and quantitative methods. People's socioeconomic status was estimated, employing a household asset-based approach.

Results
Malaria was identified as djèkouadjo, the local folk name of the disease. Although people were aware of malaria-related symptoms and their association with mosquitoes, folk perceptions were common. In terms of treatment, a wide array of modern and traditional remedies was employed, often in combination. Individuals with a sound knowledge of the causes and symptoms of malaria continued to use traditional treatments and only a few people sleep under bed nets, whereas folk beliefs did not necessarily translate into refusal of modern treatments. Perceived causes of malaria were linked to the household's socioeconomic status with wealthier individuals reporting mosquitoes more frequently than poorer households. Bed nets were more frequently used in wealthier social strata, whereas other protective measures – perceived to be cheaper – were more prominent among the poorest.

Conclusion
Equitable access to resources at household, community and health system levels are essential in order to enable community members to prevent and treat malaria. There is a need for community-based approaches that match health care services with poor people's needs and resources.
Eating habits and obesity among Lebanese university students
Authors: Yahia Najat , Achkar Alice , Abdallah Abbass , Rizk Sandra 
Published: October 2008

Abstract

Background
In the past year Lebanon has been experiencing a nutritional transition in food choices from the typical Mediterranean diet to the fast food pattern. As a consequence, the dietary habits of young adults have been affected; thus, overweight and obesity are increasingly being observed among the young. The purpose of this study is to assess the prevalence of overweight and obesity on a sample of students from the Lebanese American University (in Beirut) and to examine their eating habits.

Methods
A cross-sectional survey of 220 students (43.6% male and 56.4% female), aged 20 ± 1.9 years, were chosen randomly from the Lebanese American University (LAU) campus during the fall 2006 semester. Students were asked to fill out a self-reported questionnaire that included questions on their eating, drinking and smoking habits. Also, their weight, height, percentage body fat and body mass index were measured. Body mass index (BMI) was used to assess students' weight status. Statistical analyses were performed using the Statistical Package for Social Sciences software (version 13.0) to determine overweight and obesity among students and to categorize eating habits.

Results
This study showed that the majority of the students (64.7%) were of normal weight (49% male students compared to 76.8% female students). The prevalence of overweight and obesity was more common among male students compared to females (37.5% and 12.5% vs. 13.6% and 3.2%, respectively). In contrast, 6.4% female students were underweight as compared to 1% males. Eating habits of the students showed that the majority (61.4%) reported taking meals regularly. Female students showed healthier eating habits compared to male students in terms of daily breakfast intake and meal frequency. 53.3% of female students reported eating breakfast daily or three to four times per week compared to 52.1% of male students. There was a significant gender difference in the frequency of meal intake (P = 0.001). Intake of colored vegetables and fruits was common among students. A total of 30.5% reported daily intake of colored vegetables with no gender differences (31.5% females vs. 29.2% males). Alcohol intake and smoking were not common among students.

Conclusion
In spite of the overall low prevalence of overweight and obesity in the studied sample, results indicate that university students would possibly benefit from a nutrition and health promotion program to reduce the tendency of overweight and obesity, especially among male students, and to improve students' eating habits.