Breast cancer stem cells with tumor- versus metastasis-initiating capacities are modulated by TGFBR1 inhibition

Cancer stem cells (CSCs) are defined by their ability to regenerate a tumor upon transplantation. However, it is not yet clear whether tumors contain a single CSC population or different subsets of cells with mixed capacities for initiating primary and secondary tumors. Using two different identification strategies, we studied the overlap between metastatic stem cells and tumor-initiating cells (TICs) in the MMTV-PyMT model. Our results show that in the MMTV-PyMT model, Lin−CD90−ALDHhigh cells retained a high tumor-initiating potential (TIP) in orthotopic transplants, in contrast to Lin−CD24+CD90+, which retained higher metastatic capacity. Interestingly, suppression of TGFβ signaling increased TIC numbers. We here describe the existence of distinct populations of CSCs with differing capacities to initiate tumors in the primary or the secondary site. Inhibiting TGFβ signaling shifts the balance toward the former, which may have unanticipated implications for the therapeutic use of TGFβ/TGFBR1 inhibitors

Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate

<p>Abstract</p> <p>Background</p> <p>The human Sex Hormone Binding Globulin (SHBG) gene, located at 17p13.1, comprises, at least, two different transcription units regulated by two different promoters. The first transcription unit begins with the exon 1 sequence and is responsible for the production of plasma SHBG by the hepatocytes, while the second begins with an alternative exon 1 sequence, which replaces the exon 1 present in liver transcripts. Alternative exon 1 transcription and translation has only been demonstrated in the testis of transgenic mice containing an 11-kb human SHBG transgene and in the human testis. Our goal has been to further characterize the 5' end of the SHBG gene and analyze the presence of the SHBG alternative transcripts in human prostate tissue and derived cell lines.</p> <p>Results</p> <p>Using a combination of <it>in silico </it>and <it>in vitro </it>studies, we have demonstrated that the SHBG gene, along with exon 1 and alternative exon 1 (renamed here exon 1A), contains four additional alternative first exons: the novel exons 1B, 1C, and 1E, and a previously identified exon 1N, which has been further characterized and renamed as exon 1D. We have shown that these four alternative first exons are all spliced to the same 3' splice site of SHBG exon 2, and that exon 1A and the novel exon 1B can be spliced to exon 1. We have also demonstrated the presence of SHBG transcripts beginning with exons 1B, 1C and 1D in prostate tissues and cell lines, as well as in several non-prostatic cell lines. Finally, the alignment of the SHBG mammalian sequences revealed that, while exons 1C, 1D and 1E are very well conserved phylogenetically through non-primate mammal species, exon 1B probably aroused in apes due to a single nucleotide change that generated a new 5' splice site in exon 1B.</p> <p>Conclusion</p> <p>The identification of multiple transcription start sites (TSS) upstream of the annotated first exon of human SHBG, and the detection of the alternative transcripts in human prostate, concur with the prediction of the ENCODE (ENCyclopedia of DNA Elements) project, and suggest that the regulation of SHBG is much more complex than previously reported.</p

Gravity and magnetic anomalies in the allochthonous Órdenes Complex (Variscan belt, northwest Spain): Assessing its internal structure and thickness

The Órdenes Complex is the largest Variscan allochthonous structure of NW Iberia, and preserves the suture of a long-standing Paleozoic ocean, probably the Rheic. Gravity and magnetic data, the latter specifically acquired on land for this study, show that the complex occupies the core of an open synform with a maximum depth of 9–10 km, which contrasts with the flat geometry of the lower crust and Moho discontinuity beneath. The maximum depth reached by the ophiolitic rocks marking the suture is around 7 km. The allochthonous units formed by basic and ultrabasic rocks are lens-shaped in section, and occur not only at the periphery of the complex, but form wide ribbons trending NE-SW to N-S. The Bouguer anomaly related with the longest of them, the Fornás Unit, previously used to support an autochthonous interpretation of the complexes, is modeled as a rootless, massive amphibolite body with a maximum thickness of 6 km located at the downthrown block of a large normal fault cutting across previous thrust faults and extensional detachments. The main magnetic anomalies are associated with ultrabasic rocks cropping out in the NW and SE, but a weak, wide anomaly in the central part of the complex is related with one or more thin layers of amphibolite partly mineralized with massive sulphides. The weakly arcuate geometry of this anomaly and of the Bouguer anomaly caused by the Fornás Unit may reflect the NE flank of the Central Iberian arc, an orocline whose core is occupied by the allochthonous complexes.FEDER, Ministerio de Ciencia e Innovación (Ramón y Cajal

The Efficacy of Short-Term Supplemental Nutrition Education on Nutrition Knowledge and Dietary Behaviors of Urban Middle School Children

Background: Children and adolescents are not meeting the dietary guidelines and overweight and obesity related diseases are on the rise among youth in the United States. However, research is inconsistent with regard to the most effective method of educating urban youth. Purpose: To determine the effect of a supplemental nutrition education on the knowledge and behaviors of urban school students. Methods: Six nutrition lessons were provided to students attending the Boys and Girls Club of Metro Atlanta (BGCMA) in Atlanta, GA. A pre- and posttest was administered to assess differences in students’ nutrition knowledge and behaviors. Chi-square analysis compared the number of correct answers for the entire intervention population and after stratification by gender and number of classes missed. The Wilcoxon signed rank test compared the median number of correct answers in pre- vs. posttest responses for all participants and by the number of classes missed. Results: 15 students enrolled in the study. 2 students did not complete the study. A significant but negative change in knowledge was found in 1 of 15 nutrition questions. A significant negative change in the median number of total answers correct on the pre- vs. posttest was also observed (p=0.049). Approximately 60% of the participants reported that they were more likely to make positive, nutrition-related behavior changes after the intervention. Conclusion: We found a negative association between the nutrition education intervention and knowledge gain. This study suggests that nutrition education alone does not have a significant effect on nutrition knowledge of urban youth

On becoming a Collaborative Professional: From Paradigm Shifting to Transformative Learning through Critical Reflection and Dialogue

In Part II, I provide a brief overview of CL and its underlying assumptions. A description of CL training and learning objectives follows in Parts III and IV. In Parts V and VI, I review the paradigm shifting and transformative learning literature. I provide an overview of the study in Part VII, followed by my analysis of the data in Parts VIII and IX. In Part X, I conclude with a discussion of critical reflection and dialogue in a CL training context

Obsea: a decadal balance for a cabled observatory deployment

The study of the effects of climate change on the marine environment requires the existence of sufficiently long time series of key parameters. The study of these series allows both to characterize the range of variability in each particular region and to detect trends or changes that could be attributed to anthropogenic causes. For this reason, networks of permanent cabled observation systems are being deployed in the ocean. This paper presents a balance of a decade of activity at the OBSEA cabled observatory, as an example of ocean monitoring success and drawbacks. It is not the objective of this article to analyze the scientific and technical aspects already presented by the authors in different publications (Table 4). We will evaluate the overall experience by retracing the different steps of infrastructure deployment and maintenance, focusing on routines for in situ control, damages experienced, breakdowns and administrative constraints by local administrations. We will conclude by providing a set of guidelines to improve cabled observatories scientific outreach, societal projection, and economic efficiency. As a result of this work, a 10-years dataset has been published in Pangaea that is available for the community.Peer ReviewedPostprint (published version

Myths, Miscues, and Misconceptions: No-Aid Separationism and the Establishment Clause

In neutrality theory the recipients of vouchers, grants, and purchase-of-service contracts are eligible to participate as providers in government social service programs without regard to their religious character. Indeed, religious beliefs and practices are prohibited bases for screening out those who want to be welfare program providers. Notable examples of congressional social service legislation conforming to the rule of religious neutrality are the ‘charitable choice‘ feature imbedded in the Welfare Reform Act of 1996 and the Community Services Block Grant Act of 1998, as well as the provision allowing issuance of child care vouchers to indigent parents in the Child Care and Development Block Grant Program of 1990. Likewise, federal grants-in-aid programs, for example the Church Arson Prevention Act of 1996, the Telecommunication Act of 1996, and the President\u27s Values-Based Violence Prevention Initiative to reduce youth violence and gang activity, adhere to the principle of religious neutrality