DIGITAL THREATS ON CAMPUS: EXAMINING THE DUTY OF COLLEGES TO PROTECT THEIR SOCIAL NETWORKING STUDENTS

The revolution of social networking is changing society faster than possibly all other revolutions combined. As it is with any societal change, society needs to properly and promptly address the harms that flow from such change. This Article discusses the duty of colleges in light of the harms stemming from social networking—what some may consider to be today’s most influential and consuming revolution. While courts largely expelled the in loco parentis doctrine because of its inconsistency with the needs of modern education, perhaps, in light of this next evolution in modern life and the associated threats for college students, a return to the in loco parentis doctrine may be needed to address such threats. Stretching existing concepts of liability to address the harms of social networking may not be appropriate. The presence of new and constantly evolving threats from social networking may demand the resurgence of a broad special duty between colleges and students. Colleges need to act, and students need to be protected. The new and developing harms to college students posed by social networking expose students to dangers unknown fifty years ago when courts limited a college’s duty to its students. Modern society, which now extends to a virtual world, must decide who should and who is in the best position to provide the protection that students need and what protection should be provided. As courts decide how the law should respond to the social networking revolution, the likely source of reform to address the threats posed by social networking may be federal and state legislators. In light of the amount of federal and state funding to colleges, such legislators could swiftly act to protect social networking college students. Until that happens, courts, colleges, parents and students alike will continue to struggle to address and to protect students from the harms of social networking

Reduced BMP4 abundance in Gata2 hypomorphic mutant mice result in uropathies resembling human CAKUT

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71406/1/j.1365-2443.2007.01158.x.pd

Spry1 Is Expressed in Hemangioblasts and Negatively Regulates Primitive Hematopoiesis and Endothelial Cell Function

Development of the hematopoietic and endothelial lineages derives from a common mesodermal precursor, the Flk1(+) hemangioblast. However, the signaling pathways that regulate the development of hematopoietic and endothelial cells from this common progenitor cell remains incompletely understood. Using mouse models with a conditional Spry1 transgene, and a Spry1 knockout mouse, we investigated the role of Spry1 in the development of the endothelial and hematopoietic lineages during development.Quantitative RT-PCR analysis demonstrates that Spry1, Spry2, and Spry4 are expressed in Flk1(+) hemangioblasts in vivo, and decline significantly in c-Kit(+) and CD41(+) hematopoietic progenitors, while expression is maintained in developing endothelial cells. Tie2-Cre-mediated over-expression of Spry1 results in embryonic lethality. At E9.5 Spry1;Tie2-Cre embryos show near normal endothelial cell development and vessel patterning but have reduced hematopoiesis. FACS analysis shows a reduction of primitive hematopoietic progenitors and erythroblastic cells in Spry1;Tie2-Cre embryos compared to controls. Colony forming assays confirm the hematopoietic defects in Spry1;Tie2-Cre transgenic embryos. Immunostaining shows a significant reduction of CD41 or CD71 and dpERK co-stained cells in Spry1;Tie2-Cre embryos compared to controls, whereas the number of VEC(+) and dpERK co-stained cells is comparable. Compared to controls, Spry1;Tie2-Cre embryos also show a decrease in proliferation and an increase in apoptosis. Furthermore, loss of Spry1 results in an increase of CD41(+) and CD71(+) cells at E9.5 compared with controls.These data indicate that primitive hematopoietic cells derive from Tie2-expressing hemangioblasts and that Spry1 over expression inhibits primitive hematopoietic progenitor and erythroblastic cell development and expansion while having no obvious effect on endothelial cell development

Hematopoietic (stem) cell development-how divergent are the roads taken?

textabstractThe development of the hematopoietic system during early embryonic stages occurs in spatially and temporally distinct waves. Hematopoietic stem cells (HSC), the most potent and self-renewing cells of this system, are produced in the final ‘definitive’ wave of hematopoietic cell generation. In contrast to HSCs in the adult, which differentiate via intermediate progenitor populations to produce functional blood cells, the generation of hematopoietic cells in the embryo prior to HSC generation occurs in the early waves by producing blood cells without intermediate progenitors (such as the ‘primitive’ hematopoietic cells). The lineage relationship between the early hematopoietic cells and the cells giving rise to HSCs, the genetic networks controlling their emergence, and the precise temporal determination of HSC fate remain topics of intense research and debate. This Review article discusses the current knowledge on the step-wise embryonic establishment of the adult hematopoietic system, examines the roles of pivotal intrinsic regulators in this process, and raises questions concerning the temporal onset of HSC fate determination

Modeling Reveals Bistability and Low-Pass Filtering in the Network Module Determining Blood Stem Cell Fate

Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad—a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models

A molecular roadmap of the AGM region reveals BMP ER as a novel regulator of HSC maturation

In the developing embryo, hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region, but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA sequencing over these spatiotemporal transitions in the AGM region and supportive OP9 cell line. Screening several proteins through an ex vivo reaggregate culture system, we identify BMP ER as a novel positive regulator of HSC development. We demonstrate that BMP ER is associated with BMP signaling inhibition, but is transcriptionally induced by BMP4, suggesting that BMP ER contributes to the precise control of BMP activity within the AGM region, enabling the maturation of HSCs within a BMP-negative environment. These findings and the availability of our transcriptional data through an accessible interface should provide insight into the maintenance and potential derivation of HSCs in culture.Peer reviewe

Identification of Novel Targets of CSL-Dependent Notch Signaling in Hematopoiesis

Somatic activating mutations in the Notch1 receptor result in the overexpression of activated Notch1, which can be tumorigenic. The goal of this study is to understand the molecular mechanisms underlying the phenotypic changes caused by the overexpression of ligand independent Notch 1 by using a tetracycline inducible promoter in an in vitro embryonic stem (ES) cells/OP9 stromal cells coculture system, recapitulating normal hematopoiesis. First, an in silico analysis of the promoters of Notch regulated genes (previously determined by microarray analysis) revealed that the motifs recognized by regulatory proteins known to mediate hematopoiesis were overrepresented. Notch 1 does not bind DNA but instead binds the CSL transcription factor to regulate gene expression. The in silico analysis also showed that there were putative CSL binding sites observed in the promoters of 28 out of 148 genes. A custom ChIP-chip array was used to assess the occupancy of CSL in the promoter regions of the Notch1 regulated genes in vivo and showed that 61 genes were bound by activated Notch responsive CSL. Then, comprehensive mapping of the CSL binding sites genome-wide using ChIP-seq analysis revealed that over 10,000 genes were bound within 10 kb of the TSS (transcription start site). The majority of the targets discovered by ChIP-seq belong to pathways that have been shown by others to crosstalk with Notch signaling. Finally, 83 miRNAs were significantly differentially expressed by greater than 1.5-fold during the course of in vitro hematopoiesis. Thirty one miRNA were up-regulated and fifty two were down-regulated. Overexpression of Notch1 altered this pattern of expression of microRNA: six miRNAs were up-regulated and four were down regulated as a result of activated Notch1 overexpression during the course of hematopoiesis. Time course analysis of hematopoietic development revealed that cells with Notch 1 overexpression mimic miRNA expression of cells in a less mature stage, which is consistent with our previous biological characterization

DIGITAL THREATS ON CAMPUS: EXAMINING THE DUTY OF COLLEGES TO PROTECT THEIR SOCIAL NETWORKING STUDENTS

The revolution of social networking is changing society faster than possibly all other revolutions combined. As it is with any societal change, society needs to properly and promptly address the harms that flow from such change. This Article discusses the duty of colleges in light of the harms stemming from social networking—what some may consider to be today’s most influential and consuming revolution. While courts largely expelled the in loco parentis doctrine because of its inconsistency with the needs of modern education, perhaps, in light of this next evolution in modern life and the associated threats for college students, a return to the in loco parentis doctrine may be needed to address such threats. Stretching existing concepts of liability to address the harms of social networking may not be appropriate. The presence of new and constantly evolving threats from social networking may demand the resurgence of a broad special duty between colleges and students. Colleges need to act, and students need to be protected. The new and developing harms to college students posed by social networking expose students to dangers unknown fifty years ago when courts limited a college’s duty to its students. Modern society, which now extends to a virtual world, must decide who should and who is in the best position to provide the protection that students need and what protection should be provided. As courts decide how the law should respond to the social networking revolution, the likely source of reform to address the threats posed by social networking may be federal and state legislators. In light of the amount of federal and state funding to colleges, such legislators could swiftly act to protect social networking college students. Until that happens, courts, colleges, parents and students alike will continue to struggle to address and to protect students from the harms of social networking