Regulation of SPARC Gene Expression by the Activator Protein 1 Transcription Factor

Overexpression of the c-Jun proto-oncogene in MCF7 breast cancer cells results in a variety of phenotypic changes related to malignant progression including a shift to estrogen independent growth, increased cell motility and invasion. Concurrent with these phenotypic changes are alterations to cellular gene expression patterns. One gene that becomes highly upregulated is SPARC (secreted protein acidic and rich in cysteine). Increased SPARC expression is associated with malignant progression in a variety of different cancers, although little is known regarding the mechanisms of SPARC gene regulation. Therefore, the objectives of this study were: (1) to determine the mechanisms by which c-Jun regulates SPARC gene expression, and (2) to determine the contribution of SPARC to c-Jun induced phenotype in a MCF7 breast cancer model system. In order to determine the role of SPARC in c-Jun mediated oncogenic progression, we over-expressed SPARC in MCF7 cells and blocked its expression in the c-Jun/MCF7 cell line. We found that antisense mediated suppression of SPARC dramatically inhibits both cell motility and invasion in this c-Jun/MCF7 model. In contrast, stable overexpression of SPARC in the parental MCF7 cell line was not sufficient to stimulate cell motility or invasion suggesting that SPARC cooperates with other c-Jun target genes to establish a pro-invasive phentoytpe. In order to determine the mechanism(s) of c-Jun induced SPARC gene activation, we started by analyzing DNA binding and transactivation using the human SPARC promoter. The activity of the full-length SPARC promoter (-1409/+28) was 15-30 fold higher in c-Jun over-expressing cells compared to vector control cells. Promoter deletion analysis revealed that a region between -120 and -70 conferred c-Jun responsiveness. This region does not contain an AP-1 binding site, but does contain a GC rich element which is recognized in vitro and in vivo by Sp1. Importantly, chromatin immunoprecipitation analysis demonstrated that c-Jun is physically associated with the SPARC proximal promoter region during gene activation. Further analysis of the SPARC promoter sequence, including the c-Jun responsive region, revealed the presence of multiple CpG sequences. Methylation of cytosine residues in a CpG context has been shown to inhibit gene expression. Therefore, we examined the contribution of DNA methylation to SPARC gene regulation. Analysis of MCF7 cells, in which SPARC expression is undetectable, revealed methylation of the SPARC promoter at both distal and proximal sites

A Proof of the (n,k,t)(n,k,t) Conjectures

An $(n,k,t)$-graph is a graph on $n$ vertices in which every set of $k$ vertices contain a clique on $t$ vertices. Tur\'an's Theorem (complemented) states that the unique minimum $(n,k,2)$-graph is a disjoint union of cliques. We prove that minimum $(n,k,t)$-graphs are always disjoint unions of cliques for any $t$ (despite nonuniqueness of extremal examples), thereby generalizing Tur\'an's Theorem and confirming two conjectures of Hoffman et al

Packing Hamilton Cycles Online

It is known that w.h.p. the hitting time $\tau_{2\sigma}$ for the random graph process to have minimum degree $2\sigma$ coincides with the hitting time for $\sigma$ edge disjoint Hamilton cycles. In this paper we prove an online version of this property. We show that, for a fixed integer $\sigma\geq 2$, if random edges of $K_n$ are presented one by one then w.h.p. it is possible to color the edges online with $\sigma$ colors so that at time $\tau_{2\sigma}$, each color class is Hamiltonian.Comment: Minor change

Transversals and colorings of simplicial spheres

Motivated from the surrounding property of a point set in $\mathbb{R}^d$ introduced by Holmsen, Pach and Tverberg, we consider the transversal number and chromatic number of a simplicial sphere. As an attempt to give a lower bound for the maximum transversal ratio of simplicial $d$-spheres, we provide two infinite constructions. The first construction gives infintely many $(d+1)$-dimensional simplicial polytopes with the transversal ratio exactly $\frac{2}{d+2}$ for every $d\geq 2$. In the case of $d=2$, this meets the previously well-known upper bound $1/2$ tightly. The second gives infinitely many simplicial 3-spheres with the transversal ratio greater than $1/2$. This was unexpected from what was previously known about the surrounding property. Moreover, we show that, for $d\geq 3$, the facet hypergraph $\mathcal{F}(\mathsf{K})$ of a $d$-dimensional simplicial sphere $\mathsf{K}$ has the chromatic number $\chi(\mathcal{F}(\mathsf{K})) \in O(n^{\frac{\lceil d/2\rceil-1}{d}})$, where $n$ is the number of vertices of $\mathsf{K}$. This slightly improves the upper bound previously obtained by Heise, Panagiotou, Pikhurko, and Taraz.Comment: 22 pages, 2 figure

They’re Just Here for Ball: Proposing a Multi-Level Analysis on the Impact of Collegiate Athletics at Historically White Institutions on Black Male Collegiate Athlete Holistic Identity

As the overrepresentation of Black male collegiate athletes (BMCA) increases in National Collegiate Athletic Association (NCAA) Division I (DI) revenue-generating sports, coaches and athletic staff continue to overemphasize sport performance, while graduation rates for BMCA remain persistently lower than their peers and research continues to document transition out of sport concerns for this population. Proposing a multi-level approach, we explore the collegiate athletic factors that influence the holistic identity development of DI revenue generating BMCA at historically White institutions (HWIs) leading to difficulty transitioning out of sport. At the macro-level, the NCAA and its policies on eligibility are analyzed. At the meso-level, HWIs collegiate athletic departments and the impact of organizational practices are examined in regards to their impact on BMCA’s identity development, overall experiences and transition out of sport. Lastly, at the micro-level, we explore research focused on BMCAs’ experiences, expectations, and issues at HWIs. By identifying salient factors influencing BMCAs’ identity development and experiences, collegiate athletic stakeholders can use this information to create more effective programming and improve campus cultures that foster BMCAs’ holistic development on a systematized basis creating an environment where BMCAs are prepared to move into the next stage of life after sport ends

Cooperative conditions for the existence of rainbow matchings

Let $k>1$, and let $\mathcal{F}$ be a family of $2n+k-3$ non-empty sets of edges in a bipartite graph. If the union of every $k$ members of $\mathcal{F}$ contains a matching of size $n$, then there exists an $\mathcal{F}$-rainbow matching of size $n$. Upon replacing $2n+k-3$ by $2n+k-2$, the result can be proved both topologically and by a relatively simple combinatorial argument. The main effort is in gaining the last $1$, which makes the result sharp

Badges and rainbow matchings

Drisko proved that $2n-1$ matchings of size $n$ in a bipartite graph have a rainbow matching of size $n$. For general graphs it is conjectured that $2n$ matchings suffice for this purpose (and that $2n-1$ matchings suffice when $n$ is even). The known graphs showing sharpness of this conjecture for $n$ even are called badges. We improve the previously best known bound from $3n-2$ to $3n-3$, using a new line of proof that involves analysis of the appearance of badges. We also prove a "cooperative" generalization: for $t>0$ and $n \geq 3$, any $3n-4+t$ sets of edges, the union of every $t$ of which contains a matching of size $n$, have a rainbow matching of size $n$.Comment: Accepted for publication in Discrete Mathematics. 19 pages, 2 figure