Osteopontin (OPN) plays an important functional role in both physiologic and pathologic states. OPN is implicated in the progression of fibrosis, cancer, and metastatic disease in several organ systems. The epithelial-mesenchymal transition (EMT), first described in embryology, is increasingly being recognized as a significant contributor to fibrotic phenotypes and tumor progression. Several well-established transcription factors regulate EMT and are conserved across tissue types and organ systems, including TWIST, zinc finger E-box-binding homeobox (ZEB), and SNAIL-family members. Recent literature points to an important relationship between OPN and EMT, implicating OPN as a key regulatory component of EMT programs. In this review, OPN’s interplay with traditional EMT activators, both directly and indirectly, will be discussed. Also, OPN’s ability to restructure the tissue and tumor microenvironment to indirectly modify EMT will be reviewed. Together, these diverse pathways demonstrate that OPN is able to modulate EMT and provide new targets for directing therapeutics.

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Craniosynostosis repair is safe; however, the risk of complications increases with age at intervention. Presence of a syndromic congenital deformity at any age carries the greatest increased risk of perioperative complications. This suggests that optimal timing of intervention is within the first year of life, especially in those cases with additional factors increasing perioperative risk. These data support the importance of counseling patients of the increased risk associated with delaying craniosynostosis repair.

Objective We hypothesized that perioperative hospital resources could overcome the “weekend effect” (WE) in patients undergoing emergent/urgent surgeries. Summary Background Data The WE is the observation that surgeon-independent patient outcomes are worse on the weekend compared with weekdays. The WE is often explained by differences in staffing and resources resulting in variation in care between the week and weekend. Methods Emergent/urgent surgeries were identified using the Healthcare Cost and Utilization Project State Inpatient Database (Florida) from 2007 to 2011 and linked to the American Hospital Association (AHA) Annual Survey Database to determine hospital level characteristics. Extended median length of stay (LOS) on the weekend compared with the weekdays (after controlling for hospital, year, and procedure type) was selected as a surrogate for WE. Results Included were 126,666 patients at 166 hospitals. A total of 17 hospitals overcame the WE during the study period. Logistic regression, controlling for patient characteristics, identified full adoption of electronic medical records (OR 4.74), home health program (OR 2.37), pain management program [odds ratio (OR) 1.48)], increased registered nurse-to-bed ratio (OR 1.44), and inpatient physical rehabilitation (OR 1.03) as resources that were predictors for overcoming the WE. The prevalence of these factors in hospitals exhibiting the WE for all 5 years of the study period were compared with those hospitals that overcame the WE (P <0.001). Conclusions Specific hospital resources can overcome the WE seen in urgent general surgery procedures. Improved hospital perioperative infrastructure represents an important target for overcoming disparities in surgical care.

Mcm1 is an essential protein required for the efficient replication of minichromosomes and the transcriptional regulation of early cell cycle genes in Saccharomyces cerevisiae. In this study, we report that Mcm1 is an abundant protein that associates globally with chromatin in a punctate pattern. We show that Mcm1 is localized at replication origins and plays an important role in the initiation of DNA synthesis at a chromosomal replication origin in vivo. Using purified Mcm1 protein, we show that Mcm1 binds cooperatively to multiple sites at autonomously replicating sequences. These results suggest that, in addition to its role as a transcription factor for the expression of replication genes, Mcm1 may influence the local structure of replication origins by direct binding.

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Replication of DNA must be inherently accurate and precisely regulated. It is therefore not surprising that the mechanism for the initiation of DNA replication is both complex and conserved. Initiation of DNA synthesis involves the assembly of a multicomponent complex at designated sites known as replication origins. While the protein components of the prereplication complex (pre-RC) used in this initiation process are conserved in all eukaryotes (5), there is little in common between the nucleotide sequences of replication origins within each eukaryote and between different eukaryotes (29).In Saccharomyces cerevisiae, replication origins (ORI) consist of defined sequences of about 200 bp that can replicate autonomously independently of their native chromosomal environment. These autonomously replicating sequences (ARSs) are modular in structure. They contain a ubiquitous 11-bp (5Ј-WTTTAYRTTTW) ARS consensus sequence (ACS) (11,22,63) where the origin recognition complex (ORC) binds (4). In certain ARSs, a 10-of-11 match of the ACS is sufficient for ORC recognition (64). The ACS is essential but not sufficient for autonomous replication. cis elements on the 5Ј (C domain) or the 3Ј (B domain) flanking sequences of the ACS are also required (12). Elements in the B domain of one particular ARS, ARS1, have been characterized in great detail. Three elements, known as B1, B2, and B3, have been identified (44). B1 is protected by the ORC (55), whereas B3 is protected by Abf1 (41) or Mcm1 (17) in in vitro footprinting analyses. Initiation of DNA synthesis at ARS1 has been mapped to a region between the B1 and B2 elements (6). Two of the three B elements in combination with the ACS are sufficient to promote autonomous replication. Although B elements of different ARSs are not conserved in nucleotide sequence, they are interchangeable between certain ARSs (31, 54, 61). The differences in size and modular composition of replication origins suggest that there are many ways to assemble a functional replication origin from a finite set of modules (60)(61)(62)65). The plasticity in the organization of replication origins is further illustrated by the dispensability of the B elements altogether in the presence of the C domain in several telomeric ARSs (13). However, because the C domain is generally larger, elements in the C domain have not been characterized.The redundant functions of the B and C domains in promoting replication initiation suggest that although the process of pre-RC assembly may be conserved, there are many ways to create an environment conducive to this assembly process. The concept of alternative pathways for creating an environment for pre-RC assembly is especially appealing in higher eukaryotes, where there appears not to be a unifying mechanism for site selection for pre-RC assembly. In Xenopus oocytes, replication initiation occurs at random sequences (38). In mammalian cells, initiation occurs at multiple sites within replication zones that are defined by their chromosomal contexts rather than nucleotide...

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