Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG.

At the Crossroads of Science and Society: Careers in Science Policy.

Science policy offers a challenging and rewarding career path for scientists interested in the social, ethical, and legal implications of their field. This topic encompasses a broad spectrum of activities all in support of advancing the scientific enterprise. Science policy spans various sectors, and policy careers are found in many different organizations, including the federal government, scientific societies, and professional organizations.

Regulation of Telomere Length Requires a Conserved N-Terminal Domain of Rif2 in Saccharomyces cerevisiae.

The regulation of telomere length equilibrium is essential for cell growth and survival since critically short telomeres signal DNA damage and cell cycle arrest. While the broad principles of length regulation are well established, the molecular mechanism of how these steps occur is not fully understood. We mutagenized the RIF2 gene in Saccharomyces cerevisiae to understand how this protein blocks excess telomere elongation.

ChIP-Seq to Analyze the Binding of Replication Proteins to Chromatin.

Chromatin immunoprecipitation (ChIP) is a widely used method to study interactions between proteins and discrete chromosomal loci in vivo. ChIP was originally developed for in vivo analysis of protein associations with candidate DNA sequences known or suspected to bind the protein of interest. The advent of DNA microarrays enabled the unbiased, genome-scale identification of all DNA sequences enriched by ChIP, providing a genomic map of a protein's chromatin binding.

Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae.

The replication of eukaryotic chromosomes is organized temporally and spatially within the nucleus through epigenetic regulation of replication origin function. The characteristic initiation timing of specific origins is thought to reflect their chromatin environment or sub-nuclear positioning, however the mechanism remains obscure. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing.

Non-human leukocyte antigen antibodies reactive with endothelial cells could be involved in early loss of renal allografts.

Preformed donor-specific human leukocyte antigen (HLA) antibodies have been associated with allograft dysfunction and failure. However, recipients of HLA-identical kidneys can develop acute humoral rejection, implicating putative pathogenic antibodies that are directed against non-HLA antigens. We investigated the presence of endothelial cell-reactive antibodies in 11 patients who experienced early loss of their transplanted kidneys owing to humoral rejection and 1 loss from renal venal thrombosis.

Prognostic evaluation of pT1 and pT2 colorectal cancer.

Authors analyze the characteristics of the stage pT1 and pT2 colorectal cancer and carry their experience on 68 patients operated. The survival of the colon carcinoma has been of 91% to 2 years and 88% to 5 years, while for the rectum has been of 90% to 2 years and 84% to 5 years. The attitude of the Authors has been to perform radical surgery.

Strategies for analyzing highly enriched IP-chip datasets.

Background: Chromatin immunoprecipitation on tiling arrays (ChIP-chip) has been employed to examine features such as protein binding and histone modifications on a genome-wide scale in a variety of cell types. Array data from the latter studies typically have a high proportion of enriched probes whose signals vary considerably (due to heterogeneity in the cell population), and this makes their normalization and downstream analysis difficult.

Results: Here we present strategies for analyzing such experiments, focusing our discussion on the analysis of Bromodeoxyruridine (BrdU) immunoprecipitation on tiling array (BrdU-IP-chip) datasets.

To promote and protect: coordinating DNA replication and transcription for genome stability.

Duplication of the eukaryotic genome occurs in the context of a chromatin template that is actively engaged in regulating gene expression and other protein-DNA interactions. Chromatin structures influence the dynamics of DNA replication by regulating the selection of replication origin sites as well as the initiation timing of the selected origins. Recent studies indicate that active origins frequently localize with active or potentially active gene promoters, suggesting coordination of these fundamental DNA transactions.

ChIP-chip to analyze the binding of replication proteins to chromatin using oligonucleotide DNA microarrays.

Chromatin immunoprecipitation (ChIP) is a widely used method to study the interactions between proteins and discrete chromosomal loci in vivo. Originally, ChIP was developed for analysis of protein associations with DNA sequences known or suspected to bind the protein of interest. The advent of DNA microarrays has enabled the identification of all DNA sequences enriched by ChIP, providing a genomic view of protein binding.

Genome-wide replication profiles indicate an expansive role for Rpd3L in regulating replication initiation timing or efficiency, and reveal genomic loci of Rpd3 function in Saccharomyces cerevisiae.

In higher eukaryotes, heritable gene silencing is associated with histone deacetylation and late replication timing. In Saccharomyces cerevisiae, the histone deacetylase Rpd3 regulates gene expression and also modulates replication timing; however, these mechanisms have been suggested to be independent, and no global association has been found between replication timing and gene expression levels. Using 5-Bromo-2'-deoxyuridine (BrdU) incorporation to generate genome-wide replication profiles, we identified >100 late-firing replication origins that are regulated by Rpd3L, which is specifically targeted to promoters to silence transcription.

Rad53 regulates replication fork restart after DNA damage in Saccharomyces cerevisiae.

Replication fork stalling at a DNA lesion generates a damage signal that activates the Rad53 kinase, which plays a vital role in survival by stabilizing stalled replication forks. However, evidence that Rad53 directly modulates the activity of replication forks has been lacking, and the nature of fork stabilization has remained unclear. Recently, cells lacking the Psy2-Pph3 phosphatase were shown to be defective in dephosphorylation of Rad53 as well as replication fork restart after DNA damage, suggesting a mechanistic link between Rad53 deactivation and fork restart.

New vectors for simplified construction of BrdU-Incorporating strains of Saccharomyces cerevisiae.

The thymidine analogue BrdU is a powerful tool for analysing nucleotide incorporation in studies of DNA replication or repair. S. cerevisiae lacks the thymidine salvage pathway that enables efficient cellular uptake and incorporation of thymidine analogues into DNA.

Mrc1 is required for normal progression of replication forks throughout chromatin in S. cerevisiae.

Mrc1 associates with replication forks, where it transmits replication stress signals and is required for normal replisome pausing in response to nucleotide depletion. Mrc1 also plays a poorly understood role in DNA replication, which appears distinct from its role in checkpoint signaling. Here, we demonstrate that Mrc1 functions constitutively to promote normal replication fork progression.

The Rpd3-Sin3 histone deacetylase regulates replication timing and enables intra-S origin control in Saccharomyces cerevisiae.

The replication of eukaryotic genomes follows a temporally staged program, in which late origin firing often occurs within domains of altered chromatin structure(s) and silenced genes. Histone deacetylation functions in gene silencing in some late-replicating regions, prompting an investigation of the role of histone deacetylation in replication timing control in Saccharomyces cerevisiae. Deletion of the histone deacetylase Rpd3 or its interacting partner Sin3 caused early activation of late origins at internal chromosomal loci but did not alter the initiation timing of early origins or a late-firing, telomere-proximal origin.