A view on the role of epigenetics in the biology of malaria parasites

Cells and unicellular organisms are similar to their progenitors because information is transmitted from one generation to the next. The information is mainly transmitted in the primary sequence of the genome (genetic information), but there are heritable traits that are transmitted by other mechanisms. Epigenetics studies these alternative modes of inheritance. According to classic definitions, epigenetics refers to heritable differences between cells or organisms that occur without changes in DNA sequence, and do not depend on different external conditions

Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation independent manner

Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs play specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP ribose) polymerase hyperactivation and cell death, and reduced tumor growth and cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. These data predict a novel and totally unexpected biological role for the nucleoside transporter protein hCNT1 that appears to be independent of its role as mediator of nucleoside uptake by cells, thereby suggesting a transceptor function. Cell Death & Disease Anastasis Stephanou Receiving Editor Cell Death & Disease 19th Apr 2013 Dr Perez-Torras Av/ Diagonal 643. Edif. Prevosti, Pl -1 Barcelona 08028 Spain RE: Manuscript CDDIS-13-0136R, 'CDDIS-13-0136R' Dear Dr Perez-Torras, It is a pleasure to inform you that your manuscript has been evaluated at the editorial level and has now been officially accepted for publication in Cell Death & Disease, pending you meet the following editorial requirements: 1) the list of the abbreviations is missing please include Could you send us the revised text as word file via e-mail and we will proceed and transfer the paper onto our typesetters. Please download, print, sign, and return the Licence to Publish Form using the link below. This must be returned via FAX to ++ 39 06 7259 6977 before your manuscript can be published

Implementing Thermometry on Silicon Surfaces Functionalized by Lanthanide-Doped Self-Assembled Polymer Monolayers

The thermal gradients generated at submicrometer scale by the millions of transistors contained in integrated circuits are becoming the key limiting factor for device integration in micro- and nanoelectronics. Noncontact thermometric techniques with high-spatial resolution are, thus, essential for noninvasive off-chip characterization and heat management on Si surfaces. Here, the first ratiometric luminescent molecular thermometer implemented in a self-assembled polymer monolayer functionalized Si surface is reported. The functionalization of Si surfaces with luminescent thermometers constitutes a proof-of-concept that foretells a wide range of applications in Si-based micro- and nanostructures. The thermometric functionalization of the Si surface with Tb3+ and Eu3+ complexes leads to a thermal sensitivity up to 1.43% K-1, a cycle-recycle reliability of 98.6%, and a temperature uncertainty of less than 0.3 K. The functionalized surface presents reversible bistability that can be used as an optically active molecular demultiplexer

Isolation and in Vitro Culture of Rare Cancer Stem Cells from Patient-Derived Xenografts of Pancreatic Ductal Adenocarcinoma

Described is the construction of a large array of releasable microstructures (micropallets) along with screening and isolation protocols for sorting rare, approximately 1 in 10,000, cancer stem cells (CSCs) from a heterogeneous cell population. A 10.1 × 7.1 cm array of micropallets (50 × 50 × 75 μm structures and 25 μm micropallet gap) was fabricated on a large glass substrate, providing an array of approximately 1.3 million releasable microstructures. Image analysis algorithms were developed to permit array screening for identification of fluorescently labeled cells in less than 15 minutes using an epifluorescent wide-field microscope with a computer controlled translational stage. Device operation was tested by culturing HeLa cells transfected with green fluorescent protein (GFP) admixed with wild-type HeLa cells at ratios of 1:10(4) to 1:10(6) on the array followed by screening to identify flourescent cells. Micropallets containing cells of interest were then selectively released by a focused laser pulse and collected on a numbered poly(dimethylsiloxane (PDMS) substrate with high viability. A direct comparison of this technology with fluorescence-activated cell sorting (FACS) demonstrated that micropallet arrays offered enhanced post sorting purity (100%), yield (100%) and viability (94 – 100%) for rare cell isolation. As a demonstration of the technology’s value, pancreatic tumor cells from Panc-1 cell lines and patient-derived xenografts were screened for the presence of CD24, CD44 and CD326; surface markers of pancreatic CSCs. Following cell isolation and culture, 63 ± 23% of the isolated Panc-1 cells and 35% of sorted human xenograft cells formed tumor spheroids retaining high expression levels of CD24, CD44 and CD326. The ability to isolate rare cells from relatively small sample sizes will facilitate our understanding of cell biology and the development of new therapeutic strategies