Chromatin Assembly Factor-1, a Marker of Clinical Value to Distinguish Quiescent from Proliferating Cells

Histone synthesis and chromatin assembly are mainly associated with DNA replication and are thus intimately involved in cell cycle regulation. The expression of key components involved in these events in human cells was studied in relation to cell-proliferative status. Among several chromatin assembly factors, chromatin assembly factor (CAF)-1 stood out as the most discriminating marker of the proliferative state. We show, using both immunofluorescence and Western blot analysis, that the expression of both CAF-1 large subunits, p150 and p60, is massively down-regulated during quiescence in several cell lines. Upon exit from the quiescent state, the CAF-1 subunits are re-expressed early, before DNA replication. The amounts of either total or chromatin-associated pools of CAF-1 proteins correlate directly with cell proliferation. Regulation of CAF-1 expression is partly controlled at the RNA level, as shown by quantitative reverse transcription-PCR and Northern blot experiments. Biological material from benign and malignant human breast tumors analyzed by immunocytochemistry and immunohistochemistry exhibits a strong positive correlation between CAF-1 p60 expression and the following proliferation markers: S-phase fraction (r = 0.84, P < 0.0001); Ki-67 (r = 0.94, P < 0.0001); and proliferating cell nuclear antigen (r = 0.95, P = 0.0001). We discuss the advantages of using CAF-1 to assess cell proliferation. High CAF-1 p60 levels are also shown to be associated with various prognostic factors. Our data highlight the precise association of CAF-1 expression with the proliferative state and validate the use of this factor as a useful proliferation marker and prognostic indicator in malignant and benign breast lesions

Clinical significance and prognostic value of chromatin assembly factor-1 overexpression in human solid tumours

Polo S E, Theocharis S E, Grandin L, Gambotti L, Antoni G, Savignoni A, Asselain B, Patsouris E & Almouzni G-(2010) Histopathology-57, 716-724-Clinical significance and prognostic value of chromatin assembly factor-1 overexpression in human solid tumoursAims:- Chromatin assembly factor-1 (CAF-1), whose function is critical for maintaining chromatin stability during DNA replication and repair, has been identified as a proliferation marker in breast cancer. The aim was to investigate CAF-1 as a proliferation marker in a wide variety of solid tumours, and to assess its potential value in predicting clinical outcome.Methods and results:- Using immunocytochemistry on paraffin-embedded tissue sections, the CAF-1 labelling index was compared with known proliferation markers Ki-67 and minichromosome maintenance (MCM), and its association with clinicopathological data and patients' outcome analysed. CAF-1 expression showed a strong positive correlation with Ki-67, used routinely to detect proliferating cells, while it generally displayed weaker correlations with MCM markers, known to label cells with replicative potential. CAF-1 expression was associated significantly with histological grade in breast, cervical, endometrial and renal cell carcinomas, and with disease stage in endometrial and renal carcinomas. Furthermore, high expression of CAF-1 was an independent predictor of adverse clinical outcome in renal, endometrial and cervical carcinomas.Conclusions:- CAF-1 is a proliferation marker in various malignant tumours with prognostic value in renal, endometrial and cervical carcinomas, which supports the value of CAF-1 as a clinical marker of cancer progression. © 2010 Blackwell Publishing Limited

An alternative incoming correction for cosmic-ray neutron sensing observations using local muon measurement.

Measuring the variability of incoming neutrons locally would be usefull for the cosmic-ray neutron sensing (CRNS) method. As the measurement of high energy neutrons is not so easy, alternative particles can be considered for such purpose. Among them, muons are particles created from the same cascade of primary cosmic-ray fluxes that generate neutrons at the ground. In addition, they can be easily detected by small and relatively inexpensive detectors. For these reasons they could provide a suitable local alternative to incoming corrections based on remote neutron monitor data. The reported measurements demonstrated that muon detection system can detect incoming cosmic-ray variations locally. Furthermore the precision of this measurement technique is considered adequate for many CRNS applications

Muscle stem cells undergo extensive clonal drift during tissue growth via meox1-mediated induction of G2 cell-cycle arrest

Organ growth requires a careful balance between stem cell self-renewal and lineage commitment to ensure proper tissue expansion. The cellular and molecular mechanisms that mediate this balance are unresolved in most organs, including skeletal muscle. Here we identify a long-lived stem cell pool that mediates growth of the zebrafish myotome. This population exhibits extensive clonal drift, shifting from random deployment of stem cells during development to reliance on a small number of dominant clones to fuel the vast majority of muscle growth. This clonal drift requires Meox1, a homeobox protein that directly inhibits the cell-cycle checkpoint gene ccnb1. Meox1 initiates G2 cell-cycle arrest within muscle stem cells, and disrupting this G2 arrest causes premature lineage commitment and the resulting defects in muscle growth. These findings reveal that distinct regulatory mechanisms orchestrate stem cell dynamics during organ growth, beyond the G0/G1 cell-cycle inhibition traditionally associated with maintaining tissue-resident stem cells.Phong Dang Nguyen, David Baruch Gurevich, Carmen Sonntag, Lucy Hersey, Sara Alaei, Hieu Tri Nim ... al et

Combustion at the late Early Pleistocene site of Cueva Negra del Estrecho del Río Quípar (Murcia, Spain)

Control of fire was a hallmark of developing human cognition and an essential technology for the colonisation of cooler latitudes. In Europe, the earliest evidence comes from recent work at the site of Cueva Negra del Estrecho del Río Quípar in south-eastern Spain. Charred and calcined bone and thermally altered chert were recovered from a deep, 0.8-million-year-old sedimentary deposit. A combination of analyses indicated that these had been heated to 400-600°C, compatible with burning. Inspection of the sediment and hydroxyapatite also suggests combustion and degradation of the bone. The results provide new insight into Early Palaeolithic use of fire and its significance for human evolution.Small mammal analyses were funded by Spanish project CGL2010-19825Peer Reviewe