Distinct t(7;9)(q34;q32) breakpoints in healthy individuals and individuals with T-ALL

After V(D)J-mediated translocations, signal joints are retained on one of the derivative chromosomes. We report here that such signal joints are highly reactive and constitute unstable genomic elements with potential oncogenic properties.     

B7-H6/NKp30 interaction: a mechanism of alerting NK cells against tumors

Natural killer (NK) cells are lymphocytes of the innate immune system that sense target cells through a panel of activating and inhibitory receptors. Together with NKG2D, the natural cytotoxicity receptors (NCRs) are major activating receptors involved in tumor cell detection. Although numerous NKG2D ligands have been identified, characterization of the molecules interacting with the NCRs is still incomplete. The identification of B7-H6 as a counter structure of the NCR NKp30 shed light on the molecular basis of NK cell immunosurveillance. We review here the current knowledge on NKp30 and B7-H6, and we discuss their potential role in anti-tumor immunity.     

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes

Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcinomas included TP53 (11/15 tumors), PIK3CA (3/15) and ARID1A (3/15). Cell adhesion was the most enriched biological pathway among the frequently mutated genes. A prevalence screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers (6/110) and FAT4 genomic deletions in 4% (3/83) of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occurred in 47% of the gastric cancers. We detected ARID1A mutations in 8% of tumors (9/110), which were associated with concurrent PIK3CA mutations and microsatellite instability. In functional assays, we observed both FAT4 and ARID1A to exert tumor-suppressor activity. Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers.     

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size.     

Changes in plant community composition lag behind climate warming in lowland forests

Climate change is driving latitudinal and altitudinal shifts in species distribution worldwide, leading to novel species assemblages. Lags between these biotic responses and contemporary climate changes have been reported for plants and animals. Theoretically, the magnitude of these lags should be greatest in lowland areas, where the velocity of climate change is expected to be much greater than that in highland areas. We compared temperature trends to temperatures reconstructed from plant assemblages (observed in 76,634 surveys) over a 44-year period in France (1965-2008). Here we report that forest plant communities had responded to 0.54 °C of the effective increase of 1.07 °C in highland areas (500-2,600 m above sea level), while they had responded to only 0.02 °C of the 1.11 °C warming trend in lowland areas. There was a larger temperature lag (by 3.1 times) between the climate and plant community composition in lowland forests than in highland forests. The explanation of such disparity lies in the following properties of lowland, as compared to highland, forests: the higher proportion of species with greater ability for local persistence as the climate warms, the reduced opportunity for short-distance escapes, and the greater habitat fragmentation. Although mountains are currently considered to be among the ecosystems most threatened by climate change (owing to mountaintop extinction), the current inertia of plant communities in lowland forests should also be noted, as it could lead to lowland biotic attrition.     

Ancestry of modern Europeans: contributions of ancient DNA

Understanding the peopling history of Europe is crucial to comprehend the origins of modern populations. Of course, the analysis of current genetic data offers several explanations about human migration patterns which occurred on this continent, but it fails to explain precisely the impact of each demographic event. In this context, direct access to the DNA of ancient specimens allows the overcoming of recent demographic phenomena, which probably highly modified the constitution of the current European gene pool. In recent years, several DNA studies have been successfully conducted from ancient human remains thanks to the improvement of molecular techniques. They have brought new fundamental information on the peopling of Europe and allowed us to refine our understanding of European prehistory. In this review, we will detail all the ancient DNA studies performed to date on ancient European DNA from the Middle Paleolithic to the beginning of the protohistoric period.     

Insensitivity of the ferritin iron core to heat treatment.

To test whether the reactivity of ferritin iron is affected by the heat treatment used in ferritin isolation, we prepared ferritin from the same horse spleen with or without heating. Both samples exhibited similar reactivity upon reduction or chelation of iron.     

Observation of high-energy neutrinos using Cerenkov detectors embedded deep in Antarctic ice

Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water or ice. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations.     

Effect of protein kinase C activation and depletion on insulin stimulation of glycogen synthesis in cultured hepatoma cells

Insulin stimulation of glycogen synthesis was nearly abolished in hepatoma cells shortly treated with 4 beta-phorbol 12 beta-myristate, 13 alpha-acetate (protein kinase C activation) but remained unmodified in cells chronically treated with the phorbol ester (protein kinase C depletion). Thus, although exogenous activation of protein kinase C results in an inhibition of insulin action, protein kinase C depletion has no influence on this process. The results suggest that, in hepatoma cells, no endogenous activation of protein kinase C may occur in response to the signal triggered by insulin.