Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited

BACKGROUND: Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia) and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL), considers the spatial proximity of loci in interphase nuclei (static "contact first" model). The second model is based on the dynamics of double strand break ends during repair processes (dynamic "breakage first" model). Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4) and a less frequent partner gene (ENL), should elucidate the MLL translocation mechanism. METHODS: Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. RESULTS: In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value < 0.0001). According to the static "contact first" model of the translocation mechanism, a minimal distance between loci would indicate a greater probability of the occurrence of t(11;19)(q23;p13.3) compared to t(4;11)(q21;q23). However this is in contradiction to the epidemiology of 11q23 translocation. CONCLUSION: The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static "contact first" model of translocation. The recently proposed dynamic "breakage first" model offers an attractive alternative explanation

Evaluating the suitability of coupled biophysical models for fishery management

The potential role of coupled biophysical models in enhancing the conservation, management, and recovery of fish stocks is assessed, with emphasis on anchovy, cod, herring, and sprat in European waters. The assessment indicates that coupled biophysical models are currently capable of simulating transport patterns, along with temperature and prey fields within marine ecosystems; they therefore provide insight into the variability of early-life-stage dynamics and connectivity within stocks. Moreover, the influence of environmental variability on potential recruitment success may be discerned from model hindcasts. Based on case studies, biophysical modelling results are shown to be capable of shedding light on whether stock management frameworks need re-evaluation. Hence, key modelling products were identified that will contribute to the development of viable stock recovery plans and management strategies. The study also suggests that approaches combining observation, process knowledge, and numerical modelling could be a promising way forward in understanding and simulating the dynamics of marine fish populations

Validation of MIPAS-ENVISAT NO2 operational data

The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument was launched aboard the environmental satellite ENVISAT into its sun-synchronous orbit on 1 March 2002. The short-lived species NO₂ is one of the key target products of MIPAS that are operationally retrieved from limb emission spectra measured in the stratosphere and mesosphere. Within the MIPAS validation activities, a large number of independent observations from balloons, satellites and ground-based stations have been compared to European Space Agency (ESA) version 4.61 operational NO₂ data comprising the time period from July 2002 until March 2004 where MIPAS measured with full spectral resolution. Comparisons between MIPAS and balloon-borne observations carried out in 2002 and 2003 in the Arctic, at mid-latitudes, and in the tropics show a very good agreement below 40 km altitude with a mean deviation of roughly 3%, virtually without any significant bias. The comparison to ACE satellite observations exhibits only a small negative bias of MIPAS which appears not to be significant. The independent satellite instruments HALOE, SAGE II, and POAM III confirm in common for the spring-summer time period a negative bias of MIPAS in the Arctic and a positive bias in the Antarctic middle and upper stratosphere exceeding frequently the combined systematic error limits. In contrast to the ESA operational processor, the IMK/IAA retrieval code allows accurate inference of NO₂ volume mixing ratios under consideration of all important non-LTE processes. Large differences between both retrieval results appear especially at higher altitudes, above about 50 to 55 km. These differences might be explained at least partly by non-LTE under polar winter conditions but not at mid-latitudes. Below this altitude region mean differences between both processors remain within 5% (during night) and up to 10% (during day) under undisturbed (September 2002) conditions and up to 40% under perturbed polar night conditions (February and March 2004). The intercomparison of ground-based NDACC observations shows no significant bias between the FTIR measurements in Kiruna (68&deg; N) and MIPAS in summer 2003 but larger deviations in autumn and winter. The mean deviation over the whole comparison period remains within 10%. A mean negative bias of 15% for MIPAS daytime and 8% for nighttime observations has been determined for UV-vis comparisons over Harestua (60&deg; N). Results of a pole-to-pole comparison of ground-based DOAS/UV-visible sunrise and MIPAS mid-morning column data has shown that the mean agreement in 2003 falls within the accuracy limit of the comparison method. Altogether, it can be indicated that MIPAS NO₂ profiles yield valuable information on the vertical distribution of NO₂ in the lower and middle stratosphere (below about 45 km) during day and night with an overall accuracy of about 10&ndash;20% and a precision of typically 5&ndash;15% such that the data are useful for scientific studies. In cases where extremely high NO₂ occurs in the mesosphere (polar winter) retrieval results in the lower and middle stratosphere are less accurate than under undisturbed atmospheric conditions

Million-year-scale alternation of warm–humid and semi-arid periods as a mid-latitude climate mode in the Early Jurassic (late Sinemurian, Laurasian Seaway)

Clay mineral and stable isotope (C, O) data are reported from the upper Sinemurian (Lower Jurassic) of the Cardigan Bay Basin (Llanbedr–Mochras Farm borehole, northwestern Wales) and the Paris Basin (Montcornet borehole, northern France) to highlight the prevailing environmental and climatic conditions. In both basins, located at similar palaeolatitudes of 30–35∘ N, the clay mineral assemblages comprise chlorite, illite, illite–smectite mixed layers (R1 I-S), smectite, and kaolinite in various proportions. Because the influence of burial diagenesis and authigenesis is negligible in both boreholes, the clay minerals are interpreted to be derived from the erosion of the Caledonian and Variscan massifs, including their basement and pedogenic cover. In the Cardigan Bay Basin, the variations in the proportions of smectite and kaolinite are inversely related to each other through the entire upper Sinemurian. As in the succeeding Pliensbachian, the upper Sinemurian stratigraphic distribution reveals an alternation of kaolinite-rich intervals reflecting strong hydrolysing conditions and smectite-rich intervals indicating a semi-arid climate. Kaolinite is particularly abundant in the upper part of the obtusum zone and in the oxynotum zone, suggesting more intense hydrolysing conditions likely coeval with warm conditions responsible for an acceleration of the hydrological cycle. In the north of the Paris Basin, the succession is less continuous compared to the Cardigan Bay Basin site, as the oxynotum zone and the upper raricostatum zone are either absent or highly condensed. The clay assemblages are dominantly composed of illite and kaolinite without significant stratigraphic trends, but a smectite-rich interval identified in the obtusum zone is interpreted as a consequence of the emersion of the London–Brabant Massif following a lowering of sea level. Following a slight negative carbon isotope excursion at the obtusum–oxynotum zone transition, a long-term decrease in δ13Corg from the late oxynotum–early raricostatum zones is recorded in the two sites and may precede or partly include the negative carbon isotope excursion of the Sinemurian–Pliensbachian Boundary Event, which is recognised in most basins worldwide and interpreted to signify a late pulse of the Central Atlantic Magmatic Province volcanism

ALL-1/MLL1, a homologue of Drosophila TRITHORAX, modifies chromatin and is directly involved in infant acute leukaemia

Rearrangements of the ALL-1/MLL1 gene underlie the majority of infant acute leukaemias, as well as of therapy-related leukaemias developing in cancer patients treated with inhibitors of topoisomerase II, such as VP16 and doxorubicin. The rearrangements fuse ALL-1 to any of \u3e50 partner genes or to itself. Here, we describe the unique features of ALL-1-associated leukaemias, and recent progress in understanding molecular mechanisms involved in the activity of the ALL-1 protein and of its Drosophila homologue TRITHORAX

Identification of Colorectal Cancer Related Genes with mRMR and Shortest Path in Protein-Protein Interaction Network

One of the most important and challenging problems in biomedicine and genomics is how to identify the disease genes. In this study, we developed a computational method to identify colorectal cancer-related genes based on (i) the gene expression profiles, and (ii) the shortest path analysis of functional protein association networks. The former has been used to select differentially expressed genes as disease genes for quite a long time, while the latter has been widely used to study the mechanism of diseases. With the existing protein-protein interaction data from STRING (Search Tool for the Retrieval of Interacting Genes), a weighted functional protein association network was constructed. By means of the mRMR (Maximum Relevance Minimum Redundancy) approach, six genes were identified that can distinguish the colorectal tumors and normal adjacent colonic tissues from their gene expression profiles. Meanwhile, according to the shortest path approach, we further found an additional 35 genes, of which some have been reported to be relevant to colorectal cancer and some are very likely to be relevant to it. Interestingly, the genes we identified from both the gene expression profiles and the functional protein association network have more cancer genes than the genes identified from the gene expression profiles alone. Besides, these genes also had greater functional similarity with the reported colorectal cancer genes than the genes identified from the gene expression profiles alone. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying colorectal cancer genes. It has not escaped our notice that the method can be applied to identify the genes of other diseases as well