Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma

AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFκB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision

Persistent Place-Making in Prehistory: the Creation, Maintenance, and Transformation of an Epipalaeolithic Landscape

Most archaeological projects today integrate, at least to some degree, how past people engaged with their surroundings, including both how they strategized resource use, organized technological production, or scheduled movements within a physical environment, as well as how they constructed cosmologies around or created symbolic connections to places in the landscape. However, there are a multitude of ways in which archaeologists approach the creation, maintenance, and transformation of human-landscape interrelationships. This paper explores some of these approaches for reconstructing the Epipalaeolithic (ca. 23,000–11,500 years BP) landscape of Southwest Asia, using macro- and microscale geoarchaeological approaches to examine how everyday practices leave traces of human-landscape interactions in northern and eastern Jordan. The case studies presented here demonstrate that these Epipalaeolithic groups engaged in complex and far-reaching social landscapes. Examination of the Early and Middle Epipalaeolithic (EP) highlights that the notion of “Neolithization” is somewhat misleading as many of the features we use to define this transition were already well-established patterns of behavior by the Neolithic. Instead, these features and practices were enacted within a hunter-gatherer world and worldview

A halotolerant laccase from Chaetomium strain isolated from desert soil and its ability for dye decolourization

13 p.-6 fig.-3 tab.A novel fungal laccase produced by the ascomycete Chaetomium sp. isolated from arid soil was purified and characterized and its ability to remove dyes was determined. Extracellular laccase was purified 15-fold from the crude culture to homogeneity with an overall yield of 50% using ultrafiltration and anion-exchange chromatography. The purified enzyme was found to be a monomeric protein with a molecular mass of 68 kDa, estimated by SDS-PAGE, and with an isoelectric point of 5.5. The optimal temperature and pH value for laccase activity toward 2,6-DMP were 60 °C and 3.0, respectively. It was stable at temperatures below 50 °C and at alkaline conditions. Kinetic study showed that this laccase showed higher affinity on ABTS than on 2,6-DMP. Its activity was enhanced by the presence of several metal ions such as Mg2+, Ca2+ and Zn2+, while it was strongly inhibited by Fe2+, Ag+ and Hg2+. The novel laccase also showed high, remarkable sodium chloride tolerance. Its ability to decolorize different dyes, with or without HBT (1-hydroxy-benzotriazole), as redox mediator, suggests that this protein may be useful for different industrial applications and/or bioremediation processes.Peer reviewe

Genomic history of the origin and domestication of common bean unveils its closest sister species

Background: Modern civilization depends on only a few plant species for its nourishment. These crops were derived via several thousands of years of human selection that transformed wild ancestors into high-yielding domesticated descendants. Among cultivated plants, common bean (Phaseolus vulgaris L.) is the most important grain legume. Yet, our understanding of the origins and concurrent shaping of the genome of this crop plant is limited. Results: We sequenced the genomes of 29 accessions representing 12 Phaseolus species. Single nucleotide polymorphism-based phylogenomic analyses, using both the nuclear and chloroplast genomes, allowed us to detect a speciation event, a finding further supported by metabolite profiling. In addition, we identified ~1200 protein coding genes (PCGs) and ~100 long non-coding RNAs with domestication-associated haplotypes. Finally, we describe asymmetric introgression events occurring among common bean subpopulations in Mesoamerica and across hemispheres. Conclusions: We uncover an unpredicted speciation event in the tropical Andes that gave rise to a sibling species, formerly considered the “wild ancestor” of P. vulgaris, which diverged before the split of the Mesoamerican and Andean P. vulgaris gene pools. Further, we identify haplotypes strongly associated with genes underlying the emergence of domestication traits. Our findings also reveal the capacity of a predominantly autogamous plant to outcross and fix loci from different populations, even from distant species, which led to the acquisition by domesticated beans of adaptive traits from wild relatives. The occurrence of such adaptive introgressions should be exploited to accelerate breeding programs in the near future.This work was supported by the Ibero-American Programme for Science, Technology and Development - CYTED (PhasIbeAm project); Spanish Government - Ministry of Economy and Competitiveness (EUI2009-04052, BIO2011-26205), “Centro de Excelencia Severo Ochoa 2013-2017,” SEV-2012-0208 and Project PT13/0001/0021 (ISCIII - Subdirección General de Evaluación y Fomento de la Investigación/FEDER “Una Manera de hacer Europa”); Brazilian Government—National Council for Scientific and Technological Development - CNPq/Prosul (490725/2010-4); Ministerio de Ciencia, Tecnología e Innovación Productiva de la República Argentina; Consejo Nacional de Ciencia y Tecnología - Conacyt, Mexico (J010-214-2009, Fronteras 2015-2/814); and U.S. government: USDA National Institute of Food and Agriculture (2013-67013-21224. M. R-A. and J.M.M.-V. are indebted to Conacyt for a doctoral fellowship