First-generation linkage map for the common frog Rana temporaria reveals sex-linkage group

The common frog (Rana temporaria) has become a model species in the fields of ecology and evolutionary biology. However, lack of genomic resources has been limiting utility of this species for detailed evolutionary genetic studies. Using a set of 107 informative microsatellite markers genotyped in a large full-sib family (800 F1 offspring), we created the first linkage map for this species. This partial map—distributed over 15 linkage groups—has a total length of 1698.8 cM. In line with the fact that males are the heterogametic sex in this species and a reduction of recombination is expected, we observed a lower recombination rate in the males (map length: 1371.5 cM) as compared with females (2089.8 cM). Furthermore, three loci previously documented to be sex-linked (that is, carrying male-specific alleles) in adults from the wild mapped to the same linkage group. The linkage map described in this study is one of the densest ones available for amphibians. The discovery of a sex linkage group in Rana temporaria, as well as other regions with strongly reduced male recombination rates, should help to uncover the genetic underpinnings of the sex-determination system in this species. As the number of linkage groups found (n=15) is quite close to the actual number of chromosomes (n=13), the map should provide a useful resource for further evolutionary, ecological and conservation genetic work in this and other closely related species

Green Synthesis of Nanoparticles and Their Application in Cancer Therapy

none6simixedValeria De Matteis; Mariafrancesca Cascione; Loris Rizzello; Eva Liatsi-Douvitsa; Azzurra Apriceno; Rosaria RinaldiDE MATTEIS, Valeria; Cascione, Mariafrancesca; Rizzello, Loris; Liatsi-Douvitsa, Eva; Apriceno, Azzurra; Rinaldi, Rosari

Context- and Cell-Dependent Effects of Delta-Like 4 Targeting in the Bone Marrow Microenvironment

This work was supported by FCT PTDC/SAU-ORG/113617/2009 (www.fct.pt). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank other members of the Angiogenesis Lab for their input and suggestions. The Program for Advanced Medical Education is sponsored by Fundacao Calouste Gulbenkian, Fundacao Champalimaud, Ministerio da Saude and Fundacao para a Ciencia e Tecnologia, Portugal.Delta-like 4 (Dll4) is a ligand of the Notch pathway family which has been widely studied in the context of tumor angiogenesis, its blockade shown to result in non-productive angiogenesis and halted tumor growth. As Dll4 inhibitors enter the clinic, there is an emerging need to understand their side effects, namely the systemic consequences of Dll4:Notch blockade in tissues other than tumors. The present study focused on the effects of systemic anti-Dll4 targeting in the bone marrow (BM) microenvironment. Here we show that Dll4 blockade with monoclonal antibodies perturbs the BM vascular niche of sub-lethally irradiated mice, resulting in increased CD31+, VE-Cadherin+ and c-kit+ vessel density, and also increased megakaryocytes, whereas CD105+, VEGFR3+, SMA+ and lectin+ vessel density remained unaltered. We investigated also the expression of angiocrine genes upon Dll4 treatment in vivo, and demonstrate that IGFbp2, IGFbp3, Angpt2, Dll4, DHH and VEGF-A are upregulated, while FGF1 and CSF2 are reduced. In vitro treatment of endothelial cells with anti-Dll4 reduced Akt phosphorylation while maintaining similar levels of Erk 1/2 phosphorylation. Besides its effects in the BM vascular niche, anti-Dll4 treatment perturbed hematopoiesis, as evidenced by increased myeloid (CD11b+), decreased B (B220+) and T (CD3+) lymphoid BM content of treated mice, with a corresponding increase in myeloid circulating cells. Moreover, anti-Dll4 treatment also increased the number of CFU-M and -G colonies in methylcellulose assays, independently of Notch1. Finally, anti-Dll4 treatment of donor BM improved the hematopoietic recovery of lethally irradiated recipients in a transplant setting. Together, our data reveals the hematopoietic (BM) effects of systemic anti-Dll4 treatment result from qualitative vascular changes and also direct hematopoietic cell modulation, which may be favorable in a transplant setting.publishersversionpublishe

Trace element geochemistry as a tool for interpreting microbialites

Microbialites are critical for documenting early life on earth and-possibly elsewhere in the solar system. However, criteria for microbialite identification are controversial. Trace element geochemistry provides two types of information that aid interpretation of putative microbialites. Firstly, because most microbialites-consist of hydrogenous precipitates, trace elements can be used to investigate the fluids in which the structures formed, thus aiding identification of environments of formation. For example, rare earth elements preserved in microbialites have proven very useful in discriminating depositional environments. Secondly, microbes utilize and concentrate a wide range of elements, including many metals. Preservation of such elemental enrichments may provide a valuable biosignature. Although research in this field is relatively young, high precision, in situ measurement of metals in microbialites using techniques such as laser ablation-inductively coupled plasma-mass spectrometry, now with spatial mapping, have identified consistent enrichments in biologically important metals in microbialites. Hence, trace element studies are finding increasing utility in studying microbialites, and so long as diagenesis and the degree to which specific precipitates represent microenvironments are taken into account, trace element inventories may provide important information about depositional settings and, potentially, metabolic processes within biofilms