Size diversity in Swiss Bronze Age cattle.

To date, osteometric data for Swiss Bronze Age cattle, particularly from Alpine sites, are scarce. In the present study, using a large dataset generated by combining preexisting data with recent data obtained from a large Alpine site, cattle size from the Late Neolithic to the Late Bronze Age (LBA) in populations from different sites and regions was evaluated using the logarithmic size index and other statistical analysis. Additionally, the finite mixture model and a meta-analytic technique were used to observe possible effects of sex ratios on cattle size. Results indicated that sex ratios did not affect size distribution. Cattle populations did not differ over time, but the Alpine cattle were smaller than the Central Plateau cattle. There were two distinct sizes in the Alpine cattle populations. It is suggested that the different economic interrelationships between Alpine and other geographically related communities might have led to the emergence of size diversity in Swiss Bronze Age cattle. Further interdisciplinary studies with larger sample sizes are required to confirm these possibilities.

[History and economic importance of cattle (Bos taurus L.) in Switzerland from Neolithic to Early Middle Ages]. / Geschichte und wirtschaftliche Bedeutung des Hausrindes (Bos taurus L.) in der Schweiz von der Jungsteinzeit bis ins frühe Mittelalter.

In Switzerland domestic cattle (Bos primigenius f. taurus resp. Bos taurus L.) first appear with the earliest Neolithic settlements (approximately 5000 BC). With the gradual deforestation of the landscape caused by human exploitation of the environment, cattle were used more intensive and in many ways. There is evidence that cattle were used as draught animal since ca. 3400 BC, probably even earlier milk was regularly used. The size of domestic cattle gradually decreased from Early Neolithic until Iron Age. Only with Roman influence larger animals are found. However, after the withdrawal of Romans the average size of cattle decreased again. Archaeogenetic studies will have to show, whether this is due to novel breeding strategies or the import of breeding stock. First genetic results showed that a female genetic type, which is rare in European breeds, is present in Swiss Evolène cattle and in one animal of Roman time cattle from Augusta Raurica. Is this a sign for influence of Roman cattle on today's Swiss breeds?

Protease-activated receptor-1 inhibits proliferation but enhances leukemia stem cell activity in acute myeloid leukemia.

Eradication of leukemia stem cells (LSCs) is the ultimate goal of treating acute myeloid leukemia (AML). We recently showed that the combined loss of Runx1/Cbfb inhibited the development of MLL-AF9-induced AML. However, c-Kit+/Gr-1- cells remained viable in Runx1/Cbfb-deleted cells, indicating that suppressing RUNX activity may not eradicate the most immature LSCs. In this study, we found upregulation of several hemostasis-related genes, including the thrombin-activatable receptor PAR-1 (protease-activated receptor-1), in Runx1/Cbfb-deleted MLL-AF9 cells. Similar to the effect of Runx1/Cbfb deletion, PAR-1 overexpression induced CDKN1A/p21 expression and attenuated proliferation in MLL-AF9 cells. To our surprise, PAR-1 deficiency also prevented leukemia development induced by a small number of MLL-AF9 leukemia stem cells (LSCs) in vivo. PAR-1 deficiency also reduced leukemogenicity of AML1-ETO-induced leukemia. Re-expression of PAR-1 in PAR-1-deficient cells combined with a limiting-dilution transplantation assay demonstrated the cell-dose-dependent role of PAR-1 in MLL-AF9 leukemia: PAR-1 inhibited rapid leukemic proliferation when there were a large number of LSCs, while a small number of LSCs required PAR-1 for their efficient growth. Mechanistically, PAR-1 increased the adherence properties of MLL-AF9 cells and promoted their engraftment to bone marrow. Taken together, these data revealed a multifaceted role for PAR-1 in leukemogenesis, and highlight this receptor as a potential target to eradicate primitive LSCs in AML.

UBASH3B/Sts-1-CBL axis regulates myeloid proliferation in human preleukemia induced by AML1-ETO.

The t(8;21) rearrangement, which creates the AML1-ETO fusion protein, represents the most common chromosomal translocation in acute myeloid leukemia (AML). Clinical data suggest that CBL mutations are a frequent event in t(8;21) AML, but the role of CBL in AML1-ETO-induced leukemia has not been investigated. In this study, we demonstrate that CBL mutations collaborate with AML1-ETO to expand human CD34+ cells both in vitro and in a xenograft model. CBL depletion by shRNA also promotes the growth of AML1-ETO cells, demonstrating the inhibitory function of endogenous CBL in t(8;21) AML. Mechanistically, loss of CBL function confers hyper-responsiveness to thrombopoietin and enhances STAT5/AKT/ERK/Src signaling in AML1-ETO cells. Interestingly, we found the protein tyrosine phosphatase UBASH3B/Sts-1, which is known to inhibit CBL function, is upregulated by AML1-ETO through transcriptional and miR-9-mediated regulation. UBASH3B/Sts-1 depletion induces an aberrant pattern of CBL phosphorylation and impairs proliferation in AML1-ETO cells. The growth inhibition caused by UBASH3B/Sts-1 depletion can be rescued by ectopic expression of CBL mutants, suggesting that UBASH3B/Sts-1 supports the growth of AML1-ETO cells partly through modulation of CBL function. Our study reveals a role of CBL in restricting myeloid proliferation of human AML1-ETO-induced leukemia, and identifies UBASH3B/Sts-1 as a potential target for pharmaceutical intervention.

Near East mtDNA haplotype variants in Roman cattle from Augusta Raurica, Switzerland, and in the Swiss Evolène breed.

Typical Near East mitochondrial haplotypes of the T2 lineage were found in one cattle metacarpus sample from the Roman period and in two present-day Evolène cattle in Switzerland. Sequences from eight additional Evolène and four Raetian Grey aligned to the European haplotype T3. Analysis of nucleotide diversity within the mitochondrial D-loop of both studied Swiss cattle breeds revealed high haplotype diversity and similar diversity to a European cattle reference group. Mitochondrial T3 haplotypes radiated star-like from two similarly frequent haplotypes, possibly indicating two different expansion routes. The breed structure of Evolène cattle can be explained either by an introduction of diverse female lineages from the domestication centre or by later admixture. The introduction of the Near East lineage to Switzerland must have happened during the Roman time or earlier.