The Leukemia-Specific Fusion Gene ETV6/RUNX1 Perturbs Distinct Key Biological Functions Primarily by Gene Repression

-positive leukemic cell lines.-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories “stem cell properties”, “B-cell differentiation”, “immune response”, “cell adhesion” and “DNA damage” with RT-qPCR. fusion gene interferes with key regulatory functions that shape the biology of this leukemia subtype. E/R may thus indeed constitute the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets

Dynamics of bacterial communities during the ripening process of different Croatian cheese types derived from raw ewe's milk cheeses.

Microbial communities play an important role in cheese ripening and determine the flavor and taste of different cheese types to a large extent. However, under adverse conditions human pathogens may colonize cheese samples during ripening and may thus cause severe outbreaks of diarrhoea and other diseases. Therefore in the present study we investigated the bacterial community structure of three raw ewe's milk cheese types, which are produced without the application of starter cultures during ripening from two production sites based on fingerprinting in combination with next generation sequencing of 16S rRNA gene amplicons. Overall a surprisingly high diversity was found in the analyzed samples and overall up to 213 OTU97 could be assigned. 20 of the major OTUs were present in all samples and include mostly lactic acid bacteria (LAB), mainly Lactococcus, and Enterococcus species. Abundance and diversity of these genera differed to a large extent between the 3 investigated cheese types and in response to the ripening process. Also a large number of non LAB genera could be identified based on phylogenetic alignments including mainly Enterobacteriaceae and Staphylococcacae. Some species belonging to these two families could be clearly assigned to species which are known as potential human pathogens like Staphylococcus saprophyticus or Salmonella spp. However, during cheese ripening their abundance was reduced. The bacterial genera, namely Lactobacillus, Streptococcus, Leuconostoc, Bifidobacterium, Brevibacterium, Corynebacterium, Clostridium, Staphylococcus, Thermoanerobacterium, E. coli, Hafnia, Pseudomonas, Janthinobacterium, Petrotoga, Kosmotoga, Megasphaera, Macrococcus, Mannheimia, Aerococcus, Vagococcus, Weissella and Pediococcus were identified at a relative low level and only in selected samples. Overall the microbial composition of the used milk and the management of the production units determined the bacterial community composition for all cheese types to a large extend, also at the late time points of cheese ripening

Relative abundance (%) of sequences which could be assigned to genus level (OTU₉₅; about 60000 reads in total)) in three Croatian raw ewe's milk cheeses (Cheese A, B and C) based on partial sequence analysis of the 16S rRNA gene gene after direct DNA extraction and PCR amplification.

<p>Samples were taken from two production sites (F1 and F2). The numbers on x- axis represents ripening time in days: 0d, 45d and 90d.</p

Venn diagram showing the number of specific and common OTUs (OTU₉₇) between three Croatian raw ewés milk cheeses (Cheese A, B and C) obtained from two production sites (F1 and F2) throughout the ripening period (0, 45 and 90d) based on partial sequence analysis of the 16S rRNA gene after direct DNA extraction and PCR amplification.

<p>Venn diagram showing the number of specific and common OTUs (OTU₉₇) between three Croatian raw ewés milk cheeses (Cheese A, B and C) obtained from two production sites (F1 and F2) throughout the ripening period (0, 45 and 90d) based on partial sequence analysis of the 16S rRNA gene after direct DNA extraction and PCR amplification.</p

Relative abundance (%) of bacterial species OTUs (OTU₉₇) during different time points of ripening (0d, 45d, 90d) of three different Croatian raw ewe's milk cheeses (Cheese A, B and C) obtained from two different farms (F1 and F2) based on partial sequencing of the 16S rRNA gene after direct DNA extraction and PCR amplification. “n” indicates the number of analyzed reads.

<p>Relative abundance (%) of bacterial species OTUs (OTU₉₇) during different time points of ripening (0d, 45d, 90d) of three different Croatian raw ewe's milk cheeses (Cheese A, B and C) obtained from two different farms (F1 and F2) based on partial sequencing of the 16S rRNA gene after direct DNA extraction and PCR amplification. “n” indicates the number of analyzed reads.</p

Rarefaction curves of partial sequences of the bacterial 16S rRNA gene after direct DNA extraction and PCR amplification from three Croatian raw ewe's milk cheeses (Cheese A, B and C) throughout the ripening period (0, 45 and 90d) obtained from two production sites (F1 and F2) at a 97% similarity level normalized with respect to sample size.

<p>As the most variability were related to F2 only those results are presented.</p