Noticeable DNA synthesis by reverse transcription, which precedes DNA polymerase-dependent DNA replication in mouse pronuclei [ 27], could be the first phase of DNA replication and serve as the epigenetic mechanism implicated in the establishment of the initial replication timing program and chromatin architecture.
These cells do not derive from hematopoietic precursors, and it has been clearly observed that mice defective for FDCs present a delay in the development of the clinical diseases, showing that the initial replication of infectivity in FDCs is critical for neuroinvasion [5], [6], [7].
While the initial replication efforts in East Asian populations were inconsistent [ 16, 17], a growing number of studies have provided evidence that genetic variation in FTO influences BMI and obesity risk also in Chinese, Japanese, Korean and Filipino populations [ 18– 27].
This result indicated that GrzM had no influence on the initial infection of, or on the initial replication of the bacterium in, resident macrophages.
Genes with the most reproducible differential expression were identified by selecting genes in the initial and replication data sets with Log2FC≥1 and P≤0.05, and then assessing the combined statistical significance using the Fisher's combined P method [29].
This average-model was used to initialise a final round of training using the same 48 thousand sequences of 2000 bases as were used in the initial eight replications.
This supports a model in which, after initial replication stalling, the G-quadruplex structure is unwound and faithfully replicated.
In mice, VEEV also disseminates to the spleen after initial replication in the draining lymph node (35).
Based on the expression of 22,000 genes, a p value<0.05, a false discovery rate of 10%, and fold change of 2 (Log2 ratio of 1), with a standard deviation of 0.3, a sample size of 3 subjects per group gives 80% power in each the initial and replication cohorts [30].
