ABSTRACT
The purpose of this study is to determine the effect of the partial replacement of dietary hay with sugar beet pulp (SBP) on the composition and predicted function of the fecal microbiota of healthy adult horses. Fecal samples were collected daily for 12 days from six adult horses after removal from pasture, including a five-day acclimation period, and a seven-day period following the introduction of SBP into their diet, and compared to six untreated horses over a comparable period. Fecal DNA was subjected to 16S rRNA amplicon sequencing and a longitudinal analysis was performed comparing the composition and predicted function. While no significant treatment-associated changes in the richness, alpha diversity, or beta diversity were detected, random forest regression identified several high-importance taxonomic features associated with change over time in horses receiving SBP. A similar analysis of the predicted functional pathways identified several high-importance pathways, including those involved in the production of L-methionine and butyrate. These data suggest that feeding SBP to healthy adult horses acutely increases the relative abundance of several Gram-positive taxa, including Cellulosilyticum sp., Moryella sp., and Weissella sp., and mitigates the predicted functional changes associated with removal from pasture. Large-scale studies are needed to assess the protective effect of SBP on the incidence of the gastrointestinal conditions of horses.
ABSTRACT
Pathways adopted by developing cancer cells for evasion of cellular surveillance mechanism deserve attention for therapeutic exploitation as well as for better prognosis. A novel mitotic kinase, PDZ-binding kinase or PBK, which is upregulated in a variety of neoplasms including hematological malignancies, has been the focus of our attention with a goal to understand its role in malignant conversion and to examine as a possible new therapeutic target in disparate types of cancer. Earlier, we reported that PBK expression was downregulated during macrophage differentiation of HL60 promyelocytic leukemia cells, during doxorubicin-induced growth arrest in G2/M phase and that PBK was regulated by cell cycle-specific transcription factors E2F and CREB/ATF. Here, we demonstrate that HT1080 fibrosarcoma cells become adapted to doxorubicin-induced DNA damage checkpoint upon ectopic expression of a phosphomimetic mutant of PBK as indicated by the accumulation of polyploid cells. Aberrant entry into the mitotic phase by these cells is suggested by the appearance of a mitotic phase-specific marker, MPM-2. We propose that the effect is due to downregulation of p53 caused by direct physical interaction with PBK as detected by both a biochemical means as well as by yeast two-hybrid analysis. Together, our studies provide a plausible explanation for the role of PBK augmenting tumor cell growth following transient appearance in different types of progenitor cells in vivo as reported.
