Biology subjects

Peterson, M. L.

Publications and source records attributed to Peterson, M. L..

4 recordsLinked to original sources

bioRxiv2023

Estimates of Fall-run Chinook Salmon Escapement in Two San Joaquin River Tributaries from Device-based and Survey-based Methods

Monitoring the escapement (i.e., spawner abundance) of adult salmonids is a fundamental component of fisheries stock assessment and evaluating recovery goals. Whereas multiple methods exist for estimating escapement, they exhibit trade-offs between degree of accuracy and implementation expenses and effort. Various methods are used throughout the Central Valley to estimate escapement of the four runs of Chinook Salmon (Oncorhynchus tshawytscha), but few rivers have more than one escapement monitoring program. Fall-run Chinook Salmon escapement to the Stanislaus and Tuolumne rivers is estimated by two independent monitoring programs on each river. Since 1952, California Department of Fish and Wildlife has performed carcass surveys that provide an index of escapement. Beginning in 2003 (Stanislaus River) and 2009 (Tuolumne River), private contractors have seasonally installed and operated weirs with fish counting devices to enumerate returning adults. We used the overlapping time series to evaluate the relationship between estimates from carcass surveys and the counting weirs. With few exceptions, estimates from counting adult salmon at the weirs as they entered the spawning grounds were greater than estimates from carcass surveys on both rivers. Escapement estimates from the Stanislaus weir were on average 1.7 (SE = 0.07) times greater than estimates from carcass surveys, while estimates at the Tuolumne weir were 2.5 (SE = 0.17) times greater than estimates from carcass surveys. Estimates from both methods were highly correlated, with r2 values > 96% for both rivers. The high degree of covariation between methods indicates escapement estimates are robust and can be used in population models that incorporate additional data sources, such as estimates of juvenile production. Having multiple sources of data on fall-run Chinook Salmon will be increasingly useful for guiding and evaluating management actions in these heavily managed rivers.

zoology↗

bioRxiv2022

Zinc Fingers and Homeoboxes 2 is Required for Diethylnitrosamine-induced Liver Tumor Formation in C57BL/6 Mice

Liver cancer, comprised mainly of hepatocellular carcinoma (HCC), is the third leading cause of cancer deaths worldwide and increasing in Western countries. We previously identified the transcription factor Zinc Fingers and Homeoboxes 2 (Zhx2) as a regulator of hepatic gene expression, and many Zhx2 target genes are dysregulated in HCC. Here, we investigate HCC in Zhx2-deficient mice using the Diethylnitrosamine (DEN)-induced liver tumor model. Our study using whole-body Zhx2 knock-out (Zhx2KO) mice revealed the complete absence of liver tumors 9 and 10 months after DEN exposure.Analysis soon after DEN treatment showed no differences in expression of the DEN bioactivating enzyme CYP2E1 and DNA polymerase delta 2, or in the numbers of {gamma}H2AX foci between Zhx2KO and wild-type (Zhx2wt) mice. The absence of Zhx2, therefore, did not alter DEN bioactivation or DNA damage. Zhx2KO livers showed fewer positive foci for Ki67 staining and reduced IL-6 and AKT2 expression compared to Zhx2wt livers, suggesting that Zhx2 loss reduces liver cell proliferation and may account for reduced tumor formation. Tumors were reduced but not absent in DEN-treated liver-specific Zhx2 knock-out mice, suggesting that Zhx2 acts in both hepatocytes and non-parenchymal cells to inhibit tumor formation. Analysis of data from The Cancer Genome Atlas and Clinical Proteomic Tumor Consortium indicated that ZHX2 mRNA and protein levels were significantly higher in HCC patients and associated with clinical pathological parameters. ConclusionsIn contrast to previous studies in human hepatoma cell lines and other HCC mouse models showing that Zhx2 acts as a tumor suppressor, our data indicate that Zhx2 acts as an oncogene in the DEN-induced HCC model and is consistent with the higher ZHX2 expression in HCC patients.

cancer biology↗

bioRxiv2022

Elongation of Very Long Chain Fatty Acids Like- 3 (Elovl3) is activated by ZHX2 and is a regulator of cell cycle progression

Zinc fingers and homeoboxes 2 (ZHX2) functions as a tumor suppressor in several models of hepatocellular carcinoma (HCC), presumably through its control of target genes. Previous microarray data suggested that Elongation of Very Long Chain Fatty Acids 3 (Elovl3), a member of the Elovl family which synthesize very long chain fatty acids (VLCFAs), is a putative ZHX2 target gene. VLCFAs are core component of ceramides and other bioactive sphingolipids, which are often dysregulated in diseases, including HCC. Since several previously identified ZHX2 targets become dysregulated in HCC, we investigated the relationship between ZHX2 and Elovl3 in liver damage and HCC. Here, using mouse and cell models, we demonstrate that Zhx2 positively regulates Elovl3 expression in the liver and that male-biased hepatic Elovl3 expression is established between 4-8 weeks of age in mice. Elovl3 is dramatically repressed in mouse models of liver regeneration and HCC and the reduced Elovl3 levels in the regenerating liver are associated with changes in hepatic very long chain fatty acids. Human hepatoma cell lines with forced Elovl3 expression have lower rates of cell growth; analysis of synchronized cells indicate that this reduced proliferation correlates with cells stalling in S-phase. Taken together, these data indicate that Elovl3 expression helps regulate cellular proliferation, possibly through control of VLCFAs, and its repression may be a contributing factor to HCC and explain, in part, the function of ZHX2 as a suppressor of HCC progression.

molecular biology↗

bioRxiv2022

Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR

Impaired activity of the chloride channel CFTR is the cause of cystic fibrosis. 14-3-3 proteins have been shown to stabilize CFTR and increase its biogenesis and activity. Here, we report the identification and mechanism of action of a macrocycle stabilizing the 14-3-3/CFTR complex, a first-in-class molecular glue. This molecule rescues plasma membrane localization and chloride transport of F508del-CFTR and works additively with the CFTR pharmacological chaperone corrector lumacaftor (VX-809).

biochemistry↗