bioRxiv Science⌕ Search

Biology subjects

Siemann, M. J.

Publications and source records attributed to Siemann, M. J..

3 recordsLinked to original sources

Validating static food web model diet matrices using stable isotope simulation

End-to-end ecosystem models, such as Ecopath with Ecosim (EwE), are valuable tools for resource management. Within these frameworks, trophic interactions, typically derived from stomach contents analyses, govern system-wide energy flow via consumption. However, stomach contents data may be unrepresentative of long-term average diets and assimilated consumption due to factors including differential digestion rates and identifiability of prey, introducing model uncertainty. Because trophic interactions define model structure, variation in modeled diets can alter predictions and management conclusions. Consequently, evaluating and reducing uncertainty in diet matrix compositions is critical for operational acceptance of ecosystem models. Stable isotope analysis provides complementary, time-integrated insight into average diets, but its application for EwE validation has largely been limited to evaluating trophic levels and isotopic niche space. Here, we present a quantitative framework for simulating consumer stable isotope signatures across food webs from parent ecosystem models using a matrix-based mixing model. Using a published Northern Gulf of Mexico EwE model as a case study, we demonstrate Monte Carlo simulation to propagate uncertainty from basal source signatures and trophic discrimination factors. Comparison of predicted signatures with empirical {delta}13C and {delta}34S measurements enables validation of primary carbon sources and benthic-pelagic pathway contributions, revealing agreement in isotope space alongside mismatch in energy pathways. Diagnostic residuals identify discrepancies in diet composition. Model scoring provides a reproducible framework for ranking alternative diet configurations. Redundancy analysis further identifies within-group species coverage differences between stomach contents and isotope datasets as a primary driver of mismatch, highlighting an important consideration for sampling design.

ecology↗

Metabolic Reprogramming by Mutant GNAS Creates an Actionable Dependency in Intraductal Papillary Mucinous Neoplasms of the Pancreas

ObjectiveOncogenic "hotspot" mutations of KRAS and GNAS are two major driver alterations in Intraductal Papillary Mucinous Neoplasms (IPMNs), which are bona fide precursors to pancreatic ductal adenocarcinoma. We previously reported that pancreas-specific KrasG12D and GnasR201C co-expression in p48Cre; KrasLSL-G12D; Rosa26LSL-rtTA; Tg (TetO-GnasR201C) mice ("Kras;Gnas" mice) caused development of cystic lesions recapitulating IPMNs. Here, we aim to unveil the consequences of mutant GnasR201C expression on phenotype, transcriptomic profile, and genomic dependencies. DesignWe performed multimodal transcriptional profiling (bulk RNA sequencing, single cell RNA sequencing, and spatial transcriptomics) in the "Kras;Gnas" autochthonous model and tumor-derived cell lines (Kras;Gnas cells), where GnasR201C expression is inducible. A genome-wide CRISPR/Cas9 screen was conducted to identify potential vulnerabilities in KrasG12D;GnasR201Cco-expressing cells. ResultsInduction of GnasR201C - and resulting G(s)alpha signaling - leads to the emergence of a gene signature of gastric (pyloric type) metaplasia in pancreatic neoplastic epithelial cells. CRISPR screening identified the synthetic essentiality of glycolysis-related genes Gpi1 and Slc2a1 in KrasG12D;GnasR201C co-expressing cells. Real-time metabolic analyses in Kras;Gnas cells and autochthonous Kras;Gnas model confirmed enhanced glycolysis upon GnasR201C induction. Induction of GnasR201C made KrasG12D expressing cells more dependent on glycolysis for their survival. Protein kinase A-dependent phosphorylation of the glycolytic intermediate enzyme PFKFB3 was a driver of increased glycolysis upon GnasR201C induction. ConclusionMultiple orthogonal approaches demonstrate that KrasG12D and GnasR201C co-expression results in a gene signature of gastric pyloric metaplasia and glycolytic dependency during IPMN pathogenesis. The observed metabolic reprogramming may provide a potential target for therapeutics and interception of IPMNs. SUMMARYO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIActivating "hotspot" mutations of KRAS and GNAS are found in a majority of Intraductal Papillary Mucinous Neoplasms (IPMNs). C_LIO_LIExpression of mutant KRAS and GNAS drives development of IPMN-like cystic lesions in the murine pancreas that eventually progress to pancreatic ductal adenocarcinoma (PDAC). C_LI What this study addsO_LIMutant GNAS and the resulting aberrant G(s)alpha signaling drives a transcriptional signature of gastric (pyloric type) metaplasia in IPMNs with mucin production. C_LIO_LIAberrant G(s)alpha signaling enhances glycolysis via protein kinase A-dependent phosphorylation of the glycolytic enzyme PFKFB3. C_LIO_LIEnhanced glycolysis in KRAS;GNAS-mutated IPMN cells is validated via multiple orthogonal approaches in vitro and in vivo and represents an actionable metabolic vulnerability. C_LI How this study might affect research, practice or policyO_LIThe present study provides mechanistic insight into how aberrant G(s)alpha signaling alters the biology of Kras-mutant pancreatic epithelial neoplasia through metaplastic and metabolic reprogramming. C_LIO_LITargeting glycolysis in IPMNs may represent both a therapeutic avenue as well as an opportunity for intercepting progression to invasive cancer. C_LI

cancer biology↗

The influence of sponge-dwelling gobies (Elacatinus horsti) on the feeding efficiency of their Caribbean tube sponge ( Aplysina sp.) hosts

Mutualistic associations between benthic marine invertebrates and reef taxa are common. Sponge-dwelling gobies benefit from protection within sponge tubes and greater food availability. Sponge-dwelling gobies are hypothesized to increase sponge pump rates by consuming polychaete parasites, but such increases have not yet been demonstrated. We investigated the association between sponge-dwelling gobies (Elacatinus horsti) and two species of tube sponge (Aplysina lacunosa and Aplysina archeri) in Bonaire, Caribbean Netherlands. We visually assessed goby presence in sponges and used in situ methods with fluorescein dye to estimate feeding rates via pump rates. Aplysina archeri were more likely to host a goby than A. lacunosa. For both sponge species, pump rates of tubes with gobies were higher on average than those of tubes without gobies. Our observations, therefore, suggest that E. horsti associations with Aplysina are likely mutualistic relationships in which sponges benefit from higher feeding rates when gobies are present.

ecology↗