A critical comparison of integral projection and matrix projection models for demographic analysis

Structured demographic models are among the most common and useful tools in population biology. However, the introduction of integral projection models (IPMs) has caused a profound shift in the way many demographic models are conceptualized. Some researchers have argued that IPMs, by explicitly representing demographic processes as continuous functions of state variables such as size, are more statistically efficient, biologically realistic, and accurate than classic matrix projection models, calling into question the usefulness of the many studies based on matrix models. Here, we evaluate how IPMs and matrix models differ, as well as the extent to which these differences matter for estimation of key model outputs, including population growth rates, sensitivity patterns, and life spans. First, we detail the steps in constructing and using each type of model. Second, we present a review of published demographic models, concentrating on size-based studies, which shows significant overlap in the way IPMs and matrix models are constructed and analyzed. Third, to assess the impact of various modeling decisions on demographic predictions, we ran a series of simulations based on size-based demographic data sets for five biologically diverse species. We found little evidence that discrete vital rate estimation is less accurate than continuous functions across a wide range of sample sizes or size classes (equivalently bin numbers or mesh points). Most model outputs quickly converged with modest class numbers (≥10), regardless of most other modeling decisions. Another surprising result was that the most commonly used method to discretize growth rates for IPM analyses can introduce substantial error into model outputs. Finally, we show that empirical sample sizes generally matter more than modeling approach for the accuracy of demographic outputs. Based on these results, we provide specific recommendations to those constructing and evaluating structured population models. Both our literature review and simulations question the treatment of IPMs as a clearly distinct modeling approach or one that is inherently more accurate than classic matrix models. Importantly, this suggests that matrix models, representing the vast majority of past demographic analyses available for comparative and conservation work, continue to be useful and important sources of demographic information.Support for this work was provided by NSF awards 1146489, 1242558, 1242355, 1353781, 1340024, 1753980, and 1753954, 1144807, 0841423, and 1144083. Support also came from USDA NIFA Postdoctoral Fellowship (award no. 2019-67012-29726/project accession no. 1019364) for R. K. Shriver; the Swiss Polar Institute of Food and Agriculture for N. I. Chardon; the ICREA under the ICREA Academia Programme for C. Linares; and SERDP contract RC-2512 and USDA National Institute of Food and Agriculture, Hatch project 1016746 for A .M. Louthan. This is Contribution no. 21-177-J from the Kansas Agricultural Experiment Station

Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release

The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing αβγ heterotrimer responsible for energy homeostasis. Pharmacological inhibition of AMPK is regarded as a therapeutic strategy in some disease settings including obesity and cancer; however, the broadly used direct AMPK inhibitor compound C suffers from poor selectivity. We have discovered a dihydroxyquinoline drug (MT47-100) with novel AMPK regulatory properties, being simultaneously a direct activator and inhibitor of AMPK complexes containing the β1 or β2 isoform, respectively. Allosteric inhibition by MT47-100 was dependent on the β2 carbohydrate-binding module (CBM) and determined by three non-conserved CBM residues (Ile81, Phe91, Ile92), but was independent of β2-Ser108 phosphorylation. Whereas MT47-100 regulation of total cellular AMPK activity was determined by β1/β2 expression ratio, MT47-100 augmented glucose-stimulated insulin secretion from isolated mouse pancreatic islets via a β2-dependent mechanism. Our findings highlight the therapeutic potential of isoform-specific AMPK allosteric inhibitors