Follicle-stimulating hormone receptor (FSHR) is a G-protein coupled receptor (GPCR) and a prototype of the glycoprotein hormone receptors subfamily of GPCRs. Structural data of the FSHR ectodomain in complex with follicle-stimulating hormone suggests a “pull and lift” activation mechanism that triggers a conformational change on the seven α-helix transmembrane domain (TMD). To analyze the conformational changes of the FSHR TMD resulting from sequence variants associated with reproductive impairment in humans, we set up a computational approach combining helix modeling and molecular simulation methods to generate conformational ensembles of the receptor at room (300 K) and physiological (310 K) temperatures. We examined the receptor dynamics in an explicit membrane environment of polyunsaturated phospholipids and solvent water molecules. The analysis of the conformational dynamics of the functional (N680 and S680) and dysfunctional (mutations at D408) variants of the FSHR allowed us to validate the FSHR-TMD model. Functional variants display a concerted motion of flexible intracellular regions at TMD helices 5 and 6. Disruption of side chain interactions and conformational dynamics were detected upon mutation at D408 when replaced with alanine, arginine, or tyrosine. Dynamical network analysis confirmed that TMD helices 2 and 5 may share communication pathways in the functional FSHR variants, whereas no connectivity was detected in the dysfunctional mutants, indicating that the global dynamics of the FSHR was sensitive to mutations at amino acid residue 408, a key position apparently linked to misfolding and variable cell surface plasma membrane expression of FSHRs with distinct mutations at this position.

We describe a novel method to study drastic change in ecosystems, based on generic functions used in the study of phase transitions and related physical phenomena. We illustrate its use by applying it to the problem of shallow lake eutrophication, and express our results in terms of an interplay between phosphorus content in the water column and fluxes of this substance between the lake and both its biological community and its surroundings. We contrast our solution to this problem with a previous one based on the concept of resilience, and on bifurcation analysis of a dynamical equation that also involves phosphorus concentration and fluxes. We then suggest a generalized dynamical scheme incorporating the generic functions above, that reduces to our original method in the stationary condition, and allows in addition dealing with cyclic and chaotic regimes, as illustrated through a particular example.

One of the new status lengths (M-C) qualitatively indicates the transmission risk to an upcoming concurrent partner. The set of four status lengths may be useful in the context of epidemiological models with partnership dynamics.

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