Search

Scale and hierarchy have received less attention in aquatic compared to terrestrial systems. Walleye (Sander vitreus) spawning habitat offers an opportunity to investigate scale's importance. We estimated lake-, transect-, and quadrat-scale influences on nearshore walleye egg deposition in 28 Minnesota lakes from 2016-2018. Random forest models (RFM) estimated importance of predictive variables to walleye egg deposition. Predictive accuracies of a multi-scale classification tree (CT) and a quadrat-scale CT were compared. RFM results suggested that five of our variables were unimportant when predicting egg deposition. The multi-scale CT was more accurate than the quadrat-scale CT when predicting egg deposition. Both model results suggest that in-lake egg deposition by walleye is regulated by hierarchical abiotic processes and that silt-clay abundance at the transectscale (reef-scale) is more important than abundance at the quadrat-scale (within-reef). Our results show machine learning can be used for scale-optimization and potentially to determine cross-scale interactions. Further incorporation of scale and hierarchy into studies of aquatic systems will increase our understanding of species-habitat relationships, especially in lentic systems where multi-scale approaches are rarely used. Moins d'attention est accordee a l'echelle et a la hierarchie dans l'etude des systemes aquatiques que dans celle des systemes terrestres. L'habitat de frai du dore jaune (Sander vitreus) offre l'occasion d'etudier l'importance de l'echelle. Nous estimons les influences a l'echelle du lac, du transect et du quadrat sur la ponte pres du rivage de dores dans 28 lacs du Minnesota de 2016 a 2018. Des modeles de foret aleatoire (MFA) permettent d'estimer l'importance de variables predictives pour la ponte des dores. L'exactitude des predictions d'un arbre de classification (AC) multiechelle et d'un AC a l'echelle du quadrat a ete comparee. Les resultats des MFA donnent a penser que cinq des variables examinees ne sont pas importantes pour la prediction de la ponte. L'AC multiechelle est plus exact que l'AC a l'echelle du quadrat pour la prediction de la ponte. Les resultats des deux modeles indiqueraient que la ponte en lac par les dores est modulee par des processus abiotiques hierarchiques et que l'abondance de limon-argile a l'echelle du transect (echelle du recif) est plus importante que l'abondance a l'echelle du quadrat (intra-recif). Nos resultats montrent que l'apprentissage automatique peut etre utilise pour l'optimisation de l'echelle et, eventuellement, pour cerner les interactions inter-echelles. L'integration plus poussee de l'echelle et de la hierarchie dans les etudes de systemes aquatiques rehaussera la comprehension des relations especes-habitats, particulierement dans les systemes lentiques pour lesquels des approches multiechelles sont rarement utilisees. [Traduit par la Redaction], Introduction The spatial unit at which an ecological phenomenon is observed or measured is referred to as 'scale' in ecological literature. The importance of scale when observing an ecological phenomenon [...]

Background and Aim: This study aimed to compare the determinants and impact of hepatocellular carcinoma (HCC) surveillance rates for people with metabolic dysfunction‐associated steatotic liver disease (MASLD) versus other chronic liver diseases. Methods: A dataset of HCC patients from a UK hospital (2007–2022) was analyzed. The Mann–Whitney U‐test compared continuous variables. The χ2 and two‐tailed Fisher exact tests compared categorical data. Regression modeling analyzed the impact of MASLD on the size and number of HCC nodules and curative treatment. The Cox proportional hazards model assessed the influence of MASLD on overall survival. Results: A total of 176 of 687 (25.6%) HCC patients had MASLD. Fewer people with MASLD HCC were enrolled in HCC surveillance compared to non‐MASLD HCC (38 [21.6%] vs 215 [42.1%], P < 0.001). Patients with MASLD HCC were less likely to have been under secondary care (n = 57 [32.4%] vs 259 [50.7%], P < 0.001) and less likely to have cirrhosis (n = 113 [64.2%] vs 417 [81.6%], P < 0.001). MASLD was associated with a 12.3‐mm (95% confidence interval [CI] 10.8–14.0 mm) greater tumor diameter compared to people without MASLD (P = 0.002). Patients with MASLD HCC had 0.62 reduced odds (95% CI 0.43–0.91) of receiving curative treatment compared to non‐MASLD HCC (P = 0.014). Overall survival was similar for patients with MASLD HCC versus non‐MASLD HCC (hazard ratio 1.03, 95% CI 0.85–1.25, P = 0.748). Conclusion: Patients with MASLD are less likely to have been enrolled in HCC surveillance due to undiagnosed cirrhosis or presenting with non‐cirrhotic HCC. Patients with MASLD HCC present with larger tumors and are less likely to receive curative treatment. [ABSTRACT FROM AUTHOR]

For small helical membrane proteins, their structures are highly sensitive to their environment, and solid state NMR is a structural technique that can characterize these membrane proteins in native-like lipid bilayers and proteoliposomes. To date, a systematic method by which to evaluate the effect of the solubilizing detergent on proteoliposome preparations for solid state NMR of membrane proteins has not been presented in the literature. A set of experiments are presented aimed at determining the conditions most amenable to dialysis mediated reconstitution sample preparation. A membrane protein from M. tuberculosis is used to illustrate the method. The results show that a detergent that stabilizes the most protein is not always ideal and sometimes cannot be removed by dialysis. By focusing on the lipid and protein binding properties of the detergent, proteoliposome preparations can be readily produced, which provide double the signal-to-noise ratios for both the oriented sample and magic angle spinning solid state NMR. The method will allow more membrane protein drug targets to be structurally characterized in lipid bilayer environments.

The validation of protein structures through functional assays has been the norm for many years. Functional assays perform this validation for water-soluble proteins very well, but they need to be performed in the same environment as that used for the structural analysis. This is difficult for membrane proteins that are often structurally characterized in detergent environments, although functional assays for these proteins are most frequently performed in lipid bilayers. Because the structure of membrane proteins is known to be sensitive to the membrane mimetic environment, such functional assays are appropriate for validating the protein construct, but not the membrane protein structure. Here, we compare oriented sample solid-state NMR spectral data of diacylglycerol kinase previously published with predictions of such data from recent structures of this protein. A solution NMR structure of diacylglycerol kinase has been obtained in detergent micelles and three crystal structures have been obtained in a monoolein cubic phase. All of the structures are trimeric with each monomer having three transmembrane and one amphipathic helices. However, the solution NMR structure shows typical perturbations induced by a micelle environment that is reflected in the predicted solid-state NMR resonances from the structural coordinates. The crystal structures show few such perturbations, especially for the wild-type structure and especially for the monomers that do not have significant crystal contacts. For these monomers the predicted and observed data are nearly identical. The thermostabilized constructs do show more perturbations, especially the A41C mutation that introduces a hydrophilic residue into what would be the middle of the lipid bilayer inducing additional hydrogen bonding between trimers. These results demonstrate a general technique for validating membrane protein structures with minimal data obtained from membrane proteins in liquid crystalline lipid bilayers by oriented sample solid-state NMR.

Solid-state NMR spectroscopy has been used successfully for characterizing the structure and dynamics of membrane proteins as well as their interactions with other proteins in lipid bilayers. Such an environment is often necessary for achieving native-like structures. Sample preparation is the key to this success. Here we present a detailed description of a robust protocol that results in high-quality membrane protein samples for both magic-angle spinning and oriented-sample solid-state NMR. The procedure is demonstrated using two proteins: CrgA (two transmembrane helices) and Rv1861 (three transmembrane helices), both from Mycobacterium tuberculosis. The success of this procedure relies on two points. First, for samples for both types of NMR experiment, the reconstitution of the protein from a detergent environment to an environment in which it is incorporated into liposomes results in 'complete' removal of detergent. Second, for the oriented samples, proper dehydration followed by rehydration of the proteoliposomes is essential. By using this protocol, proteoliposome samples for magic-angle spinning NMR and uniformly aligned samples (orientational mosaicity of

Evidence that membrane proteins respond conformationally and functionally to their environment is growing. Structural models, by necessity, have been characterized in preparations where the protein has been removed from its native environment. Different structural methods have used various membrane mimetics that have recently included lipid bilayers as a more native-like environment. Structural tools applied to lipid bilayer-embedded integral proteins are informing us about important generic characteristics of how membrane proteins respond to the lipid environment as compared with their response to other nonlipid environments. Here, we review the current status of the field, with specific reference to observations of some well-studied α-helical membrane proteins, as a starting point to aid the development of possible generic principles for model refinement.