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Understanding how traits affect species responses to threats like habitat loss may help prevent extinctions. This may be especially true for understudied taxa for which we have little data to identify declines before it is too late to intervene. We used a metric derived from citizen science data on snake occurrences to determine which traits were most correlated with species' sensitivity to human land use. We found that snake species that feed primarily on vertebrates, that use a high proportion of aquatic habitats, and that have small geographic ranges occurred in more natural and less human-dominated landscapes. In contrast, body size, clutch (or litter) size, the degree of exposure to human-dominated landscapes, reproductive mode, habitat specialization, and whether a species was venomous or not had less effect on their sensitivity to human land use. Our results extend previous findings that higher trophic position is correlated with extinction risk in many vertebrates by showing that snake species that feed primarily on vertebrates are more sensitive to human land use – a primary driver of extinction. It is likely that conversion of natural landscapes for human land use alters biotic communities, causing losses of important trophic groups, especially in aquatic and riparian communities. Practitioners should therefore prioritize preserving aquatic habitat and natural landscapes with intact biotic communities that can support species at higher trophic levels, as well as focus monitoring on populations of range-restricted species.

Much of the western United States is managed by state and federal agencies for multiple uses, including recreation, grazing, extraction, and defense. Biological inventories are integral to proper management and conservation of biodiversity on these lands. We surveyed for amphibians and reptiles occurring on Naval Air Station Fallon (NAS Fallon), Nevada, USA, using a variety of methods. We documented the presence of a majority of the amphibian and reptile species native to this region of the Great Basin. We found 5 species on NAS Fallon that are listed as Species of Conservation Priority by the Nevada Department of Wildlife: the Great Basin Spadefoot (Spea intermontana), Western Toad (Anaxyrus boreas boreas), Northern Desert Horned Lizard (Phrynosoma platyrhinos platyrhinos), Long-nosed Leopard Lizard (Gambelia wizlizenii), and Great Basin Collared Lizard (Crotaphytus bicinctores). However, we found no evidence of any narrowly distributed species of conservation concern, such as the Northern Leopard Frog (Lithobates pipiens) or Northern Rubber Boa (Charina bottae), that could have occurred on installation lands based on historical or recent observations in nearby areas. Our results indicate that this property, while primarily used for military training, can support a diverse, representative herpetofaunal community. Therefore, NAS Fallon should be considered a valuable part of the network of state and federally managed lands necessary for regional conservation planning in the face of future change. Our study also provides a baseline against which future inventories of this federally managed land can be compared.

Western Pond Turtles (Actinemys marmorata) are endemic to western North America and are found in a diversity of aquatic habitats. To date, few studies have examined the ecology of populations in ephemeral or intermittent ponds. Here, we studied the terrestrial habitat requirements of Western Pond Turtles in an intermittent pond that dries in years with below-average rainfall. We tracked terrestrial movements of Western Pond Turtles in an ephemeral pond at the San Joaquin Experimental Range in Madera County, California, USA, in the western foothills of the Sierra Nevada. We used radiotelemetry in 2012-13 to record their terrestrial locations and timing of departure from, and return to, the pond. Also, we examined the terrestrial microhabitat turtles selected for aestivation and overwintering. Turtles began leaving the pond as it dried in the late spring and early summer, spending an average of 235 d out of water, and their return to the pond was correlated with increasing rainfall during late winter. The majority of terrestrial locations were concealed completely in litter or duff and 95% of terrestrial locations during the study occurred within 187 m of the pond edge. Turtles in our study generally exhibited terrestrial habitat use similar to that of populations in intermittent lotic systems such as the many snow-melt and rain-fed rivers in northern California. Our results reinforce the importance of terrestrial habitat in the life history of Western Pond Turtles and the context-dependence of their habitat needs.

Northern Watersnakes, Nerodia sipedon, have been introduced into California's Central Valley and pose an important new challenge for the management of biodiversity in the state's already greatly distressed freshwater ecosystems. Nonnative watersnakes will likely compete with federally threatened Giant Gartersnakes, Thamnophis gigas, and prey on native amphibians and fish, including young salmonids, many of which are imperiled. We used three types of aquatic funnel traps and three different methods to estimate the abundance and density of N. sipedon in a small wetland in Roseville, California. Capture rates did not differ significantly among the three trap types but snakes captured in large box funnel traps were nearly 300 mm longer on average than those captured in minnow traps. Our estimates of the abundance of N. sipedon in our 2-ha trapping area were similar for the mark-recapture model, Leslie depletion curve, and the actual number of snakes removed over 57 days (112.4-119 individuals; approximately 56.2 snakes/ha). Extrapolating to the entire 6.2-ha aquatic area, the population likely numbered approximately 348 individuals. Several females were gravid, demonstrating successful reproduction by this species outside its native range. We caught more small N. sipedon compared with studies in its native range. This may be due to a sampling bias in our trapping methods but more likely reflects a population growing rapidly from a few initial founders with relatively fewer large adults. We recommend immediate action to prevent the spread and broader establishment of N. sipedon across the Central Valley of California. Copyright 2013 Society for the Study of Amphibians and Reptiles.

Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood. Here, we show that mechanical tension, modeled using cell culture substrate rigidity, influences senescent cell markers like SA-β-gal and secretory phenotypes. Comparing human primary pulmonary fibroblasts (IMR-90) cultured on physiological (2 kPa), fibrotic (50 kPa), and plastic (approximately 3 GPa) substrates, followed by senescence induction using doxorubicin, we identified unique high-stiffness-driven secretory protein profiles using mass spectrometry and transcriptomic signatures, both showing an enrichment in collagen proteins. Consistently, clusters of p21 + cells are seen in fibrotic regions of bleomycin induced pulmonary fibrosis in mice. Computational meta-analysis of single-cell RNA sequencing datasets from human interstitial lung disease confirmed these stiffness SASP genes are highly expressed in disease fibroblasts and strongly correlate with mechanotransduction and senescence-related pathways. Thus, mechanical forces shape cell senescence and their secretory phenotypes., Competing Interests: Declarations. Competing interests: D.F. and D.A.W. are co-founders of Cosmica Biosciences, a company that studies altered biological aging under changes in mechanical force., (© 2025. The Author(s), under exclusive licence to American Aging Association.)

Lysine succinylation, and its reversal by sirtuin-5 (SIRT5), is known to modulate mitochondrial fatty acid β-oxidation (FAO). We recently showed that feeding mice dodecanedioic acid, a 12-carbon dicarboxylic acid (DC 12 ) that can be chain-shortened four rounds to succinyl-CoA, drives high-level protein hypersuccinylation in the peroxisome, particularly on peroxisomal FAO enzymes. However, the ability of SIRT5 to reverse DC 12 -induced peroxisomal succinylation, or to regulate peroxisomal FAO in this context, remained unexplored. Here, we showed that feeding DC 12 strongly recruits SIRT5 into hepatic peroxisomes. Knocking out SIRT5 impaired peroxisomal FAO as evidenced by reduced 14 C-DC 12 flux in liver homogenates and elevated levels of partially shortened DC 12 catabolites in urine. Further, mass spectrometry revealed a trend toward less peroxisomal protein succinylation in SIRT5 knockout liver. This is consistent with a reduced flux of DC 12 through the peroxisomal FAO pathway, thereby reducing the production of the succinyl-CoA that chemically reacts with lysine residues to produce protein succinylation. Mass spectrometry comparisons of site-level succinylation in wildtype and SIRT5 knockout liver did not reveal any clear pattern of SIRT5 target sites in the peroxisome after DC 12 feeding. However, SIRT5 co-immunoprecipitated with 15 peroxisomal proteins, including the key peroxisomal FAO enzymes acyl-CoA oxidase-1 and enoyl-CoA/3-hydroxyacyl-CoA dehydrogenase (EHHADH). In vitro, recombinant SIRT5 partially desuccinylated chemically modified recombinants ACOX1a, ACOX1b, and EHHADH. Desuccinylation by SIRT5 had no effect on enzyme activity for ACOX1a and EHHADH. For ACOX1b, SIRT5-mediated desuccinylation decreased activity by ~15%. Possible interpretations of these data are discussed.

Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood. Here, we show that mechanical tension, modeled using cell culture substrate rigidity, influences senescent cell markers like SA-β-gal and secretory phenotypes. Comparing human primary pulmonary fibroblasts (IMR-90) cultured on physiological (2 kPa), fibrotic (50 kPa), and plastic (approximately 3 GPa) substrates, followed by senescence induction using doxorubicin, we identified unique high-stiffness-driven secretory protein profiles using mass spectrometry and transcriptomic signatures, both showing an enrichment in collagen proteins. Consistently, clusters of p21+ cells are seen in fibrotic regions of bleomycin induced pulmonary fibrosis in mice. Computational meta-analysis of single-cell RNA sequencing datasets from human interstitial lung disease confirmed these stiffness SASP genes are highly expressed in disease fibroblasts and strongly correlate with mechanotransduction and senescence-related pathways. Thus, mechanical forces shape cell senescence and their secretory phenotypes.

Xylan is one of the major hemicelluloses in plant cell walls and its xylosyl backbone is often decorated at O-2 with glucuronic acid (GlcA) and/or methylglucuronic acid (MeGlcA) residues. The GlcA/MeGlcA side chains may be further substituted with 2-O-arabinopyranose (Arap) or 2-O-galactopyranose (Gal) residues in some plant species, but the enzymes responsible for these substitutions remain unknown. During our endeavor to investigate the enzymatic activities of Arabidopsis MUR3-clade members of the GT47 glycosyltransferase family, we found that one of them was able to transfer Arap from UDP-Arap onto O-2 of GlcA side chains of xylan, and thus it was named xylan 2-O-arabinopyranosyltransferase 1 (AtXAPT1). The function of AtXAPT1 was verified in planta by its T-DNA knockout mutation showing a loss of the Arap substitution on xylan GlcA side chains. Further biochemical characterization of XAPT close homologs from other plant species demonstrated that while the poplar ones had the same catalytic activity as AtXAPT1, those from Eucalyptus, lemon-scented gum, sea apple, 'Ohi'a lehua, duckweed and purple yam were capable of catalyzing both 2-O-Arap and 2-O-Gal substitutions of xylan GlcA side chains albeit with differential activities. Sequential reactions with XAPTs and glucuronoxylan methyltransferase 3 (GXM3) showed that XAPTs acted poorly on MeGlcA side chains, whereas GXM3 could efficiently methylate arabinosylated or galactosylated GlcA side chains of xylan. Furthermore, molecular docking and site-directed mutagenesis analyses of Eucalyptus XAPT1 revealed critical roles of several amino acid residues at the putative active site in its activity. Together, these findings establish that XAPTs residing in the MUR3 clade of family GT47 are responsible for 2-O-arabinopyranosylation and 2-O-galactosylation of GlcA side chains of xylan., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Sirtuin-2 (Sirt2), an NAD+-dependent lysine deacylase enzyme, has previously been implicated as a regulator of glucose metabolism, but the specific mechanisms remain poorly defined. Here, we observed that Sirt2-/- males, but not females, have decreased body fat, moderate hypoglycemia upon fasting, and perturbed glucose handling during exercise compared to wild type controls. Conversion of injected lactate, pyruvate, and glycerol boluses into glucose via gluconeogenesis was impaired, but only in males. Primary Sirt2-/- male hepatocytes exhibited reduced glycolysis and reduced mitochondrial respiration. RNAseq and proteomics were used to interrogate the mechanisms behind this liver phenotype. Loss of Sirt2 did not lead to transcriptional dysregulation, as very few genes were altered in the transcriptome. In keeping with this, there were also negligible changes to protein abundance. Site-specific quantification of the hepatic acetylome, however, showed that 13% of all detected acetylated peptides were significantly increased in Sirt2-/- male liver versus wild type, representing putative Sirt2 target sites. Strikingly, none of these putative target sites were hyperacetylated in Sirt2-/- female liver. The target sites in the male liver were distributed across mitochondria (44%), cytoplasm (32%), nucleus (8%), and other compartments (16%). Despite the high number of putative mitochondrial Sirt2 targets, Sirt2 antigen was not detected in purified wild type liver mitochondria, suggesting that Sirt2's regulation of mitochondrial function occurs from outside the organelle. We conclude that Sirt2 regulates hepatic protein acetylation and metabolism in a sex-specific manner.

Plant cell walls are largely composed of polysaccharide polymers, including cellulose, hemicelluloses (xyloglucan, xylan, mannan, and mixed-linkage β-1,3/1,4-glucan), and pectins. Among these cell wall polysaccharides, xyloglucan, xylan, mannan, and pectins are often O -acetylated, and polysaccharide O -acetylation plays important roles in cell wall assembly and disease resistance. Genetic and biochemical analyses have implicated the involvement of three groups of proteins in plant cell wall polysaccharide O -acetylation: trichome birefringence-like (TBL)/domain of unknown function 231 (DUF231), reduced wall acetylation (RWA), and altered xyloglucan 9 (AXY9). Although the exact roles of RWAs and AXY9 are yet to be identified, members of the TBL/DUF231 family have been found to be O -acetyltransferases responsible for the O -acetylation of xyloglucan, xylan, mannan, and pectins. Here, we provide a comprehensive overview of the occurrence of O -acetylated cell wall polysaccharides, the biochemical properties, structural features, and evolution of cell wall polysaccharide O -acetyltransferases, and the potential biotechnological applications of manipulations of cell wall polysaccharide acetylation. Further in-depth studies of the biochemical mechanisms of cell wall polysaccharide O -acetylation will not only enrich our understanding of cell wall biology, but also have important implications in engineering plants with increased disease resistance and reduced recalcitrance for biofuel production.

Objectives: Chondrocyte metabolic dysfunction plays an important role in osteoarthritis (OA) development during aging and obesity. Protein post-translational modifications (PTMs) have recently emerged as an important regulator of cellular metabolism. We aim to study one type of PTM, lysine malonylation (MaK) and its regulator Sirt5 in OA development., Methods: Human and mouse cartilage tissues were used to measure SIRT5 and MaK levels. Both systemic and cartilage-specific conditional knockout mouse models were subject to high-fat diet (HFD) treatment to induce obesity and OA. Proteomics analysis was performed in Sirt5 -/- and WT chondrocytes. SIRT5 mutation was identified in the Utah Population Database (UPDB)., Results: We found that SIRT5 decreases while MAK increases in the cartilage during aging. A combination of Sirt5 deficiency and obesity exacerbates joint degeneration in a sex dependent manner in mice. We further delineate the malonylome in chondrocytes, pinpointing MaK's predominant impact on various metabolic pathways such as carbon metabolism and glycolysis. Lastly, we identified a rare coding mutation in SIRT5 that dominantly segregates in a family with OA. The mutation results in substitution of an evolutionally invariant phenylalanine (Phe-F) to leucine (Leu-L) (F101L) in the catalytic domain. The mutant protein results in higher MaK level and decreased expression of cartilage ECM genes and upregulation of inflammation associated genes., Conclusions: We found that Sirt5 mediated MaK is an important regulator of chondrocyte cellular metabolism and dysregulation of Sirt5-MaK could be an important mechanism underlying aging and obesity associated OA development.

Background and Aims: The California Floristic Province (CA-FP) is the most species-rich region of North America north of Mexico. One of several proposed hypotheses explaining the exceptional diversity of the region is that the CA-FP harbours myriad recently diverged lineages with nascent reproductive barriers. Salvia subgenus Audibertia is a conspicuous element of the CA-FP, with multiple sympatric and compatible species., Methods: Using 305 nuclear loci and both organellar genomes, we reconstruct species trees, examine genomic discordance, conduct divergence-time estimation, and analyse contemporaneous patterns of gene flow and mechanical reproductive isolation., Key Results: Despite strong genomic discordance, an underlying bifurcating tree is supported. Organellar genomes capture additional introgression events not detected in the nuclear genome. Most interfertility is found within clades, indicating that reproductive barriers arise with increasing genetic divergence. Species are generally not mechanically isolated, suggesting that it is unlikely to be the primary factor leading to reproductive isolation., Conclusions: Rapid, recent speciation with some interspecific gene flow in conjunction with the onset of a Mediterranean-like climate is the underlying cause of extant diversity in Salvia subgenus Audibertia. Speciation has largely not been facilitated by gene flow. Its signal in the nuclear genome seems to mostly be erased by backcrossing, but organellar genomes each capture different instances of historical gene flow, probably characteristic of many CA-FP lineages. Mechanical reproductive isolation appears to be only part of a mosaic of factors limiting gene flow., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Senescence emerged as a significant mechanism of aging and age-related diseases, offering an attractive target for clinical interventions. Senescent cells release a senescence-associated secretory phenotype (SASP), including exosomes that may act as signal transducers between distal tissues, propagating secondary or bystander senescence and signaling throughout the body. However, the composition of exosome SASP remains underexplored, presenting an opportunity for novel unbiased discovery. Here, we present a detailed proteomic and lipidomic analysis of exosome SASP using mass spectrometry from human plasma from young and older individuals and from tissue culture of senescent primary human lung fibroblasts. We identified ~1,300 exosome proteins released by senescent fibroblasts induced by three different senescence inducers causing most exosome proteins to be differentially regulated with senescence. In parallel, a human plasma cohort from young and old individuals revealed over 1,350 exosome proteins and 171 plasma exosome proteins were regulated when comparing old vs young individuals. Of the age-regulated plasma exosome proteins, we observed 52 exosome SASP factors that were also regulated in exosomes from the senescent fibroblasts, including serine protease inhibitors (SERPINs), Prothrombin, Coagulation factor V, Plasminogen, and Reelin. In addition, 247 lipids were identified with high confidence in all exosome samples. Following the senescence inducers, a majority of the identified phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin species increased significantly indicating cellular membrane changes. The most notable categories of significantly changed proteins were related to extracellular matrix remodeling and inflammation, both potentially detrimental pathways that can damage surrounding tissues and even induce secondary or bystander senescence. Our findings reveal mechanistic insights and potential senescence biomarkers, enabling a better approach to surveilling the senescence burden in the aging population and offering promising therapeutic targets for interventions.

Lysine malonylation is a protein posttranslational modification. We present a protocol to generate stable gene-knockdown K562 cell lines through lentiviral infection of a CRISPR interference (CRISPRi) system followed by lysine malonylation measurement using mass spectrometry (MS). We detail guide RNA (gRNA) vector cloning, lentiviral infection, cell line purification, protein digestion, malonyl-lysine enrichment, desalting, and MS acquisition and analysis. For complete details on the use and execution of this protocol, please refer to Zhang et al. 1 and Bons et al. 2 ., Competing Interests: Declaration of interests E.V. is a scientific co-founder of Napa Therapeutics and serves on the scientific advisory board of Seneque., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

During cellular senescence, persistent growth arrest and changes in protein expression programs are accompanied by a senescence-associated secretory phenotype (SASP). In this study, we detected the upregulation of the SASP-related protein dipeptidyl peptidase 4 (DDP4) in human primary lung cells rendered senescent by exposure to ionizing radiation. DPP4 is an exopeptidase that plays a crucial role in the cleavage of various proteins, resulting in the loss of N-terminal dipeptides and proinflammatory effects. Interestingly, our data revealed an association between severe coronavirus disease 2019 (COVID-19) and DDP4, namely that DPP4 levels increased in the plasma of patients with COVID-19 and were correlated with age and disease progression. Although we could not determine the direct effect of DDP4 on viral replication, mechanistic studies in cell culture revealed a negative impact on the expression of the tight junction protein zonula occludens-1 (ZO-1), which contributes to epithelial barrier function. Mass spectrometry analysis indicated that DPP4 overexpressing cells exhibited a decrease in ZO-1 and increased expression of pro-inflammatory cytokines and chemokines. By investigating the effect of DPP4 on the barrier function of human primary cells, we detected an increase in ZO-1 using DPP4 inhibitors. These results provide an important contribution to our understanding of DPP4 in the context of senescence, suggesting that DPP4 plays a major role as part of the SASP. Our results provide evidence that cellular senescence, a hallmark of aging, has an important impact on respiratory infections.

Main Conclusion: A member of the rice GT61 clade B is capable of transferring both 2-O-xylosyl and 2-O-arabinosyl residues onto xylan and another member specifically catalyses addition of 2-O-xylosyl residue onto xylan. Grass xylan is substituted predominantly with 3-O-arabinofuranose (Araf) as well as with some minor side chains, such as 2-O-Araf and 2-O-(methyl)glucuronic acid [(Me)GlcA]. 3-O-Arabinosylation of grass xylan has been shown to be catalysed by grass-expanded clade A members of the glycosyltransferase family 61. However, glycosyltransferases mediating 2-O-arabinosylation of grass xylan remain elusive. Here, we performed biochemical studies of two rice GT61 clade B members and found that one of them was capable of transferring both xylosyl (Xyl) and Araf residues from UDP-Xyl and UDP-Araf, respectively, onto xylooligomer acceptors, whereas the other specifically catalysed Xyl transfer onto xylooligomers, indicating that the former is a xylan xylosyl/arabinosyl transferase (named OsXXAT1 herein) and the latter is a xylan xylosyltransferase (named OsXYXT2). Structural analysis of the OsXXAT1- and OsXYXT2-catalysed reaction products revealed that the Xyl and Araf residues were transferred onto O-2 positions of xylooligomers. Furthermore, we demonstrated that OsXXAT1 and OsXYXT2 were able to substitute acetylated xylooligomers, but only OsXXAT1 could xylosylate GlcA-substituted xylooligomers. OsXXAT1 and OsXYXT2 were predicted to adopt a GT-B fold structure and molecular docking revealed candidate amino acid residues at the predicted active site involved in binding of the nucleotide sugar donor and the xylohexaose acceptor substrates. Together, our results establish that OsXXAT1 is a xylan 2-O-xylosyl/2-O-arabinosyl transferase and OsXYXT2 is a xylan 2-O-xylosyltransferase, which expands our knowledge of roles of the GT61 family in grass xylan synthesis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRII ocy-/- ) that suppresses PLR. The control aged bone displayed decreased TGFβ signaling and PLR, but aging did not worsen the existing PLR suppression in male TβRII ocy-/- bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFβ. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity., (© 2024. The Author(s).)

Permeation enhancers (PEs) are a class of molecules that interact with the epithelial membrane and transiently increase its transcellular permeability. Although there have been few clinical trials of PE coformulated drugs, the mechanism of action of PEs remains elusive. In this paper, the interaction between two archetypes of PEs [salcaprozate sodium (SNAC) and sodium caprate (C10)] and membranes is investigated with extensive all-atom molecular dynamics simulations. The simulations show that (1) the association between the neutral PEs and membranes is favored in free energy, (2) the propensity of neutral PE aggregation is larger in aqueous solution than in lipid bilayers, (3) the equilibrium distribution of neutral PEs in membranes is fast, e.g., accessible with unbiased MD simulations, and (4) the micelle of neutral PEs formed in aqueous solution does not rupture the membranes (e.g., not forming pores or breaking up the membrane) under simulation conditions. All results combined, this study indicates that PEs insert into the membranes in an equilibrium or near equilibrium process. This study lays the foundation for future investigations of how PEs impact the free energy of permeation for small molecules.

Whereas prior research has found that people are influenced by both internal (e.g., dimensional) and external (e.g., social) comparative information in academic contexts, we experimentally examined the influence of such comparisons in a health fitness context. Participants engaged in "physical and mental fitness" tasks (e.g., performing sit-ups, memorizing words) and were randomly assigned to receive (1) social comparative feedback indicating their physical or mental fitness was better or worse than their peers or (2) dimensional comparative feedback indicating their performance in a target domain (e.g., mental fitness) was better or worse than a referent domain (e.g., physical fitness). Results showed that participants who made upward comparisons had lower fitness self-evaluations and more negative (less positive) emotional reactions to the feedback for the target domain, with the effect being nominally stronger for social than dimensional comparisons and for mental than physical fitness. Findings are discussed in the context of comparison-based models and health behavior theories., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Significance Statement: In this study, we demonstrate that a common, low-cost compound known as octanedioic acid (DC 8 ) can protect mice from kidney damage typically caused by ischemia-reperfusion injury or the chemotherapy drug cisplatin. This compound seems to enhance peroxisomal activity, which is responsible for breaking down fats, without adversely affecting mitochondrial function. DC 8 is not only affordable and easy to administer but also effective. These encouraging findings suggest that DC 8 could potentially be used to assist patients who are at risk of experiencing this type of kidney damage., Background: Proximal tubules are rich in peroxisomes, which are damaged during AKI. Previous studies demonstrated that increasing peroxisomal fatty acid oxidation (FAO) is renoprotective, but no therapy has emerged to leverage this mechanism., Methods: Mice were fed with either a control diet or a diet enriched with dicarboxylic acids, which are peroxisome-specific FAO substrates, then subjected to either ischemia-reperfusion injury-AKI or cisplatin-AKI models. Biochemical, histologic, genetic, and proteomic analyses were performed., Results: Both octanedioic acid (DC 8 ) and dodecanedioic acid (DC 12 ) prevented the rise of AKI markers in mice that were exposed to renal injury. Proteomics analysis demonstrated that DC 8 preserved the peroxisomal and mitochondrial proteomes while inducing extensive remodeling of the lysine succinylome. This latter finding indicates that DC 8 is chain shortened to the anaplerotic substrate succinate and that peroxisomal FAO was increased by DC 8 ., Conclusions: DC 8 supplementation protects kidney mitochondria and peroxisomes and increases peroxisomal FAO, thereby protecting against AKI., (Copyright © 2023 by the American Society of Nephrology.)

People vary in their individual tendencies to compare to others-referred to as social comparison orientation (SCO). Researchers have heretofore developed and validated a scale to assess SCO-the Iowa-Netherlands Comparison Orientation Measure (INCOM). The standard INCOM assesses non-directional comparisons, but not directional comparisons to better- and worse-off others. The goal of the present research was to examine the factor structure and validity of directional (and non-directional) comparison tendencies using the expanded INCOM. Across four archival studies and one pre-registered study using student and non-student samples, we provide evidence for 1) a 3-factor structure for the INCOM with non-directional, directional-upward, and directional-downward SCO dimensions, 2) inter-correlations among the SCO dimensions suggesting convergent validity of the directional scales, 3) greater endorsement of non-directional, then directional-upward, and directional-downward SCO, 4) lower SCO among older individuals and members of racial/ethnic minority groups, and 5) strong and consistent associations of directional-upward SCO with well-being and affect, appearance beliefs (e.g., body satisfaction), social emotions (e.g., envy), and agency-related motivations and consequences in interpersonal contexts, but smaller and less consistent associations of non-directional and directional-downward SCO with outcomes (with notable exceptions). Taken together, this research indicates that SCO is a multi-faceted individual difference variable.

Assessing perceived vulnerability to a health threat is essential to understanding how people conceptualize their risk, and to predicting how likely they are to engage in protective behaviors. However, there is limited consensus about which of many measures of perceived vulnerability predict behavior best. We tested whether the ability of different measures to predict protective intentions varies as a function of the type of information people learn about their risk. Online participants (N = 909) read information about a novel respiratory disease before answering measures of perceived vulnerability and vaccination intentions. Type-of-risk information was varied across three between-participant groups. Participants learned either: (1) only information about their comparative standing on the primary risk factors (comparative-only), (2) their comparative standing as well as the base-rate of the disease in the population (+ base-rate), or (3) their comparative standing as well as more specific estimates of their absolute risk (+ absolute-chart). Experiential and affective measures of perceived vulnerability predicted protective intentions well regardless of how participants learned about their risk, while the predictive ability of deliberative numeric and comparative measures varied based on the type of risk information provided. These results broaden the generalizability of key prior findings (i.e., some prior findings about which measures predict best may apply no matter how people learn about their risk), but the results also reveal boundary conditions and critical points of distinction for determining how to best assess perceived vulnerability., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The ovarian microenvironment becomes fibrotic and stiff with age, in part due to increased collagen and decreased hyaluronan. However, the extracellular matrix (ECM) is a complex network of hundreds of proteins, glycoproteins, and glycans which are highly tissue specific and undergo pronounced changes with age. To obtain an unbiased and comprehensive profile of age-associated alterations to the murine ovarian proteome and ECM, we used a label-free quantitative proteomic methodology. We validated conditions to enrich for the ECM prior to proteomic analysis. Following analysis by data-independent acquisition (DIA) and quantitative data processing, we observed that both native and ECM-enriched ovaries clustered separately based on age, indicating distinct age-dependent proteomic signatures. We identified a total of 4,721 proteins from both native and ECM-enriched ovaries, of which 383 proteins were significantly altered with advanced age, including 58 ECM proteins. Several ECM proteins upregulated with age have been associated with fibrosis in other organs, but to date their roles in ovarian fibrosis are unknown. Pathways regulating DNA metabolism and translation were downregulated with age, whereas pathways involved in ECM remodeling and immune response were upregulated. Interestingly, immune-related pathways were upregulated with age even in ECM-enriched ovaries, suggesting a novel interplay between the ECM and the immune system. Moreover, we identified putative markers of unique immune cell populations present in the ovary with age. These findings provide evidence from a proteomic perspective that the aging ovary provides a fibroinflammatory milieu, and our study suggests target proteins which may drive these age-associated phenotypes for future investigation.

Dysregulation of cell signaling in chondrocytes and in bone cells, such as osteocytes, osteoblasts, osteoclasts, and an elevated burden of senescent cells in cartilage and bone, are implicated in osteoarthritis (OA). Mass spectrometric analyses provides a crucial molecular tool-kit to understand complex signaling relationships in age-related diseases, such as OA. Here we introduce a novel mass spectrometric workflow to promote proteomic studies of bone. This workflow uses highly specialized steps, including extensive overnight demineralization, pulverization, and incubation for 72 h in 6 M guanidine hydrochloride and EDTA, followed by proteolytic digestion. Analysis on a high-resolution Orbitrap Eclipse and Orbitrap Exploris 480 mass spectrometer using Data-Independent Acquisition (DIA) provides deep coverage of the bone proteome, and preserves post-translational modifications, such as hydroxyproline. A spectral library-free quantification strategy, directDIA, identified and quantified over 2,000 protein groups (with ≥ 2 unique peptides) from calcium-rich bone matrices. Key components identified were proteins of the extracellular matrix (ECM), bone-specific proteins (e.g., secreted protein acidic and cysteine rich, SPARC, and bone sialoprotein 2, IBSP), and signaling proteins (e.g., transforming growth factor beta-2, TGFB2), and lysyl oxidase homolog 2 (LOXL2), an important protein in collagen crosslinking. Post-translational modifications (PTMs) were identified without the need for specific enrichment. This includes collagen hydroxyproline modifications, chemical modifications for collagen self-assembly and network formation. Multiple senescence factors were identified, such as complement component 3 (C3) protein of the complement system and many matrix metalloproteinases, that might be monitored during age-related bone disease progression. Our innovative workflow yields in-depth protein coverage and quantification strategies to discover underlying biological mechanisms of bone aging and to provide tools to monitor therapeutic interventions. These novel tools to monitor the bone proteome open novel horizons to investigate bone-specific diseases, many of which are age-related., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rose et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

For endangered species persisting in a few populations, reintroductions to unoccupied habitat are a popular conservation action to increase viability in the long term. Identifying the reintroduction strategy that is most likely to result in viable founder and donor populations is essential to optimally use resources available for conservation. The San Francisco gartersnake (Thamnophis sirtalis tetrataenia) is an endangered sub-species that persists in a small number of populations in a highly urbanized region of California. Most of the extant populations of San Francisco gartersnakes have low adult abundance and effective population size, heightening the need for establishment of more populations for insurance against the risk of extinction. We used simulations from demographic models to project the probability of quasi-extinction for reintroduced populations of San Francisco gartersnakes based on the release of neonate, juvenile, adult, or mixed-age propagules. Our simulation results indicated that the release of head-started juveniles resulted in the greatest viability of reintroduced populations, and that releases would need to continue for at least 15 years to ensure a low probability of quasi-extinction. Releasing captive-bred juvenile snakes would also have less effect on the viability of the donor population, compared to strategies that require more adult snakes to be removed from the donor population for translocation. Our models focus on snake demography, but the genetic makeup of donor, captive, and reintroduced populations will also be a major concern for any proposed reintroduction plan. This study demonstrates how modeling can be used to inform reintroduction strategies for highly imperiled species., Competing Interests: The authors have declared that no competing interests exits., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Biogeographic disjunctions, including intercontinental disjunctions, are frequent across plant lineages and have been of considerable interest to biologists for centuries. Their study has been reinvigorated by molecular dating and associated comparative methods. One of the "classic" disjunction patterns is that between Eastern Asia and North America. It has been speculated that this pattern is the result of vicariance following the sundering of a widespread Acrto-Teritary flora. Subtribe Nepetinae in the mint family (Lamiaceae) is noteworthy because it contains three genera with this disjunction pattern: Agastache, Dracocephalum, and Meehania. These disjunctions are ostensibly the result of three separate events, allowing for concurrent testing of the tempo, origin, and type of each biogeographic event. Using four plastid and four nuclear markers, we estimated divergence times and analyzed the historical biogeography of Nepetinae, including comprehensive sampling of all major clades for the first time. We recover a well-supported and largely congruent phylogeny of Nepetinae between genomic compartments, although several cases of cyto-nuclear discordance are evident. We demonstrate that the three disjunctions are pseudo-congruent, with unidirectional movement from East Asia at slightly staggered times during the late Miocene and early Pliocene. With the possible exception of Meehania, we find that vicariance is likely the underlying driver of these disjunctions. The biogeographic history of Meehania in North America may be best explained by long-distance dispersal, but a more complete picture awaits deeper sampling of the nuclear genome and more advanced biogeographical models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Premise: Floral evolution in large clades is difficult to study not only because of the number of species involved, but also because they often are geographically widespread and include a diversity of outcrossing pollination systems. The cosmopolitan blueberry family (Ericaceae) is one such example, most notably pollinated by bees and multiple clades of nectarivorous birds., Methods: We combined data on floral traits, pollination ecology, and geography with a comprehensive phylogeny to examine the structuring of floral diversity across pollination systems and continents. We focused on ornithophilous systems to test the hypothesis that some Old World Ericaceae were pollinated by now-extinct hummingbirds., Results: Despite some support for floral differentiation at a continental scale, we found a large amount of variability within and among landmasses, due to both phylogenetic conservatism and parallel evolution. We found support for floral differentiation in anther and corolla traits across pollination systems, including among different ornithophilous systems. Corolla traits show inconclusive evidence that some Old World Ericaceae were pollinated by hummingbirds, while anther traits show stronger evidence. Some major shifts in floral traits are associated with changes in pollination system, but shifts within bee systems are likely also important., Conclusions: Studying the floral evolution of large, morphologically diverse, and widespread clades is feasible. We demonstrate that continent-specific radiations have led to widespread parallel evolution of floral morphology. We show that traits outside of the perianth may hold important clues to the ecological history of lineages., (© 2023 Botanical Society of America.)

Objective: Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RA) and fibroblast growth factor-21 (FGF21) confer similar metabolic benefits. GLP-1RA induce FGF21, leading us to investigate mechanisms engaged by the GLP-1RA liraglutide to increase FGF21 levels and the metabolic relevance of liraglutide-induced FGF21., Methods: Circulating FGF21 levels were measured in fasted male C57BL/6J, neuronal GLP-1R knockout, β-cell GLP-1R knockout, and liver peroxisome proliferator-activated receptor alpha knockout mice treated acutely with liraglutide. To test the metabolic relevance of liver FGF21 in response to liraglutide, chow-fed control and liver Fgf21 knockout (Liv Fgf21-/- ) mice were treated with vehicle or liraglutide in metabolic chambers. Body weight and composition, food intake, and energy expenditure were measured. Since FGF21 reduces carbohydrate intake, we measured body weight in mice fed matched diets with low- (LC) or high-carbohydrate (HC) content and in mice fed a high-fat, high-sugar (HFHS) diet. This was done in control and Liv Fgf21-/- mice and in mice lacking neuronal β-klotho (Klb) expression to disrupt brain FGF21 signaling., Results: Liraglutide increases FGF21 levels independently of decreased food intake via neuronal GLP-1R activation. Lack of liver Fgf21 expression confers resistance to liraglutide-induced weight loss due to attenuated reduction of food intake in chow-fed mice. Liraglutide-induced weight loss was impaired in Liv Fgf21-/- mice when fed HC and HFHS diets but not when fed a LC diet. Loss of neuronal Klb also attenuated liraglutide-induced weight loss in mice fed HC or HFHS diets., Conclusions: Our findings support a novel role for a GLP-1R-FGF21 axis in regulating body weight in a dietary carbohydrate-dependent manner., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

To identify factors that increase risk for nonadherence to recommended health protective behaviors during pandemics, this study examined the prospective relations of substance use frequency to both adherence to social distancing recommendations and social distancing intentions during the COVID-19 pandemic, as well as the role of social distancing self-efficacy in these relations. A U.S. community sample of 377 adults completed a prospective online study, including an initial assessment between March 27 and April 5, 2020, and a follow-up assessment one-month later. Results revealed a significant direct relation of baseline substance use frequency to lower adherence to social distancing recommendations one-month later. Results also revealed significant indirect relations of greater substance use frequency to lower levels of both social distancing behaviors and intentions one-month later through lower social distancing self-efficacy. Results highlight the relevance of substance use and social distancing self-efficacy to lower adherence to social distancing during the COVID-19 pandemic., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In 2020, a novel emerging infectious disease - COVID-19 - became a global pandemic and prompted unprecedented social distancing measures. We examined the associations of voluntary stay-at-home (SAH) orders during the COVID-19 pandemic with vulnerability assessments and precautionary intentions (e.g. social distancing, hand washing). A quasi-experimental study using an online adult sample was conducted in U.S. states with and without voluntary SAH orders during the COVID-19 pandemic. Self-report surveys assessed vulnerability assessments and precautionary intentions. Participants living in states with SAH orders showed inflated vulnerability assessments for contracting COVID-19, and this association was stronger for affect-laden than cognitively-based assessments. Moreover, only affect-laden vulnerability assessments were uniquely associated with precautionary intentions and accounted for the relationship between SAH orders and precautionary intentions. Our study was among the first to explore the impact of voluntary SAH orders on vulnerability assessments and precautionary intentions. Results are discussed in terms of their implications for health behavioral models and applications for promoting self-protective actions during a pandemic.

Despite evidence often showing differences between groups with Autism Spectrum Disorder (ASD) and neurotypical controls in moral judgment, the precise nature of these differences has been difficult to establish. At least two reasons for this are (1) that ASD (and its associated characteristics) is difficult to define and (2) that morality, and the inclinations that undergird it, are hard to measure empirically. These challenges have made conclusive associations between ASD and particular patterns of moral judgment hard to come by. Thus, in the current study, participants levels of a traits associated with ASD were assessed by their responses to a questionnaire (i.e., the Iowa Screener) before they made moral judgments across a set of 20 moral dilemmas that independently assess utilitarian and deontological processing. Interestingly, results indicated that increased levels of autistic traits were associated with fewer moral judgments corresponding to either moral theory; that is, higher levels of autistic traits were associated with atypical patterns of moral judgment. In addition, and consistent with some prior methods (e.g., Gaeth et al., 2016), participant scores on the Iowa Screener, as well as their self-identification, were used to categorize participants between two groups (i.e., ASD and Typical) for exploratory purposes. Taken together, this research better informs the relationship between ASD and its associated traits with moral judgment and can inform certain discrepant findings in the field. Implications and ideas for future research are discussed, such as whether traits associated with ASD might relate to alternative moral inclinations, beyond deontology and utilitarianism., Competing Interests: Declaration of competing interest The authors of the manuscript entitled “Increased Levels of Autistic Traits are Associated with Atypical Moral Judgments” have no conflicts of interest to report in any form, including funding and relationships., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Vaccine hesitancy-delays in vaccine uptake when one is readily available-is an important public health issue. During the COVID-19 pandemic, the role of psychosocial factors in influencing cognitions and behaviors related to vaccine uptake have been examined. Using an online sample of unvaccinated U.S. adults (N = 300), we examined the influence of COVID-19-related social media-based comparison information (e.g., others' attitudes about taking the vaccine)-as well as the moderating impact of (dis)similarity mindsets and indirect influence of affective associations, norm perceptions, and self-evaluations of efficacy-on vaccination uptake intentions. Participants reported higher intentions for vaccine uptake following exposure to cautious comparison models (e.g., those that engaged in health prevention behaviors, intended to get vaccinated) versus risky comparison models (e.g., those who did not engage in health prevention behaviors, did not intend to get vaccinated) and neutral comparison models and this effect was indirect through positive affective associations about taking the vaccine. There were no main or interactive effects of (dis)similarity mindsets. Understanding the psychosocial factors that influence health cognitions and behaviors in the context of an infectious disease pandemic will advance theoretical development and aid in creating interventions targeting vaccine uptake., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

We have previously suggested that a shift from bee to hummingbird pollination, in concert with floral architecture modifications, occurred at the crown of Salvia subgenus Calosphace in North America ca. 20 mya (Kriebel et al. 2020 and references therein). Sazatornil et al. (2022), using a hidden states model, challenged these assertions, arguing that bees were the ancestral pollinator of subg. Calosphace and claiming that hummingbirds could not have been the ancestral pollinator of subg. Calosphace because hummingbirds were not contemporaneous with crown subg. Calosphace in North America. Here, using a variety of models, we demonstrate that most analyses support hummingbirds as ancestral pollinators of subg. Calosphace and show that Sazatornil et al. (2022) erroneously concluded that hummingbirds were absent from North America ca. 20 mya. We contend that "biological realism" - based on timing and placement of hummingbirds in Mexico ca. 20 mya and the correlative evolution of hummingbird associated floral traits - must be considered when comparing models based on fit and complexity, including hidden states models., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Society for the Study of Evolution (SSE). All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Glucagon-like peptide-1 receptor (GLP-1R) agonists and fibroblast growth factor 21 (FGF21) confer similar metabolic benefits. Studies report that GLP-1RA induce FGF21. Here, we investigated the mechanisms engaged by the GLP-1R agonist liraglutide to increase FGF21 levels and the metabolic relevance of liraglutide-induced FGF21. We show that liraglutide increases FGF21 levels via neuronal GLP-1R activation. We also demonstrate that lack of liver Fgf21 expression confers partial resistance to liraglutide-induced weight loss. Since FGF21 reduces carbohydrate intake, we tested whether the contribution of FGF21 to liraglutide-induced weight loss is dependent on dietary carbohydrate content. In control and liver Fgf21 knockout (Liv Fgf21 -/- ) mice fed calorically matched diets with low- (LC) or high-carbohydrate (HC) content, we found that only HC-fed Liv Fgf21 -/- mice were resistant to liraglutide-induced weight loss. Similarly, liraglutide-induced weight loss was partially impaired in Liv Fgf21 -/- mice fed a high-fat, high-sugar (HFHS) diet. Lastly, we show that loss of neuronal β-klotho expression also diminishes liraglutide-induced weight loss in mice fed a HC or HFHS diet, indicating that FGF21 mediates liraglutide-induced weight loss via neuronal FGF21 action. Our findings support a novel role for a GLP-1R-FGF21 axis in regulating body weight in the presence of high dietary carbohydrate content.

The perennial herb Western Jacob's Ladder (Polemonium occidentale, Polemoniaceae) is widespread in the mountains of western North America but reappears as a disjunct in the Great Lakes Region in Minnesota and Wisconsin, USA as the narrow endemic P. occidentale subsp. lacustre. This distribution is shown by a diverse assemblage of angiosperms. It has been hypothesized that these species became isolated just after the Last Glacial Maximum, but this has not been tested. Additionally, the genetic diversity and population connectivity of the endemic Great Lakes flora has been understudied, with important conservation implications. Using genotyping-by-sequencing, we examined the relationship of P. occidentale subsp. lacustre to its closest relatives, relationships among all known populations, and genetic diversity within these populations. Polemonium occidentale subsp. lacustre represents an isolated, unique lineage that diverged from its closest relatives 1.3 Ma and arrived in the Great Lakes Region by at least 38 ka. Nearly all extant populations diverged prior to the Last Glacial Maximum, are genetically distinct, and show little within-population genetic diversity. Clonality may mitigate reduction in diversity due to drift. Mixed population signal between Wisconsin and some Minnesota populations may be due to gene flow during the Late Pleistocene. While populations of P. occidentale subsp. lacustre may be relictual from a now extinct western relative, it is best treated as a distinct species. Conservation efforts should focus more on ensuring that current populations remain rather than maintaining large populations sizes across a few populations. However, encouraging habitat heterogeneity may accomplish both simultaneously., (© 2022 John Wiley & Sons Ltd.)

Numerous health behavior models have emphasized absolute risk perceptions as prominent predictors of future behavior and intentions, but more recent research has shown that people also attend to comparative risk information. While most research highlights external (social) comparisons as the primary way people contextualize risk, it is also possible that people use internal comparisons, such as comparing their current risk to their past risk (temporal comparisons) or comparing their risk for one health threat to their risk for another health threat (dimensional comparisons). Objective: The current research sought to examine differences in absolute, external, and internal comparative risk perceptions across a variety of health threats. Design: This study utilized a cross-sectional design wherein participants completed all study materials online. Main outcome measures: MTurk workers ( N  = 654) responded to questions about absolute and comparative risk perceptions, concern, and precautionary intentions. Results: Hierarchical regression analyses revealed that although absolute risk perceptions were positively associated with concern and precautionary intentions for all health threats, comparative risk perceptions also accounted for unique variance in all models. Internal comparisons were uniquely associated with concern and intentions even when accounting for absolute and external comparative risk perceptions in nearly all models. Conclusion: These findings provide the first systematic evidence for the utility of incorporating internal comparisons into models of risk perception.

Estimates of demographic rates for animal populations and individuals have many applications for ecological and conservation research. In many animals, survival is size-dependent, but estimating the form of the size-survival relationship presents challenges. For elusive species with low recapture rates, individuals' size will be unknown at many points in time. Integrating growth and capture-mark-recapture models in a Bayesian framework empowers researchers to impute missing size data, with uncertainty, and include size as a covariate of survival, capture probability, and presence on-site. If there is no theoretical expectation for the shape of the size-survival relationship, spline functions can allow for fitting flexible, data-driven estimates. We use long-term capture-mark-recapture data from the endangered San Francisco gartersnake ( Thamnophis sirtalis tetrataenia ) to fit an integrated growth-survival model. Growth models showed that females reach longer asymptotic lengths than males and that the magnitude of sexual size dimorphism differed among populations. The capture probability and availability of San Francisco gartersnakes for capture increased with snout-vent length. The survival rate of female snakes exhibits a nonlinear relationship with snout-vent length (SVL), with survival flat between 300 mm and 550 mm SVL before decreasing for females between 550 mm and 700 mm SVL. For male snakes, survival decreased for adult males >550 mm SVL. The survival rates of the smallest and largest San Francisco gartersnakes were highly uncertain because recapture rates were very low for these sizes. By integrating growth and survival models and using penalized splines, we found support for size-dependent survival in San Francisco gartersnakes. Our results have applications for devising management activities for this endangered subspecies, and our methods could be applied broadly to the study of size-dependent demography among animals., Competing Interests: We have no conflict of interest to disclose., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Ecology and Evolution published by John Wiley & Sons Ltd.)

A protocol that accurately assesses the intestinal permeability of small molecule compounds plays an essential role in decreasing the cost and time in inventing a new drug. This manuscript presents a novel computational method to study the passive permeation of small molecule drugs based on the inhomogeneous solubility-diffusion model. The multidimensional free energy surface of the drug transiting through a lipid bilayer is computed with transition-tempered metadynamics that accurately captures the mechanisms of passive permeation. The permeability is computed by following the diffusion motion of the drug molecules along the minimal free energy path found on the multidimensional free energy surface. This computational method is assessed by studying the permeability of five small molecule drugs (ketoprofen, naproxen, metoprolol, propranolol, and salicylic acid). The results demonstrate a remarkable agreement between the computed permeabilities and those measured with the intestinal assay. The in silico method reported in this manuscript also reproduces the permeability measured from the intestinal assay ( in vivo ) better than the cell-based assays (e.g., PAMPA and Caco-2) do. In addition, the multidimensional free energy surface reveals the interplay between the structure of the small molecule and its permeability, shedding light on strategies of drug optimization.

Oral drug absorption modeling has developed at a rapid pace in the 40 years or so since the first ideas for mathematical approaches to oral absorption were introduced. The success of compartmental approaches accelerated the uptake of absorption modeling, and over the last 20 years, work on absorption modeling has shifted almost exclusively to the compartmental framework. This report describes a new noncompartmental absorption modeling framework, the Lilly Absorption Modeling Platform (LAMP). LAMP connects a well-mixed stomach to a continuous tube model of the small intestine with plug flow. Within the continuous tube framework, the model includes intestinal mixing and a novel highly tunable precipitation model that can describe a combination of rapid nucleation and slow growth. The framework is designed to balance speed, consistency, and ease of use with a minimum of model complexity to capture the essential features of gastrointestinal (GI) physiology and critical elements of the oral absorption process. The model was validated based on predictions of the fraction absorbed and the maximum absorbable dose for a set of Eli Lilly and Company clinical compounds.

Next-generation sequencing technologies have facilitated new phylogenomic approaches to help clarify previously intractable relationships while simultaneously highlighting the pervasive nature of incongruence within and among genomes that can complicate definitive taxonomic conclusions. Salvia L., with ∼1,000 species, makes up nearly 15% of the species diversity in the mint family and has attracted great interest from biologists across subdisciplines. Despite the great progress that has been achieved in discerning the placement of Salvia within Lamiaceae and in clarifying its infrageneric relationships through plastid, nuclear ribosomal, and nuclear single-copy genes, the incomplete resolution has left open major questions regarding the phylogenetic relationships among and within the subgenera, as well as to what extent the infrageneric relationships differ across genomes. We expanded a previously published anchored hybrid enrichment dataset of 35 exemplars of Salvia to 179 terminals. We also reconstructed nearly complete plastomes for these samples from off-target reads. We used these data to examine the concordance and discordance among the nuclear loci and between the nuclear and plastid genomes in detail, elucidating both broad-scale and species-level relationships within Salvia . We found that despite the widespread gene tree discordance, nuclear phylogenies reconstructed using concatenated, coalescent, and network-based approaches recover a common backbone topology. Moreover, all subgenera, except for Audibertia , are strongly supported as monophyletic in all analyses. The plastome genealogy is largely resolved and is congruent with the nuclear backbone. However, multiple analyses suggest that incomplete lineage sorting does not fully explain the gene tree discordance. Instead, horizontal gene flow has been important in both the deep and more recent history of Salvia . Our results provide a robust species tree of Salvia across phylogenetic scales and genomes. Future comparative analyses in the genus will need to account for the impacts of hybridization/introgression and incomplete lineage sorting in topology and divergence time estimation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rose, Kriebel, Kahan, DiNicola, González-Gallegos, Celep, Lemmon, Lemmon, Sytsma and Drew.)

The present study aimed to provide a precise, meta-analytic estimate of the prevalence of obsessive-compulsive disorder (OCD) amongst those with a current primary eating disorder (ED) diagnosis, and to isolate its predictors. An online search of PubMed and PsycINFO was conducted with a Boolean search phrase incorporating keywords related to OCD, EDs, comorbidity, prevalence, and epidemiology, complemented by references coded from related review articles and contact with experts in the field. Articles were included if they (a) reported an observational study examining current ED diagnoses, (b) used a semi-structured or structured diagnostic interview for OCD and ED diagnosis, (c) applied DSM or ICD criteria, (d) included adolescent or adult samples (age > 12), (e) included patient or community samples, and (f) reported lifetime or current OCD comorbidity. From the 846 articles identified, 35 lifetime and 42 current estimates were calculated. OCD prevalence was extracted from each study for each ED diagnostic category, along with eleven additional potential moderators. Analyses revealed an aggregate lifetime OCD prevalence of 13.9% CI 95% [10.4 to 18.1] and current OCD prevalence of 8.7% CI 95% [5.8 to 11.8] across EDs. Moderator analyses revealed the prevalence of and risk for OCD in EDs to be greatest in anorexia nervosa binge-eating purging type (ANBP). Further, OCD is most prevalent amongst patient samples than samples recruited from the community., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Natural selection by pollinators is an important factor in the morphological diversity and adaptive radiation of flowering plants. Selection by similar pollinators in unrelated plants leads to convergence in floral morphology, or "floral syndromes." Previous investigations into floral syndromes have mostly studied relatively small and/or simple systems, emphasizing vertebrate pollination. Despite the importance of multiple floral traits in plant-pollinator interactions, these studies have examined few quantitative traits, so their co-variation and phenotypic integration have been underexplored. To gain better insights into pollinator-trait dynamics, we investigate the model system of the phlox family (Polemoniaceae), a clade of ∼400 species pollinated by a diversity of vectors. Using a comprehensive phylogeny and large dataset of traits and observations of pollinators, we reconstruct ancestral pollination system, accounting for the temporal history of pollinators. We conduct phylogenetically controlled analyses of trait co-variation and association with pollinators, integrating many analyses over phylogenetic uncertainty. Pollinator shifts are more heterogeneous than previously hypothesized. The evolution of floral traits is partially constrained by phylogenetic history and trait co-variation, but traits are convergent and differences are associated with different pollinators. Trait shifts are usually gradual, rather than rapid, suggesting complex genetic and ecological interactions of flowers at macroevolutionary scales., (© 2021 The Authors. Evolution © 2021 The Society for the Study of Evolution.)

Background: Adherence to COVID-19 social distancing guidelines varies across individuals., Purpose: This study examined the relations of pseudoscientific and just world beliefs, generalized and institutional trust, and political party affiliation to adherence to COVID-19 social distancing guidelines over three months, as well as the explanatory role of COVID-19 risk perceptions in these relations., Methods: A U.S. nationwide sample of 430 adults (49.8% women; mean age = 40.72) completed a prospective online study, including an initial assessment (between March 27 and April 5, 2020), a 1 month follow-up (between April 27 and May 21, 2020), and a 3 month follow-up (between June 26 and July 15, 2020). We hypothesized that greater pseudoscientific and just world beliefs, lower governmental, institutional, and dispositional trust, and Republican Party affiliation would be associated with lower initial adherence to social distancing and greater reductions in social distancing over time and that COVID-19 risk perceptions would account for significant variance in these relations., Results: Results revealed unique associations of lower governmental trust, greater COVID-19 pseudoscientific beliefs, and greater trust in the Centers for Disease Control and Prevention (CDC) to lower initial adherence to social distancing. Whereas greater COVID-19 risk perceptions and CDC trust were associated with less steep declines in social distancing over time, both Republican (vs. Democratic) Party affiliation and greater COVID-19 pseudoscientific beliefs were associated with steeper declines in social distancing over time (relations accounted for by lower COVID-19 risk perceptions)., Conclusions: Results highlight the utility of public health interventions aimed at improving scientific literacy and emphasizing bipartisan support for social distancing guidelines., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Occupancy methods propelled the quantitative study of species distributions forward by separating the observation process, or the imperfect detectability of species, from the ecological processes of interest governing species distributions. Occupancy studies come at a cost, however: the collection of additional data to account for nondetections at sites where the species is present. The most common occupancy designs (repeated-measures designs) require repeat visits to sites or the use of multiple observers or detection methods. Time-to-detection methods have been identified as a potentially efficient alternative, requiring only one visit to each site by a single observer. A comparison of time-to-detection methods to repeated-measures designs for visual encounter surveys would allow researchers to evaluate whether time-to-detection methods might be appropriate for their study system and can inform optimal survey design. We collected time-to-detection data during two different repeated-measures design occupancy surveys for four amphibians and compared the performance of time-to-detection methods to the other designs using the location (potential bias) and precision of posterior distributions for occurrence parameters. We further used results of time-to-detection surveys to optimize survey design. Time-to-detection methods performed best for species that are widespread and have high detection probabilities and rates, but performed less well for cryptic species with lower probability of occurrence or whose detection was strongly affected by survey conditions. In all cases, single surveys were most efficient in terms of person-hours expended, but under some conditions the survey duration required to achieve high detection probabilities would be prohibitively long for a single survey. Regardless of occupancy survey design, time-to-detection methods provide important information that can be used to optimize surveys, allowing researchers and resource managers to efficiently achieve monitoring and conservation goals. Collecting time-to-detection data while conducting repeated-measures occupancy surveys requires only small modifications to field methods but could have large benefits in terms of time spent surveying in the long term., (© 2020 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of Ecological Society of America.)