Tracing the origin of adult intestinal stem cells.

Adult intestinal stem cells are located at the bottom of crypts of Lieberkühn, where they express markers such as LGR51,2 and fuel the constant replenishment of the intestinal epithelium1. Although fetal LGR5-expressing cells can give rise to adult intestinal stem cells3,4, it remains unclear whether this population in the patterned epithelium represents unique intestinal stem-cell precursors. Here we show, using unbiased quantitative lineage-tracing approaches, biophysical modelling and intestinal transplantation, that all cells of the mouse intestinal epithelium-irrespective of their location and pattern of LGR5 expression in the fetal gut tube-contribute actively to the adult intestinal stem cell pool. Using 3D imaging, we find that during fetal development the villus undergoes gross remodelling and fission. This brings epithelial cells from the non-proliferative villus into the proliferative intervillus region, which enables them to contribute to the adult stem-cell niche. Our results demonstrate that large-scale remodelling of the intestinal wall and cell-fate specification are closely linked. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissues following damage5-9, revealing that stem-cell identity is an induced rather than a hardwired property.

Development of a complex Interdisciplinary Nurse-coordinated SELf-MAnagement (INSELMA) intervention for patients with inflammatory arthritis.

BACKGROUND: Apart from a consistent focus on treating inflammation, patients with inflammatory arthritis (IA) report a range of unmet needs. Many experience not only residual symptoms but also various other physical, psychological, and social effects. Therefore, this study aimed to develop a complex Interdisciplinary Nurse-coordinated self-management (INSELMA) intervention for patients with IA, as an add-on treatment to usual outpatient care for those with substantial disease impact. METHODS: This study followed the British Medical Research Council's updated framework for developing complex interventions. The process encompassed the following steps: (1) The evidence base was identified; (2) workshops were held, involving 38 relevant stakeholders (managers, physicians, nurses, physiotherapists, occupational therapists, social workers, psychologists from hospitals and municipalities, and two patient research partners), to discuss and further develop the preliminary ideas; (3) relevant theories were identified (i.e., self-efficacy, acceptance and commitment therapy, and health literacy); (4) the intervention was modeled and remodeled and (5) the results, describing the final INSELMA intervention and outcomes. RESULTS: The INSELMA intervention encompasses an initial biopsychosocial assessment, which is performed by a rheumatology nurse. Then, activities that the participant wishes to improve are identified and goals are set. The nurse refers the participant to a multidisciplinary team and coordinates their support and relevant services in the participant's municipality. In addition, the health professionals have the opportunity to hold two interdisciplinary conferences during the intervention period. The participant and the health professionals work to achieve the set goals during a 6-month period, which ends with a status assessment and a discussion of further needs. The INSELMA intervention aims to increase self-management, reduce the impact of IA (e.g., pain, fatigue, sleep problems, and absenteeism), and increase self-efficacy, quality of life, mental well-being, work ability, and physical activity. CONCLUSIONS: The development of the INSELMA intervention involved stakeholders from two Danish rheumatology outpatient clinics, patient research partners and municipalities. We believe that we have identified important mechanisms to increase the self-management and quality of life of people with IA and to decrease the disease impact in those who are substantially affected. The health professionals involved have developed competences in delivering the intervention and it is ready to be tested in a feasibility study.

Molecular Manipulations and Intestinal Stem Cell-Derived Organoids in Inflammatory Bowel Disease.

The pathogenesis of inflammatory bowel diseases (IBD) involves genetic predisposition, environmental factors, and a broadly dysregulated intestinal immune response to the commensal intestinal microflora. The interface between genetic predisposition and environmental factors is reflected in the epigenetic regulation at the transcriptional level. Treatment targets now involve mucosal and histological healing, but the future might additionally include normalization of intestinal cellular functions also at the molecular level, for example comprising complete restoration of phenotypic, genotypic, and epigenetic states. Recent developments in patient-derived epithelial intestinal stem cell (ISC) organoid technologies have opened exciting new therapeutic opportunities to potentially attain molecular healing by combining stem cell therapy with molecular manipulations using (epi)drugs and/or CRISPR/Cas9 genome editing. Here, we are the first to discuss the possibility for phenotypic, genotypic, and epigenetic restoration via molecular manipulations and stem cell therapy in IBD from a clinical perspective.

Lrig1 expression identifies airway basal cells with high proliferative capacity and restricts lung squamous cell carcinoma growth.

BACKGROUND: Lung squamous cell carcinoma (LUSC) accounts for a significant proportion of cancer deaths worldwide, and is preceded by the appearance of progressively disorganised pre-invasive lesions in the airway epithelium. Yet the biological mechanisms underlying progression of pre-invasive lesions into invasive LUSC are not fully understood. LRIG1 (leucine-rich repeats and immunoglobulin-like domains 1) is downregulated in pre-invasive airway lesions and invasive LUSC tumours and this correlates with decreased lung cancer patient survival. METHODS AND RESULTS: Using an Lrig1 knock-in reporter mouse and human airway epithelial cells collected at bronchoscopy, we show that during homeostasis LRIG1 is heterogeneously expressed in the airway epithelium. In basal airway epithelial cells, the suspected cell of origin of LUSC, LRIG1 identifies a subpopulation of progenitor cells with higher in vitro proliferative and self-renewal potential in both the mouse and human. Using the N-nitroso-tris-chloroethylurea (NTCU)-induced murine model of LUSC, we find that Lrig1 loss-of-function leads to abnormally high cell proliferation during the earliest stages of pre-invasive disease and to the formation of significantly larger invasive tumours, suggesting accelerated disease progression. CONCLUSION: Together, our findings identify LRIG1 as a marker of basal airway progenitor cells with high proliferative potential and as a regulator of pre-invasive lung cancer progression. This work highlights the clinical relevance of LRIG1 and the potential of the NTCU-induced LUSC model for functional assessment of candidate tumour suppressors and oncogenes.

Selective N-Terminal Acylation of Peptides and Proteins with Tunable Phenol Esters.

Selective modification of peptides and proteins is of foremost importance for the development of biopharmaceuticals and exploring biochemical pathways, as well as other applications. Here, we present a study on the development of a general and easily applicable selective method for N-terminal acylation of biomolecules, applying a new type of phenol esters. Key to the success was the development of highly tunable phenol activators bearing in the ortho-position, sulfonic acid or sulfonamide, acting as a steric shield for hydrolysis, and electron-withdrawing groups in the other ortho- and para-position for controlling the reactivity of the activated phenol esters. A library of heptapeptides, testing all 20 natural amino acids positioned at the N-terminal, were acylated in a selective manner at the N-terminus. The majority showed high conversion and excellent Nα-selectivity. Several biologically relevant biomolecules, including DesB30 insulin and human growth hormone, could also be modified at the N-terminal in a highly selective way, exemplified by either a fluorophore or a fatty acid sidechain. Finally, taking advantage of the possibility to accurately adjust the reactivity of the phenol esters, we present a potential strategy for the construction of dual active biopharmaceuticals through the employment of a bifunctional acylation linker and demonstrate its use in the creation of a GLP-1 insulin analogue, coupled through the lysine residue of GLP-1 and the N-terminal PheB1 amine of DesB30 insulin.

New Phenol Esters for Efficient pH-Controlled Amine Acylation of Peptides, Proteins, and Sepharose Beads in Aqueous Media.

This paper describes the discovery, synthesis, and use of novel water-soluble acylation reagents for efficient and selective modification, cross-linking, and labeling of proteins and peptides, as well as for their use in the effective modification of sepharose beads under pH control in aqueous media. The reagents are based on a 2,4-dichloro-6-sulfonic acid phenol ester core combined with a variety of linker structures. The combination of these motifs leads to an ideal balance between hydrolytic stability and reactivity. At high pH, good to excellent conversions (up to 95%) and regioselectivity (up to 99:1 Nε/Nα amine ratio) in the acylation were realized, exemplified by the chemical modification of incretin peptides and insulin. At neutral pH, an unusually high preference toward the N-terminal phenylalanine in an insulin derivative was observed (>99:1 Nα/Nε), which is up until now unprecedented in the literature for more elaborate reagents. In addition, the unusually high hydrolytic stability of these reagents and their ability to efficiently react at low concentrations (28 µM or 0.1 mg/mL) are exemplified with a hydroxy linker-based reagent and are a unique feature of this work.

Mapping sex differences in the effects of protein and carbohydrates on lifespan and reproduction in Drosophila melanogaster: is measuring nutrient intake essential?

Understanding how diet affects reproduction and survival is a central aim in evolutionary biology. Although this relationship is likely to differ between the sexes, we lack data relating diet to male reproductive traits. One exception to this general pattern is Drosophila melanogaster, where male dietary intake was quantified using the CApillary FEeder (CAFE) method. However, CAFE feeding reduces D. melanogaster survival and reproduction, so may distort diet-fitness outcomes. Here, we use the Geometric Framework of Nutrition to create nutrient landscapes that map sex-specific relationships between protein, carbohydrate, lifespan and reproduction in D. melanogaster. Rather than creating landscapes with consumption data, we map traits onto the nutrient composition of forty agar-based diets, generating broad coverage of nutrient space. We find that male and female lifespan was maximised on low protein, high carbohydrate blends (~ 1P:15.9C). This nutrient ratio also maximised male reproductive rates, but females required more protein to maximise daily fecundity (1P:1.22C). These results are consistent with CAFE assay outcomes. However, the approach employed here improved female fitness relative to CAFE assays, while effects of agar versus CAFE feeding on male fitness traits depended on the nutrient composition of experimental diets. We suggest that informative nutrient landscapes can be made without measuring individual nutrient intake and that in many cases, this may be preferable to using the CAFE approach. The most appropriate method will depend on the question and species being studied, but the approach adopted here has the advantage of creating nutritional landscapes when dietary intake is hard to quantify.

Survival and predation rate of wild-caught and commercially produced Orius majusculus (Reuter) (Hemiptera: Anthocoridae).

The quality of biological control agents used in augmentative releases may be affected by rearing conditions due to inbreeding or laboratory adaptation, or to phenotypic effects of the rearing environment. We hypothesized that individuals from a wild population would be in better body condition and kill more prey than individuals from a commercially produced population. We caught wild Orius majusculus (Reuter) in a maize field and compared their initial body mass, survival, and prey reduction capacity to commercially produced O. majusculus. Predation capacity and survival were compared in short-term Petri dish tests with Frankliniella tenuicornis (Uzel) thrips, Ephestia kuehniella (Zeller) moth eggs, or Rhopalosiphum padi (L.) aphids as prey, and in longer-term outdoor mesocosms containing live seedling wheat grass with thrips or aphids as prey. Wild-caught O. majusculus were typically heavier and overall had higher survival during tests than commercially produced O. majusculus. Females were heavier than males and typically killed more prey. However, we found no difference between wild-caught and commercially produced individuals on prey reduction, neither in Petri dishes nor in mesocosms. Our study suggests that commercially produced O. majusculus have lower body condition than wild O. majusculus due to their lower body mass and survival, but that this does not have any negative effect on the number of pest prey killed over the timelines and conditions of our tests. Commercially produced O. majusculus thus did not have a lower impact on pest prey numbers than wild-caught individuals and therefore had similar biological control value under our study conditions.

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia.

Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders such as Hirschsprung disease.

A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides.

A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that 13 C-labeled NiII -acyl complexes, formed from a 13 CO insertion step with NiII -alkyl intermediates, rapidly react in less than one minute with 2,2'-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of 13 C-SilaCOgen or 13 C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired 13 C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII -acyl complexes and the disulfide providing a reactive NiIII -acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13 C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.

SPOP promotes transcriptional expression of DNA repair and replication factors to prevent replication stress and genomic instability.

Mutations in SPOP, the gene most frequently point-mutated in primary prostate cancer, are associated with a high degree of genomic instability and deficiency in homologous recombination repair of DNA but the underlying mechanisms behind this defect are currently unknown. Here we demonstrate that SPOP knockdown leads to spontaneous replication stress and impaired recovery from replication fork stalling. We show that this is associated with reduced expression of several key DNA repair and replication factors including BRCA2, ATR, CHK1 and RAD51. Consequently, SPOP knockdown impairs RAD51 foci formation and activation of CHK1 in response to replication stress and compromises recovery from replication fork stalling. An SPOP interactome analysis shows that wild type (WT) SPOP but not mutant SPOP associates with multiple proteins involved in transcription, mRNA splicing and export. Consistent with the association of SPOP with transcription, splicing and RNA export complexes, the decreased expression of BRCA2, ATR, CHK1 and RAD51 occurs at the level of transcription.

Inhibiting RHOA Signaling in Mice Increases Glucose Tolerance and Numbers of Enteroendocrine and Other Secretory Cells in the Intestine.

BACKGROUND & AIMS: Glucagon-like peptide 1 (GLP1) is produced by L cells in the intestine, and agonists of the GLP1 receptor are effective in the treatment of diabetes. Levels of GLP1 increase with numbers of L cells. Therefore, agents that increase numbers of L cell might be developed for treatment of diabetes. Ras homologue family member A (RhoA) signaling through Rho-associated coiled-coil-containing protein kinases 1 and 2 (ROCK1 and ROCK2) controls cell differentiation, but it is not clear whether this pathway regulates enteroendocrine differentiation in the intestinal epithelium. We investigated the effects of Y-27632, an inhibitor of ROCK1 and ROCK2, on L-cell differentiation. METHODS: We collected intestinal tissues from GLU-Venus, GPR41-RFP, and Neurog3-RFP mice, in which the endocrine lineage is fluorescently labeled, for in vitro culture and histologic analysis. Small intestine organoids derived from these mice were cultured with Y-27632 and we measured percentages of L cells, expression of intestinal cell-specific markers, and secretion of GLP1 in medium. Mice were fed a normal chow or a high-fat diet and given Y-27632 or saline (control) and blood samples were collected for measurement of GLP1, insulin, and glucose. RESULTS: Incubation of intestinal organoids with Y-27632 increased numbers of L cells and secretion of GLP1. These increases were associated with upregulated expression of genes encoding intestinal hormones, neurogenin 3, neurogenic differentiation factor 1, forkhead box A1 and A2, and additional markers of secretory cells. Mice fed the normal chow diet and given Y-27632 had increased numbers of L cells in intestinal tissues, increased plasma levels of GLP1 and insulin, and lower blood levels of glucose compared with mice fed the normal chow diet and given saline. In mice with insulin resistance induced by the high-fat diet, administration of Y-27632 increased secretion of GLP1 and glucose tolerance compared with administration of saline. CONCLUSIONS: In mouse intestinal organoids, an inhibitor of RhoA signaling increased the differentiation of the secretory lineage and the development of enteroendocrine cells. Inhibitors of RhoA signaling or other strategies to increase numbers of L cells might be developed for treatment of patients with type 2 diabetes or for increasing glucose tolerance.

Electrolyte Effects on the Electrocatalytic Performance of Iridium-Based Nanoparticles for Oxygen Evolution in Rotating Disc Electrodes.

Proton exchange membrane water electrolysers are very promising renewable energy conversion devices that produce hydrogen from sustainable feedstocks. These devices are mainly limited by the sluggish kinetics of the oxygen evolution reaction (OER). Ir-based nanoparticles are both reasonably active and stable for the OER in acidic media. The electrolyte composition and the pH may play a crucial role in electrocatalysis, yet they have been widely overlooked for the OER. Herein, we present a study on the effects of the composition and concentration of the electrolyte on commercial Ir black nanoparticles using concentrations of 0.05 M, 0.1 M and 0.5 M of both sulphuric and perchloric acid. The results show an important effect of the electrolyte composition on the catalytic performance of the Ir nanoparticles. The concentration of H2 SO4 interferes on the oxidation of Ir and decreases the catalytic performance of the catalyst. HClO4 does not show strong interferences in the electrochemistry of Ir. Higher catalytic performances are observed in HClO4 electrolytes in comparison to H2 SO4 with little effect of the concentration of HClO4 .

Ab Initio Cyclic Voltammetry on Cu(111), Cu(100) and Cu(110) in Acidic, Neutral and Alkaline Solutions.

Electrochemical reactions depend on the electrochemical interface between the electrode surfaces and the electrolytes. To control and advance electrochemical reactions there is a need to develop realistic simulation models of the electrochemical interface to understand the interface from an atomistic point-of-view. Here we present a method for obtaining thermodynamic realistic interface structures, a procedure we use to derive specific coverages and to obtain ab initio simulated cyclic voltammograms. As a case study, the method and procedure is applied in a matrix study of three Cu facets in three different electrolytes. The results have been validated by direct comparison to experimental cyclic voltammograms. The alkaline (NaOH) cyclic voltammograms are described by H* and OH*, while in neutral medium (KHCO3 ) the CO 3* species are dominating and in acidic (KCl) the Cl* species prevail. An almost one-to-one mapping is observed from simulation to experiments giving an atomistic understanding of the interface structure of the Cu facets. Atomistic understanding of the interface at relevant eletrolyte conditions will further allow realistic modelling of electrochemical reactions of importance for future eletrocatalytic studies.

Prey-specific impact of cold pre-exposure on kill rate and reproduction.

Temperature influences biological processes of ectotherms including ecological interactions, but interaction strengths may depend on species-specific traits. Furthermore, ectotherms acclimate to prevailing thermal conditions by adjusting physiological parameters, which often implies costs to other fitness-related parameters. Both predators and prey may therefore pay thermal acclimation costs following exposure to suboptimal temperatures. However, these costs may be asymmetrical between predator and prey, and between the predator and different species of concurrent prey. We investigated whether thermal pre-exposure affected subsequent kill rate and predator fitness when foraging on prey that differ in ease of capture, and whether changes were primarily caused by predator or by prey pre-exposure effects. Specifically, we were interested in whether there were interactions between predator pre-exposed temperature and specific prey. Using the mesostigmatid mite Gaeolaelaps aculeifer as a generalist predator and the collembolans Folsomia candida and Protaphorura fimata as prey, we measured the impact of present temperature, predator pre-exposure temperature, prey pre-exposure temperature (all 10 or 20°C), prey species, and all interactions on prey numbers killed, predator eggs produced, and exploitation of killed prey in a full factorial design. Mites killed P. fimata in equal numbers independent of the presence of F. candida, but killed F. candida when P. fimata was absent. Mite kill rate and reproduction were significantly affected by mite pre-exposure temperature and test temperature, but not by prey pre-exposure temperature. Significantly more of the slower prey was killed than of the quicker prey. Importantly, we found significant synergistic negative interaction effects between predator cold pre-exposure and hunting prey of higher agility on predator kill rate and reproduction. Our findings show that the negative effects of cold and cold pre-exposure on kill rate and reproduction may be more severe when predators forage on quick prey. The study implies that predator cold exposure has consequences for specific prey survival following cold due to altered predation pressures, which in nature should influence the specific prey population dynamics and apparent competition outcomes. The findings exemplify how not only current but also preceding conditions affect ecological interactions, and that effect strength depends on the species involved.

Facilitators and barriers to teaching undergraduate medical students in general practice.

CONTEXT: Globally, primary health care is facing workforce shortages. Longer and higher-quality placements in primary care increase the likelihood of medical students choosing this specialty. However, the recruitment and retention of community primary care teachers are challenging. Relevant research was predominantly carried out in the 1990s. We seek to understand contemporary facilitators and barriers to general practitioner (GP) engagement with undergraduate education. Communities of practice (CoP) theory offers a novel conceptualisation, which may be pertinent in other community-based teaching settings. METHODS: Semi-structured interviews were undertaken with 24 GP teachers at four UK medical schools. We purposively sampled GPs new to teaching, established GP teachers and GPs who had recently stopped teaching. We undertook NVivo-assisted deductive and inductive thematic analysis of transcripts. We used CoP theory to interpret data. RESULTS: Communities of practice theory illustrated that teachers negotiate membership of three CoPs: (i) clinical practice; (ii) the medical school, and (iii) teaching. The delivery of clinical care and teaching may be integrated or exist in tension. This can depend upon the positioning of the teaching and teacher as central or peripheral to the clinical CoP. Remuneration, workload, space and the expansion of GP trainee numbers impact on this. Teachers did not identify strongly as members of the medical school or a teaching community. Perceptions of membership were affected by medical school communication and support. The findings demonstrate gaps in medical school recruitment. CONCLUSIONS: This research demonstrates the marginalisation of primary care-based teaching and proposes a novel explanation rooted in CoP theory. Concepts including identity and membership may be pertinent to other community-based teaching settings. We recommend that medical schools review and broaden recruitment methods. Teacher retention may be improved by optimising the interface between medical schools and teachers, fostering a teaching community, increasing professional rewards for teaching involvement and altering medical school expectations of learning in primary care.

The Geometry of Nutrient Space-Based Life-History Trade-Offs: Sex-Specific Effects of Macronutrient Intake on the Trade-Off between Encapsulation Ability and Reproductive Effort in Decorated Crickets.

Life-history theory assumes that traits compete for limited resources, resulting in trade-offs. The most commonly manipulated resource in empirical studies is the quantity or quality of diet. Recent studies using the geometric framework for nutrition, however, suggest that trade-offs are often regulated by the intake of specific nutrients, but a formal approach to identify and quantify the strength of such trade-offs is lacking. We posit that trade-offs occur whenever life-history traits are maximized in different regions of nutrient space, as evidenced by nonoverlapping 95% confidence regions of the global maximum for each trait and large angles (θ) between linear nutritional vectors and Euclidean distances (d) between global maxima. We then examined the effects of protein and carbohydrate intake on the trade-off between reproduction and aspects of immune function in male and female Gryllodes sigillatus. Female encapsulation ability and egg production increased with the intake of both nutrients, whereas male encapsulation ability increased with protein intake but calling effort increased with carbohydrate intake. The trade-offs between traits was therefore larger in males than in females, as demonstrated by significant negative correlations between the traits in males, nonoverlapping 95% confidence regions, and larger estimates of θ and d. Under dietary choice, the sexes had similar regulated intakes, but neither optimally regulated nutrient intake for maximal trait expression. We highlight the fact that greater consideration of specific nutrient intake is needed when examining nutrient space-based trade-offs.

Active-Phase Formation and Stability of Gd/Pt(111) Electrocatalysts for Oxygen Reduction: An In Situ Grazing Incidence X-Ray Diffraction Study.

Alloys of platinum and gadolinium present significant activity enhancement over pure Pt for the oxygen reduction reaction (ORR), both in the form of extended electrode surfaces and nanoparticulate catalysts. The active phase consists of a compressed Pt overlayer formed on Pt5 Gd electrodes upon exposure to the electrolyte by acid leaching. Here, we investigate the formation, strain and correlation lengths of the active Pt overlayer by using in situ synchrotron grazing incidence X-ray diffraction on Gd/Pt(111) single-crystalline electrodes. The overlayer forms upon exposure to electrolyte under open circuit conditions; the compressive strain relaxes slightly upon repeated electrochemical cycling in the potential range 0.6 to 1.0 V versus the reversible hydrogen electrode (RHE). In addition, the strain relaxes strongly when exposing the electrode to 1.2 V versus RHE, and the thickness of the crystalline portion of the overlayer increases with potential above 1.3 V versus RHE.

Genotype-by-sex-by-diet interactions for nutritional preference, dietary consumption, and lipid deposition in a field cricket.

Changes in feeding behaviour, especially the overconsumption of calories, has led to a rise in the rates of obesity, diabetes, and other associated disorders in humans and a range of animals inhabiting human-influenced environments. However, understanding the relative contribution of genes, the nutritional environment, and their interaction to dietary intake and lipid deposition in the sexes still remains a major challenge. By combining nutritional geometry with quantitative genetics, we determined the effect of genes, the nutritional environment, and their interaction on the total nutritional preference (TP), total diet eaten (TE), and lipid mass (LM) of male and female black field crickets (Teleogryllus commodus) fed one of four diet pairs (DPs) differing in the ratio of protein to carbohydrate and total nutritional content. We found abundant additive genetic variance for TP, TE, and LM in both sexes and across all four DPs, with significant genetic correlations between TE and TP and between TP and LM in males. We also found significant genotype-by-DP and genotype-by-sex-by-DP interactions for each trait and significant genotype-by-sex interactions for TE and LM. Complex interactions between genes, sex, and the nutritional environment, therefore, play an important role in nutrient regulation and lipid deposition in T. commodus. This finding may also help explain the increasing rate of obesity and the maintenance of sex differences in obesity observed across many animal species, including humans.