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Abstract Assessing the biological relevance of variance components estimated using Markov chain Monte Carlo (MCMC)‐based mixed‐effects models is not straightforward. Variance estimates are constrained to be greater than zero and their posterior distributions are often asymmetric. Different measures of central tendency for these distributions can therefore vary widely, and credible intervals cannot overlap zero, making it difficult to assess the size and statistical support for among‐group variance. Statistical support is often assessed through visual inspection of the whole posterior distribution and so relies on subjective decisions for interpretation. We use simulations to demonstrate the difficulties of summarizing the posterior distributions of variance estimates from MCMC‐based models. We then describe different methods for generating the expected null distribution (i.e. a distribution of effect sizes that would be obtained if there was no among‐group variance) that can be used to aid in the interpretation of variance estimates. Through comparing commonly used summary statistics of posterior distributions of variance components, we show that the posterior median is predominantly the least biased. We further show how null distributions can be used to derive a p‐value that provides complementary information to the commonly presented measures of central tendency and uncertainty. Finally, we show how these p‐values facilitate the implementation of power analyses within an MCMC framework. The use of null distributions for variance components can aid study design and the interpretation of results from MCMC‐based models. We hope that this manuscript will make empiricists using mixed models think more carefully about their results, what descriptive statistics they present and what inference they can make.

Splenosis describes ectopic splenic implants that usually occur after trauma and splenectomy. We present a case of omental splenosis discovered during robot-assisted prostatectomy. [ABSTRACT FROM AUTHOR]

We often quantify the rate at which a behaviour occurs by counting the number of times it occurs within a specific, short observation period. Measuring behaviour in such a way is typically unavoidable but induces error. This error acts to systematically reduce effect sizes, including metrics of particular interest to behavioural and evolutionary ecologists such as R2, repeatability (intra-class correlation, ICC) and heritability. Through introducing a null model, the Poisson process, for modelling the frequency of behaviour, we give a mechanistic explanation of how this problem arises and demonstrate how it makes comparisons between studies and species problematic, because the magnitude of the error depends on how frequently the behaviour has been observed as well as how biologically variable the behaviour is. Importantly, the degree of error is predictable and so can be corrected for. Using the example of parental provisioning rate in birds, we assess the applicability of our null model for modelling the frequency of behaviour. We then survey recent literature and demonstrate that the error is rarely accounted for in current analyses. We highlight the problems that arise from this and provide solutions. We further discuss the biological implications of deviations from our null model, and highlight the new avenues of research that they may provide. Adopting our recommendations into analyses of behavioural counts will improve the accuracy of estimated effect sizes and allow meaningful comparisons to be made between studies.

Abstract The trade‐off between reproduction and self‐maintenance is a cornerstone of life history theory, yet its proximate underpinnings are elusive. Here, we used an artificial selection approach to create replicated lines of Japanese quail (Coturnix japonica) that differ genetically in their reproductive investment. Whole transcriptome sequencing revealed that females from lines selected for high reproductive output show a consistent upregulation of genes associated with reproduction but a simultaneous downregulation of immune genes. Concordant phenotypic differences in immune function (i.e., specific antibody response against keyhole limpet hemocyanin) were observed between the selection lines, even in males who do not provide parental care. Our findings demonstrate the key role of obligate transcriptional constraints in the maintenance of life history variation. These constraints set fundamental limits to productivity and health in natural and domestic animal populations.

Abstract Maternal effects are prevalent in nature and significantly contribute to variation in phenotypic trait expression. However, little attention has been paid to the factors shaping variation in the traits mediating these effects (maternal effectors). Specific maternal effectors are often not identified, and typically they are assumed to be inherited in an additive genetic and autosomal manner. Given that these effectors can cause long‐lasting effects on offspring phenotype, it is likely that they may also affect themselves in the next generation. Although the existence of such cascading maternal effects has been discussed and modeled, empirical examples of such effects are rare, let alone quantitative estimates of their strength and evolutionary consequences. Here, we demonstrate that the investment a mother makes in her eggs positively affects the egg investment of her daughters. Through reciprocally crossing artificially selected lines for divergent prenatal maternal investment in Japanese quail (Coturnix japonica), we demonstrate that the size of eggs daughters lay resembles the egg size of their maternal line significantly more than that of their paternal line, highlighting that egg size is in part maternally inherited. Correspondingly, we find that variation in the daughters' egg size is in part determined by maternal identity, in addition to substantial additive genetic effects. Furthermore, this maternal variance in offspring egg size is fully explained by maternal egg size, demonstrating the presence of a positive cascading effect of maternal egg size on offspring egg size. Finally, we use an evolutionary model to quantify the consequences of covariance between cascading maternal and additive genetic effects for both maternal effector and offspring body mass evolution. Our study demonstrates that by amplifying the amount of variation available for selection to act on, positive cascading maternal effects can significantly enhance the evolutionary potential of maternal effectors and the offspring traits that they affect.

Abstract Many trait measurements are size-dependent, and while we often divide these traits by size before fitting statistical models to control for the effect of size, this approach does not account for allometry and the intermediate outcome problem. We describe these problems and outline potential solutions.

In species with biparental care, behavioral coordination in the provisioning of the progeny is hypothesized to increase the number of offspring that survive to independence. Coordination is often quantified by two metrics, alternation and synchrony. Turn-taking (leading to an alternation pattern) can result when one parent's investment strategy is based on the investment of its partner (i.e., conditional cooperation). This should increase the overall provisioning rate and improve offspring body condition. Synchrony might equalize food delivery among offspring and therefore decrease the variance in offspring body condition within the brood. Overall, offspring survival could be increased by parental coordination. Finally, pairs with low coordination, and with potentially lower reproductive success, are expected to be more likely to divorce. In this study, we use a dataset on 473 pairs of house sparrows in a natural insular population to test these hypotheses. We found no effect of the pair's apparent coordination on offspring condition, offspring survival, or divorce rate, questioning the adaptive significance of this behavior. We argue that, in this species, the detection of a higher frequency of alternation and synchrony, when compared to chance expectation, might be induced by the environment, rather than result from an emergent pair behavior selected for fitness benefits.

Behavioral coordination when provisioning offspring, through alternation and synchrony, has been hypothesized to influence rearing success. However, studying coordination at the pair level presents two analytical difficulties. First, alternating or synchronous (i.e., simultaneous) feeding can occur randomly and be induced by a shared environment. Therefore, a null model must account for this apparent coordination that occurs by chance. Second, alternation and synchrony in provisioning are intrinsically linked to the rate of provisioning itself, and the effects of coordination and provisioning rate, for instance on fitness, need to be distinguished. In this paper, we explore several randomization procedures and simulation scenarios to tease apart true coordination from random alternation and synchrony, and to find an appropriate statistical model for analyzing coordination. First, to establish a baseline of alternated or synchronous visits expected by chance, we took data from a natural population of house sparrows and randomized inter-feeding intervals in various ways. Alternation and synchrony in the observed dataset were higher than expected by chance under any of our randomizations. However, it was impossible to exclude that alternation and synchrony patterns did not arise due to the pair's shared environment. Second, to identify a way of statistically modeling coordination without generating spurious effects due to intrinsic mathematical relationships between coordination and provisioning rates, we simulated data according to different scenarios. Only one out of five candidate models for analyzing alternation was deemed appropriate, and gave similarly appropriate results for analyzing synchrony. This work highlights the importance and difficulty of finding an adequate null model for studying behavioral coordination and other emergent behaviors. In addition, it demonstrates that analyzing simulated data, prior to analyzing empirical data, enables researchers to avoid spurious effects.

Reduction of [K 2 {( t Bu pyrr 2 pyr)Fe} 2 (μ-N 2 )] (1) with two equiv. of KC 8 in the presence of crown-ether 18-C-6 yields the N 2 adduct [{K(18-C-6)} 2 ( t Bu pyrr 2 pyr)Fe(N 2 )] (2). Complex 2 heterolytically splits the C sp 2 -H bond of benzene to form [{K(18-C-6)}( t Bu pyrr 2 pyr)Fe(C 6 H 5 )] (3), whereby usage of a diboron B 2 pin 2 promotes hydride elimination to form the salt [K(18-C-6)HB 2 Pin 2 ] (4). Similarly, 3 can also be formed by cleavage of the C-F bond of fluorobenzene. Reaction of 3 with ClBcat yields [K(18-C-6)(thf) 2 ][( t Bu pyrr 2 pyr)FeCl] (5) and PhBcat and the former can be reduced to 2 to complete a synthetic cycle for heterolytic benzene C-H activation and borylation.

The discovery that homeotic genes in Drosophila are conserved and utilized for embryonic development throughout the animal kingdom, including humans, revolutionized the fields of developmental biology and evolutionary developmental biology (evo-devo). In a pair of back-to-back papers published in Cell in 1984, researchers at the Biozentrum in Basel, Switzerland, showed that the homeobox - previously identified as a sequence shared by homeotic genes in Drosophila - was also present in the genome of diverse animals. The first paper (McGinnis et al., 1984a) showed that genomes of both invertebrates and vertebrates contain sequences that cross-hybridized with Drosophila homeobox probes. The second paper (Carrasco et al., 1984) identified a cross-hybridizing sequence in the model system Xenopus laevis. They then isolated the first vertebrate homeobox-containing gene by cloning and sequencing of the corresponding genomic region. Finally, they showed that this gene (AC1, later renamed HoxC6) was expressed during embryonic development, the first evidence that developmentally expressed Drosophila genes could be used to isolate regulators of vertebrate embryonic development. These findings led to a flurry of activity in the evo-devo field, initially focused on isolating Hox genes across diverse species, and then expanding to isolation of other gene families based on Drosophila orthologs, an approach that continues today. This led to the notion of a conserved genetic toolkit for embryonic development, currently accepted, but unexpected at the time of its discovery. We attempt to provide some context for the sea-change in thinking that these discoveries brought about by referring to Jean Piaget's theories about the sequential acquisition of scientific knowledge., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Morphological features of organismal body plans are often highly conserved within large taxa. For example, segmentation is a shared and defining feature of all insects. Screens in Drosophila identified genes responsible for the development of body segments, including the "pair-rule" genes (PRGs), which subdivide embryos into double-segment units in a previously unexpected pre-patterning step. Here we show that the milkweed bug Oncopeltus fasciatus also uses a pair rule for embryo subdivision but Oncopeltus employs different genes for this process. We identified the gene Blimp1 as an Oncopeltus PRG based on its expression pattern, tested its function with RNA interference and CRISPR-Cas9, and generated the first PR mutant in this species. Although it does not have PR function in Drosophila , like Drosophila PRGs, Blimp1 encodes a transcription factor required for embryonic viability. Thus, pair-rule subdivision of the insect body plan is more highly conserved than the factors mediating this process, suggesting a developmental constraint on this pre-patterning step.

Objectives: Transjugular intrahepatic portosystemic shunt (TIPS) is a catheter-based, minimally invasive procedure to reduce portal hypertension. The aim of the study was to investigate dysfunction and mortality after TIPS and to identify factors associated with these events., Methods: A retrospective analysis of 834 patients undergoing TIPS implantation in a single center from 1993-2018 was performed. Cumulative incidence curves were estimated, and frailty models were used to assess associations between potentially influential variables and time to dysfunction or death., Results: 1-, 2-, and 5-year mortality rates were 20.9% (confidence interval (CI) 17.7-24.1), 22.5% (CI 19.1-25.8), and 25.0% (CI: 21.1-28.8), 1-year, 2-year, and 5-year dysfunction rates were 28.4% (CI 24.6-32.3), 38.9% (CI 34.5-43.3), and 52.4% (CI 47.2-57.6). The use of covered stents is a protective factor regarding TIPS dysfunction (hazard ratio (HR) 0.47, CI 0.33-0.68) but does not play a major role in survival (HR 0.95, CI 0.58-1.56). Risk factors for mortality are rather TIPS in an emergency setting (HR 2.78, CI 1.19-6.50), a previous TIPS dysfunction (HR 2.43, CI 1.28-4.62), and an increased Freiburg score (HR 1.45, CI 0.93-2.28)., Conclusion: The use of covered stents is an important protective factor regarding TIPS dysfunction. Whereas previous TIPS dysfunction, emergency TIPS implantation, and an elevated Freiburg score are associated with increased mortality. Awareness of risk factors could contribute to a better selection of patients who may benefit from a TIPS procedure and improve clinical follow-up with regard to early detection of thrombosis/stenosis., Critical Relevance Statement: The use of covered stents reduces the risk of dysfunction after transjugular intrahepatic portosystemic shunt (TIPS). TIPS dysfunction, emergency TIPS placement, and a high Freiburg score are linked to higher mortality rates in TIPS patients., Key Points: The risk of dysfunction is higher for uncovered stents compared to covered stents. Transjugular intrahepatic portosystemic shunt dysfunction increases the risk of instantaneous death after the intervention. A higher Freiburg score increases the rate of death after the intervention. Transjugular intrahepatic portosystemic shunt implantations in emergency settings reduce survival rates., (© 2024. The Author(s).)

Rotational moulding is a unique low-shear process used to manufacture hollow parts. The process is an excellent process method for batch processing, minimal waste and stress-free parts. However, the process has drawbacks such as long cycle times, gas dependency and a limited palette of materials relative to other process methods. This review aimed to shed light on the current state-of-the-art research contributing towards sustainability in rotational moulding. The scope of this review broadly assessed all areas of the process such as material development, process adaptations and development, modelling, simulation and contributions towards applications carving a more sustainable society. The PRISMA literature review method was adopted, finding that the majority of publications focus on material development, specifically on the use of waste, fillers, fibres and composites as a way to improve sustainability. Significant focus on biocomposites and natural fibres highlighted the strong research interest, while recyclate studies appeared to be less explored to date. Other research paths are process modification, modelling and simulation, motivated to increase energy efficiency, reduction in scrap and attempts to reduce cycle time with models. An emerging research interest in rotational moulding is the contribution towards the hydrogen economy, particularly type IV hydrogen vessels.

The regulation of gene expression in precise, rapidly changing spatial patterns is essential for embryonic development. Multiple enhancers have been identified for the evolving expression patterns of the cascade of Drosophila segmentation genes that establish the basic body plan of the fly. Classic reporter transgene experiments identified multiple cis-regulatory elements (CREs) that are sufficient to direct various aspects of the evolving expression pattern of the pair-rule gene fushi tarazu (ftz). These include enhancers that coordinately activate expression in all seven stripes and stripe-specific elements that activate expression in one or more ftz stripes. Of the two 7-stripe enhancers, analysis of reporter transgenes demonstrated that the upstream element (UPS) is autoregulatory, requiring direct binding of Ftz protein to direct striped expression. Here, we asked about the endogenous role of the UPS by precisely deleting this 7-stripe enhancer. In ftzΔUPS 7S homozygotes, ftz stripes appear in the same order as wildtype, and all but stripe 4 are expressed at wildtype levels by the end of the cellular blastoderm stage. This suggests that the zebra element and UPS harbor information to direct stripe 4 expression, although previous deletion analyses failed to identify a stripe-specific CRE within these two 7-stripe enhancers. However, the UPS is necessary for late ftz stripe expression, with all 7 stripes decaying earlier than wildtype in ftzΔUPS 7S homozygotes. Despite this premature loss of ftz expression, downstream target gene regulation proceeds as in wildtype, and segmentation is unperturbed in the overwhelming majority of animals. We propose that this late-acting enhancer provides a buffer against perturbations in gene expression but is not required for establishment of Ftz cell fates. Overall, our results demonstrate that multiple enhancers, each directing distinct aspects of an overall gene expression pattern, contribute to fine-tuning the complex patterns necessary for embryonic development., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Here we report the use of a base metal complex [( tBu pyrpyrr 2 )Fe(OEt 2 )] (1-OEt 2 ) ( tBu pyrpyrr 2 2- =3,5-tBu 2 -bis(pyrrolyl)pyridine) as a catalyst for intermolecular amination of C sp3 -H bonds of 9,10-dihydroanthracene (2 a) using 2,4,6-trimethyl phenyl azide (3 a) as the nitrene source. The reaction is complete within one hour at 80 °C using as low as 2 mol % 1-OEt 2 with control in selectivity for single C-H amination versus double C-H amination. Catalytic C-H amination reactions can be extended to other substrates such as cyclohexadiene and xanthene derivatives and can tolerate a variety of aryl azides having methyl groups in both ortho positions. Under stoichiometric conditions the imido radical species [( tBu pyrpyrr 2 )Fe{=N(2,6-Me 2 -4-tBu-C 6 H 2 )] (1-imido) can be isolated in 56 % yield, and spectroscopic, magnetometric, and computational studies confirmed it to be an S = 1 Fe IV complex. Complex 1-imido reacts with 2 a to produce the ferrous aniline adduct [( tBu pyrpyrr 2 )Fe{NH(2,6-Me 2 -4-tBu-C 6 H 2 )(C 14 H 11 )}] (1-aniline) in 45 % yield. Lastly, it was found that complexes 1-imido and 1-aniline are both competent intermediates in catalytic intermolecular C-H amination., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Signaling networks are redeployed across different developmental times and places to generate phenotypic diversity from a limited genetic toolkit. Hormone signaling networks in particular have well-studied roles in multiple developmental processes. In insects, the ecdysone pathway controls critical events in late embryogenesis and throughout post-embryonic development. While this pathway has not been shown to function in the earliest stage of embryonic development in the model insect Drosophila melanogaster, one component of the network, the nuclear receptor E75A, is necessary for proper segment generation in the milkweed bug Oncopeltus fasciatus. Published expression data from several other species suggests possible conservation of this role across hundreds of millions of years of insect evolution. Previous work also demonstrates a second nuclear receptor in the ecdysone pathway, Ftz-F1, plays a role in segmentation in multiple insect species. Here we report tightly linked expression patterns of ftz-F1 and E75A in two hemimetabolous insect species, the German cockroach Blattella germanica and the two-spotted cricket Gryllus bimaculatus. In both species, the genes are expressed segmentally in adjacent cells, but they are never co-expressed. Using parental RNAi, we show the two genes have distinct roles in early embryogenesis. E75A appears necessary for abdominal segmentation in B. germanica, while ftz-F1 is essential for proper germband formation. Our results suggest that the ecdysone network is critical for early embryogenesis in hemimetabolous insects., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Insects display a vast array of eye and body colors. Genes encoding products involved in biosynthesis and deposition of pigments are ideal genetic markers, contributing, for example, to the power of Drosophila genetics. Oncopeltus fasciatus is an emerging model for hemimetabolous insects, a member of the piercing-sucking feeding order Hemiptera, that includes pests and disease vectors. To identify candidate visible markers for O. fasciatus, we used parental and nymphal RNAi to identify genes that altered eye or body color while having no deleterious effects on viability. We selected Of-vermilion for CRISPR/Cas9 genome editing, generating three independent loss-of-function mutant lines. These studies mapped Of-vermilion to the X-chromosome, the first assignment of a gene to a chromosome in this species. Of-vermilion homozygotes have bright red, rather than black, eyes and are fully viable and fertile. We used these mutants to verify a role for Of-xdh1, ortholog of Drosophila rosy, in contributing to red pigmentation using RNAi. Rather than wild-type-like red bodies, bugs lacking both vermilion and xdh1 have bright yellow bodies, suggesting that ommochromes and pteridines contribute to O. fasciatus body color. Our studies generated the first gene-based visible marker for O. fasciatus and expanded the genetic toolkit for this model system., (© 2023. The Author(s).)

The gene regulatory network for segmentation in arthropods offers valuable insights into how networks evolve owing to the breadth of species examined and the extremely detailed knowledge gained in the model organism Drosophila melanogaster. These studies have shown that Drosophila's network represents a derived state that acquired changes to accelerate segment patterning, whereas most insects specify segments gradually as the embryo elongates. Such heterochronic shifts in segmentation have potentially emerged multiple times within holometabolous insects, resulting in many mechanistic variants and difficulties in isolating underlying commonalities that permit such shifts. Recent studies identified regulatory genes that work as timing factors, coordinating gene expression transitions during segmentation. These studies predict that changes in timing factor deployment explain shifts in segment patterning relative to other developmental events. Here, we test this hypothesis by characterizing the temporal and spatial expression of the pair-rule patterning genes in the malaria vector mosquito, Anopheles stephensi. This insect is a Dipteran (fly), like Drosophila, but represents an ancient divergence within this clade, offering a useful counterpart for evo-devo studies. In mosquito embryos, we observe anterior to posterior sequential addition of stripes for many pair-rule genes and a wave of broad timer gene expression across this axis. Segment polarity gene stripes are added sequentially in the wake of the timer gene wave and the full pattern is not complete until the embryo is fully elongated. This "progressive segmentation" mode in Anopheles displays commonalities with both Drosophila's rapid segmentation mechanism and sequential modes used by more distantly related insects., (© 2021 Wiley Periodicals LLC.)

The performance of vaginal drug delivery systems is dependent on their retention. This study presents a novel mathematical method to estimate the vaginal retention of semi-solids. Using creep analysis, the elastic and residual compliances are determined from the discrete retardation spectrum and used to determine the retention times (RT), defined as the time required for the formulations to enter the terminal viscous zone of deformation and hence flow. RT of commercially available products (CAP) and selected prototype formulations were determined, the estimated RT of CAP broadly aligning with their prescribed clinical usage. Candidate formulations composed of hydroxyethylcellulose (HEC, 3%/5%w/w) and polyacrylic acid (PAA, 1%/3%w/w) were manufactured using, and further diluted with simulant vaginal fluid (SVF) or simulant seminal fluid (SSF) and their RT subsequently determined. Increasing polymer concentration and pH enhanced the estimated RT whereas dilution reduced RT. Notably, the formulation composed of 5%HEC/3% PAA (SSF) maintained its RT on dilution due to swelling of suspended PAA particles, thus representing a strategy to develop vaginal semi-solids that are resistant to dilution and hence removal. The mathematical model described is reproducible, straightforward to use and is recommended as a tool in formulation development to estimate the retention of vaginal semi-solids., 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., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)