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Co-design provides a meaningful way to engage patients in research. However, there is limited practical guidance. We used our co-design project to identify strategies for other researchers. An ethnographic case study design was used. Data included participant observation of co-design meetings, meeting minutes, analytic fieldnotes, qualitative patient interviews, and research team member self-reflections. Additionally, we got external feedback. We analyzed data iteratively. Our team included 5 patients and 6 researchers. We identified 3 strategies to include patients in co-design: (1) Deliberately build the team, from recruiting patients to specifying roles. (2) Tailor the meeting format to thoughtfully use patients’ time and expertise. (3) Disrupt traditional hierarchies, to empower patients to actively participate. Researchers seeking to include patients as team members should consider: team composition and roles, leveraging meeting formats to optimize contributions and purposefully creating a culture of collaboration, so patient expertise informs the end product. Our work provides practical guidance for researchers to incorporate patient expertise in the co-design process and meaningfully involve them in their work.

Corpus callosum dysgenesis (CCD) is a congenital brain malformation that occurs when the development of the corpus callosum is disrupted, either partially or completely. The cognitive outcomes in individuals with CCD vary greatly, but generally the neuropsychological profile is characterised by slow processing speed, poor transfer of interhemispheric sensory-motor information, and impaired complex problem solving. Core language skills are often preserved in CCD, but there is some evidence that complex language may be impaired. Thus, the current study sought to examine whether spontaneous speech output was reduced in a cohort of individuals with CCD compared to age-matched controls. We further explored a series of factors that may be contributing to poor spontaneous speech in CCD, such as difficulties generating, selecting, and sequencing ideas for expression, as well as apathy and slowed processing speed. A cohort of 25 individuals with CCD and 39 neurotypical controls were enrolled in this study. Participants completed a picture description task to measure spontaneous speech output, alongside a series of cognitive and language baseline tests. Verbal and nonverbal fluency tasks gauged idea generation and sequencing, and sentence-level selection tasks measured idea selection. We found that, despite having largely intact core language skills, individuals with CCD produced significantly less spontaneous speech on the picture description task than controls. This language profile may be described as "adynamic". Further, we found that poor spontaneous speech output in CCD was related to problems generating ideas for expression, as individuals with CCD performed below controls on the verbal and nonverbal fluency tasks. Exploratory analyses revealed that apathy and slowed processing speed may be contributing factors. Adynamia in CCD is a novel finding that may be an intervention target for improving communication skills in this population., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Premise: The history of angiosperms is marked by repeated rounds of ancient whole-genome duplications (WGDs). Here we used state-of-the-art methods to provide an up-to-date view of the distribution of WGDs in the history of angiosperms that considers both uncertainty introduced by different WGD inference methods and different underlying species-tree hypotheses., Methods: We used the distribution synonymous divergences (K s ) of paralogs and orthologs from transcriptomic and genomic data to infer and place WGDs across two hypothesized angiosperm phylogenies. We further tested these WGD hypotheses with syntenic inferences and Bayesian models of duplicate gene gain and loss., Results: The predicted number of WGDs in the history of angiosperms (~170) based on the current taxon sampling is largely similar across different inference methods, but varies in the precise placement of WGDs on the phylogeny. K s -based methods often yield alternative hypothesized WGD placements due to variation in substitution rates among lineages. Phylogenetic models of duplicate gene gain and loss are more robust to topological variation. However, errors in species-tree inference can still produce spurious WGD hypotheses, regardless of method used., Conclusions: Here we showed that different WGD inference methods largely agree on an average of 3.5 WGD in the history of individual angiosperm species. However, the precise placement of WGDs on the phylogeny is subject to the WGD inference method and tree topology. As researchers continue to test hypotheses regarding the impacts ancient WGDs have on angiosperm evolution, it is important to consider the uncertainty of the phylogeny as well as WGD inference methods., (© 2024 Botanical Society of America.)

All flowering plants are now recognized as diploidized paleopolyploids (Jiao et al., 2011; One Thousand Plant Transcriptomes Initiative, 2019), and polyploid species comprise approximately 30% of contemporary plant species (Wood et al., 2009; Barker et al., 2016a). A major implication of these discoveries is that, to appreciate the evolution of plant diversity, we need to understand the fundamental biology of polyploids and diploidization. This need is broadly recognized by our community as there is a continued, growing interest in polyploidy as a research topic. Over the past 25 years, the sequencing and analysis of plant genomes has revolutionized our understanding of the importance of polyploid speciation to the evolution of land plants., (© 2024 Botanical Society of America.)

Amyotrophic lateral sclerosis (ALS) is a multi-system disorder that commonly affects cognition and behaviour. Verbal fluency impairments are consistently reported in ALS patients, and we aimed to investigate whether this deficit extends beyond the verbal domain. We further aimed to determine whether deficits are underpinned by a primary intrinsic response generation impairment (i.e., a global reduction across tasks), potentially related to apathy, or an inability to maintain responding over time (i.e., a 'drop off' pattern). Twenty-two ALS patients and 21 demographically-matched controls completed verbal and nonverbal fluency tasks (phonemic/semantic word fluency, design fluency, gesture fluency and ideational fluency), requiring the generation of responses over a specified time period. Fluency performance was analysed in terms of the overall number of novel items produced, as well as the number of items produced in the first 'initiation' and the remaining 'maintenance' time periods. ALS patients' overall performance was not globally reduced across tasks. Patients were impaired only on meaningful gesture fluency, which requires the generation of gestures that communicate meaning (e.g., waving). On phonemic fluency, ALS patients showed a 'drop off' pattern of performance, where they had difficulty maintaining responding over time, but this pattern was not evident on the other fluency tasks. Apathy did not appear to be related to fluency performance. The selective meaningful gesture fluency deficit, in the context of preserved meaningless gesture fluency, highlights that the retrieval of action knowledge may be weakened in early ALS., (© 2023 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Model species continue to underpin groundbreaking plant science research. At the same time, the phylogenetic resolution of the land plant tree of life continues to improve. The intersection of these 2 research paths creates a unique opportunity to further extend the usefulness of model species across larger taxonomic groups. Here we promote the utility of the Arabidopsis thaliana model species, especially the ability to connect its genetic and functional resources, to species across the entire Brassicales order. We focus on the utility of using genomics and phylogenomics to bridge the evolution and diversification of several traits across the Brassicales to the resources in Arabidopsis, thereby extending scope from a model species by establishing a "model clade." These Brassicales-wide traits are discussed in the context of both the model species Arabidopsis and the family Brassicaceae. We promote the utility of such a "model clade" and make suggestions for building global networks to support future studies in the model order Brassicales., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

The geneticist Thomas Dobzhansky famously declared: 'Nothing in biology makes sense except in the light of evolution'. A key evolutionary adaptation of Metazoa is directed movement, which has been elaborated into a spectacularly varied number of behaviours in animal clades. The mechanisms by which animal behaviours have evolved, however, remain unresolved. This is due, in part, to the indirect control of behaviour by the genome, which provides the components for both building and operating the brain circuits that generate behaviour. These brain circuits are adapted to respond flexibly to environmental contingencies and physiological needs and can change as a function of experience. The resulting plasticity of behavioural expression makes it difficult to characterize homologous elements of behaviour and to track their evolution. Here, we evaluate progress in identifying the genetic substrates of behavioural evolution and suggest that examining adaptive changes in neuromodulatory signalling may be a particularly productive focus for future studies. We propose that the behavioural sequences used by ecdysozoans to moult are an attractive model for studying the role of neuromodulation in behavioural evolution., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background and Objectives: Clinical trials developing therapeutics for frontotemporal degeneration (FTD) focus on pathogenic variant carriers at preclinical stages. Objective, quantitative clinical assessment tools are needed to track stability and delayed disease onset. Natural speech can serve as an accessible, cost-effective assessment tool. We aimed to identify early changes in the natural speech of FTD pathogenic variant carriers before they become symptomatic., Methods: In this cohort study, speech samples of picture descriptions were collected longitudinally from healthy participants in observational studies at the University of Pennsylvania and Columbia University between 2007 and 2020. Participants were asymptomatic but at risk for familial FTD. Status as "carrier" or "noncarrier" was based on screening for known pathogenic variants in the participant's family. Thirty previously validated digital speech measures derived from automatic speech processing pipelines were selected a priori based on previous studies in patients with FTD and compared between asymptomatic carriers and noncarriers cross-sectionally and longitudinally., Results: A total of 105 participants, all asymptomatic, included 41 carriers: 12 men [30%], mean age 43 ± 13 years; education, 16 ± 2 years; MMSE 29 ± 1; and 64 noncarriers: 27 men [42%]; mean age, 48 ± 14 years; education, 15 ± 3 years; MMSE 29 ± 1. We identified 4 speech measures that differed between carriers and noncarriers at baseline: mean speech segment duration (mean difference -0.28 seconds, 95% CI -0.55 to -0.02, p = 0.04); word frequency (mean difference 0.07, 95% CI 0.008-0.14, p = 0.03); word ambiguity (mean difference 0.02, 95% CI 0.0008-0.05, p = 0.04); and interjection count per 100 words (mean difference 0.33, 95% CI 0.07-0.59, p = 0.01). Three speech measures deteriorated over time in carriers only: particle count per 100 words per month (β = -0.02, 95% CI -0.03 to -0.004, p = 0.009); total narrative production time in seconds per month (β = -0.24, 95% CI -0.37 to -0.12, p < 0.001); and total number of words per month (β = -0.48, 95% CI -0.78 to -0.19, p = 0.002) including in 3 carriers who later converted to symptomatic disease., Discussion: Using automatic processing pipelines, we identified early changes in the natural speech of FTD pathogenic variant carriers in the presymptomatic stage. These findings highlight the potential utility of natural speech as a digital clinical outcome assessment tool in FTD, where objective and quantifiable measures for abnormal behavior and language are lacking.

The sacred datura plant (Solanales: Solanaceae: Datura wrightii) has been used to study plant-herbivore interactions for decades. The wealth of information that has resulted leads it to have potential as a model system for studying the ecological and evolutionary genomics of these interactions. We present a de novo Datura wrightii genome assembled using PacBio HiFi long-reads. Our assembly is highly complete and contiguous (N50 = 179Mb, BUSCO Complete = 97.6%). We successfully detected a previously documented ancient whole genome duplication using our assembly and have classified the gene duplication history that generated its coding sequence content. We use it as the basis for a genome-guided differential expression analysis to identify the induced responses of this plant to one of its specialized herbivores (Coleoptera: Chrysomelidae: Lema daturaphila). We find over 3000 differentially expressed genes associated with herbivory and that elevated expression levels of over 200 genes last for several days. We also combined our analyses to determine the role that different gene duplication categories have played in the evolution of Datura-herbivore interactions. We find that tandem duplications have expanded multiple functional groups of herbivore responsive genes with defensive functions, including UGT-glycosyltranserases, oxidoreductase enzymes, and peptidase inhibitors. Overall, our results expand our knowledge of herbivore-induced plant transcriptional responses and the evolutionary history of the underlying herbivore-response genes., (© 2023. The Author(s).)