Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal 'trajectory' of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

• MeSH
• Algorithms * MeSH
• Adult MeSH
• Hippocampus diagnostic imaging   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Brain diagnostic imaging   pathology   MeSH
• Neuroimaging MeSH
• Cross-Sectional Studies MeSH
• Reproducibility of Results MeSH
• Schizophrenia * diagnostic imaging   pathology   MeSH
• Gray Matter * diagnostic imaging   pathology   MeSH
• Machine Learning MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH
• North America MeSH

Detailed knowledge of human B-cell development is crucial for the proper interpretation of inborn errors of immunity and malignant diseases. It is of interest to understand the kinetics of protein expression changes during development, but also to properly interpret the major and possibly alternative developmental trajectories. We have investigated human samples from healthy individuals with the aim of describing all B-cell developmental trajectories. We validated a 30-parameter mass cytometry panel and demonstrated the utility of "vaevictis" visualization of B-cell developmental stages. We used the trajectory inference tool "tviblindi" to exhaustively describe all trajectories leading to all developmental ends discovered in the data. Focusing on Natural Effector B cells, we demonstrated the dynamics of expression of nuclear factors (PAX-5, TdT, Ki-67, Bcl-2), cytokine and chemokine receptors (CD127, CXCR4, CXCR5) in relation to the canonical B-cell developmental stage markers. We observed branching of the memory development, where follicular memory formation was marked by CD73 expression. Lastly, we performed an analysis of two example cases of abnormal B-cell development caused by mutations in RAG-1 and Wiskott-Aldrich syndrome gene in patients with primary immunodeficiency. In conclusion, we developed, validated, and presented a comprehensive set of tools for the investigation of B-cell development in the bone marrow compartment.

• Keywords
• B‐cell development, CD73, Mass cytometry, RAG‐1, Trajectory inference, WAS,
• MeSH
• Algorithms * MeSH
• B-Lymphocytes * immunology   MeSH
• Cell Differentiation * immunology   genetics   MeSH
• Homeodomain Proteins * genetics   metabolism   MeSH
• Humans MeSH
• Mutation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Homeodomain Proteins * MeSH
• RAG-1 protein MeSH Browser

Baobab (Adansonia digitata) is a long-lived tree endemic to Africa with economic, ecological, and cultural importance, yet its genomic features are underexplored. Here, we report a chromosome-level reference genome anchored to 42 chromosomes for A. digitata, alongside draft assemblies for a sibling tree, two trees from distinct locations in Africa, and A. za from Madagascar. The baobab genome is uniquely rich in DNA transposons, which make up 33%, while LTR retrotransposons account for 10%. A. digitata experienced whole genome multiplication (WGM) around 30 million years ago (MYA), followed by a second WGM event 3-11 MYA, likely linked to autotetraploidy. Resequencing of 25 trees identify three subpopulations, with gene flow across West Africa distinct from East Africa. Gene enrichment and fixation index (Fst) analyses show baobab retained multiple circadian, flowering, and light-responsive genes, which likely support longevity through the UV RESISTANCE LOCUS 8 (UVR8) pathway. In sum, we provide genomic resources and insights for baobab breeding and conservation.

• MeSH
• Chromosomes, Plant * genetics   MeSH
• Phylogeny MeSH
• Adaptation, Physiological genetics   MeSH
• Genome, Plant * MeSH
• Evolution, Molecular * MeSH
• Retroelements genetics   MeSH
• Trees genetics   MeSH
• Gene Flow MeSH
• DNA Transposable Elements genetics   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Madagascar MeSH
• Names of Substances
• Retroelements MeSH
• DNA Transposable Elements MeSH

ConspectusPhotochemical reactions have always been the source of a great deal of mystery. While classified as a type of chemical reaction, no doubts are allowed that the general tenets of ground-state chemistry do not directly apply to photochemical reactions. For a typical chemical reaction, understanding the critical points of the ground-state potential (free) energy surface and embedding them in a thermodynamics framework is often enough to infer reaction yields or characteristic time scales. A general working principle is that the energy profile along the minimum energy paths provides the key information to characterize the reaction. These well-developed concepts, unfortunately, rarely stretch to processes involving the formation of a nonstationary state for a molecular system after light absorption.Upon photoexcitation, a molecule is likely to undergo internal conversion processes, that is, changes of electronic states mediated by couplings between nuclear and electronic motion, precisely what the celebrated Born-Oppenheimer approximation neglects. These coupled electron-nuclear processes, coined nonadiabatic processes, allow for the molecule to decay from one electronic state to the other nonradiatively. Understanding the intricate nonadiabatic dynamics is pivotal to rationalizing and predicting the outcome of a molecular photoexcitation and providing insights for experiments conducted, for example, in advanced light sources such as free-electron lasers.Nowadays, most simulations in nonadiabatic molecular dynamics are based on approximations that invoke a near-classical depiction of the nuclei. This reliance is due to practical constraints, and the classical equations of motion for the nuclei must be supplemented by techniques such as surface hopping to account for nonadiabatic transitions between electronic states. A critical but often overlooked aspect of these simulations is the selection of initial conditions, specifically the choice of initial nuclear positions and momenta for the nonadiabatic dynamics, which can significantly influence how well the simulations mimic real quantum systems across various experimental scenarios. The conventional approach for generating initial conditions for nonadiabatic dynamics typically maps the initial state onto a nuclear phase space using a Wigner quasiprobability function within a harmonic approximation, followed by a second approximation where the molecule undergoes a sudden excitation.In this Account, we aim to warn the experienced or potential user of nonadiabatic molecular dynamics about the possible limitations of this strategy for initial-condition generation and its inability to accurately describe the photoexcitation of a molecule. More specifically, we argue that the initial phase-space distribution can be more accurately represented through molecular dynamics simulations by using a quantum thermostat. This method offers a robust framework that can be applied to large, flexible, or even solvated molecular systems. Furthermore, the reliability of this strategy can be benchmarked against more rigorous approaches such as path integral molecular dynamics. Additionally, the commonly used sudden approximation, which assumes a vertical and sudden excitation of a molecule, rarely reflects the excitation triggered by laser pulses used in actual photochemical and spectroscopic experiments. We discuss here a more general approach that can generate initial conditions for any type of laser pulse. We also discuss strategies to tackle excitation triggered by a continuous-wave laser.

• Publication type
• Journal Article MeSH

This review explores the origins of intracellular parasitism, an intriguing facet of symbiosis, where one organism harms its host, potentially becoming deadly. We focus on three distantly related groups of single-celled eukaryotes, namely Kinetoplastea, Holomycota, and Apicomplexa, which contain multiple species-rich lineages of intracellular parasites. Using comparative analysis of morphological, physiological, and molecular features of kinetoplastids, microsporidians, and sporozoans, as well as their closest free-living relatives, we reveal the evolutionary trajectories and adaptations that enabled the transition to intracellular parasitism. Intracellular parasites have evolved various efficient mechanisms for host acquisition and exploitation, allowing them to thrive in a variety of hosts. Each group has developed unique features related to the parasitic lifestyle, involving dedicated protein families associated with host cell invasion, survival, and exit. Indeed, parallel evolution has led to distinct lineages of intracellular parasites employing diverse traits and approaches to achieve similar outcomes.

• Keywords
• adaptation, comparative analysis, genomic features, intracellular parasite, parallel evolution, symbiosis,
• MeSH
• Apicomplexa genetics   physiology   MeSH
• Biological Evolution * MeSH
• Eukaryota * classification   physiology   MeSH
• Phylogeny MeSH
• Host-Parasite Interactions * MeSH
• Kinetoplastida genetics   physiology   MeSH
• Humans MeSH
• Microsporidia genetics   physiology   MeSH
• Parasitic Diseases * immunology   parasitology   MeSH
• Symbiosis MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Postglacial environmental changes have influenced biodiversity and species evolution, yet the genomic and demographic responses of parasites remain underexplored. This study investigates the population genetics and demographic history of the flatworm Phyllodistomum umblae, a generalist trematode at the definitive host level infecting Coregonus spp. across perialpine and subarctic postglacial lakes. Additionally, we compare its demographic patterns to Proteocephalus fallax, a whitefish specialist tapeworm, to elucidate how ecological strategies shape evolutionary responses to environmental fluctuations. Genomic data from ddRAD sequencing revealed clear genetic differentiation in P. umblae between subarctic and perialpine regions, likely driven by geographic isolation during glacial cycles. Low genetic differentiation suggests hydrological connectivity and the parasite's ability to utilise several host species as definitive hosts. Demographic inference uncovered distinct evolutionary trajectories between P. umblae and Pr. fallax. During the Last Glacial Period (~115-11 kya), P. umblae populations underwent declines, followed by rapid postglacial expansions after the Last Glacial Maximum (~15-10 kya). In contrast, Pr. fallax exhibited older historical fluctuations, including pronounced bottlenecks during the Middle Pleistocene (~300 kya). Its populations remained stable during the LGP, likely due to host persistence in glacial refugia unavailable in earlier glaciation periods. These findings align with the taxon pulse concept within the Stockholm Paradigm, highlighting how glacial cycles triggered episodic population contractions and expansions. By integrating genomic and historical data, this study (1) underscores parasites as models for understanding ecological and evolutionary processes and (2) provides insights into biodiversity resilience and adaptation to past and future environmental changes.

• Keywords
• Trematoda, ddRAD‐seq, demographic inference, freshwater, population genetics,
• Publication type
• Journal Article MeSH

PURPOSE: To examine the influence of growth and maturation in the trajectory of stretch-shortening cycle capability. METHOD: Using a mixed-longitudinal design, absolute and relative leg stiffness and reactive strength index (RSI) were measured 3 times over a 3-year period in 44 youth team-sport players. Maturation was determined as maturity offset and included within the Bayesian inference analysis as a covariate alongside chronological age. RESULTS: Irrespective of age and maturation, there was no change in absolute leg stiffness, however relative leg stiffness decreased over time. Maturation and age reduced this decline, but the decline remained significant (Bayesian factor [10] = 5097, model averaged R2 = .61). The RSI increased over time and more so in older more mature youth players (Bayesian factor [10] = 9.29e8, model averaged R2 = .657). CONCLUSION: In youth players who are at/post peak height velocity, relative leg stiffness appears to decline, which could have an impact on both performance and injury risk. However, RSI increases during this period, and these data reinforce that leg stiffness and RSI reflect different components of stretch-shortening cycle capability. Practitioners should consider these differences when planning training to maximize stretch-shortening cycle capability during growth and maturation in athletes on the developmental performance pathway.

• Keywords
• Bayesian analysis, growth, leg stiffness, reactive strength index, spring mass model,
• MeSH
• Bayes Theorem MeSH
• Leg physiology   MeSH
• Muscle, Skeletal physiology   MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Adolescent MeSH
• Youth Sports MeSH
• Athletes * MeSH
• Muscle Contraction * MeSH
• Muscle Strength MeSH
• Team Sports MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Diplomonads are anaerobic flagellates classified within Metamonada. They contain both host-associated commensals and parasites that reside in the intestinal tracts of animals, including humans (e.g., Giardia intestinalis), as well as free-living representatives that inhabit freshwater and marine anoxic sediments (e.g., Hexamita inflata). The evolutionary trajectories within this group are particularly unusual as the free-living taxa appear to be nested within a clade of host-associated species, suggesting a reversal from host-dependence to a secondarily free-living lifestyle. This is thought to be an exceedingly rare event as parasites often lose genes for metabolic pathways that are essential to a free-living life strategy, as they become increasingly reliant on their host for nutrients and metabolites. To revert to a free-living lifestyle would require the reconstruction of numerous metabolic pathways. All previous studies of diplomonad evolution suffered from either low taxon sampling, low gene sampling, or both, especially among free-living diplomonads, which has weakened the phylogenetic resolution and hindered evolutionary insights into this fascinating transition. RESULTS: We sequenced transcriptomes from 1 host-associated and 13 free-living diplomonad isolates; expanding the genome scale data sampling for diplomonads by roughly threefold. Phylogenomic analyses clearly show that free-living diplomonads form several branches nested within endobiotic species. Moreover, the phylogenetic distribution of genes related to an endobiotic lifestyle suggest their acquisition at the root of diplomonads, while traces of these genes have been identified in free-living diplomonads as well. Based on these results, we propose an evolutionary scenario of ancestral and derived lifestyle transitions across diplomonads. CONCLUSIONS: Free-living taxa form several clades nested within endobiotic taxa in our phylogenomic analyses, implying multiple transitions between free-living and endobiotic lifestyles. The evolutionary history of numerous virulence factors corroborates the inference of an endobiotic ancestry of diplomonads, suggesting that there have been several reversals to a free-living lifestyle. Regaining host independence may have been facilitated by a subset of laterally transferred genes. We conclude that the extant diversity of diplomonads has evolved from a non-specialized endobiont, with some taxa becoming highly specialized parasites, others becoming free-living, and some becoming capable of both free-living and endobiotic lifestyles.

• Keywords
• Diplomonads, Parasitic ancestry signals, Phylogenetics, Phylogenomics, Transcriptomics,
• MeSH
• Biological Evolution MeSH
• Diplomonadida * genetics   MeSH
• Phylogeny * MeSH
• Publication type
• Journal Article MeSH

The escape of DNA from mitochondria into the nuclear genome (nuclear mitochondrial DNA, NUMT) is an ongoing process. Although pervasively observed in eukaryotic genomes, their evolutionary trajectories in a mammal-wide context are poorly understood. The main challenge lies in the orthology assignment of NUMTs across species due to their fast evolution and chromosomal rearrangements over the past 200 million years. To address this issue, we systematically investigated the characteristics of NUMT insertions in 45 mammalian genomes and established a novel, synteny-based method to accurately predict orthologous NUMTs and ascertain their evolution across mammals. With a series of comparative analyses across taxa, we revealed that NUMTs may originate from nonrandom regions in mtDNA, are likely found in transposon-rich and intergenic regions, and unlikely code for functional proteins. Using our synteny-based approach, we leveraged 630 pairwise comparisons of genome-wide microsynteny and predicted the NUMT orthology relationships across 36 mammals. With the phylogenetic patterns of NUMT presence-and-absence across taxa, we constructed the ancestral state of NUMTs given the mammal tree using a coalescent method. We found support on the ancestral node of Fereuungulata within Laurasiatheria, whose subordinal relationships are still controversial. This study broadens our knowledge on NUMT insertion and evolution in mammalian genomes and highlights the merit of NUMTs as alternative genetic markers in phylogenetic inference.

• Keywords
• evolution, genome microsynteny, mammal, nuclear mitochondrial DNA segment (NUMT),
• MeSH
• Cell Nucleus genetics   MeSH
• Phylogeny MeSH
• Genome, Mitochondrial * MeSH
• Genomics * MeSH
• DNA, Mitochondrial genetics   MeSH
• Mitochondria genetics   MeSH
• Evolution, Molecular MeSH
• Mammals genetics   MeSH
• Sequence Analysis, DNA MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• DNA, Mitochondrial MeSH

Microhabitat differentiation of species communities such as vertical stratification in tropical forests contributes to species coexistence and thus biodiversity. However, little is known about how the extent of stratification changes during forest recovery and influences community reassembly. Environmental filtering determines community reassembly in time (succession) and in space (stratification), hence functional and phylogenetic composition of species communities are highly dynamic. It is poorly understood if and how these two concurrent filters-forest recovery and stratification-interact. In a tropical forest chronosequence in Ecuador spanning 34 years of natural recovery, we investigated the recovery trajectory of ant communities in three overlapping strata (ground, leaf litter, lower tree trunk) by quantifying 13 traits, as well as the functional and phylogenetic diversity of the ants. We expected that functional and phylogenetic diversity would increase with recovery time and that each ant community within each stratum would show a distinct functional reassembly. We predicted that traits related to ant diet would show divergent trajectories reflecting an increase in niche differentiation with recovery time. On the other hand, traits related to the abiotic environment were predicted to show convergent trajectories due to a more similar microclimate across strata with increasing recovery age. Most of the functional traits and the phylogenetic diversity of the ants were clearly stratified, confirming previous findings. However, neither functional nor phylogenetic diversity increased with recovery time. Community-weighted trait means had complex relationships to recovery time and the majority were shaped by a statistical interaction between recovery time and stratum, confirming our expectations. However, most trait trajectories converged among strata with increasing recovery time regardless of whether they were related to ant diet or environmental conditions. We confirm the hypothesized interaction among environmental filters during the functional reassembly in tropical forests. Communities in individual strata respond differently to recovery, and possible filter mechanisms likely arise from both abiotic (e.g. microclimate) and biotic (e.g. diet) conditions. Since vertical stratification is prevalent across animal and plant taxa, our results highlight the importance of stratum-specific analysis in dynamic ecosystems and may generalize beyond ants.

• Keywords
• Chocó, Ecuador, chronosequence, community weighted means, environmental filters, forest regeneration, functional traits, phylogeny,
• MeSH
• Biodiversity MeSH
• Ecosystem * MeSH
• Ants * MeSH
• Phylogeny MeSH
• Forests MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH