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Antiquity of microRNAs and their targets in land plants.

MicroRNAs (miRNAs) affect the morphology of flowering plants by the posttranscriptional regulation of genes involved in critical developmental events. Understanding the spatial and temporal dynamics of miRNA activity during development is therefore central for understanding miRNA functions. We describe a microarray suitable for detection of plant miRNAs. Profiling of Arabidopsis thaliana miRNAs during normal development extends previous expression analyses, highlighting differential expression of miRNA families within specific organs and tissue types. Comparison of our miRNA expression data with existing mRNA microarray data provided a global intersection of plant miRNA and mRNA expression profiles and revealed that tissues in which a given miRNA is highly expressed are unlikely to also show high expression of the corresponding targets. Expression profiling was also used in a phylogenetic survey to test the depth of plant miRNA conservation. Of the 23 families of miRNAs tested, expression of 11 was detected in a gymnosperm and eight in a fern, directly demonstrating that many plant miRNAs have remained essentially unchanged since before the emergence of flowering plants. We also describe an empirical strategy for detecting miRNA target genes from unsequenced transcriptomes and show that targets in nonflowering plants as deeply branching as ferns and mosses are homologous to the targets in Arabidopsis. Therefore, several individual miRNA regulatory circuits have ancient origins and have remained intact throughout the evolution and diversification of plants.

Arabidopsis↗

The criminal activity of sexual offenders in adulthood: revisiting the specialization debate.

Two major hypotheses have been put forward to describe the criminal activity of sexual offenders in adulthood. The first hypothesis states that sexual offenders are specialists who tend to repeat sexual crimes. The second hypothesis describes sexual offenders as generalists who do not restrict themselves to one particular type of crime. The current state of knowledge provides empirical support for both the specialization and the generality hypothesis. The presence of both generality and specialization in the offending behavior of sexual offenders is not as contradictory as it may first appear. However, methodological problems limit the possibility of drawing firm conclusions. Indeed, the specialization hypothesis is based on just one parameter of criminal activity, that is, recidivism, which only takes into account two consecutive crimes. The generality hypothesis is focused mainly on two criminal activity parameters, participation and variety, which do not take into account the dynamic nature of criminal activity over time. Developmental criminology provides a new paradigm to explore the issue of generality and specialization in the offending behavior of sexual offenders.

Adult↗

Marking the anniversary: adolescents and the September 11 healing process.

Clinical data are presented from a day spent at a New Jersey high school severely impacted by the World Trade Center disaster. Dissociation, a sense of numbness, anger, and guilt about feelings induced by the tragedy are all common dynamics in adolescents responding to trauma. The developmental issues that adolescents are confronting are described and discussed in terms of the challenges they present to the healing process. An argument is made that using groups to aid in the long recovery process with our young people should be a top public health priority.

Adaptation, Psychological↗

Geometric mechanogenomics: engineering boundary conditions for deterministic cell fate control.

In tissue development and regeneration, cellular behavior has traditionally been interpreted through biochemical signaling frameworks. However, cells exist within physically defined environments, where geometric boundary conditions - including confinement, curvature, anisotropy, and multicellular architecture - define the mechanical state space in which mechanical forces are generated, transmitted, and interpreted. Here, we introduce geometric mechanogenomics, a conceptual framework that positions geometry as an upstream spatial regulator linking tissue-scale boundary conditions to nuclear mechanics, chromatin organization, and genome regulation. We propose a boundary-to-nucleus axis through which geometric information is decoded by adhesion-mediated mechanotransduction, cytoskeletal force transmission, and nuclear mechanoregulation to regulate chromatin accessibility, epigenetic remodeling, and transcriptional programs. Rather than introducing new mechanotransduction pathways, this framework emphasizes that geometry spatially organizes conserved mechanotransductive machinery to generate context-dependent mechanogenomic outcomes. We further discuss how engineered geometries reduce morphogenetic stochasticity, coordinate multicellular organization, and establish mechanical memory that influences long-term cell fate. Finally, we highlight current challenges in establishing predictive geometry-to-genome relationships and discuss emerging opportunities enabled by spatial omics, artificial intelligence-assisted inverse design, and dynamic biomaterials for programmable mechanobiology, regenerative medicine, developmental biology, and disease modeling.

genome organization↗

Middle ear defects associated with the double knock out mutation of murine goosecoid and Msx1 genes.

A number of developmental regulatory genes, including homeobox genes, are dynamically expressed in the mammalian cephalic ectomesenchyme during craniofacial morphogenesis. Owing to the vast amount of gene knock out experiments, functions of such genes are now being revealed in the mammalian skeletal patterning process. The murine goosecoid (Gsc) and Msx1 genes are expressed during craniofacial development and each mutant mouse displays intriguing facial abnormalities including those of middle ear ossicles, suggesting that both genes play roles in spatial programming of craniofacial regions. In order to examine whether these genes could function in concert to direct particular craniofacial morphogenesis, double knock out mice were analyzed. The phenotype of the double mutant mice was restricted to the first arch derivatives and was apparently additive of the single gene mutant mice, implying region specific genetic interactions of these homeobox genes expressed in overlapping regions of middle ear forming ectomesenchyme. Our results also suggested that the patterning of distal portions of the malleus depends on the tympanic membrane, for which normal expressions of both the genes are prerequisite.

Animals↗

Chemotherapy sensitization by rituximab: experimental and clinical evidence.

For most lymphomas, chemotherapy is palliative because of an inability to overcome drug resistance within the lymphoma cells and attempts at overcoming specific drug resistance mechanisms, such as multidrug resistance, have had limited success. However, accumulating evidence suggests that the ability to activate apoptotic pathways may be an important determinant of chemotherapy sensitivity and presents a potentially important new therapeutic strategy. Studies have shown that distinct cellular thresholds exist for apoptosis, and it is likely that multiple developmental and environmental factors converge in a dynamic process to regulate this set point. If the threshold for inducing apoptosis is limiting, then strategies to modulate these pathways may profoundly enhance the efficacy of cytotoxic therapy. Monoclonal antibodies against the CD20 receptor have been shown to directly induce apoptosis and may serve to modulate the threshold for chemotherapy-induced apoptosis. Recent clinical studies of the monoclonal antibody, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA), and combination chemotherapy have produced unexpectedly high rates of response and progression-free survival, suggesting rituximab improves the efficacy of chemotherapy. Taken together, the results from in vitro and clinical studies suggest that rituximab may modulate the sensitivity of B-cell lymphomas to chemotherapy.

Antibodies, Monoclonal↗

[Cerebrovascular disorders--clinical aspects and follow-up].

The observation of the spontaneous course of the extracranial vascular process as a characteristic cause of cerebral ischemia has shown that vascular changes occur largely independently from the appearance of cerebral functional disturbances in the associated vascular territory. Hemodynamic factors play a minor role; while with the present standard methods available, embolic mechanisms can be insufficiently analyzed. The prospective developmental observations of morphologic and fluid-dynamic aspects and supplemental cell biology and metabolic analysis provide new criteria for an individual risk evaluation of the various mechanisms causing pathologically different cerebral function disturbances, and their analysis has crucial significance for a therapy plan.

Adult↗

[Quality of life in children with chronic disease. Review of the literature and conceptual aspects].

Most studies of the literature concerning the quality of life of children with chronic illness have been conducted in the somatic field, using objective criteria. However the concept of quality of life has evolved: while the first studies took into consideration the effects of somatic diseases on children or on their families, the recent studies tend to focus on the coping strategies developed by the families. The authors emphasize two main points concerning the evaluation and the concept of quality of life: 1) the measures of the quality of life should be "dynamic", i.e. they should deal with the developmental changes of the child; 2) due to the difficulty to clearly define the concept and to the variability of the available informations, a "convergence" notion should be preferably used: i.e. information should be collected from several sources (professionals, families and children) and should concern most domains of the child's life: school, health, games, relational life.

Adaptation, Psychological↗

Developmental changes in parvalbumin regulate presynaptic Ca2+ signaling.

Certain interneurons contain large concentrations of specific Ca2+-binding proteins (CBPs), but consequences on presynaptic Ca2+ signaling are poorly understood. Here we show that expression of the slow CBP parvalbumin (PV) in cerebellar interneurons is cell specific and developmentally regulated, leading to characteristic changes in presynaptic Ca2+ dynamics (Ca(i)). Using whole-cell recording and fluorescence imaging, we studied action potential-evoked Ca(i) transients in axons of GABA-releasing interneurons from mouse cerebellum. At early developmental stages [postnatal days 10-12 (P10-P12)], decay kinetics were significantly faster for basket cells than for stellate cells, whereas at P19-P21 both interneurons displayed fast decay kinetics. Biochemical and immunocytochemical analysis showed parallel changes in the expression levels and cellular distribution of PV. By comparing wild-type and PV(-/-) mice, PV was shown to accelerate the initial decay of action potential-evoked Ca(i) signals in single varicosities and to introduce an additional slow phase that summates during bursts of action potentials. The fast initial Ca(i) decay accounts for a previous report that PV elimination favors synaptic facilitation. The slow decay component is responsible for a pronounced, PV-dependent, delayed transmitter release that we describe here at interneuron-interneuron synapses after presynaptic bursts of action potentials. Numerical simulations account for the effect of PV on Ca(i) kinetics, allow estimates for the axonal PV concentration (approximately 150 microm), and predict the time course of volume-averaged Ca(i) in the absence of exogenous buffer. Overall, PV arises as a major contributor to presynaptic Ca(i) signals and synaptic integration in the cerebellar cortex.

Action Potentials↗

Emotion and cognition: an intricately bound developmental process.

Regulatory aspects of development can best be understood by research that conceptualizes relations between cognition and emotion. The neural mechanisms associated with regulatory processes may be the same as those associated with higher order cognitive processes. Thus, from a developmental cognitive neuroscience perspective, emotion and cognition are dynamically linked and work together to process information and execute action. This article highlights the authors' recent efforts at integrating emotion regulation and cognitive processing during the first year of life by focusing on the methodological criteria outlined by Cole, Martin, and Dennis (this issue), and it discusses the idea that emotion and cognition are an intricately bound developmental process.

Child↗

Dynamic dissolved oxygen concentration control for enhancing the formation rate of torpedo-stage embryos in carrot somatic embryo culture.

In utilizing somatic embryogenesis for transplant production, torpedo-stage embryos are harvested. In order to enhance the formation rate of torpedo-stage embryos to total embryos of all developmental stages in the culture at the time of harvest, a dynamic dissolved oxygen concentration (DO) control algorithm is proposed. The algorithm is based on the difference in developmental response of somatic embryogenesis to DO level depending on developmental stages, and the culture period was divided into three phases of different DO levels. The timing of the phase change was determined based on the formation rate of the embryos in each developmental stage in the suspension assessed by noninvasive monitoring of the culture. The induction of carrot (Daucus carroa L.) somatic embryogenesis resulted in doubled formation rate of torpedo-stage embryos by dynamic DO control compared to the 20% oxygen gas aeration, and 1.4 times higher formation rate compared to 6% oxygen gas aeration, while the total number of embryos did not differ among DO treatments. Plant conversion rate of torpedo-stage embryos cultured by the dynamic DO control was 70%, and was approximately the same as that in the control cultures. The relations between variations of medium pH and somatic embryogenesis were also analyzed.

Journal Article↗

Evolutionary dynamics of genes controlling floral development.

Advances in the understanding of floral developmental genetics in model species such as Arabidopsis continue to provide an important foundation for comparative studies in other flowering plants. In particular, floral organ identity genes are the focus of many projects that are addressing both ancient and recent evolutionary questions. Expanded analyses of the evolution of these gene lineages have highlighted the dynamic nature of the gene birth-and-death process, and may have significant implications for the evolution of genetic pathways. Crucial functional studies of floral organ identity genes in diverse taxa are allowing the first real insight into the conservation of gene function, while findings on the genetic control of organ elaboration offer to open up new avenues for investigation. Taken together, these trends show that the field of floral developmental evolution continues to make significant progress towards elucidating the processes that have shaped the evolution of flower development and morphology.

Evolution, Molecular↗

scMultiNODE: Integrative and Scalable Framework for Multi-Modal Temporal Single-Cell Data.

Measuring single-cell genomic profiles at different timepoints enables our understanding of cell development. This understanding is more comprehensive when we perform an integrative analysis of multiple measurements (or modalities) across various developmental stages. However, obtaining such measurements from the same set of single cells is resource-intensive, restricting our ability to study them jointly. We introduce scMultiNODE, an unsupervised integration model that combines gene expression and chromatin accessibility measurements in developing single cells, while preserving cell type variations and cellular dynamics. First, scMultiNODE uses a scalable, Quantized Gromov-Wasserstein optimal transport to align a large number of cells across different measurements. Next, it utilizes neural ordinary differential equations to explicitly model cell development with a regularization term to learn a dynamic latent space. Experiments on six real-world developmental single-cell datasets demonstrate that scMultiNODE can integrate temporally profiled multi-modal single-cell measurements more effectively than existing methods that focus on cell type variations and often overlook cellular dynamics. We also demonstrate that scMultiNODE's joint latent space facilitates several insightful downstream analyses of single-cell development, including the investigation of complex cell trajectories and the enabling of cross-modal label transfer. The data and code are publicly available at https://github.com/rsinghlab/scMultiNODE.

autoencoders↗

Chaotic possibilities: toward a new model of development.

Most psychoanalytic models of development and change assume an orderly, sequential and predetermined unfolding of psychological functions and structures. Interferences with orderly unfolding challenge the individual and may lead to pathology. These models derive from a worldview associated with the descriptions of change through linear differential equations, which predict a smooth, orderly world. The study of complex systems and their associated non-linear dynamics predicts a very different kind of world: a world with abrupt changes, discontinuities, idiosyncratic developmental lines, and disproportions between causes and effects. The worldview of non-linear dynamics suggests new possibilities for the psychoanalytic model of change and development, and invites confrontation with the adequacy of many widely accepted models. These new possibilities include discontinuous, sudden and qualitative shifts not only in manifest behavior but also in in-depth psychological functioning.

Humans↗

Early organization of the nonlinear right brain and development of a predisposition to psychiatric disorders.

The concepts of self-organization, state changes, and energy flow are central to dynamic systems theory. In this work 1 suggest that to apply these general principles to the study of normal and abnormal development, these constructs must be specifically defined in reference to current knowledge of brain development. Toward that end, I present an overview of the properties of self-organizing developmental systems, and then propose a model of attachment dynamics as synchronized energy exchanges that cocreate nonlinear changes of state, discuss the roles of bioamines and energy-generating brain mitochondria in state regulation, and describe the energy-dependent imprinting of synaptic connectivity and neural circuitry in the infant brain. In this application of nonlinear concepts to developmental models of both resistance against and vulnerability to mental disorders, particular emphasis is placed upon the experience-dependent maturation of a system in the orbital prefrontal cortex that regulates psychobiological state and organismic energy balance. This frontolimbic system is expanded in the nonlinear right hemisphere that generates stress-regulating coping strategies, and it serves as the hierarchical apex of the limbic and autonomic nervous systems. Early forming microstructural alterations and energetic limitations of this regulatory system are suggested to be associated with a predisposition to psychiatric disorders.

Biogenic Monoamines↗

The violent adolescent: the urge to destroy versus the urge to feel alive.

The dynamics of adolescent violence are explored from theoretical and developmental perspectives applied to the review of psychoanalytic studies of violence and three cases: the case of Willie Bosket, presented in Fox Butterfield's All God's Children, an adolescent treated by one of the authors, and observation of staff dynamics in a juvenile detention facility. Studies indicate that violence is used to preserve a sense of existence and psychic equilibrium as well as to express rage and destroy unwanted projected parts of the self and dangerous intrusions into a fragile self-coherence. In the case studies, violent activity serves a number of psychic functions: it leads to high arousal states and the feeling of being alive thereby disavowing underlying feelings of deadness and depression, it serves to contain and discharge overwhelming chaotic and rageful feelings, and it enacts object ties and the unconscious fantasies of the parent. Staff dynamics in a treatment setting for juvenile offenders reflect the intrapsychic dynamics of the juvenile offender prone to acting out, projection, hypervigilance to signs of disrespect, and disavowal of unwanted affects including helplessness and vulnerability.

Adolescent↗

Narp and NP1 form heterocomplexes that function in developmental and activity-dependent synaptic plasticity.

Narp is a neuronal immediate early gene that plays a role in excitatory synaptogenesis. Here, we report that native Narp in brain is part of a pentraxin complex that includes NP1. These proteins are covalently linked by disulfide bonds into highly organized complexes, and their relative ratio in the complex is dynamically dependent upon the neuron's activity history and developmental stage. Complex formation is dependent on their distinct N-terminal coiled-coil domains, while their closely homologous C-terminal pentraxin domains mediate association with AMPA-type glutamate receptors. Narp is substantially more effective in assays of cell surface cluster formation, coclustering of AMPA receptors, and excitatory synaptogenesis, yet their combined expression results in supraadditive effects. These studies support a model in which Narp can regulate the latent synaptogenic activity of NP1 by forming mixed pentraxin assemblies. This mechanism appears to contribute to both activity-independent and activity-dependent excitatory synaptogenesis.

Amino Acid Sequence↗

Cell wall-forming chitin synthases in a chytrid fungus.

Chitin is a critical structural component of fungal cell walls, yet our understanding of its synthesis across the kingdom Fungi remains limited. Here, we investigate chitin synthase diversity, transcription and localisation in the aquatic saprotrophic chytrid Rhizoclosmatium globosum, expanding insights into fungal cell wall biology beyond Dikaryan models. We identified 20 chitin synthase genes in the R. globosum genome, mostly canonical Division I and II types with conserved functional motifs. Transcriptomic analysis through zoospore, germling and immature thallus developmental stages revealed stage-specific expression patterns, with active gene diversity correlating with increasing morphological complexity. Using electroporation-based transformation and fluorescent fusion constructs, we indicate expression and localisation of two chitin synthases during cell development. Localisation patterns suggest dynamic redistribution from cytoplasmic dispersion in early encysted cells to concentrated signals at the sporangium wall. Expression in and around the apophysis indicates the importance of these structures in cell maintenance. Our findings highlight functional specialisation among chitin synthases and underscore the importance of cell wall integrity in chytrid development. This work establishes R. globosum as a genetically tractable model for studying chytrid cell biology and contributes to a broader understanding of fungal evolution and cell wall dynamics.

Biotechnology↗