Developmental regulation of lupulin gland-associated genes in aromatic and bitter hops (Humulus lupulus L.)

Background Hop (Humulus lupulus L.) bitter acids are valuable metabolites for the brewing industry. They are biosynthesized and accumulate in glandular trichomes of the female inflorescence (hop cone). The content of alpha bitter acids, such as humulones, in hop cones can differentiate aromatic from bitter hop cultivars. These contents are subject to genetic and environmental control but significantly correlate with the number and size of glandular trichomes (lupulin glands). Results We evaluated the expression levels of 37 genes involved in bitter acid biosynthesis and morphological and developmental differentiation of glandular trichomes to identify key regulatory factors involved in bitter acid content differences. For bitter acid biosynthesis genes, upregulation of humulone synthase genes, which are important for the biosynthesis of alpha bitter acids in lupulin glands, could explain the higher accumulation of alpha bitter acids in bitter hops. Several transcription factors, including HlETC1, HlMYB61 and HlMYB5 from the MYB family, as well as HlGLABRA2, HlCYCB2–4, HlZFP8 and HlYABBY1, were also more highly expressed in the bitter hop cultivars; therefore, these factors may be important for the higher density of lupulin glands also seen in the bitter hop cultivars. Conclusions Gene expression analyses enabled us to investigate the differences between aromatic and bitter hops. This study confirmed that the bitter acid content in glandular trichomes (lupulin glands) is dependent on the last step of alpha bitter acid biosynthesis and glandular trichome density.

The Structure of Developmental Variation in Early Childhood

Do children’s abilities develop in tandem or on their own separate timetables? Piaget proposed that development proceeded globally through stages; more recent theories view development as more modular with different abilities developing independently and on different time-scales. The developmental differentiation hypothesis suggests that the structure of a child’s development is unitary early in infancy but becomes more complex with age. Despite an abundance of theoretical interest in this question, there is little empirical work on the macrostructure of developmental changes in early childhood. We investigate this structure using two large datasets of parent-reported developmental milestones. Applying item response theory models, we find that variation in development across infancy and early childhood is multidimensional. Consistent with the differentiation hypothesis, differences among older children are better described by higher-dimensional models. In addition, in longitudinal data, we find that, within-person changes in underlying abilities are highly coupled early in life but their coupling decreases by age 12 months. Our work provides a model-based method for linking holistic descriptions of early development to basic theoretical questions about the nature of change in childhood.

Two pathways to self-harm in adolescence

The behavioural and emotional profiles underlying adolescent self-harm, and its developmental risk factors, are relatively unknown. We aimed to identify sub-groups of young people who self-harm (YPSH) and longitudinal predictors leading to self-harm. Participants were from the Millennium Cohort Study (n=10,827). A clustering algorithm identified sub-groups who self-harmed with different behavioural and emotional profiles at age 14. Feature selection analyses were then used to identify longitudinal predictors of self-harming behaviour. There were two distinct sub-groups at age 14: a smaller group (n = 379) who reported a long history of psychopathology, and a second, much larger group (n = 905) without. Notably, both groups could be predicted almost a decade before the reported self-harm. They were similarly characterised by sleep problems and low self-esteem, but there was developmental differentiation. From an early age, the first group had poorer emotion regulation, were bullied, and their caregivers faced emotional challenges. The second group showed less consistency in early childhood, but later reported more willingness to take risks and less security with peers/family. Our results uncover two distinct pathways to self-harm: a psychopathology pathway, associated with early and persistent emotional difficulties and bullying; and an adolescent risky behaviour pathway, where risk-taking and external challenges emerge later into adolescence and predict self-harm. These two pathways have long developmental histories, providing an extended window for interventions as well as potential improvements in the identification of children at risk, biopsychosocial causes, and treatment or prevention of self-harm.

A mechanism for sensing of and adaptation to K+ deprivation in plants

SummaryPotassium ions (K+) are essential for manifold cellular processes. Organismal K+ homoeostasis requires sensing of K+ availability, efficient uptake and defined distribution. Roots are the organ for K+ uptake in plants and soil K+ availability shapes root growth and architecture1. Important channels and transporters conveying cellular K+ fluxes have been described2,3. Understanding K+ sensing and the mechanisms that orchestrate downstream responses exemplifies how environmental conditions integrate with root development and is essential to advance plant nutrition for sustainable agriculture. Here, we report where plants sense K+ deprivation and how this translates into spatially defined ROS signals to trigger HAK5 K+ uptake transporter induction and accelerated maturation of the Casparian strip (CS) paracellular barrier. We define the organ scale K+ pattern of roots and identify a postmeristematic K+-sensing niche (KSN) defined by rapid K+ decline and Ca2+ signals. We discover a Ca2+-triggered bifurcating low-K+ signalling (LKS) axis in that LK-enhanced CIF peptide signalling reinforces SGN3-LKS4/SGN1 receptor kinase complex activation. As consequence, activation of the NOXs RBOHC and RBOHD conveys transcriptome adaptation including HAK5 induction and accelerated CS maturation superimposed on the RBOHF-executed default CS formation. These mechanisms synchronise developmental differentiation and transcriptome reprogramming for maintaining K+ homoeostasis and optimising nutrient foraging by roots.

Developmental differentiation in a cytoplasm-dwelling obligate intracellular bacterium

Developmental differentiation has been described for several vacuole-dwelling obligate intracellular bacteria but never for an obligate intracellular bacterium that resides in the cytoplasm. Here, we show that the cytoplasm-dwelling obligate intracellular bacterium Orientia tsutsugamushi (Ot) exists in five distinct subpopulations. We show that Ot differentiates into a distinct, metabolically inactive, extracellular state upon budding from the surface of host cells and that this stage is preceded by a surface-associated maturation stage. We identify proteins that are differentially expressed in intracellular, replicative bacteria and extracellular, metabolically inactive bacteria. Metabolic activity resumes rapidly upon entry into the cytoplasm and is triggered by the host cell reducing environment. This example of developmental differentiation in a species of Rickettsiaceae provides a new model system for studying synchronized differentiation in a bacterium that has a minimal genome and where the interactions between bacterium and host cell are more direct than they are for bacteria separated from the eukaryote cell host by a vacuolar membrane.Author SummaryScrub typhus is a life-threatening human infection that is caused by the bacterium Orientia tsutsugamushi and spread by mites. Although the disease is estimated to affect at least one million people annually and is often fatal, the infectious agent is much less well understood than many other pathogens. O. tsutsugamushi is an intracellular bacterium that can only grow and divide within eukaryotic cells. During infection, it is found primarily in the cells that make up the lining of blood vessels and in certain immune cell types. O. tsutsugamushi bacteria can remain inside a single infected cell for seven days or more before budding out. The ways in which the bacterium itself changes during the course of an intracellular infection cycle have not been studied. In the current work, we used a range of techniques to show that O. tsutsugamushi differentiates into five distinct subpopulations, and that these are associated with measurable differences in metabolic activity, replication and infectivity. This work opens new avenues of research into the regulation and mechanisms of differentiation of O. tsutsugamushi, which could lead to improved diagnosis and treatments. It also provides a new model system for studying fundamental questions about bacterial development.

Progress in Research on Brain Development and Function of Mice During Weaning

Lactation is a critical phase for brain function development. New dietary experiences of mouse caused by weaning can regulate brain development and function, increase their response to food and environment, and eventually give rise to corresponding behavioral changes. Changes in weaning time induce the alteration of brain tissues morphology and molecular characteristics, glial cell activity and behaviors in the offspring. In addition, it is also sensitive to the intervention of environment and drugs during this period. That is to say, the study focused on brain development and function based on mouse weaning is critical to demonstrate the underlying pathogenesis of neuropsychiatric diseases and find new drug targets. This article mainly focuses on the developmental differentiation of the brain during lactation, especially during weaning in mice.

Exposure to an Environmentally Relevant Phthalate Mixture During Prostate Development Induces MicroRNA Upregulation and Transcriptome Modulation in Rats

Environmental exposure to phthalates during intrauterine development might increase susceptibility to neoplasms in reproductive organs such as the prostate. Although studies have suggested an increase in prostatic lesions in adult animals submitted to perinatal exposure to phthalates, the molecular pathways underlying these alterations remain unclear. Genome-wide levels of mRNAs and miRNAs were monitored with RNA-seq to determine if perinatal exposure to a phthalate mixture in pregnant rats is capable of modifying gene expression during prostate development of the filial generation. The mixture contains diethyl-phthalate, di-(2-ethylhexyl)-phthalate, dibutyl-phthalate, di-isononyl-phthalate, di-isobutyl-phthalate, and benzylbutyl-phthalate. Pregnant females were divided into 4 groups and orally dosed daily from GD10 to PND21 with corn oil (Control: C) or the phthalate mixture at 3 doses (20 μg/kg/day: T1; 200 μg/kg/day: T2; 200 mg/kg/day: T3). The phthalate mixture decreased anogenital distance, prostate weight, and decreased testosterone level at the lowest exposure dose at PND22. The mixture also increased inflammatory foci and focal hyperplasia incidence at PND120. miR-184 was upregulated in all treated groups in relation to control and miR-141-3p was only upregulated at the lowest dose. In addition, 120 genes were deregulated at the lowest dose with several of these genes related to developmental, differentiation, and oncogenesis. The data indicate that phthalate exposure at lower doses can cause greater gene expression modulation as well as other downstream phenotypes than exposure at higher doses. A significant fraction of the downregulated genes were predicted to be targets of miR-141-3p and miR-184, both of which were induced at the lower exposure doses.