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The flow of signalling molecules across a field of cells to generate a pattern that is then transduced into a differential response in those cells is a fundamental concept in developmental biology. Recent studies have identified a system that regulates the flux of the growth factor auxin through plant tissues via the subcellular asymmetric localization of specific transporters. The recurrent use of this auxin transport system in different developmental and physiological contexts reveals a fundamental mechanism underpinning organogenesis, stem cell positioning and the growth response of the plant to the environment. Here, I will discuss key advances in the identification of auxin transporters and their integration with auxin signal transduction pathways. [Copyright &y& Elsevier]

Whether morphogenesis is cell division-driven or organismal-based has been a long-running debate in plant biology. This article is a summary of a series of experiments aimed at distinguishing these alternate views by local manipulation of parameters of cell division frequency, orientation, and growth within the shoot apical meristem. These data, put in the context of other investigations in this area, support an organismal view of plant morphogenesis and support the idea that the cell wall plays a key role in the mechanism by which this is achieved. At the same time, the data indicate that the intimate but variable relationship between cell growth and division within the organism means that cell proliferation can indirectly influence this process, leading to a context-dependent influence on morphogenesis. Finally, cell growth and proliferation are intimately related with the process of differentiation as cells exit the meristem. In the final part of the article the molecular mechanism by which these basic cellular parameters are intertwined is discussed. [ABSTRACT FROM PUBLISHER]

A number of recent publications have assessed the outcome on leaf development of targeted manipulation of cell proliferation. The results of these investigations have awakened interest in the long-standing debate in plant biology on the precise role of cell division in morphogenesis. Does cell proliferation drive morphogenesis (cell theory) or is it subservient to a mechanism which acts at the whole organ level to regulate morphogenesis (organismal theory)? In this review, the central role of growth processes (distinct from cell proliferation) in morphogenesis is highlighted and the limitations in our understanding of the basic mechanisms of plant growth control are highlighted. Finally, an attempt is made to demonstrate how sequential local co-ordination of growth might provide an interpretation of some of the recent observations on cell proliferation and leaf morphogenesis. [ABSTRACT FROM AUTHOR]

Summary 1I. Introduction 1II. The shoot apical meristem: the creation of a field of cells from which leaves can be formed 2III. Patterning: the selection of leaf initiation site 2IV. Morphogenesis: the initial stages of leaf formation 4V. Differentiation and determination: transcriptional networks controlling determinancy 6VI. The elaboration of leaf form 6VII. Early steps in leaf histogenesis 7VIII. Later steps in leaf differentiation: epidermal cell fate 8IX. Compound and simple leaves: variation on a theme? 9X. Changes in leaf form: developmental and environmental influences 9XI. A model of leaf formation 9 Acknowledgements 10 References 10The formation of a leaf is a basic aspect of plant development. This review provides an overview of our present understanding of the process from initiation to the final form of the leaf. Molecular genetic and cell biology approaches have yielded significant advances in this area, adding not only to our knowledge of leaf development but also to fundamental principles in plant biology. These principles will be highlighted, as well as areas where our understanding is still incomplete, in particular the problem of coordinating the multifaceted steps involved in the generation of the leaf structure.New Phytologist(2004)doi: 10.1111/j.1469-8137.2004.01292.x© New Phytologist(2004) [ABSTRACT FROM AUTHOR]

Leaves are made in an iterative pattern by the shoot apical meristem. The mechanism of this pattern formation has fascinated biologists, mathematicians and poets for centuries. Over the past year, fundamental insights into the molecular basis of this process have been gained. Patterns of auxin polar transport dictate when and where new leaf primordia are formed on the surface of the apical meristem. Subsequent events are still obscure but appear to involve both alteration of cell wall characteristics (to facilitate a new vector of growth) and a cascade of spatially co-ordinated transcription factor activity (to determine the fate of cells that are incorporated into new lateral organs). The co-ordinated signalling events involved in these processes are beginning to be elucidated. [Copyright &y& Elsevier]

The shoot apical meristem of angiosperms shows a highly conserved cellular architecture in which a change of cell division orientation correlates with early events of leaf initiation. However, the causal role of this altered cellular parameter in leaf formation is debatable. We have used the dynamin-like protein phragmopiastin as a tool to modify the pattern of cell division within the apical meristem. Taking a microinduction approach, we show that local alteration in cell division orientation is not sufficient to induce morphogenesis in the meristem. Surprisingly, an altered cell division pattern did lead to an altered pattern of expression of genes implicated in aspects of leaf formation. Our data identify inducible expression of phragmoplastin as a tool to manipulate cell division pattern. Furthermore, they indicate that a mechanism exists by which cells in the meristem can respond at the level of gene expression to altered parameters of cell division. These data are discussed in the context of a model linking leaf morphogenesis and differentiation. [ABSTRACT FROM AUTHOR]

Synthetic Aperture Radar (SAR) imagery is the primary data type used for sea ice mapping due to its spatiotemporal coverage and the ability to detect sea ice independent of cloud and lighting conditions. Automatic sea ice detection using SAR imagery remains problematic due to the presence of ambiguous signal and noise within the image. Conversely, ice and water are easily distinguishable using multispectral imagery (MSI), but in the polar regions the ocean's surface is often occluded by cloud or the sun may not appear above the horizon for many months. To address some of these limitations, this paper proposes a new tool trained using concurrent multispectral Visible and SAR imagery for sea Ice Detection (ViSual_IceD). ViSual_IceD is a convolution neural network (CNN) that builds on the classic U-Net architecture by containing two parallel encoder stages, enabling the fusion and concatenation of MSI and SAR imagery containing different spatial resolutions. The performance of ViSual_IceD is compared with U-Net models trained using concatenated MSI and SAR imagery as well as models trained exclusively on MSI or SAR imagery. ViSual_IceD outperforms the other networks, with a F1 score 1.30% points higher than the next best network, and results indicate that ViSual_IceD is selective in the image type it uses during image segmentation. Outputs from ViSual_IceD are compared to sea ice concentration products derived from the AMSR2 Passive Microwave (PMW) sensor. Results highlight how ViSual_IceD is a useful tool to use in conjunction with PMW data, particularly in coastal regions. As the spatial-temporal coverage of MSI and SAR imagery continues to increase, ViSual_IceD provides a new opportunity for robust, accurate sea ice coverage detection in polar regions. • ViSual_IceD is a convolutional neural network (CNN) trained for sea ice detection. • The CNN inputs multispectral and radar images outperforming single image tools. • The network selects the most informative image type during segmentation. • Network outputs are more accurate than coastal AMSR2 sea ice concentration data. [ABSTRACT FROM AUTHOR]

• Active AFM cantilever with piezoelectric actuation and piezoresistive sensing. • No requirement for an additional doping step for piezoresistor fabrication. • Compatible with a commercial MEMS fabrication process. • Feedthrough reduction by utilizing separate actuation and sensing phenomena. Active atomic force microscope cantilevers with on-chip actuation and sensing provide several advantages over passive cantilevers which rely on piezoacoustic base-excitation and optical beam deflection measurement. Active microcantilevers exhibit a clean frequency response, provide a path-way to miniturization and parallelization and avoid the need for optical alignment. However, active microcantilevers are presently limited by the feedthrough between actuators and sensors, and by the cost associated with custom microfabrication. In this work, we propose a hybrid cantilever design with integrated piezoelectric actuators and a piezoresistive sensor fabricated from the silicon device layer without requiring an additional doping step. As a result, the design can be fabricated using a commercial five-mask microelectromechanical systems fabrication process. The theoretical piezoresistor sensitivity is compared with finite element simulations and experimental results obtained from a prototype device. The proposed approach is demonstrated to be a promising alternative to conventional microcantilever actuation and deflection sensing. [ABSTRACT FROM AUTHOR]

Focuses on the correlation between human ecology and history in Scotland's Saint Kilda islands. Description of how the islands' ecological structure contributed to the communal self-management approach to the local economy in the 17th century; Details of historical accounts in the publication `Voyage to Saint Kilda,' written by Martin Martin in the 17th century.

It is argued that the field data do not support the claims made by Tilley in his A Phenomenology of Landscape (1994) for intentional relationships between the placing of Welsh megalithic tombs and natural features of the landscape. The critique relates to sample quality, observational rigour and failure to examine alternative hypotheses concerning the siting factors involved in the placing of the tombs. [ABSTRACT FROM AUTHOR]

Embryos derived from somatic tissues proceed through a series of morphological stages very similar to those observed during zygotic embryo development. However, somatic embryos do show some developmental characteristics distinct from those of zygotic embryos (e.g. curtailed cotyledon filling, precocious germination) which are not observed in zygotic embryos in vivo. Whether these differences reflect the abnormality of the in vitro culture environment or whether they are due to biochemical or developmental peculiarities of the somatic embryos is unclear. Using a system of secondary embryogenesis in Brassica napus. Primer, we have attempted to address this problem by analysing the level of napin storage protein transcripts and their regulation by ABA throughout somatic embryo development. We have in addition measured the endogenous levels of ABA in the embryos, and characterised the effect of ABA (and other medium components) on napin transcript level, embryo germination, and embryo survival. Our analysis, in conjunction with the published data on zygotic and microspore-derived embryo development, allows us to conclude that although somatic and zygotic embryos show the same basic pattern of napin gene expression and regulation. the secondary embryos are characterised by a basal constitutive derepression of the napin gene, in contrast to the tight developmental control reported in zygotic embryos. [ABSTRACT FROM AUTHOR]

Informs about the role that expansin, an extracellular protein, plays in the increasing of plant cell wall extensibility. Expansin inducing tissue expansion in vivo; Localized control of tissue expansion possibly sufficient to induce leaf formation; Suggestion of a role for biophysical forces in the regulation of plant development.

This Note describes a new technique for estimating the resolution of nanopositioning systems. By recording the voltage applied to an actuator and performing a filtering operation, the position noise and resolution can be estimated. This technique is simple to apply in practice and does not require any additional sensors or specialized equipment. [ABSTRACT FROM AUTHOR]

The article provides a quantitative analysis of the process of capitulum growth and the gradual but controlled process by which elements within the capitulum become destined to form individual flowers. The data provide a foundation for the modelling of flower formation and for linking the observed parameters of floral morphogenesis with the wealth of molecular data on organogenesis in plants. An analysis of auxin flux and distribution during leaf initiation is also presented. The situation in the capitulum may be linked with the spatial and temporal control of factors specific to flower formation.

Microcantilever probes for tip-enhanced Raman spectroscopy (TERS) have a grainy metal coating that may exhibit multiple plasmon hotspots near the tip apex, which may compromise spatial resolution and introduce imaging artefacts. It is also possible that the optical hotspot may not occur at the mechanical apex, which introduces an offset between TERS and atomic force microscope maps. In this article, a gold nanocone TERS probe is designed and fabricated for 638 nm excitation. The imaging performance is compared to grainy probes by analysing high-resolution TERS cross-sections of single-walled carbon nanotubes. Compared to the tested conventional TERS probes, the nanocone probe exhibited a narrow spot diameter, comparable optical contrast, artefact-free images, and collocation of TERS and atomic force microscope topographic maps. The 1/e² spot diameter was 12.5 nm and 19 nm with 638 nm and 785 nm excitation, respectively. These results were acquired using a single gold nanocone probe to experimentally confirm feasibility. Future work will include automating the fabrication process and statistical analysis of many probes. [ABSTRACT FROM AUTHOR]

Accurate quantification of iceberg populations is essential to inform estimates of Southern Ocean freshwater and heat balances as well as shipping hazards. The automated operational monitoring of icebergs remains challenging, largely due to a lack of generality in existing approaches. Previous efforts to map icebergs have often exploited synthetic aperture radar (SAR) data but the majority are designed for open water situations, require significant operator input, and are susceptible to the substantial spatial and temporal variability in backscatter that characterises SAR time-series. We propose an adaptive unsupervised classification procedure based on Sentinel 1 SAR data and a recursive Dirichlet Process implementation of Bayesian Gaussian Mixture Model. The approach is robust to inter-scene variability and can identify icebergs even within complex environments containing mixtures of open water, sea ice and icebergs of various sizes. For the study area in the Amundsen Sea Embayment, close to the calving front of Thwaites Glacier, our classifier achieved a mean pixel-wise F1 score against manual iceberg delineations from the SAR scenes of 0. 960 ± 0. 018 with a corresponding object-level F1 score of 0. 729 ± 0. 086. The method provides an excellent basis for estimation of total near-shore iceberg populations and has inherent potential for scalability that other approaches lack. [Display omitted] • Unsupervised method as basis for scalable operational iceberg monitoring and tracking. • Icebergs reliably segmented within open water, sea ice and adjacent to calving fronts. • Adaptive method accounts for inter-scene variability without prior knowledge. [ABSTRACT FROM AUTHOR]

Summary: Land plants evolved multiple adaptations to restrict transpiration. However, the underlying molecular mechanisms are not sufficiently understood.We used an ozone‐sensitivity forward genetics approach to identify Arabidopsis thaliana mutants impaired in gas exchange regulation.High water loss from detached leaves and impaired decrease of leaf conductance in response to multiple stomata‐closing stimuli were identified in a mutant of MURUS1 (MUR1), an enzyme required for GDP‐l‐fucose biosynthesis. High water loss observed in mur1 was independent from stomatal movements and instead could be linked to metabolic defects. Plants defective in import of GDP‐l‐Fuc into the Golgi apparatus phenocopied the high water loss of mur1 mutants, linking this phenotype to Golgi‐localized fucosylation events. However, impaired fucosylation of xyloglucan, N‐linked glycans, and arabinogalactan proteins did not explain the aberrant water loss of mur1 mutants.Partial reversion of mur1 water loss phenotype by borate supplementation and high water loss observed in boron uptake mutants link mur1 gas exchange phenotypes to pleiotropic consequences of l‐fucose and boron deficiency, which in turn affect mechanical and morphological properties of stomatal complexes and whole‐plant physiology. Our work emphasizes the impact of fucose metabolism and boron uptake on plant–water relations. [ABSTRACT FROM AUTHOR]

Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited as an autosomal dominant trait, due to a single heterozygous loss-of-function variant, usually in ACVRL1 (encoding activin receptor-like kinase 1 [ALK1]), ENG (encoding endoglin [CD105]), or SMAD4. In a consecutive single-centre series of 37 positive clinical genetic tests performed in 2021–2023, a skewed distribution pattern was noted, with 30 of 32 variants reported only once, but ACVRL1 c.1231C>T (p.Arg411Trp) identified as the disease-causal gene in five different HHT families. In the same centre's non-overlapping 1992–2020 series where 110/134 (82.1%) HHT-causal variants were reported only once, ACVRL1 c.1231C>T (p.Arg411Trp) was identified in nine further families. In a 14-country, four-continent HHT Mutation Database where 181/250 (72.4%) HHT-causal variants were reported only once, ACVRL1 c.1231C>T (p.Arg411Trp) was reported by 12 different laboratories, the adjacent ACVRL1 c.1232G>A (p.Arg411Gln) by 14, and ACVRL1 c.1120C>T (p.Arg374Trp) by 18. Unlike the majority of HHT-causal ACVRL1 variants, these encode ALK1 protein that reaches the endothelial cell surface but fails to signal. Six variants of this type were present in the three series and were reported 6.8–25.5 (mean 8.9) times more frequently than the other ACVRL1 missense variants (all p-values < 0.0039). Noting lower rates of myocardial infarction reported in HHT, we explore potential mechanisms, including a selective paradigm relevant to ALK1′s role in the initiating event of atherosclerosis, where a plausible dominant negative effect of these specific variants can be proposed. In conclusion, there is an ~9-fold excess of kinase-inactive, cell surface-expressed ACVRL1/ALK1 pathogenic missense variants in HHT. The findings support further examination of differential clinical and cellular phenotypes by HHT causal gene molecular subtypes. [ABSTRACT FROM AUTHOR]

Summary: C4 plants typically operate a CO2 concentration mechanism from mesophyll (M) cells into bundle sheath (BS) cells. NADH dehydrogenase‐like (NDH) complex is enriched in the BS cells of many NADP‐malic enzyme (ME) type C4 plants and is more abundant in C4 than in C3 plants, but to what extent it is involved in the CO2 concentration mechanism remains to be experimentally investigated.We created maize and rice mutants deficient in NDH function and then used a combination of transcriptomic, proteomic, and metabolomic approaches for comparative analysis.Considerable decreases in growth, photosynthetic activities, and levels of key photosynthetic proteins were observed in maize but not rice mutants. However, transcript abundance for many cyclic electron transport (CET) and Calvin–Benson cycle components, as well as BS‐specific C4 enzymes, was increased in maize mutants. Metabolite analysis of the maize ndh mutants revealed an increased NADPH : NADP ratio, as well as malate, ribulose 1,5‐bisphosphate (RuBP), fructose 1,6‐bisphosphate (FBP), and photorespiration intermediates.We suggest that by optimizing NADPH and malate levels and adjusting NADP‐ME activity, NDH functions to balance metabolic and redox states in the BS cells of maize (in addition to ATP supply), coordinating photosynthetic transcript abundance and protein content, thus directly regulating the carbon flow in the two‐celled C4 system of maize. [ABSTRACT FROM AUTHOR]

All cells of an adult plant are ultimately derived from divisions that occur in small groups of cells distributed throughout the plant, termed meristems. A new study shows that carbohydrate post-translational modification of a peptide signal influences meristem and, as a consequence, fruit size in tomato. [ABSTRACT FROM AUTHOR]

Background: As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings. Methods: We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering. Results: For 36/65 gene-disease pairs, loss of function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using the CardiacG2P dataset as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches. Conclusions: Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is a pre-requisite for scalable genomic testing. [ABSTRACT FROM AUTHOR]

Charge drive circuits can significantly reduce piezoelectric nonlinearity; however, they are rarely used in practice because of their limited low-frequency performance, their dependence of voltage gain on the load capacitance, and their requirement for time-consuming tuning procedures. In this report, a new charge drive circuit is proposed that uses a controlled current source with voltage feedback to stabilize the low-frequency behavior. This approach eliminates many of the present difficulties and allows extremely low transition frequencies without a long transient response. Experimental results demonstrate that the proposed charge amplifier can effectively reduce piezoelectric hysteresis and creep to less than 1.3% at scan-rates of 10, 1, and 0.1 Hz. [ABSTRACT FROM AUTHOR]

Tillering and yield are linked in rice, with significant efforts being invested to understand the genetic basis of this phenomenon. However, in addition to genetic factors, tillering is also influenced by the environment. Exploiting experiments in which seedlings were first grown in elevated CO2 (eCO2) before transfer and further growth under ambient CO2 (aCO2) levels, we found that even moderate exposure times to eCO2 were sufficient to induce tillering in seedlings, which was maintained in plants grown to maturity plants in controlled environment chambers. We then explored whether brief exposure to eCO2 (eCO2 priming) could be implemented to regulate tiller number and yield in the field. We designed a cost-effective growth system, using yeast to increase the CO2 level for the first 24 days of growth, and grew these seedlings to maturity in semi-field conditions in Malaysia. The increased growth caused by eCO2 priming translated into larger mature plants with increased tillering, panicle number, and improved grain filling and 1000 grain weight. In order to make the process more appealing to conventional rice farmers, we then developed a system in which fungal mycelium was used to generate the eCO2 via respiration of sugars derived by growing the fungus on lignocellulosic waste. Not only does this provide a sustainable source of CO2, it also has the added financial benefit to farmers of generating economically valuable oyster mushrooms as an end-product of mycelium growth. Our experiments show that the system is capable of generating sufficient CO2 to induce increased tillering in rice seedlings, leading eventually to 18% more tillers and panicles in mature paddy-grown crop. We discuss the potential of eCO2 priming as a rapidly implementable, broadly applicable and sustainable system to increase tillering, and thus yield potential in rice. [ABSTRACT FROM AUTHOR]

The fossil record suggests stomata-like pores were present on the surfaces of land plants over 400 million years ago. Whether stomata arose once or whether they arose independently across newly evolving land plant lineages has long been a matter of debate. In Arabidopsis, a genetic toolbox has been identified that tightly controls stomatal development and patterning. This includes the basic helix-loop-helix (bHLH) transcription factors SPEECHLESS (SPCH), MUTE, FAMA, and ICE/SCREAMs (SCRMs), which promote stomatal formation. These factors are regulated via a signaling cascade, which includes mobile EPIDERMAL PATTERNING FACTOR (EPF) peptides to enforce stomatal spacing. Mosses and hornworts, the most ancient extant lineages to possess stomata, possess orthologs of these Arabidopsis (Arabidopsis thaliana) stomatal toolbox genes, and manipulation in the model bryophyte Physcomitrella patens has shown that the bHLH and EPF components are also required for moss stomatal development and patterning. This supports an ancient and tightly conserved genetic origin of stomata. Here, we review recent discoveries and, by interrogating newly available plant genomes, we advance the story of stomatal development and patterning across land plant evolution. Furthermore, we identify potential orthologs of the key toolbox genes in a hornwort, further supporting a single ancient genetic origin of stomata in the ancestor to all stomatous land plants. [ABSTRACT FROM AUTHOR]

This article presents a high-speed single- and dual-stage vertical positioners for applications in optical systems. Each positioner employs a unique end-constraint method with orthogonal flexures to preload a piezoelectric stack actuator. This end-constraint method also significantly increases the first mechanical resonance frequency. The single-stage positioner has a displacement range of 7.6 μm and a first resonance frequency of 46.8 kHz. The dual-stage design consists of a long-range slow-stage and a short-range fast-stage. An inertial counterbalance technique was implemented on the fast-stage to cancel inertial forces resulting from high-speed motion. The dual-stage positioner has a combined travel range of approximately 10 μm and a first evident resonance frequency of 130 kHz. [ABSTRACT FROM AUTHOR]

Summary: Leaf structure plays an important role in photosynthesis. However, the causal relationship and the quantitative importance of any single structural parameter to the overall photosynthetic performance of a leaf remains open to debate. In this paper, we report on a mechanistic model, eLeaf, which successfully captures rice leaf photosynthetic performance under varying environmental conditions of light and CO2.We developed a 3D reaction‐diffusion model for leaf photosynthesis parameterised using a range of imaging data and biochemical measurements from plants grown under ambient and elevated CO2 and then interrogated the model to quantify the importance of these elements.The model successfully captured leaf‐level photosynthetic performance in rice. Photosynthetic metabolism underpinned the majority of the increased carbon assimilation rate observed under elevated CO2 levels, with a range of structural elements making positive and negative contributions. Mesophyll porosity could be varied without any major outcome on photosynthetic performance, providing a theoretical underpinning for experimental data.eLeaf allows quantitative analysis of the influence of morphological and biochemical properties on leaf photosynthesis. The analysis highlights a degree of leaf structural plasticity with respect to photosynthesis of significance in the context of attempts to improve crop photosynthesis. [ABSTRACT FROM AUTHOR]

Summary: How are the transcriptional events that control form actually transduced into the shape of an organism? Analysis of plant tissue mechanical properties shows that control of the extracellular matrix is key. [ABSTRACT FROM AUTHOR]

The use of integrated on-chip actuation simplifies the identification of a cantilever resonance, can improve imaging speed, and enables the use of smaller cantilevers, which is required for low-force imaging at high speed. This article describes a cantilever with on-chip actuation and novel dual-sensing capabilities for AFM. The dual-sensing configuration allows for tip displacement and tip force to be measured simultaneously. A mathematical model is developed and validated with finite element analysis. A physical prototype is presented, and its calibration and validation are presented. The cantilever is optimized for use in off-resonance tapping modes. Experimental results demonstrate an agreement between the on-chip sensors and external force and displacement measurements. [Display omitted] • Faster imaging allows for the detection of rapidly changing phenomena in samples. • Indirect tip displacement can induce errors in the imaging data. • OBD measures angle and it is not linear for large amplitudes. • Integrated sensors and actuator are compatible with microelectromechanical devices. [ABSTRACT FROM AUTHOR]

Simple Summary: The telomerase enzyme adds repetitive genetic sequences to the ends of chromosomes called telomeres to prevent cellular senescence. Gain of telomerase function is one of the hallmarks of human cancer. The telomerase protein is coded by the gene TERT and increased TERT RNA levels have been associated with disease relapse in Wilms tumor, the most common kidney cancer of childhood. This study aimed to determine the mechanisms of increased TERT expression in Wilms tumor. This study found mutations in the TERT promoter, increased methylation of the TERT promoter, and genomic copy number amplifications of TERT as potential mechanisms of TERT activation. Conversely, this study found that inactivating WT1 mutation was associated with low TERT RNA levels and telomerase activity. N-MYC overexpression in Wilms tumor cells resulted in increased TERT promoter activity and TERT transcription. TERT transcription is associated with molecular and histologic subgroups in Wilms tumor and telomere-targeted therapies warrant future investigation. Increased TERT mRNA is associated with disease relapse in favorable histology Wilms tumor (WT). This study sought to understand the mechanism of increased TERT expression by determining the association between TERT and WT1 and N-MYC, two proteins important in Wilms tumor pathogenesis that have been shown to regulate TERT expression. Three out of 45 (6.7%) WTs and the corresponding patient-derived xenografts harbored canonical gain-of-function mutations in the TERT promoter. This study identified near ubiquitous hypermethylation of the TERT promoter region in WT compared to normal kidney. WTs with biallelic inactivating mutations in WT1 (7/45, 15.6%) were found to have lower TERT expression by RNA-seq and qRT-PCR and lower telomerase activity determined by the telomerase repeat amplification protocol. Anaplastic histology and increased percentage of blastema were positively correlated with higher TERT expression and telomerase activity. In vitro shRNA knockdown of WT1 resulted in decreased expression of TERT, reduced colony formation, and decreased proliferation of WiT49, an anaplastic WT cell line with wild-type WT1. CRISPR-Cas9-mediated knockout of WT1 resulted in decreased expression of telomere-related gene pathways. However, an inducible Wt1-knockout mouse model showed no relationship between Wt1 knockout and Tert expression in normal murine nephrogenesis, suggesting that WT1 and TERT are coupled in transformed cells but not in normal kidney tissues. N-MYC overexpression resulted in increased TERT promoter activity and TERT transcription. Thus, multiple mechanisms of TERT activation are involved in WT and are associated with anaplastic histology and increased blastema. This study is novel because it identifies potential mechanisms of TERT activation in Wilms tumor that could be of therapeutic interests. [ABSTRACT FROM AUTHOR]

Parental depression places offspring at elevated risk for multiple, co-occurring problems. The purpose of this study was to develop and preliminarily evaluate Project Hope, a family intervention for the prevention of both depression and substance use among adolescent-aged children ( M = 13.9 years) of depressed parents. The program was created by blending two empirically supported interventions: one for depression and another for substance use. Thirty families were randomly assigned to either Project Hope ( n = 16) or a wait-list control condition ( n = 14). Pretests, posttests ( n = 29), and 5-month follow-ups ( n = 28) were conducted separately with parents and youth via phone interviews. Questions asked about the family depression experience, family interactions, family management, coping, adolescent substance use beliefs and refusal skills, adolescent depression, and adolescent substance use. Project Hope was fully developed, manualized, and implemented with a small sample of targeted families. Engagement in the program was relatively high. Preliminary outcome analyses were conducted using 2 (Group) ×3 (Time) analyses of covariance. Results provided some evidence for significant improvements among intervention compared to control participants in indicators of the family depression experience, family management, and coping, and a statistically significant decrease from pretest to posttest in alcohol quantity for intervention compared to control youth. Next steps for this program of research are discussed. [ABSTRACT FROM AUTHOR]