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18 pages, 4417 KiB  
Article
Children’s Drawing and Graphic Development: An Empirical Study of the Developmental Stages According to Lowenfeld
by Paula Gil-Ruiz, Victoria Martinez-Verez, William Ospina Toro and Walter Castañeda Marulanda
Educ. Sci. 2025, 15(6), 681; https://doi.org/10.3390/educsci15060681 - 30 May 2025
Viewed by 940
Abstract
Children’s graphic development reflects cognitive, emotional, motor and social processes, and is an indicator of the infant’s integral development. This study analyzed the validity of Viktor Lowenfeld’s developmental model in children aged 3 to 5 years, assessing whether the stages proposed by the [...] Read more.
Children’s graphic development reflects cognitive, emotional, motor and social processes, and is an indicator of the infant’s integral development. This study analyzed the validity of Viktor Lowenfeld’s developmental model in children aged 3 to 5 years, assessing whether the stages proposed by the author correspond to the patterns of graphic representation currently observed. A mixed design with a descriptive–comparative approach was used. The sample consisted of 218 drawings collected in educational centers in Madrid. Each drawing was evaluated according to criteria derived from Lowenfeld’s model (stroke, motor control, symbolism, use of color, spatial organization) and classified into one of the five developmental stages. The analysis included descriptive statistics, chi-squared tests (χ2 = 104.92, gl = 10, p < 0.0001), and Spearman correlations (ρ = 0.661, p < 0.0001), in addition to qualitative interpretation by inter-rater consensus. The results confirm that the general graphic sequence follows Lowenfeld’s scheme, but with notable variations in the age of onset of each stage. Pre-schematic manifestations were observed in children as young as 3 years old and persistence of scribbling in some 5-year-olds. These findings point to the influence of individual, sociocultural, and technological factors on the rate of graphic development. Lowenfeld’s model remains a valid framework for observing children’s drawing, but its application should be flexible. Interindividual differences and contemporary visual culture require a pedagogical adaptation that addresses the diversity of developmental rhythms. Its integration with inclusive methodologies and future cross-cultural studies is suggested. Full article
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16 pages, 219 KiB  
Article
Breastfeeding and Its Influence on Psychomotor Development: An Investigation Based on the LAyDI Study (PAPenRed)
by Silvia Martín-Ramos, Begoña Domínguez-Aurrecoechea, Marta Carballal-Mariño, Guadalupe Del Castillo-Aguas, Gonzalo Solís-Sánchez and on behalf of the “Red de Investigación en Pediatría de Atención Primaria” (PAPenRed)
Nutrients 2025, 17(6), 967; https://doi.org/10.3390/nu17060967 - 10 Mar 2025
Viewed by 789
Abstract
Objectives: To analyse whether breastfeeding (BF) is related to better psychomotor development in the first two years of life. Methods: Prospective longitudinal study of a cohort of children born in Spain (between April 2017 and March 2018) and followed during the first two [...] Read more.
Objectives: To analyse whether breastfeeding (BF) is related to better psychomotor development in the first two years of life. Methods: Prospective longitudinal study of a cohort of children born in Spain (between April 2017 and March 2018) and followed during the first two years of life by their primary care paediatrician in eight visits (LAyDI study—PAPenRed research network). The Haizea-Llevant development chart was used to assess the psychomotor development (DPM), and the subjects were divided according to whether or not they met each milestone. Results: The initial sample was 1946 children (50.1% boys), which varied at each visit from 1946 on the first and second visit to 1076 on the last visit; DPM at 12, 18 and 24 months was compared according to the type of BF at 6 months; at 24 months, significant differences were found in the achievement of milestones in the BF-at-6-months group (“scribbles spontaneously”, p 0.007 and “descends stair”, p 0.002). When comparing the mean duration of BF and exclusive breastfeeding, according to milestones reached or not, statistically significant differences were observed in more milestones at the 24-month visit, including “eats with a spoon” (5.6 months in the group that reached it vs. 2.4 months in the group that did not, p 0.014), and again for the milestone ‘scribbles spontaneously’ (5.6 months vs. 1.8 months, p 0.021), among others. Conclusions: In our study, psychomotor development in the first two years of life does not show major differences in relation to the type of feeding; from this age onwards, the differences may be greater. Many factors influence psychomotor development in the first years of life, with breastfeeding not being an isolated factor. Full article
(This article belongs to the Special Issue Own or Donated Human Milk: Its Role in Today's Society)
25 pages, 4283 KiB  
Article
Shape-Aware Adversarial Learning for Scribble-Supervised Medical Image Segmentation with a MaskMix Siamese Network: A Case Study of Cardiac MRI Segmentation
by Chen Li, Zhong Zheng and Di Wu
Bioengineering 2024, 11(11), 1146; https://doi.org/10.3390/bioengineering11111146 - 13 Nov 2024
Viewed by 1231
Abstract
The transition in medical image segmentation from fine-grained to coarse-grained annotation methods, notably scribble annotation, offers a practical and efficient preparation for deep learning applications. However, these methods often compromise segmentation precision and result in irregular contours. This study targets the enhancement of [...] Read more.
The transition in medical image segmentation from fine-grained to coarse-grained annotation methods, notably scribble annotation, offers a practical and efficient preparation for deep learning applications. However, these methods often compromise segmentation precision and result in irregular contours. This study targets the enhancement of scribble-supervised segmentation to match the accuracy of fine-grained annotation. Capitalizing on the consistency of target shapes across unpaired datasets, this study introduces a shape-aware scribble-supervised learning framework (MaskMixAdv) addressing two critical tasks: (1) Pseudo label generation, where a mixup-based masking strategy enables image-level and feature-level data augmentation to enrich coarse-grained scribbles annotations. A dual-branch siamese network is proposed to generate fine-grained pseudo labels. (2) Pseudo label optimization, where a CNN-based discriminator is proposed to refine pseudo label contours by distinguishing them from external unpaired masks during model fine-tuning. MaskMixAdv works under constrained annotation conditions as a label-efficient learning approach for medical image segmentation. A case study on public cardiac MRI datasets demonstrated that the proposed MaskMixAdv outperformed the state-of-the-art methods and narrowed the performance gap between scribble-supervised and mask-supervised segmentation. This innovation cuts annotation time by at least 95%, with only a minor impact on Dice performance, specifically a 2.6% reduction. The experimental outcomes indicate that employing efficient and cost-effective scribble annotation can achieve high segmentation accuracy, significantly reducing the typical requirement for fine-grained annotations. Full article
(This article belongs to the Section Biosignal Processing)
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20 pages, 9189 KiB  
Article
The Cyst Epithelium in Polycystic Kidney Disease Patients Displays Normal Apical-Basolateral Cell Polarity
by Samuel Loft Sandegaard, Andreas Riishede, Henrik Birn, Helle Hasager Damkier and Jeppe Praetorius
Int. J. Mol. Sci. 2024, 25(3), 1904; https://doi.org/10.3390/ijms25031904 - 5 Feb 2024
Cited by 1 | Viewed by 2149
Abstract
The main characteristic of polycystic kidney disease is the development of multiple fluid-filled renal cysts. The discovery of mislocalized sodium-potassium pump (Na,K-ATPase) in the apical membrane of cyst-lining epithelia alluded to reversal of polarity as a possible explanation for the fluid secretion. The [...] Read more.
The main characteristic of polycystic kidney disease is the development of multiple fluid-filled renal cysts. The discovery of mislocalized sodium-potassium pump (Na,K-ATPase) in the apical membrane of cyst-lining epithelia alluded to reversal of polarity as a possible explanation for the fluid secretion. The topic of apical Na,K-ATPase in cysts remains controversial. We investigated the localization of the Na,K-ATPase and assessed the apical-basolateral polarization of cyst-lining epithelia by means of immunohistochemistry in kidney tissue from six polycystic kidney disease patients undergoing nephrectomy. The Na,K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical targeting protein Syntaxin-3 also immunolocalized to the apical domain of cyst-lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Thus, no deviations from the typical epithelial distribution of basic cell polarity proteins were observed in the cysts from the six patients. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst-lining epithelia in polycystic kidney disease. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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17 pages, 27372 KiB  
Article
Cluster2Former: Semisupervised Clustering Transformers for Video Instance Segmentation
by Áron Fóthi, Adrián Szlatincsán and Ellák Somfai
Sensors 2024, 24(3), 997; https://doi.org/10.3390/s24030997 - 3 Feb 2024
Cited by 1 | Viewed by 1907
Abstract
A novel approach for video instance segmentation is presented using semisupervised learning. Our Cluster2Former model leverages scribble-based annotations for training, significantly reducing the need for comprehensive pixel-level masks. We augment a video instance segmenter, for example, the Mask2Former architecture, with similarity-based constraint loss [...] Read more.
A novel approach for video instance segmentation is presented using semisupervised learning. Our Cluster2Former model leverages scribble-based annotations for training, significantly reducing the need for comprehensive pixel-level masks. We augment a video instance segmenter, for example, the Mask2Former architecture, with similarity-based constraint loss to handle partial annotations efficiently. We demonstrate that despite using lightweight annotations (using only 0.5% of the annotated pixels), Cluster2Former achieves competitive performance on standard benchmarks. The approach offers a cost-effective and computationally efficient solution for video instance segmentation, especially in scenarios with limited annotation resources. Full article
(This article belongs to the Special Issue Deep Learning-Based Neural Networks for Sensing and Imaging)
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11 pages, 603 KiB  
Article
From Scribbles to Script: Graphomotor Skills’ Impact on Spelling in Early Primary School
by Michelle N. Maurer, Lidia Truxius, Judith Sägesser Wyss and Michael Eckhart
Children 2023, 10(12), 1886; https://doi.org/10.3390/children10121886 - 1 Dec 2023
Cited by 2 | Viewed by 2352
Abstract
The acquisition of handwriting skills is a crucial goal in early primary school. Yet our comprehension of handwriting development, encompassing graphomotor skills and spelling, remains fragmented. The identification of predictors for handwriting skills is essential for providing early support. This longitudinal study aimed [...] Read more.
The acquisition of handwriting skills is a crucial goal in early primary school. Yet our comprehension of handwriting development, encompassing graphomotor skills and spelling, remains fragmented. The identification of predictors for handwriting skills is essential for providing early support. This longitudinal study aimed to explore the predictive roles of gender, working memory, and motivation to handwrite for graphomotor skills six months later and spelling skills one year later. Paper-and-pencil tasks (graphomotor skills, spelling), a tablet task (working memory), and a questionnaire (teachers’ ratings of children’s handwriting motivation) were employed. This study included 363 first-grade children (49.8% girls) aged 6–9 years. Results from a structural equation model, controlling for age and socioeconomic background, revealed that girls exhibited superior performance in graphomotor skills, while boys tended to spell more accurately. Furthermore, working memory predicted graphomotor skills but not spelling. Additionally, motivation to handwrite predicted both first-grade graphomotor skills and second-grade spelling. This study extends contemporary evidence, demonstrating that graphomotor skills predict spelling while considering gender and motivation. The findings underscore the pivotal role of graphomotor skills in spelling acquisition and suggest their contribution to spelling difficulties. Full article
(This article belongs to the Special Issue Motor Learning of Handwriting and Developmental Dysgraphia)
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19 pages, 8038 KiB  
Article
A Novel Unsupervised Segmentation Method of Canopy Images from UAV Based on Hybrid Attention Mechanism
by Jiaqi Li, Yin Wu, Haojia Zhang and Hancong Wang
Electronics 2023, 12(22), 4682; https://doi.org/10.3390/electronics12224682 - 17 Nov 2023
Cited by 1 | Viewed by 1713
Abstract
Crown segmentation is a pivotal process in the acquisition of tree parameters. In light of the high expenses associated with satellite remote sensing and LiDAR technologies, our study leverages the cost-effective and efficient UAV remote sensing technology for capturing crown images. In addition, [...] Read more.
Crown segmentation is a pivotal process in the acquisition of tree parameters. In light of the high expenses associated with satellite remote sensing and LiDAR technologies, our study leverages the cost-effective and efficient UAV remote sensing technology for capturing crown images. In addition, considering the expense and sensitivity associated with labeling data for supervised learning and its implications on model generalization and label quality, this paper introduces an innovative unsupervised learning framework based on convolutional neural networks (CNN). To address the limited receptive field of CNN, we have introduced a novel hybrid attention module following each CNN module. This enhancement ensures the integrity of the segmentation results and the coherence of the boundaries. Furthermore, in response to the growing need for user interaction, we have incorporated a scribble interaction function. Through the semantic segmentation of the collected crown images, our proposed method attains remarkable results, achieving an accuracy of 98.15%, an F1_score of 97.01%, and an mIoU of 95.58%. Additionally, we have conducted a comparative analysis of our proposed method with two clustering algorithms, namely K-Means and GMM, and two CNN models, DeepLab and U-Net. The results reveal that our segmentation structures outperform other methods significantly. The experimental findings demonstrate the immense application potential of this method in diverse fields, including forestry management, environmental protection, and ecosystem monitoring. Full article
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16 pages, 3264 KiB  
Article
Molecular Alterations and Putative Therapeutic Targeting of Planar Cell Polarity Proteins in Breast Cancer
by Ioannis A. Voutsadakis
J. Clin. Med. 2023, 12(2), 411; https://doi.org/10.3390/jcm12020411 - 4 Jan 2023
Cited by 8 | Viewed by 2496
Abstract
Background: Treatment and outcomes of breast cancer, one of the most prevalent female cancers, have improved in recent decades. However, metastatic breast cancer remains incurable in most cases, and new therapies are needed to ameliorate prognosis. Planar cell polarity (PCP) is a characteristic [...] Read more.
Background: Treatment and outcomes of breast cancer, one of the most prevalent female cancers, have improved in recent decades. However, metastatic breast cancer remains incurable in most cases, and new therapies are needed to ameliorate prognosis. Planar cell polarity (PCP) is a characteristic of epithelial cells that form layers and is integral to the communication of these cells with neighboring cells. Dysfunction of PCP is observed in cancers and may confer a targetable vulnerability. Methods: The breast cancer cohorts from The Cancer Genome Atlas (TCGA) and the METABRIC study were interrogated for molecular alterations in genes of the PCP pathway. The groups with the most prevalent alterations were characterized, and survival was compared with counterparts not possessing PCP alterations. Breast cancer cell lines with PCP alterations from the Cancer Cell Line Encyclopedia (CCLE) were interrogated for sensitivity to drugs affecting PCP. Results: Among genes of the PCP pathway, VANGL2, NOS1AP and SCRIB display amplifications in a sizable minority of breast cancers. Concomitant up-regulation at the mRNA level can be observed mostly in basal cancers, but it does not correlate well with the amplification status of the genes, as it can also be observed in non-amplified cases. In an exploration of cell line models, two of the four breast cancer cell line models with amplifications in VANGL2, NOS1AP and SCRIB display sensitivity to drugs inhibiting acyl-transferase porcupine interfering with the WNT pathway. This sensitivity suggests a possible therapeutic role of these inhibitors in cancers bearing the amplifications. Conclusion: Molecular alterations in PCP genes can be observed in breast cancers with a predilection for the basal sub-type. An imperfect correlation of copy number alterations with mRNA expression suggests that post-translational modifications are important in PCP regulation. Inhibitors of acyl-transferase porcupine may be rational candidates for combination therapy development in PCP-altered breast cancers. Full article
(This article belongs to the Section Oncology)
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12 pages, 1992 KiB  
Article
Using Artificial Intelligence to Analyze Non-Human Drawings: A First Step with Orangutan Productions
by Benjamin Beltzung, Marie Pelé, Julien P. Renoult, Masaki Shimada and Cédric Sueur
Animals 2022, 12(20), 2761; https://doi.org/10.3390/ani12202761 - 14 Oct 2022
Cited by 6 | Viewed by 3185
Abstract
Drawings have been widely used as a window to the mind; as such, they can reveal some aspects of the cognitive and emotional worlds of other animals that can produce them. The study of non-human drawings, however, is limited by human perception, which [...] Read more.
Drawings have been widely used as a window to the mind; as such, they can reveal some aspects of the cognitive and emotional worlds of other animals that can produce them. The study of non-human drawings, however, is limited by human perception, which can bias the methodology and interpretation of the results. Artificial intelligence can circumvent this issue by allowing automated, objective selection of features used to analyze drawings. In this study, we use artificial intelligence to investigate seasonal variations in drawings made by Molly, a female orangutan who produced more than 1299 drawings between 2006 and 2011 at the Tama Zoological Park in Japan. We train the VGG19 model to first classify the drawings according to the season in which they are produced. The results show that deep learning is able to identify subtle but significant seasonal variations in Molly’s drawings, with a classification accuracy of 41.6%. We use VGG19 to investigate the features that influence this seasonal variation. We analyze separate features, both simple and complex, related to color and patterning, and to drawing content and style. Content and style classification show maximum performance for moderately complex, highly complex, and holistic features, respectively. We also show that both color and patterning drive seasonal variation, with the latter being more important than the former. This study demonstrates how deep learning can be used to objectively analyze non-figurative drawings and calls for applications to non-primate species and scribbles made by human toddlers. Full article
(This article belongs to the Special Issue Recent Advances in Animal Cognition and Ethology)
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20 pages, 6968 KiB  
Article
Subjective Experiences of At-Risk Children Living in a Foster-Care Village Who Participated in an Open Studio
by Michal Bat Or and Reut Zusman-Bloch
Children 2022, 9(8), 1218; https://doi.org/10.3390/children9081218 - 12 Aug 2022
Cited by 10 | Viewed by 3705
Abstract
The open studio art therapy model offers a space for free creation; in this space, the art therapist supports the participants’ art process. According to this model, the creative process is the central component of the therapeutic work. This qualitative study seeks to [...] Read more.
The open studio art therapy model offers a space for free creation; in this space, the art therapist supports the participants’ art process. According to this model, the creative process is the central component of the therapeutic work. This qualitative study seeks to learn, through an analysis of interviews and artwork, about the subjective experiences of at-risk children living in a foster-care village who participated in an open studio. In addition, it seeks to identify changes in the artwork over time. This study involves a qualitative thematic analysis, while the analysis of visual data is based on the phenomenological approach to art therapy. The data include interviews and 82 artworks of five participants, aged 7–10 years. Five main themes emerged from the analysis of the visual and verbal data: (a) engaging in relationships; (b) moving along the continuum from basic, primary, art expressions (e.g., smearing, scribbling, etc.) to controlled expressions; (c) visibility, on a range between disclosure and concealment; (d) holding versus falling/instability; and (e) experiencing and expressions of change. The discussion expands on the themes in relation to key concepts in the field of psychodynamic psychotherapy and art therapy. It also examines the unique characteristics of this population in reference to empirical studies on developmental trauma and challenges of out-of-home placement. Finally, it discusses the study’s limitations and presents recommendations for further research. Full article
(This article belongs to the Special Issue Arts Therapies with Children and Adolescents)
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18 pages, 3856 KiB  
Article
AUnet: A Deep Learning Framework for Surface Water Channel Mapping Using Large-Coverage Remote Sensing Images and Sparse Scribble Annotations from OSM Data
by Sarah Mazhar, Guangmin Sun, Anas Bilal, Bilal Hassan, Yu Li, Junjie Zhang, Yinyi Lin, Ali Khan, Ramsha Ahmed and Taimur Hassan
Remote Sens. 2022, 14(14), 3283; https://doi.org/10.3390/rs14143283 - 8 Jul 2022
Cited by 9 | Viewed by 3483
Abstract
Water is a vital component of life that exists in a variety of forms, including oceans, rivers, ponds, streams, and canals. The automated methods for detecting, segmenting, and mapping surface water have improved significantly with the advancements in satellite imagery and remote sensing. [...] Read more.
Water is a vital component of life that exists in a variety of forms, including oceans, rivers, ponds, streams, and canals. The automated methods for detecting, segmenting, and mapping surface water have improved significantly with the advancements in satellite imagery and remote sensing. Many strategies and techniques to segment water resources have been presented in the past. However, due to the variant width and complex appearance, the segmentation of the water channel remains challenging. Moreover, traditional supervised deep learning frameworks have been restricted by the scarcity of water channel datasets that include precise water annotations. With this in mind, this research presents the following three main contributions. Firstly, we curated a new dataset for water channel mapping in the Pakistani region. Instead of employing pixel-level water channel annotations, we used a weakly trained method to extract water channels from VHR pictures, relying only on OpenStreetMap (OSM) waterways to create sparse scribbling annotations. Secondly, we benchmarked the dataset on state-of-the-art semantic segmentation frameworks. We also proposed AUnet, an atrous convolution inspired deep learning network for precise water channel segmentation. The experimental results demonstrate the superior performance of the proposed AUnet model for segmenting using weakly supervised labels, where it achieved a mean intersection over union score of 0.8791 and outperformed state-of-the-art approaches by 5.90% for the extraction of water channels. Full article
(This article belongs to the Special Issue Earth Observation Using Satellite Global Images of Remote Sensing)
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20 pages, 4398 KiB  
Article
Remarkable Resilience of Forest Structure and Biodiversity Following Fire in the Peri-Urban Bushland of Sydney, Australia
by Elise Pendall, Alison Hewitt, Matthias M. Boer, Yolima Carrillo, Nancy F. Glenn, Anne Griebel, Jason H. Middleton, Peter J. Mumford, Peter Ridgeway, Paul D. Rymer and Greg L. Steenbeeke
Climate 2022, 10(6), 86; https://doi.org/10.3390/cli10060086 - 16 Jun 2022
Cited by 7 | Viewed by 5593
Abstract
In rapidly urbanizing areas, natural vegetation becomes fragmented, making conservation planning challenging, particularly as climate change accelerates fire risk. We studied urban forest fragments in two threatened eucalypt-dominated (scribbly gum woodland, SGW, and ironbark forest, IF) communities across ~2000 ha near Sydney, Australia, [...] Read more.
In rapidly urbanizing areas, natural vegetation becomes fragmented, making conservation planning challenging, particularly as climate change accelerates fire risk. We studied urban forest fragments in two threatened eucalypt-dominated (scribbly gum woodland, SGW, and ironbark forest, IF) communities across ~2000 ha near Sydney, Australia, to evaluate effects of fire frequency (0–4 in last 25 years) and time since fire (0.5 to >25 years) on canopy structure, habitat quality and biodiversity (e.g., species richness). Airborne lidar was used to assess canopy height and density, and ground-based surveys of 148 (400 m2) plots measured leaf area index (LAI), plant species composition and habitat metrics such as litter cover and hollow-bearing trees. LAI, canopy density, litter, and microbiotic soil crust increased with time since fire in both communities, while tree and mistletoe cover increased in IF. Unexpectedly, plant species richness increased with fire frequency, owing to increased shrub richness which offset decreased tree richness in both communities. These findings indicate biodiversity and canopy structure are generally resilient to a range of times since fire and fire frequencies across this study area. Nevertheless, reduced arboreal habitat quality and subtle shifts in community composition of resprouters and obligate seeders signal early concern for a scenario of increasing fire frequency under climate change. Ongoing assessment of fire responses is needed to ensure that biodiversity, canopy structure and ecosystem function are maintained in the remaining fragments of urban forests under future climate change which will likely drive hotter and more frequent fires. Full article
(This article belongs to the Special Issue Climate System Uncertainty and Biodiversity Conservation)
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21 pages, 5574 KiB  
Article
Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway
by Maïté M. Moreau, Susanna Pietropaolo, Jérôme Ezan, Benjamin J. A. Robert, Sylvain Miraux, Marlène Maître, Yoon Cho, Wim E. Crusio, Mireille Montcouquiol and Nathalie Sans
Cells 2022, 11(10), 1601; https://doi.org/10.3390/cells11101601 - 10 May 2022
Cited by 2 | Viewed by 3108
Abstract
Social behavior is a basic domain affected by several neurodevelopmental disorders, including ASD and a heterogeneous set of neuropsychiatric disorders. The SCRIB gene that codes for the polarity protein SCRIBBLE has been identified as a risk gene for spina bifida, the most common [...] Read more.
Social behavior is a basic domain affected by several neurodevelopmental disorders, including ASD and a heterogeneous set of neuropsychiatric disorders. The SCRIB gene that codes for the polarity protein SCRIBBLE has been identified as a risk gene for spina bifida, the most common type of neural tube defect, found at high frequencies in autistic patients, as well as other congenital anomalies. The deletions and mutations of the 8q24.3 region encompassing SCRIB are also associated with multisyndromic and rare disorders. Nonetheless, the potential link between SCRIB and relevant social phenotypes has not been fully investigated. Hence, we show that Scribcrc/+ mice, carrying a mutated version of Scrib, displayed reduced social motivation behavior and social habituation, while other behavioral domains were unaltered. Social deficits were associated with the upregulation of ERK phosphorylation, together with increased c-Fos activity. Importantly, the social alterations were rescued by both direct and indirect pERK inhibition. These results support a link between polarity genes, social behaviors and hippocampal functionality and suggest a role for SCRIB in the etiopathology of neurodevelopmental disorders. Furthermore, our data demonstrate the crucial role of the MAPK/ERK signaling pathway in underlying social motivation behavior, thus supporting its relevance as a therapeutic target. Full article
(This article belongs to the Section Cell Signaling)
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15 pages, 3887 KiB  
Article
Structural Basis of the Avian Influenza NS1 Protein Interactions with the Cell Polarity Regulator Scribble
by Airah Javorsky, Patrick O. Humbert and Marc Kvansakul
Viruses 2022, 14(3), 583; https://doi.org/10.3390/v14030583 - 11 Mar 2022
Cited by 7 | Viewed by 3081
Abstract
Scribble is a highly conserved regulator of cell polarity, a process that enables the generation of asymmetry at the cellular and tissue level in higher organisms. Scribble acts in concert with Disc-large (Dlg) and Lethal-2-giant larvae (Lgl) to form the Scribble polarity complex, [...] Read more.
Scribble is a highly conserved regulator of cell polarity, a process that enables the generation of asymmetry at the cellular and tissue level in higher organisms. Scribble acts in concert with Disc-large (Dlg) and Lethal-2-giant larvae (Lgl) to form the Scribble polarity complex, and its functional dysregulation is associated with poor prognosis during viral infections. Viruses have been shown to interfere with Scribble by targeting Scribble PDZ domains to subvert the network of interactions that enable normal control of cell polarity via Scribble, as well as the localisation of the Scribble module within the cell. The influenza A virus NS1 protein was shown to bind to human Scribble (SCRIB) via its C-terminal PDZ binding motif (PBM). It was reported that the PBM sequence ESEV is a virulence determinant for influenza A virus H5N1 whilst other sequences, such as ESKV, KSEV and RSKV, demonstrated no affinity towards Scribble. We now show, using isothermal titration calorimetry (ITC), that ESKV and KSEV bind to SCRIB PDZ domains and that ESEV unexpectedly displayed an affinity towards all four PDZs and not just a selected few. We then define the structural basis for the interactions of SCRIB PDZ1 domain with ESEV and ESKV PBM motifs, as well as SCRIB PDZ3 with the ESKV PBM motif. These findings will serve as a platform for understanding the role of Scribble PDZ domains and their interactions with different NS1 PBMs and the mechanisms that mediate cell polarity within the context of the pathogenesis of influenza A virus. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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10 pages, 1793 KiB  
Communication
An Unconventional Ligand for Scribble PDZ-4 Domain Mediates Its Interaction with Dusp26
by Raffaella Gallo, Erika De Sensi, Francesca Storino and Simona Panni
BioChem 2022, 2(1), 83-92; https://doi.org/10.3390/biochem2010006 - 15 Feb 2022
Viewed by 3550
Abstract
PDZ domains are involved in many cellular processes and are key regulators of the cell physiology. A huge number of studies have investigated the binding specificity of PDZ domains to the carboxyl-terminal sequence of target proteins, while the molecular mechanisms that mediate the [...] Read more.
PDZ domains are involved in many cellular processes and are key regulators of the cell physiology. A huge number of studies have investigated the binding specificity of PDZ domains to the carboxyl-terminal sequence of target proteins, while the molecular mechanisms that mediate the recognition of internal binding regions are largely unexplored. In the present study, we describe a ligand motif located in the catalytic domain of the phosphatase Dusp26 which mediates its binding to the PDZ-4 of Scribble. Site-directed mutagenesis identified a conserved tyrosine residue as relevant for the binding. The interaction with the PDZ domain could help the phosphatase to recruit its specific targets. Full article
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