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Abstract Boron nitride exhibits various crystal structures. The subgroup of layered boron nitrides includes several polytypes such as hexagonal (hBN), Bernal (bBN), and rhombohedral (rBN) BN. The latter two are non-centrosymmetric, potentially leading to piezoelectric or ferroelectric properties. A key challenge related to the polytypism of sp 2-bonded BN is distinguishing between these polytypes. We demonstrate that the optical response of the 4.1-eV defect can be used to differentiate hBN from rBN. Photoluminescence and cathodoluminescence measurements on samples grown by metalorganic vapor phase epitaxy (MOVPE) show a zero-phonon line at 4.096 eV for hBN and 4.143 eV for rBN. Our calculations confirm that the photoluminescence originates from a carbon dimer, CBCN (C2), which is sensitive to the local environments of different polytypes. We demonstrate that different polytypic compositions of hBN and rBN can be achieved by MOVPE, which could pave the way for future applications in large-area van der Waals heterostructures.

This paper presents an investigation into the influence of repeating cycles of hydrothermal growth processes and rapid thermal annealing (HT+RTA) on the properties of CuO thin films. An innovative hydrothermal method ensures homogeneous single-phase films initially. However, their electrical instability and susceptibility to cracking under the influence of temperature have posed a challenge to their utilization in electronic devices. To address this limitation, the HT+RTA procedure has been developed, which effectively eliminated the issue. Comprehensive surface analysis confirmed the procedure’s ability to yield continuous films in which the content of organic compounds responsible for the formation of cracks significantly decreases. Structural analysis underscored the achieved improvements in the crystalline quality of the films. The implementation of the HT+RTA procedure significantly enhances the potential of CuO films for electronic applications. Key findings from Kelvin probe force microscopy analysis demonstrate the possibility of modulating the work function of the material. In addition, scanning capacitance microscopy measurements provided information on the changes in the local carrier concentration with each repetition. These studies indicate the increased usefulness of CuO thin films obtained from the HT+RTA procedure, which expands the possibilities of their applications in electronic devices.

IntroductionColorectal cancer (CRC) is one of the main causes of deaths worldwide. Early detection and diagnosis of its precursor lesion, the polyp, is key to reduce its mortality and to improve procedure efficiency. During the last two decades, several computational methods have been proposed to assist clinicians in detection, segmentation and classification tasks but the lack of a common public validation framework makes it difficult to determine which of them is ready to be deployed in the exploration room.MethodsThis study presents a complete validation framework and we compare several methodologies for each of the polyp characterization tasks.ResultsResults show that the majority of the approaches are able to provide good performance for the detection and segmentation task, but that there is room for improvement regarding polyp classification.DiscussionWhile studied show promising results in the assistance of polyp detection and segmentation tasks, further research should be done in classification task to obtain reliable results to assist the clinicians during the procedure. The presented framework provides a standarized method for evaluating and comparing different approaches, which could facilitate the identification of clinically prepared assisting methods.

Solutions to vision tasks in gastrointestinal endoscopy (GIE) conventionally use image encoders pretrained in a supervised manner with ImageNet-1k as backbones. However, the use of modern self-supervised pretraining algorithms and a recent dataset of 100k unlabelled GIE images (Hyperkvasir-unlabelled) may allow for improvements. In this work, we study the fine-tuned performance of models with ResNet50 and ViT-B backbones pretrained in self-supervised and supervised manners with ImageNet-1k and Hyperkvasir-unlabelled (self-supervised only) in a range of GIE vision tasks. In addition to identifying the most suitable pretraining pipeline and backbone architecture for each task, out of those considered, our results suggest three general principles. Firstly, that self-supervised pretraining generally produces more suitable backbones for GIE vision tasks than supervised pretraining. Secondly, that self-supervised pretraining with ImageNet-1k is typically more suitable than pretraining with Hyperkvasir-unlabelled, with the notable exception of monocular depth estimation in colonoscopy. Thirdly, that ViT-Bs are more suitable in polyp segmentation and monocular depth estimation in colonoscopy, ResNet50s are more suitable in polyp detection, and both architectures perform similarly in anatomical landmark recognition and pathological finding characterisation. We hope this work draws attention to the complexity of pretraining for GIE vision tasks, informs this development of more suitable approaches than the convention, and inspires further research on this topic to help advance this development. Code available: https://www.github.com/ESandML/SSL4GIE.

Polyp segmentation within colonoscopy video frames using deep learning models has the potential to automate colonoscopy screening procedures. This could help improve the early lesion detection rate and in vivo characterization of polyps which could develop into colorectal cancer. Recent state-of-the-art deep learning polyp segmentation models have combined Convolutional Neural Network (CNN) architectures and Transformer Network (TN) architectures. Motivated by the aim of improving the performance of polyp segmentation models and their robustness to data variations beyond those covered during training, we propose a new CNN-TN hybrid model named the FCB-SwinV2 Transformer. This model was created by making extensive modifications to the recent state-of-the-art FCN-Transformer, including replacing the TN branch architecture with a SwinV2 U-Net. The performance of the FCB-SwinV2 Transformer is evaluated on the popular colonoscopy segmentation benchmarking datasets Kvasir-SEG, CVC-ClinicDB and ETIS-LaribPolypDB. Generalizability tests are also conducted to determine if models can maintain accuracy when evaluated on data outside of the training distribution. The FCB-SwinV2 Transformer consistently achieves higher mean Dice and mean IoU scores when compared to other models reported in literature and therefore represents new state-of-the-art performance. The importance of understanding subtleties in evaluation metrics and dataset partitioning are also demonstrated and discussed. Code available: https://github.com/KerrFitzgerald/Polyp_FCB-SwinV2Transformer

Most vision-based 3D pose estimation approaches typically rely on knowledge of object’s 3D model, depth measurements, and often require time-consuming iterative refinement to improve accuracy. However, these can be seen as limiting factors for broader real-life applications. The main motivation for this paper is to address these limitations. To solve this, a novel Convolutional Variational Auto-Encoder based Multi-Level Network for object 3D pose estimation (CVML-Pose) method is proposed. Unlike most other methods, the proposed CVML-Pose implicitly learns an object’s 3D pose from only RGB images encoded in its latent space without knowing the object’s 3D model, depth information, or performing a post-refinement. CVML-Pose consists of two main modules: (i) CVML-AE representing convolutional variational autoencoder, whose role is to extract features from RGB images, (ii) Multi-Layer Perceptron and K-Nearest Neighbor regressors mapping the latent variables to object 3D pose including, respectively, rotation and translation. The proposed CVML-Pose has been evaluated on the LineMod and LineMod-Occlusion benchmark datasets. It has been shown to outperform other methods based on latent representations and achieves comparable results to the state-of-the-art, but without use of a 3D model or depth measurements. Utilizing the t-Distributed Stochastic Neighbor Embedding algorithm, the CVML-Pose latent space is shown to successfully represent objects’ category and topology. This opens up a prospect of integrated estimation of pose and other attributes (possibly also including surface finish or shape variations), which, with real-time processing due to the absence of iterative refinement, can facilitate various robotic applications. Code available: https://github.com/JZhao12/CVML-Pose.

This paper is written by a group of Ph.D. students pursuing their work in different areas of ICT, outside the direct area of Information Quantum Technologies IQT. An ambitious task was undertaken to research, by each co-author, a potential practical influence of the current IQT development on their current work. The research of co-authors span the following areas of ICT: CMOS for IQT, QEC, quantum time series forecasting, IQT in biomedicine. The intention of the authors is to show how quickly the quantum techniques can penetrate in the nearest future other, i.e. their own, areas of ICT.

Background: The manufacture of medicinal products for human use in the European Economic Area is governed by European Directives and Regulations stipulating the relevant principles and guidelines of Good Manufacturing Practice, describing the minimum standard to be fulfilled in the production processes. Aim: To present analysis of the deficiencies reported following Good Manufacturing Practice inspections in Bulgaria in two consecutive years (2016, 2017) and to compare them with results from similar inspections reported by other EU member states. Materials and methods: A retrospective study was carried out by reviewing the complete Good Manufacturing Practice inspection reports of all manufacturers conducted by the Bulgarian Drug Agency in 2016 and 2017, according to relevant requirements and applicable local legislation. The items reviewed were scope of inspection, type of companies, classification of deficiencies – ‘critical’, ‘major’ and ‘other significant deficiencies’, their nature and reference to EU Good Manufacturing Practice. Results: The analyzed data included 55 inspections, revealing 460 various deficiencies, of which 2 were critical and 102 – major. Twenty inspections were performed in 2016 vs. 35 inspections in 2017.The pattern of deficiencies was similar to the findings of other EU regulatory agencies, showing that equivalent requirements were applied. Our analysis showed that Bulgarian Drug Agency inspectors rarely raised deficiencies related to Computer Systems, Qualification/Validation, Personnel and Qualification of Suppliers unlike other EU regulators agents. Conclusions: Our analysis of Good Manufacturing Practice inspection findings in 2016 and 2017 showed that the Bulgarian Drug Agency demonstrated its ability to detect non-compliances and take necessary regulatory actions. Quality related issues constitute the main reasons for non-compliances with the requirements.Publishing the results from the inspections performed by the national competent authorities enhances the regulatory transparency that can be useful for industry to improve its Good Manufacturing Practice compliance.

Valproic acid (VPA, valproate, Depakote) is a commonly used anti-seizure medication (ASM) in the treatment of epilepsy and a variety of other neurological disorders. While VPA and other ASMs are efficacious for management of seizures, they also increase the risk for adverse pregnancy outcomes, including neural tube defects (NTDs). Thus, the utility of these drugs during pregnancy and in women of childbearing potential presents a continuing public health challenge. Elucidating the underlying genetic or metabolic risk factors for VPA-affected pregnancies may lead to development of non-teratogenic ASMs, novel prevention strategies, or more targeted methods for managing epileptic pregnancies. To address this challenge, we performed unbiased, whole embryo metabolomic screening of E8.5 mouse embryos from two inbred strains with differential susceptibility to VPA-induced NTDs. We identified metabolites of differential abundance between the two strains, both in response to VPA exposure and in the vehicle controls. Notable enriched pathways included lipid metabolism, carnitine metabolism, and several amino acid pathways, especially cysteine and methionine metabolism. There also was increased abundance of ω-oxidation products of VPA in the more NTD-sensitive strain, suggesting differential metabolism of the drug. Finally, we found significantly reduced levels of hypotaurine in the susceptible strain regardless of VPA status. Based on this information, we hypothesized that maternal supplementation with L-carnitine (400 mg/kg), coenzyme A (200 mg/kg), or hypotaurine (350 mg/kg) would reduce VPA-induced NTDs in the sensitive strain and found that administration of hypotaurine prior to VPA exposure significantly reduced the occurrence of NTDs by close to one-third compared to controls. L-carnitine and coenzyme A reduced resorption rates but did not significantly reduce NTD risk in the sensitive strain. These results suggest that genetic variants or environmental exposures influencing embryonic hypotaurine status may be factors in determining risk for adverse pregnancy outcomes when managing the health care needs of pregnant women exposed to VPA or other ASMs.

Sonic hedgehog (Shh) signaling regulates multiple morphogenetic processes during embryonic neurogenesis and craniofacial skeletal development. Gpr161 is a known negative regulator of Shh signaling. Nullizygous Gpr161 mice are embryonic lethal, presenting with structural defects involving the neural tube and the craniofacies. However, the lineage specific role of Gpr161 in later embryonic development has not been thoroughly investigated. We studied the Wnt1-Cre lineage specific role of Gpr161 during mouse embryonic development. We observed three major gross morphological phenotypes in Gpr161 cKO (Gpr161 f/f; Wnt1-Cre) fetuses; protrusive tectum defect, encephalocele, and craniofacial skeletal defect. The overall midbrain tissues were expanded and cell proliferation in ventricular zones of midbrain was increased in Gpr161 cKO fetuses, suggesting that protrusive tectal defects in Gpr161 cKO are secondary to the increased proliferation of midbrain neural progenitor cells. Shh signaling activity as well as upstream Wnt signaling activity were increased in midbrain tissues of Gpr161 cKO fetuses. RNA sequencing further suggested that genes in the Shh, Wnt, Fgf and Notch signaling pathways were differentially regulated in the midbrain of Gpr161 cKO fetuses. Finally, we determined that cranial neural crest derived craniofacial bone formation was significantly inhibited in Gpr161 cKO fetuses, which partly explains the development of encephalocele. Our results suggest that Gpr161 plays a distinct role in midbrain development and in the formation of the craniofacial skeleton during mouse embryogenesis.

Visegrad Group (V4) containing Czechia, Hungary, Poland and Slovakia, is one of the examples of regional cooperation within the European Union (EU). Recently V4 has shown some coherence in case of migrant wave to the EU, as well as presented unifi ed position vis-à-vis climate change or leaders election in the EU. The Author has taken into consideration major political parties – both ruling and in the opposition – and their programs in all V4 countries and comes to following conclusions: 1. There is no coherence of V4, as Czech Republic and Slovakia are not ready to follow the footsteps of Hungary and Poland in creation of so called illiberal democracies. 2. All V4 countries are domestically highly polarized, with the exception of Hungary dominated by its charismatic leader Viktor Orbán. 3. Internal instability cannot bring a cohesive and unifi ed voice of V4 in the EU in more coordinated way. 4. If V4 countries will constantly undermine the core system of values, or Copenhagen criteria, of the EU, as Hungary and Poland is doing, combined with more and more problems with corruption, as all of them have, then un-famous East – West division line can reemerge in the EU and on the European continent leading to weakening of it on the global scene.

Human structural congenital malformations are the leading cause of infant mortality in the United States. Estimates from the United States Center for Disease Control and Prevention (CDC) determine that close to 3% of all United States newborns present with birth defects; the worldwide estimate approaches 6% of infants presenting with congenital anomalies. The scientific community has recognized for decades that the majority of birth defects have undetermined etiologies, although we propose that environmental agents interacting with inherited susceptibility genes are the major contributing factors. Neural tube defects (NTDs) are among the most prevalent human birth defects and as such, these malformations will be the primary focus of this review. NTDs result from failures in embryonic central nervous system development and are classified by their anatomical locations. Defects in the posterior portion of the neural tube are referred to as meningomyeloceles (spina bifida), while the more anterior defects are differentiated as anencephaly, encephalocele, or iniencephaly. Craniorachischisis involves a failure of the neural folds to elevate and thus disrupt the entire length of the neural tube. Worldwide NTDs have a prevalence of approximately 18.6 per 10,000 live births. It is widely believed that genetic factors are responsible for some 70% of NTDs, while the intrauterine environment tips the balance toward neurulation failure in at risk individuals. Despite aggressive educational campaigns to inform the public about folic acid supplementation and the benefits of providing mandatory folic acid food fortification in the United States, NTDs still affect up to 2,300 United States births annually and some 166,000 spina bifida patients currently live in the United States, more than half of whom are now adults. Within the context of this review, we will consider the role of maternal nutritional status (deficiency states involving B vitamins and one carbon analytes) and the potential modifiers of NTD risk beyond folic acid. There are several well-established human teratogens that contribute to the population burden of NTDs, including: industrial waste and pollutants [e.g., arsenic, pesticides, and polycyclic aromatic hydrocarbons (PAHs)], pharmaceuticals (e.g., anti-epileptic medications), and maternal hyperthermia during the first trimester. Animal models for these teratogens are described with attention focused on valproic acid (VPA; Depakote). Genetic interrogation of model systems involving VPA will be used as a model approach to discerning susceptibility factors that define the gene-environment interactions contributing to the etiology of NTDs.

BackgroundNeural tube defects (NTDs) are among the most common and severe congenital defects in humans. Their genetic etiology is complex and remains poorly understood. The Mediator complex (MED) plays a vital role in neural tube development in animal models. However, no studies have yet examined the role of its human homolog in the etiology of NTDs.MethodsIn this study, 48 pairs of neural lesion site and umbilical cord tissues from NTD and 21 case-parent trios were involved in screening for NTD-related somatic and germline de novo variants. A series of functional cell assays were performed. We generated a Med12 p.Arg1784Cys knock-in mouse using CRISPR/Cas9 technology to validate the human findings.ResultsOne somatic variant, MED12 p.Arg1782Cys, was identified in the lesion site tissue from an NTD fetus. This variant was absent in any other normal tissue from different germ layers of the same case. In 21 case-parent trios, one de novo stop-gain variant, MED13L p.Arg1760∗, was identified. Cellular functional studies showed that MED12 p.Arg1782Cys decreased MED12 protein level and affected the regulation of MED12 on the canonical-WNT signaling pathway. The Med12 p.Arg1784Cys knock-in mouse exhibited exencephaly and spina bifida.ConclusionThese findings provide strong evidence that functional variants of MED genes are associated with the etiology of some NTDs. We demonstrated a potentially important role for somatic variants in the occurrence of NTDs. Our study is the first study in which an NTD-related variant identified in humans was validated in mice using CRISPR/Cas9 technology.

Analysis of colonoscopy images plays a significant role in early detection of colorectal cancer. Automated tissue segmentation can be useful for two of the most relevant clinical target applications—lesion detection and classification, thereby providing important means to make both processes more accurate and robust. To automate video colonoscopy analysis, computer vision and machine learning methods have been utilized and shown to enhance polyp detectability and segmentation objectivity. This paper describes a polyp segmentation algorithm, developed based on fully convolutional network models, that was originally developed for the Endoscopic Vision Gastrointestinal Image Analysis (GIANA) polyp segmentation challenges. The key contribution of the paper is an extended evaluation of the proposed architecture, by comparing it against established image segmentation benchmarks utilizing several metrics with cross-validation on the GIANA training dataset. Different experiments are described, including examination of various network configurations, values of design parameters, data augmentation approaches, and polyp characteristics. The reported results demonstrate the significance of the data augmentation, and careful selection of the method’s design parameters. The proposed method delivers state-of-the-art results with near real-time performance. The described solution was instrumental in securing the top spot for the polyp segmentation sub-challenge at the 2017 GIANA challenge and second place for the standard image resolution segmentation task at the 2018 GIANA challenge.

We tested the hypothesis that in utero exposure to heavy metals increases autism-like behavioral phenotypes in adult animals and induces epigenetic changes in genes that have roles in the etiology of autism. Mouse dams were treated with cadmium, lead, arsenate, manganese, and mercury via drinking water from gestational days (E) 1–10. Valproic acid (VPA) injected intraperitoneally once on (E) 8.5 served as a positive control. Young male offspring were tested for behavioral deficits using four standardized behavioral assays. In this study, in utero exposure to heavy metals resulted in multiple behavioral abnormalities that persisted into adulthood. VPA and manganese induced changes in perseverative/impulsive behavior and social dominance behavior, arsenic caused changes only in perseverative/impulsive behavior, and lead induced abnormalities in social interaction in comparison to the control animals. Brain samples from Mn, Pb, and VPA treated and control animals were evaluated for changes in CpG island methylation in promoter regions and associated changes in gene expression. The Chd7 gene, essential for neural crest cell migration and patterning, was found to be hypomethylated in each experimental animal tested compared to water-treated controls. Furthermore, distinct patterns of CpG island methylation yielded novel candidate genes for further investigation.

The vitamin D3 system imposes immunosuppressive effects on monocytic cells, in part, by inhibiting NF-κB-dependent expression of proinflammatory mediators. CD55, a cell surface complement regulatory protein that promotes protective and anti-inflammatory properties, is reportedly an NF-κB target gene transiently induced in monocytic cells by the bacterial endotoxin LPS. CD55 is elevated on white cells in women experiencing preterm labor (a pathophysiology commonly associated with bacterial infection) and failure to maintain CD55 was associated with subsequent preterm delivery. We examined the influence of vitamin D3 signaling on LPS-induced expression of CD55 in human monocytic THP-1 cells using quantitative PCR, immunoblot, immunohistochemistry, and NF-κB activation pathway inhibitors. Non-NF-κB targets CD14 and CD11b, which modulate bacterial surveillance and eradication, respectively, were also examined. LPS produced a rapid transient 1.6-fold increase in CD55 mRNA. 1,25-D3 alone did not affect CD55 mRNA expression within the first 48 h. However, in 1,25-D3 pretreated cells, LPS produced a >4-fold immediate and sustained increase in CD55 mRNA and protein expression, which was blocked by NF-κB inhibitors. Our results unexpectedly suggest that vitamin D3 signaling may promote an anti-inflammatory response through an NF-κB-dependent increase in CD55 expression. As expected, LPS or 1,25-D3 alone led to sustained increases in CD14 and CD11b expression. In 1,25-D3 pretreated cells, LPS differentially regulated protein expression - CD14 (21-fold increase) and CD11b (a transient 2-fold decrease) - principally at the posttranscriptional level. The coordinated temporal expression of CD55, CD14 and CD11b would contribute to an anti-inflammatory response by providing protection against complement-mediated cell lysis during pathogen recognition and eradication. Overall, the vitamin D3 system may play a role coordinating an anti-inflammatory response pattern of the host complement immune system. This may be particularly important when considering the high rates of preterm births in blacks, a population that exhibits reduced circulating vitamin D3 levels.

The planar cell polarity effector gene Fuz regulates ciliogenesis and Fuz loss of function studies reveal an array of embryonic phenotypes. However, cilia defects can affect many signaling pathways and, in humans, cilia defects underlie several craniofacial anomalies. To address this, we analyzed the craniofacial phenotype and signaling responses of the Fuz(-/-) mice. We demonstrate a unique role for Fuz in regulating both Hedgehog (Hh) and Wnt/β-catenin signaling during craniofacial development. Fuz expression first appears in the dorsal tissues and later in ventral tissues and craniofacial regions during embryonic development coincident with cilia development. The Fuz(-/-) mice exhibit severe craniofacial deformities including anophthalmia, agenesis of the tongue and incisors, a hypoplastic mandible, cleft palate, ossification/skeletal defects and hyperplastic malformed Meckel's cartilage. Hh signaling is down-regulated in the Fuz null mice, while canonical Wnt signaling is up-regulated revealing the antagonistic relationship of these two pathways. Meckel's cartilage is expanded in the Fuz(-/-) mice due to increased cell proliferation associated with the up-regulation of Wnt canonical target genes and decreased non-canonical pathway genes. Interestingly, cilia development was decreased in the mandible mesenchyme of Fuz null mice, suggesting that cilia may antagonize Wnt signaling in this tissue. Furthermore, expression of Fuz decreased expression of Wnt pathway genes as well as a Wnt-dependent reporter. Finally, chromatin IP experiments demonstrate that β-catenin/TCF-binding directly regulates Fuz expression. These data demonstrate a new model for coordination of Hh and Wnt signaling and reveal a Fuz-dependent negative feedback loop controlling Wnt/β-catenin signaling.

This paper describes a novel method for representing different facial expressions based on the shape space vector (SSV) of the statistical shape model (SSM) built from 3D facial data. The method relies only on the 3D shape, with texture information not being used in any part of the algorithm, that makes it inherently invariant to changes in the background, illumination, and to some extent viewing angle variations. To evaluate the proposed method, two comprehensive 3D facial data sets have been used for the testing. The experimental results show that the SSV not only controls the shape variations but also captures the expressive characteristic of the faces and can be used as a significant feature for facial expression recognition. Finally the paper suggests improvements of the SSV discriminatory characteristics by using 3D facial sequences rather than 3D stills.

Adsorption/desorption isotherms from the gaseous phase (benzene vapour, nitrogen) have been determined consecutively a number of times on the same activated carbon sample. The porous structure parameters were evaluated on the basis of the experimental data using the Dubinin-Radushkevich, Dubinin-Astakhov, Finger-Büllow, Dubinin-Stoeckli and Horvath-Kawazoe equations for the calculations. Analyses of the mean values and relative errors of particular structural parameters were made as well as comparisons of the stability of the adsorption models used. It was found that the reliability of the results obtained was better for the benzene vapour adsorption isotherms determined by a gravimetric method than for those determined by a volumetric method using nitrogen as the adsorbate.

Introduction: Colorectal cancer (CRC) is one of the main causes of deaths worldwide. Early detection and diagnosis of its precursor lesion, the polyp, is key to reduce its mortality and to improve procedure efficiency. During the last two decades, several computational methods have been proposed to assist clinicians in detection, segmentation and classification tasks but the lack of a common public validation framework makes it difficult to determine which of them is ready to be deployed in the exploration room. Methods: This study presents a complete validation framework and we compare several methodologies for each of the polyp characterization tasks. Results: Results show that the majority of the approaches are able to provide good performance for the detection and segmentation task, but that there is room for improvement regarding polyp classification. Discussion: While studied show promising results in the assistance of polyp detection and segmentation tasks, further research should be done in classification task to obtain reliable results to assist the clinicians during the procedure. The presented framework provides a standarized method for evaluating and comparing different approaches, which could facilitate the identification of clinically prepared assisting methods. [ABSTRACT FROM AUTHOR]

Sonic hedgehog (Shh) signaling regulates embryonic morphogenesis utilizing the primary cilium, the cell's antenna, which acts as a signaling hub. Fuz, an effector of planar cell polarity signaling, regulates Shh signaling by facilitating cilia formation, and the G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling. The range of phenotypic malformations observed in mice bearing mutations in either of the genes encoding these proteins is similar; however, their functional relationship has not been previously explored. This study identified the genetic and biochemical linkage between Fuz and Gpr161 in mouse neural tube development. Fuz was found to be genetically epistatic to Gpr161 with respect to regulation of Shh signaling in mouse neural tube development. The Fuz protein biochemically interacts with Gpr161, and Fuz regulates Gpr161-mediated ciliary localization, a process that might utilize β-arrestin 2. Our study characterizes a previously unappreciated Gpr161-Fuz axis that regulates Shh signaling during mouse neural tube development. [ABSTRACT FROM AUTHOR]