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Dioclea violacea seed mannose-binding lectin (DvL) has attracted considerable attention because of its interesting biological activities, including antitumor, antioxidant, and anti-inflammatory activities. This study evaluated the cytotoxic effect of DvL on tumor and normal cells using the mitochondrial activity reduction (MTT) assay, the carcinogenic and anti-carcinogenic activity by the epithelial tumor test (ETT) in Drosophila melanogaster , and the anti-angiogenic effect by the chick embryo chorioallantoic membrane (CAM) assay. Data demonstrated that DvL promoted strong selective cytotoxicity against tumor cell lines, especially A549 and S180 cells, whereas normal cell lines were weakly affected. Furthermore, DvL did not promote carcinogenesis in D. melanogaster at any concentration tested, but modulated DXR-induced carcinogenesis at the highest concentrations tested. In the CAM and immunohistochemical assays, DvL inhibited sarcoma 180-induced angiogenesis and promoted the reduction of VEGF and TGF-β levels at all concentrations tested. Therefore, our results demonstrated that DvL is a potent anticancer, anti-angiogenic, and selective cytotoxic agent for tumor cells, suggesting its potential application as a prototype molecule for the development of new drugs with chemoprotective and/or antitumor effects. • Dioclea violacea lectin (DvL) promoted high selective cytotoxicity against A549 and S180 tumor cells. • DvL associated with α- d -mannose partially reversed the inhibitory effect of the lectin on A549 cell and S180 cell. • DvL modulated doxorubicin-induced tumorigenesis in Drosophila melanogaster. • DvL inhibits sarcoma 180-tumor angiogenesis and reduced VEGF and TGF-β expression in CAM assay. [ABSTRACT FROM AUTHOR]

Underwater vehicles heavily depend on the integration of inertial navigation with Doppler Velocity Log (DVL) for fusion-based localization. Given the constraints imposed by sensor costs, ensuring the optimization ability and robustness of fusion algorithms is of paramount importance. While filtering-based techniques such as Extended Kalman Filter (EKF) offer mature solutions to nonlinear problems, their reliance on linearization approximation may compromise final accuracy. Recently, Invariant EKF (IEKF) methods based on the concept of smooth manifolds have emerged to address this limitation. However, the optimization by matrix Lie groups must satisfy the "group affine" property to ensure state independence, which constrains the applicability of IEKF to high-precision positioning of underwater multi-sensor fusion. In this study, an alternative state-independent underwater fusion invariant filtering approach based on a two-frame group utilizing DVL, Inertial Measurement Unit (IMU), and Earth-Centered Earth-Fixed (ECEF) configuration is proposed. This methodology circumvents the necessity for group affine in the presence of biases. We account for inertial biases and DVL pole-arm effects, achieving convergence in an imperfect IEKF by either fixed observation or body observation information. Through simulations and real datasets that are time-synchronized, we demonstrate the effectiveness and robustness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

As the exploration of marine resources continues to deepen, the utilization of Autonomous Underwater Vehicles (AUVs) for conducting marine resource surveys and underwater environmental mapping has become a common practice. In order to successfully accomplish exploration missions, AUVs require high-precision underwater navigation information as support. A Strapdown Inertial Navigation System (SINS) can provide AUVs with accurate attitude and heading information, while a Doppler Velocity Log (DVL) is capable of measuring the velocity vector of the AUVs. Therefore, the integrated SINS/DVL navigation system can furnish the necessary navigational information required by an AUV. In response to the issue of DVL being susceptible to external environmental interference, leading to reduced measurement accuracy, this paper proposes an end-to-end deep-learning approach to enhance the accuracy of DVL velocity vector measurements. The utilization of the raw measurement data from an Inertial Measurement Unit (IMU), which includes gyroscopes and accelerometers, to assist the DVL in velocity vector estimation and to refine it towards the Global Positioning System (GPS) velocity vector, compensates for the external environmental interference affecting the DVL, therefore enhancing the navigation accuracy. To evaluate the proposed method, we conducted lake experiments using SINS and DVL equipment, from which the collected data were organized into a dataset for training and assessing the model. The research results show that the DVL vector predicted by our model can achieve a maximum improvement of 69.26% in terms of root mean square error and a maximum improvement of 78.62% in terms of relative trajectory error.

DVL is one of the small polypeptides which plays an important role in regulating plant growth and development, tissue differentiation, and organ formation in the process of coping with stress conditions. So far, there has been no comprehensive analysis of the expression profile and function of the cotton DVL gene. According to previous studies, a candidate gene related to the development of fuzz was screened, belonging to the DVL family, and was related to the development of trichomes in Arabidopsis thaliana. However, the comprehensive identification and systematic analysis of DVL in cotton have not been conducted. In this study, we employed bioinformatics approaches to conduct a novel analysis of the structural characteristics, phylogenetic tree, gene structure, expression pattern, evolutionary relationship, and selective pressure of the DVL gene family members in four cotton species. A total of 117 DVL genes were identified, including 39 members in G. hirsutum. Based on the phylogenetic analysis, the DVL protein sequences were categorized into five distinct subfamilies. Additionally, we successfully mapped these genes onto chromosomes and visually represented their gene structure information. Furthermore, we predicted the presence of cis-acting elements in DVL genes in G. hirsutum and characterized the repeat types of DVL genes in the four cotton species. Moreover, we computed the Ka/Ks ratio of homologous genes across the four cotton species and elucidated the selective pressure acting on these homologous genes. In addition, we described the expression patterns of the DVL gene family using RNA-seq data, verified the correlation between GhMDVL3 and fuzz development through VIGS technology, and found that some DVL genes may be involved in resistance to biotic and abiotic stress conditions through qRT-PCR technology. Furthermore, a potential interaction network was constructed by WGCNA, and our findings demonstrated the potential of GhM_A05G1032 to interact with numerous genes, thereby playing a crucial role in regulating fuzz development. This research significantly contributed to the comprehension of DVL genes in upland cotton, thereby establishing a solid basis for future investigations into the functional aspects of DVL genes in cotton. [ABSTRACT FROM AUTHOR]

Underwater vehicles heavily depend on the integration of inertial navigation with Doppler Velocity Log (DVL) for fusion-based localization. Given the constraints imposed by sensor costs, ensuring the optimization ability and robustness of fusion algorithms is of paramount importance. While filtering-based techniques such as Extended Kalman Filter (EKF) offer mature solutions to nonlinear problems, their reliance on linearization approximation may compromise final accuracy. Recently, Invariant EKF (IEKF) methods based on the concept of smooth manifolds have emerged to address this limitation. However, the optimization by matrix Lie groups must satisfy the “group affine” property to ensure state independence, which constrains the applicability of IEKF to high-precision positioning of underwater multi-sensor fusion. In this study, an alternative state-independent underwater fusion invariant filtering approach based on a two-frame group utilizing DVL, Inertial Measurement Unit (IMU), and Earth-Centered Earth-Fixed (ECEF) configuration is proposed. This methodology circumvents the necessity for group affine in the presence of biases. We account for inertial biases and DVL pole-arm effects, achieving convergence in an imperfect IEKF by either fixed observation or body observation information. Through simulations and real datasets that are time-synchronized, we demonstrate the effectiveness and robustness of the proposed algorithm.

Autonomous underwater vehicles (AUVs) are extensively utilized in various autonomous underwater missions, encompassing ocean environment monitoring, underwater searching, and geological exploration. Owing to their profound underwater capabilities and robust autonomy, AUVs have emerged as indispensable instruments. Nevertheless, AUVs encounter several constraints in the domain of underwater navigation, primarily stemming from the cost-intensive nature of inertial navigation devices and Doppler velocity logs, which impede the acquisition of navigation data. Underwater simultaneous localization and mapping (SLAM) techniques, along with other navigation approaches reliant on perceptual sensors like vision and sonar, are employed to augment the precision of self-positioning. Particularly within the realm of machine learning, the utilization of extensive datasets for training purposes plays a pivotal role in enhancing algorithmic performance. However, it is common for data obtained exclusively from inertial sensors, a Doppler Velocity Log (DVL), and depth sensors in underwater environments to not be publicly accessible. This research paper introduces an underwater navigation dataset derived from a controllable AUV that is equipped with high-precision fiber-optic inertial sensors, a DVL, and depth sensors. The dataset underwent rigorous testing through numerical calculations and optimization-based algorithms, with the evaluation of various algorithms being based on both the actual surfacing position and the calculated position. [ABSTRACT FROM AUTHOR]

Given the lack of systematic research on bathymetric surveys with multi-beam sonar carried by autonomous underwater vehicles (AUVs) in unfamiliar waters, this paper proposes a method for multi-beam bathymetric surveys based on the constant-depth mode of AUVs, considering equipment safety, operational efficiency, and data quality. Firstly, basic principles for multi-beam bathymetric surveys under the constant-depth mode are proposed based on multi-beam operational standards and AUV constant-depth mode characteristics. Secondly, a vertical effective height model for the vehicle is established, providing vertical constraints and a basis for determining fixed depth in constant-depth missions. Subsequently, according to these basic principles and the vertical effective height model, the operational process for multi-beam bathymetric surveys in unfamiliar waters under the AUV constant-depth mode is outlined. Finally, we validate the proposed method through sea trials in the Xisha Sea of the South China Sea. The test results show that the method proposed in this paper not only ensures the vehicle safety operation and multi-beam data quality, but also improves the operation efficiency by about 68%, demonstrating the reliability of the proposed method and its significant engineering value and guidance implications. [ABSTRACT FROM AUTHOR]

In order to effectively improve the accuracy and efficiency of unstructured environment navigation and trajectory calibration, a multi data fusion based unstructured environment navigation and trajectory calibration method was studied. Described the basic principles of the Strapdown Inertial Navigation System and Doppler Log. After introducing DVL velocity information and relative position information of underwater robots into SINS, the Kalman filter fusion algorithm was used to obtain the system's state equation and measurement equation. The navigation parameter error and device error parameters of the system were selected as the state variables. The difference between SINS output speed and DVL measurement speed, as well as the difference between SINS output position and relative position, are used as the speed and position measurements of the measurement system. Error estimation is obtained through indirect filtering, and the accuracy of navigation and positioning is improved through output correction. The experimental results show that the proposed method has a good calibration effect and can effectively improve the accuracy and efficiency of trajectory calibration in unstructured environments. [ABSTRACT FROM AUTHOR]

The Frizzled (FZD) proteins belong to class F of G protein-coupled receptors (GPCRs) and are essential for various pathways involving the secreted lipoglycoproteins of the wingless/int-1 (WNT) family. A WNT-binding cysteine-rich domain (CRD) in FZDs is N-terminally located and connected to the seven transmembrane domain-spanning receptor core by a linker domain that has a variable length in different FZD homologs. However, the function and importance of this linker domain are poorly understood. Here we used systematic mutagenesis of FZD6 to define the minimal N-terminal domain sufficient for receptor surface expression and recruitment of the intracellular scaffold protein Dishevelled (DVL). Further, we identified a triad of evolutionarily conserved cysteines in the FZD linker domain that is crucial for receptor membrane expression and recruitment of DVL. Our results are in agreement with the concept that the conserved cysteines in the linker domain of FZDs assist with the formation of a common secondary structure in this region. We propose that this structure could be involved in agonist binding and receptor activation mechanisms that are similar to the binding and activation mechanisms known for other GPCRs.

The Autonomous Underwater Vehicle (AUV) is usually equipped with multiple sensors, such as an inertial navigation system (INS), ultra-short baseline system (USBL), and Doppler velocity log (DVL), to achieve autonomous navigation. Multi-source information fusion is the key to realizing high-precision underwater navigation and positioning. To solve the problem, a fusion scheme based on factor graph optimization (FGO) is proposed. Due to multiple iterations and joint optimization of historical data, FGO could usually show a better performance than the traditional Kalman filter. In addition, considering that USBL and DVL are usually heavily influenced by the environment, outliers are often present. A robust integrated navigation algorithm based on a maximum correntropy criterion and FGO scheme is proposed. The proposed algorithm solves the problem of multi-sensor fusion and non-Gaussian noise. Numerical simulations and field tests demonstrate that the proposed FGO scheme shows a better performance and robustness than the traditional Kalman filter. Compared with the traditional Kalman filtering, the positioning accuracy is improved by 5.3%, 9.1%, and 5.1% in the east, north, and height directions. It can realize a more accurate navigation and positioning of underwater multi-sensors. [ABSTRACT FROM AUTHOR]

Abstract Background Destruction of blood–brain barrier (BBB) ​​is one of the main mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Frizzled-7 is a key protein expressed on the surface of endothelial cells that controls vascular permeability through the Wnt-canonical pathway involving WNT1-inducible signaling pathway protein 1 (WISPI). This study aimed to investigate the role of Frizzled-7 signaling in BBB preservation after ICH in mice. Methods Adult CD1 mice were subjected to sham surgery or collagenase-induced ICH. Frizzled-7 activation or knockdown was performed by administration of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) by intracerebroventricular injection at 48 h before ICH induction. WISP1 activation or WISP1 knockdown was performed to evaluate the underlying signaling pathway. Post-ICH assessments included neurobehavior, brain edema, BBB permeability, hemoglobin level, western blot and immunofluorescence. Results The brain expressions of Frizzled-7 and WISP1 significantly increased post-ICH. Frizzled-7 was expressed in endothelial cells, astrocytes, and neurons after ICH. Activation of Frizzled-7 significantly improved neurological function, reduced brain water content and attenuated BBB permeability to large molecular weight substances after ICH. Whereas, knockdown of Frizzled-7 worsened neurological function and brain edema after ICH. Activation of Frizzled-7 significantly increased the expressions of Dvl, β-Catenin, WISP1, VE-Cadherin, Claudin-5, ZO-1 and reduced the expression of phospho-β-Catenin. WISP1 knockdown abolished the effects of Frizzled-7 activation on the expressions of VE-Cadherin, Claudin-5 and ZO-1 at 24 h after ICH. Conclusions Frizzled-7 activation potentially attenuated BBB permeability and improved neurological deficits after ICH through Dvl​​/β-Catenin/WISP1 pathway. Frizzled-7 may be a potential target for the development of ICH therapeutic drugs.

Given the lack of systematic research on bathymetric surveys with multi-beam sonar carried by autonomous underwater vehicles (AUVs) in unfamiliar waters, this paper proposes a method for multi-beam bathymetric surveys based on the constant-depth mode of AUVs, considering equipment safety, operational efficiency, and data quality. Firstly, basic principles for multi-beam bathymetric surveys under the constant-depth mode are proposed based on multi-beam operational standards and AUV constant-depth mode characteristics. Secondly, a vertical effective height model for the vehicle is established, providing vertical constraints and a basis for determining fixed depth in constant-depth missions. Subsequently, according to these basic principles and the vertical effective height model, the operational process for multi-beam bathymetric surveys in unfamiliar waters under the AUV constant-depth mode is outlined. Finally, we validate the proposed method through sea trials in the Xisha Sea of the South China Sea. The test results show that the method proposed in this paper not only ensures the vehicle safety operation and multi-beam data quality, but also improves the operation efficiency by about 68%, demonstrating the reliability of the proposed method and its significant engineering value and guidance implications.

Kalman filter (KF), as an effective method to solve the attitude estimation problem in the initial alignment process of strapdown inertial navigation system (SINS), has been widely used in engineering practice. Unfortunately, in the complex underwater environment, the measurement is easily contaminated by outliers, and the measurement noise covariance is unknown or time-varying, which will degrade the performance of KF severely. To solve this problem, this paper proposes an improved KF with both robustness and adaptivity (namely VBRAKF), and applies it to the in-motion attitude estimation for Doppler velocity log (DVL) aided SINS. In the VBRAKF, the robustness is achieved by suppressing the outliers based on Mahalanobis distance (MD) of the innovation, and the adaptivity is achieved by estimating the uncertain measurement noise covariance based on variational Bayesian (VB) approximation simultaneously. The SINS/DVL shipboard tests were carried out when the outputs of DVL are contaminated by outliers or Gaussian mixture distribution noise, respectively. The tests results demonstrate the superiority of the proposed method over the traditional methods. [ABSTRACT FROM AUTHOR]

Motivated by the problem that water-track Doppler Velocity Log (DVL) cannot effectively suppress the error accumulation of strap-down inertial navigation system (SINS), this paper proposes a novel SINS/DVL integrated navigation algorithm for deep and long cruising range Human Occupied Vehicle (HOV). Such algorithm decomposes the navigation process into two tightly coupled working modes: alignment mode and navigation mode. In the alignment mode, HOV is controlled to perform horizontal circular motion for several minutes to realize Self-Aided SINS. Combining the precise navigation solutions provided by Self-Aided SINS and measurements from DVL with water track, recursive least square (RLS) algorithm is adopted to estimate heading misalignment angle between SINS and DVL and horizontal ocean current velocity. In the navigation mode, both horizontal ocean current velocity obtained in the alignment mode and DVL measurements are utilized to assist SINS, thus enabling SINS/DVL/Current integrated navigation. A square trajectory with a navigation-grade inertial measurement unit (IMU) is simulated to evaluate the proposed SINS/DVL integrated navigation algorithm. Simulation results show that the proposed SINS/DVL integrated navigation is capable of suppressing SINS error divergence effectively and efficiently. In addition, the feasibility and effectiveness of Self-Aided SINS based on horizontal circular motion is also verified by field test with real IMU data.

In underwater navigation systems, Global Navigation Satellite System (GNSS) information cannot be used for navigation. The mainstream method of autonomous underwater vehicles (AUV) underwater navigation system is Doppler Velocity Log (DVL) aided strapdown inertial navigation system (SINS). However, because the DVL is an instrument based on Doppler frequency shift to measure velocity, it is easily affected by the external environment. In a complex underwater environment, DVL output is easily polluted by outliers or even interrupted. In this paper, A new integrated navigation algorithm based on deep learning model is proposed to deal with DVL malfunctions. First, use RKF based on Mahalanobis distance algorithm to eliminate outliers, and then train the Nonlinear AutoRegressive with eXogenous input (NARX) model when DVL is available. When DVL is interrupted, use the NARX model to predict the output of DVL and continue integrated navigation. The proposed NARX-RKF scheme’s effectiveness verification was performed on the data set collected by the SINS/DVL ship-mounted experimental system. For comparison, different methods are also compared in the experiment. Experimental results show that NARX-RKF can effectively predict the output of DVL and is significantly better than other methods.

DEVIL‌ها پپتیدهای کوچکی هستند که نقش مهمی در رشد و نمو گیاهان داشته و در کنترل پاسخ‌های گیاه نسبت به تغییرات محیطی حاصل از تنش‌ها مؤثر می‌باشند. در این تحقیق به بررسی تغییرات بیان چهار ژن AlDVL1، AlDVL2، AlDVL3 و AlDVL6 به همراه ژن‌های مرجع اختصاصی بافت برگ شامل AlGTF و AlU2SnRNp و ژن‌های مرجع اختصاصی برای بافت ریشه شامل AlPRS3 و AlEF1a در گیاه شورزی آلوروپوس لیتورالیس پرداخته شد. گیاهان تحت تنش شوری 600 میلی‌مولار کلریدسدیم و در پنج دوره زمانی صفر (کنترل)، 3، 6، 48 ساعت و یک هفته قرار گرفتند. نتایج تحقیق نشان داد که الگوی بیانی ژن‌های AlDVL در اندام ریشه و برگ به شکل معنی‌داری تحت‌تأثیر تنش شوری قرار گرفته که این افزایش بیان در تمامی ژن‌ها به جز ژن AlDVL6، در اندام ریشه بیشتر از برگ گیاه بود. در بین ژن‌های مورد مطالعه، بیشترین افزایش بیان برای ژن AlDVL2 در بافت برگ در زمان 48 ساعت (12.12) و در اندام ریشه در زمان یک هفته (14.83) مشاهده شد. همچنین، الگوی رفتاری ژن‌ها در بافت‌های ریشه و برگ در حالت افزایش و یا کاهش بیان نسبت به یکدیگر تفاوت داشته و وابسته به بافت بود. بررسی همبستگی بیان ژن‌ها بیانگر تغییرات الگوی رفتاری بیان ژن‌‌ها در بافت‌های مختلف بود به‌طوری‌که همبستگی بیان ژن AlDVL6 و AlDVL3 در بافت برگ و ریشه به‌صورت منفی و معنی‌دار (0.6-) بود که نشان‌دهنده ارتباط معکوس بیان ژن در این دو بافت بوده است. با توجه به ماهیت گیاهان شورزی در تحمل شوری محیط و نیز تغییر بیان ژن‌های مورد مطالعه پس از اعمال تنش شوری، می‌توان به نقش احتمالی این ژن‌ها در افزایش قدرت تحمل گیاه اشاره نمود.

Background: Destruction of blood–brain barrier (BBB) ​​is one of the main mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Frizzled-7 is a key protein expressed on the surface of endothelial cells that controls vascular permeability through the Wnt-canonical pathway involving WNT1-inducible signaling pathway protein 1 (WISPI). This study aimed to investigate the role of Frizzled-7 signaling in BBB preservation after ICH in mice. Methods: Adult CD1 mice were subjected to sham surgery or collagenase-induced ICH. Frizzled-7 activation or knockdown was performed by administration of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) by intracerebroventricular injection at 48 h before ICH induction. WISP1 activation or WISP1 knockdown was performed to evaluate the underlying signaling pathway. Post-ICH assessments included neurobehavior, brain edema, BBB permeability, hemoglobin level, western blot and immunofluorescence. Results: The brain expressions of Frizzled-7 and WISP1 significantly increased post-ICH. Frizzled-7 was expressed in endothelial cells, astrocytes, and neurons after ICH. Activation of Frizzled-7 significantly improved neurological function, reduced brain water content and attenuated BBB permeability to large molecular weight substances after ICH. Whereas, knockdown of Frizzled-7 worsened neurological function and brain edema after ICH. Activation of Frizzled-7 significantly increased the expressions of Dvl, β-Catenin, WISP1, VE-Cadherin, Claudin-5, ZO-1 and reduced the expression of phospho-β-Catenin. WISP1 knockdown abolished the effects of Frizzled-7 activation on the expressions of VE-Cadherin, Claudin-5 and ZO-1 at 24 h after ICH. Conclusions: Frizzled-7 activation potentially attenuated BBB permeability and improved neurological deficits after ICH through Dvl​​/β-Catenin/WISP1 pathway. Frizzled-7 may be a potential target for the development of ICH therapeutic drugs. [ABSTRACT FROM AUTHOR]

Due to the complex underwater environment, the assisted velocity provided by Doppler velocity log (DVL) may be contaminated by non-Gaussian noise. This will degrade the performance of the traditional optimisation-based alignment (OBA) method. To solve this problem, this paper proposes a robust OBA (ROBA) based on projection statistics (PS) algorithm. The ROBA contains two main steps which are also the contributions of the work presented here. Firstly, ROBA makes use of PS algorithm to identify the stored abnormal auxiliary velocity accurately under the framework of Kalman filter (KF), and then a robust strategy of the observation vector is designed to achieve the robustness of OBA. The semi physical experiment of SINS underwater in-motion coarse alignment is carried out based on the ship-mounted measured data. The experimental results demonstrate the superiority of the proposed method over the traditional ones, and the yaw alignment accuracy of ROBA is at least 30% improvement over the traditional ones under the non-Gaussian conditions. [ABSTRACT FROM AUTHOR]

Because the global positioning system (GPS) is not available in underwater environments, an inertial navigation system (INS)/doppler velocity log (DVL) integrated navigation system is generally implemented. In general, an INS/DVL integrated system adopts a loosely coupled method. However, in this loosely coupled method, although the measurement equation for the filter design is simple, the velocity of the body frame cannot be accurately measured if even one of the DVL transducer signals is not received. In contrast, even if only one or two velocities are measured by the DVL transducers, the tightly coupled method can utilize them as measurements and suppress the error increase of the INS. In this paper, a filter was designed to regenerate the measurements of failed transducers by taking advantage of the tightly coupled method. The regenerated measurements were the normal DVL transducer measurements and the estimated velocity in RPM. In order to effectively estimate the velocity in RPM, a filter was designed considering the effects of the tide. The proposed filter does not switch all of the measurements to RPM if the DVL transducer fails, but only switches information from the failed transducer. In this case, the filter has the advantage of being able to be used as a measurement while continuously estimating the RPM error state. A Monte Carlo simulation was used to determine the performance of the proposed filters, and the scope of the analysis was shown by the standard deviation (1 σ, 68%). Finally, the performance of the proposed filter was verified by comparison with the conventional tightly coupled method.

Dishevelled (DVL) critically regulates Wnt signaling and contributes to a wide spectrum of diseases and is important in normal and pathophysiological settings. However, how it mediates diverse cellular functions remains poorly understood. Recent discoveries have revealed that constitutive Wnt pathway activation contributes to breast cancer malignancy, but the mechanisms by which this occurs are unknown and very few studies have examined the nuclear role of DVL. Here, we have performed DVL3 ChIP‐seq analyses and identify novel target genes bound by DVL3. We show that DVL3 depletion alters KMT2D binding to novel targets and changes their epigenetic marks and mRNA levels. We further demonstrate that DVL3 inhibition leads to decreased tumor growth in two different breast cancer models in vivo. Our data uncover new DVL3 functions through its regulation of multiple genes involved in developmental biology, antigen presentation, metabolism, chromatin remodeling, and tumorigenesis. Overall, our study provides unique insight into the function of nuclear DVL, which helps to define its role in mediating aberrant Wnt signaling. SYNOPSIS: DVL3 target genes act in diverse processes such as regulation of immune responses, signal transduction and metabolism.DVL3 binds to the histone methyltransferase KMT2D and co‐localizes with it to regulatory regions.DVL3 depletion alters KMT2D binding to novel targets and the maintenance or deposition of H3K4me3 at these regions.DVL3 depletion reduces tumor growth in vivo. This study identifies novel gene targets of nuclear Dishevelled 3 and shows that DVL3 depletion decreases binding of the histone methyltransferase KMT2D, thereby altering epigenetic marks and mRNA levels of target genes and decreasing tumor growth. [ABSTRACT FROM AUTHOR]

A Doppler velocity log (DVL) provides a three-dimensional representation of the velocity of an underwater vehicle to the vehicle’s DVL-aided inertial navigation system (INS). It is a key element in determining the precision of the INS. This paper presents an algorithm for reducing the error in the DVL as a way of improving the navigation of an autonomous underwater vehicle (AUV). We also investigate and analyze the effect that the seafloor’s deviations have on DVL measurement error. Finally, the performance of the proposed algorithm is examined through both AUV simulation and experimentally. The results show that the proposed technique can indeed effectively correct DVL errors. [ABSTRACT FROM AUTHOR]

Abstract Background Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson’s disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson’s disease patients. Methods Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis’ early development. Results Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Conclusions Our study shows for the first time that LRRK2 activates the WNT/PCP signaling pathway through its interaction to multiple WNT/PCP components. We suggest that LRRK2 regulates the balance between WNT/β-catenin and WNT/PCP signaling, depending on the binding partners. Since this balance is crucial for homeostasis of midbrain dopaminergic neurons, we hypothesize that its alteration may contribute to the pathophysiology of Parkinson’s disease.

• Our paper introduces a proposed navigation, guidance and control system of AUSV. • The proposed navigation is based GPS/DVL/MEMS-INS using ADSF Combined Filter. • The guidance and control is based on microcontroller, ultrasonic and compass sensors. • The AUSV navigation, guidance and control system is tested on reference trajectory. • The AUSV could send and returned back to base station with high efficiency. A reliable navigation, guidance and control system of Autonomous Unmanned Surface Vehicle (AUSV) is the major challenge for most researchers, especially when Global Positioning System (GPS) signal outages or its accuracy decreases in some places on the Earth's surface. Our paper introduces a novel navigation, guidance and control system of AUSV as follows; the proposed navigation system of AUSV is based on integrated Micro Electric Mechanical System –Inertial Navigation System (MEMS-INS) smartphone sensors with GPS and Doppler Velocity Log (DVL) to correct AUSV navigation system errors. The guidance and control system of AUSV is based on Ultrasonic sensors, Raspberry Pi microcontroller, and digital compass sensor. The ultrasonic sensor is used to detect and avoid obstacles on the path of AUSV. The Raspberry Pi microcontroller and digital compass are used to guide AUSV in the required path. Since the GPS and DVL signals are used as the reference sources to correct errors of MEMS-INS system, the accuracy of GPS and DVL decreases due to a bad weather and due to associated noise of DVL measurement, which effects on a whole AUSV navigation system. To resolve this problem, the Adaptive Data Sharing Factor (ADSF) using Combined Filter (CF) is used as integrated method. According to proposed ADSF CF integrated method, the reference source (GPS or DVL) which has the beast accurate system will be used to correct the navigation errors. At same time the least accuracy system will detect and avoid. The efficiency of navigation, guidance and control system of AUSV based on proposed GPS/DVL/MEMS-INS ADFS CF integrated method is tested on surface reference trajectory with four obstacles located on the path of AUSV. During GPS outages, the AUSV was able to reach the target location to implement several tasks such as monitoring, exploring, tracking and returned back to base station depending on the stored path in its memory with high efficiency. Based on estimated results, the proposed navigation system could provide continuous navigation solution and reduce the navigation error to about 85.43% compared to GPS/DVL/MEMS CKF method and to about 68.14% compared to GPS/DVL/MEMS Constant DSF Combined Filter. [ABSTRACT FROM AUTHOR]

Abstract Plant lectins have been studied owing to their structural properties and biological effects that include agglutinating activity, antidepressant-like effect and antitumor property. The results from this work showed the effects of the lectin extracted from the Dioclea violacea plant (DVL) on the C6 rat glioma cell line. DVL treatment was able to induce caspase-3 activation, apoptotic cell death and cellular membrane damage. Furthermore, DVL decreased mitochondrial membrane potential and increased the number of acidic vesicles and cleavage of LC3, indicating activation of autophagic processes. DVL also significantly inhibited cell migration. Compared to ConA, a well-studied lectin extracted from Canavalia ensiformes seeds, some effects of DVL were more potent, including decreasing C6 glioma cell viability and migration ability. Taken together, the results suggest that DVL can induce glioma cell death, autophagy and inhibition of cell migration, displaying potential anti-glioma activity. [ABSTRACT FROM AUTHOR]

To analyze and report adverse drug reactions (ADRs) in a tertiary care teaching hospital. This was an observational study, conducted to analyze and communicate the ADRs reported from July 2016 to June 2017 in a south Indian tertiary care teaching hospital. On daily basis, ADRs reported by healthcare professionals (HCPs) were analyzed and the reports that meet pharmacovigilance programme of India (PvPI) reporting criteria were communicated to PvPI through a specified updated Indian Pharmacopoeia Commission (IPC) suspected ADR reporting form. In this study, ADRs were summarised based on demographics, drug, incidence, type of reaction and its outcome. Causality, severity, seriousness, and predictability were assessed through WHO causality assessment scale, Hartwig and Siegel Severity Assessment Scale and PvPI criteria. A total of 254 ADRs communicated to PvPI through specified, updated IPC suspected ADR reporting form. The incidence of ADRs in both males and females was identical. The occurrence of ADRs in adult patients (71.26%) was significantly higher than other age groups. Of total ADRs, most of them were with Antibiotics (24.01%) followed by antipsychotics (11.42%). In causality assessment, a majority of ADRs (48.82%) were considered possibly related to the drug or treatment and 55.12% were mild in severity. Overall, 36.22% patients were recovered from ADRs. Most of the reported ADRs (54.33%) were probably preventable. The results provided an insight to the HCPs on the importance of monitoring and reporting of ADRs. High-quality data gathered through a reporting system, most of the reported ADRs were probably preventable; the proper review of patient history and monitoring by HCPs can reduce the incidence of ADR. Our study results emphasize a need for establishing a pharmacovigilance centre to ensure the safe use of drugs. [ABSTRACT FROM AUTHOR]

This paper proposes a simplified algorithm for reducing the computational load of the conventional underwater integrated navigation system. The system usually comprises a three-dimensional accelerometer, a three-dimensional gyroscope, a three-dimensional Doppler Velocity Log (DVL) and a data fusion algorithm, such as a Kalman Filter (KF). Since the expected variations of roll, pitch and depth are small, these quantities are assumed to be constant, and the proposed system is designed in a two-dimensional form. Due to the low speed of the vehicle, the nonlinear dynamic equation of the velocity can be simplified in a linear form. We also simplify the conventional KF in order to avoid matrix multiplications and matrix inversions. The performance of the designed system is evaluated in a sea trial by an Autonomous Underwater Vehicle (AUV). The results show that the proposed system can significantly reduce the computational load of the conventional integrated navigation system without a significant reduction in position and velocity accuracy. [ABSTRACT FROM AUTHOR]

In view of challenges of complex underwater environments with a high occurrence of sensor outliers, traditional Kalman filter (KF)-based localization methods are difficult to achieve precise positioning. To address this issue, a factor graph optimization (FGO)-based tightly-coupled (TC) inertial navigation system (INS)/ultra-short baseline system (USBL)/Doppler velocity log (DVL) scheme and core fusion algorithm are proposed. The FGO method is used to construct a TC INS/USBL/DVL factor graph model, and a weight function is added to adjust the weights of each factor, thereby improving the utilization of underwater sensor information and enhancing the accuracy and reliability of underwater navigation. The feasibility of the proposed scheme is verified through simulations and field tests. The results show that the proposed method outperforms KF-loosely-coupled (KF-LC), KF-TC, and FGO-LC methods, with horizontal position accuracy improvements of 29.2%, 6.6%, and 13.2%, respectively. Moreover, the proposed method exhibits smooth navigation error performance in the presence of abnormal sensor information. • Proposing a tightly-coupled INS/USBL/DVL navigation model based on FGO. • Incorporated robust M-estimation algorithm into factor graph model. • Compared the performance of KF and FGO in terms of LC and TC in INS/USBL/DVL system. • Verified the possibility of applying FGO-based underwater navigation in engineering. [ABSTRACT FROM AUTHOR]

Because of the complex task environment, long working distance, and random drift of the gyro, the positioning error gradually diverges with time in the design of a strapdown inertial navigation system (SINS)/Doppler velocity log (DVL) integrated positioning system. The use of velocity information in the DVL system cannot completely suppress the divergence of the SINS navigation error, which will result in low positioning accuracy and instability. To address this problem, this paper proposes a SINS/DVL integrated positioning system based on a filtering gain compensation adaptive filtering technology that considers the source of error in SINS and the mechanism that influences the positioning results. In the integrated positioning system, an organic combination of a filtering gain compensation adaptive filter and a filtering gain compensation strong tracking filter is explored to fuse position information to obtain higher accuracy and a more stable positioning result. Firstly, the system selects the indirect filtering method and uses the integrated positioning error to model the navigation parameters of the system. Then, a filtering gain compensation adaptive filtering method is developed by using the filtering gain compensation algorithm based on the error statistics of the positioning parameters. The positioning parameters of the system are filtered and information on errors in the navigation parameters is obtained. Finally, integrated with the positioning parameter error information, the positioning parameters of the system are solved, and high-precision positioning results are obtained to accurately position autonomous underwater vehicles (AUVs). The simulation results show that the SINS/DVL integrated positioning method, based on the filtering gain compensation adaptive filtering technology, can effectively enhance the positioning accuracy.

Dishevelled ( DVL/ Dvl) genes play roles in canonical and noncanonical Wnt signaling, both of which are essential in neural tube closing and are involved in balancing neural progenitor growth and differentiation, or neuroepithelial cell polarity, respectively. In mouse Dvl haploinsufficiency leads to neural tube defects (NTDs), which represent the second most common birth defects. However, DVL genes' genetic contributions in human NTDs are modest. We sought to explore the molecular impact on such genes in human NTDs in a Han Chinese cohort. In 47 cases with NTDs and 61 matched controls, in brain tissues, the DVL1/ 2 mRNA levels were correlated with the levels of a serine/threonine protein kinase MARK2, and in 20 cases with lumbosacral spina bifida, the mRNA levels of DVL1 and MARK2 were significantly decreased; by contrast, only an intronic rare variant was found. Moreover, in an extended population, we found merely three novel rare missense variants in 1 % of individuals with NTDs. In cell-based assays, Mark2 depletion indeed reduces Dvl gene expression and interrupts neural stem cell (NSCs) growth and differentiation, which are likely to be mediated through a decrease in class IIa HDAC phosphorylation and reduced H3K4ac and H3K27ac occupancies at the Dvl1/2 promoters. Finally, the detections of folate concentration in human brain tissue and NSCs and MEF cells indicates that folate deficiency contributes to the observed decreases in Mark2 and Dvl1 expression. Our present study raises a potential common pathogenicity mechanism in human lumbosacral spina bifida about DVL genes rather than their genetic pathogenic role. [ABSTRACT FROM AUTHOR]

Background: Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Methods: Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Results: Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Conclusions: Our study shows for the first time that LRRK2 activates the WNT/PCP signaling pathway through its interaction to multiple WNT/PCP components. We suggest that LRRK2 regulates the balance between WNT/β- catenin and WNT/PCP signaling, depending on the binding partners. Since this balance is crucial for homeostasis of midbrain dopaminergic neurons, we hypothesize that its alteration may contribute to the pathophysiology of Parkinson's disease. [ABSTRACT FROM AUTHOR]

IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQdomain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients. [ABSTRACT FROM AUTHOR]

In this paper, an integrated navigation system based on H-infinity filter is proposed for improving the performance of underwater navigation system. The proposed navigation system consists of a package with a triad of accelerometers and an Attitude and Heading Reference System (AHRS) as the main system and a Doppler Velocity Log (DVL) as an auxiliary system. In this system, the dynamic and measurement models are defined in such a way by which a H-infinity based integrated navigation system is derived. In addition, according to the specific dynamic of discussed vehicle, a scheme is proposed for estimating the performance bound parameter of H-infinity filter. The proposed system becomes robust versus the system modeling errors and noise uncertainty in comparison with the conventional Kalman Filter (KF). Furthermore, it can be effectively decrease the effect of the DVL's outlier data. The performance of the proposed system is evaluated through several sea tests using an Autonomous Underwater Vehicle (AUV). Furthermore, the conventional Dead Reckoning (DR) and KF algorithms are utilized for comparison. The experimental results demonstrate the superior performance of the proposed system compared with the conventional algorithms. [ABSTRACT FROM AUTHOR]

Inertial navigation system has drift error in underwater applications. Use of DVL with Kalman filter for position and attitude correction is common. Using velocity data decreases drift error in position estimation but this error exists and increases linearity with time. In this article the navigation system consists of inertial measurement unit (IMU) and a Doppler velocity log (DVL) along with depth sensor. With use of magnetic field measurement and earth magnetic field map a new measurement is generated. Discrete extended Kalman filter with indirect feedback is used for tightly coupled integrated navigation algorithm. This algorithm is based on inertial navigation error dynamics. This paper demonstrates the effectiveness of algorithm through simulation. The procedure of simulation is done by sensor data generation. Arbitrary trajectory with specific kinematic characteristic (linear and angular velocity and acceleration) is generated. Sensor data by adding noise and bias to kinematic characteristic of trajectory is produced. Simulation results reveal that the new algorithm with use of magnetic data and earth magnetic field map decreases the drift error with comparison to conventional INS-DVL integrated navigation algorithm. [ABSTRACT FROM AUTHOR]

An ultra-short baseline (USBL) system and a Doppler Velocity Log (DVL) system, both commonly applied for navigation and guidance of underwater vehicles, were tested with respect to their capabilities to support aquaculture net pen inspection by remote-operated-vehicles (ROVs). The data from these systems were investigated with respect to this new application and its operational demands. A series of full scale experiments indicate that the DVL system is able to detect sea pen nets equally well as the seabed, and the USBL system is able to transmit through a net pen containing industrial-scale biomass. A navigation system that uses a combination of these instruments will report the position of the ROV relatively to the net pen, and enable proper documentation of the traveled path. By equipping a suitable underwater vehicle with a combination of USBL and DVL technology, autonomous net inspections with reliable coverage can be achieved. Such a system would have considerable potential for remote and offshore aquaculture farming systems. [ABSTRACT FROM AUTHOR]

Dishevelled (DVL) proteins are components of the Wnt signalling pathways, and increased expression is associated with various malignancies. Information on DVLs in chronic lymphatic leukaemia (CLL) is limited. The aim of the present study was to investigate the role of DVLs in CLL cells and association with Wnt pathways downstream of ROR1. DVL1, 2 and 3 were exclusively expressed in CLL cells as compared to normal peripheral blood mononuclear cells (PBMCs). The expression of DVL1 and DVL3 proteins was significantly more pronounced in progressive than in non-progressive disease ( p < 0.01), whereas the level of DVL2 was significantly higher in non-progressive as compared to progressive disease ( p < 0.001). Treatment of CLL cells with anti-ROR1 specific monoclonal antibodies induced dephosphorylation of ROR1 as well as of tyrosine and serine residues of both DVL2 and DVL3. However, gene silencing of DVLs in the CLL cell line (EHEB) did not induce detectable apoptosis. Non-progressive CLL patients had a different protein activity pattern with regard to Wnt signalling pathway proteins as GSK-3β, β-catenin and AKT as compared to progressive disease. The DVL2 protein may play a role in the activation of signalling pathways in CLL during early stages of the disease, while DVL1 and 3 may have a role in later phases of the leukaemia. [ABSTRACT FROM AUTHOR]

The Wnt signaling pathway plays an important role in animal development and in the biomineralization process. At present, although the biomineralization mechanism in pearl oyster ( Pinctada fucata ) has been extensively studied, there is little research on the Wnt signaling pathway in pearl oyster. To understand the potential role of the Wnt signaling pathway in pearl oyster, we cloned and sequenced three genes from the Wnt signaling pathway in pearl oyster that encode the following proteins: β -catenin, Dishevelled (Dvl) and T-cell factor (TCF). Genomic structure analysis revealed that Pf-β-catenin genomic DNA contained 15 exons, Pf-Dvl genomic DNA contained 16 exons, and Pf-TCF genomic DNA contained 7 exons. Their deduced amino acid sequences all showed the highest identity with homologs in Crassostrea gigas . Yeast two-hybrid analysis verified that Pf- β -catenin interacted with Pf-TCF. These three genes were ubiquitously expressed in seven pearl oyster tissues analyzed with the highest expression in the gill and a certain amount of expression in the mantle, a tissue related to shell formation. After shell notching, the dynamic changes in expression of these three genes showed that they reached a maximum at 4 days, indicating their response to shell regeneration. All three genes were constitutively expressed during five developmental stages of the pearl oyster, with high levels at the early embryonic development stage. Taken together, these results suggested that Pf- β -catenin, Pf-Dvl and Pf-TCF might participate in shell formation and early embryonic and larval development in the pearl oyster. [ABSTRACT FROM AUTHOR]

Deciphering non-canonical WNT signaling has proven to be both fascinating and challenging. Discovered almost 30 years ago, non-canonical WNT ligands signal independently of the transcriptional co-activator β-catenin to regulate a wide range of morphogenetic processes during development. The molecular and cellular mechanisms that underlie non-canonical WNT function, however, remain nebulous. Recent results from various model systems have converged to define a core non-canonical WNT pathway consisting of the prototypic non-canonical WNT ligand, WNT5A, the receptor tyrosine kinase ROR, the seven transmembrane receptor Frizzled and the cytoplasmic scaffold protein Dishevelled. Importantly, mutations in each of these signaling components cause Robinow syndrome, a congenital disorder characterized by profound tissue morphogenetic abnormalities. Moreover, dysregulation of the pathway has also been linked to cancer metastasis. As new knowledge concerning the WNT5A-ROR pathway continues to grow, modeling these mutations will likely provide crucial insights into both the physiological regulation of the pathway and the etiology of WNT5A-ROR-driven diseases., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Axin and conductin (also known as axin2) are structurally related inhibitors of Wnt/β-catenin signalling that promote degradation of β-catenin. Whereas axin is constitutively expressed, conductin is a Wnt target gene implicated in Wnt negative-feedback regulation. Here, we show that axin and conductin differ in their functional interaction with the upstream Wnt pathway component Dvl. Conductin shows reduced binding to Dvl2 compared to axin, and degradation of β-catenin by conductin is only poorly blocked by Dvl2. We propose that insensitivity to Dvl is an important feature of the role of conductin as a negative-feedback regulator of Wnt signalling. [ABSTRACT FROM AUTHOR]