Scribble Subcellular Localization Modulates Recruitment of Distinct YES1 Conformations to Regulate YAP Phosphorylation

The multi-domain scaffolding protein Scribble regulates cell polarity and growth signaling at cell-cell junctions. In epithelial cancers, its mislocalization and overexpression paradoxically transforms Scribble from a tumor suppressor to a driver of tumorigenesis. Here we profiled Scribble protein-protein interactions to identify regulators of mislocalized Scribble-driven tumorigenesis. Scribble-HaloTag fusion cells were generated by CRISPR-Cas9 genome editing. Expression of the epithelial-to-mesenchymal transcription factor (EMT-TF) Snail displaced Scribble-HaloTag from the plasma membrane, mirroring the mislocalization observed in cancers. Halo-ligand affinity purification coupled with mass spectrometry analysis identified the Src-family kinase YES1 as a mislocalized Scribble interaction partner, preferentially recruiting the active, αC-helix-in (or open) conformation. Furthermore, Snail expression promotes Yes-associated kinase-1 (YAP) nuclear localization independent of the hippo pathway, while Scribble HaloPROTAC degradation and siRNA knockdown each attenuate YAP-Y357 phosphorylation. Altogether, mislocalized Scribble recruits conformationally open YES1 to promote YAP phosphorylation, linking Scribble mislocalization to amplified growth signaling. This study reveals a novel role of Scribble in the regulation of YES1-YAP oncogenic signaling pathway, identifies one of the mechanisms underlying dysregulated Hippo signaling components contribute to the tumorigenesis, and underpins the importance of proper cellular subcellular localization to a tumor suppressor protein.PHDChemical BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155220/1/donyu_1.pd

A bony-crested Jurassic dinosaur with evidence of iridescent plumage highlights complexity in early paravian evolution

The Jurassic Yanliao theropods have offered rare glimpses of the early paravian evolution and particularly of bird origins, but, with the exception of the bizarre scansoriopterygids, they have shown similar skeletal and integumentary morphologies. Here we report a distinctive new Yanliao theropod species bearing prominent lacrimal crests, bony ornaments previously known from more basal theropods. It shows longer arm and leg feathers than Anchiornis and tail feathers with asymmetrical vanes forming a tail surface area even larger than that in Archaeopteryx. Nanostructures, interpreted as melanosomes, are morphologically similar to organized, platelet-shaped organelles that produce bright iridescent colours in extant birds. The new species indicates the presence of bony ornaments, feather colour and flight- related features consistent with proposed rapid character evolution and significant diversity in signalling and locomotor strategies near bird origins

Raman laser from an optical resonator with a grafted single molecule monolayer

Raman-based technologies have enabled many ground-breaking scientific discoveries related to surface science, single molecule chemistry and biology. For example, researchers have identified surface bound molecules by their Raman vibrational modes and demonstrated polarization-dependent Raman gain. However, a surface constrained Raman laser has yet to be demonstrated because of the challenges associated with achieving a sufficiently high photon population located at a surface to transition from spontaneous to stimulated Raman scattering. Here, advances in surface chemistry and in integrated photonics are combined to demonstrate lasing based on surface stimulated Raman scattering (SSRS). By creating an oriented, constrained Si-O-Si monolayer on the surface of integrated silica optical microresonators, the requisite conditions for SSRS are achieved with low threshold powers (200microW). The expected polarization-dependence of the SSRS due to the orientation of the Si-O-Si bond is observed. Due to the ordered monolayer, the Raman lasing efficiency is improved from ~5% to over 40%.Comment: main text and SI included; accepted to Nature Photonics in 201

A Novel High Efficiency Fractal Multiview Video Codec

Multiview video which is one of the main types of three-dimensional (3D) video signals, captured by a set of video cameras from various viewpoints, has attracted much interest recently. Data compression for multiview video has become a major issue. In this paper, a novel high efficiency fractal multiview video codec is proposed. Firstly, intraframe algorithm based on the H.264/AVC intraprediction modes and combining fractal and motion compensation (CFMC) algorithm in which range blocks are predicted by domain blocks in the previously decoded frame using translational motion with gray value transformation is proposed for compressing the anchor viewpoint video. Then temporal-spatial prediction structure and fast disparity estimation algorithm exploiting parallax distribution constraints are designed to compress the multiview video data. The proposed fractal multiview video codec can exploit temporal and spatial correlations adequately. Experimental results show that it can obtain about 0.36 dB increase in the decoding quality and 36.21% decrease in encoding bitrate compared with JMVC8.5, and the encoding time is saved by 95.71%. The rate-distortion comparisons with other multiview video coding methods also demonstrate the superiority of the proposed scheme

Analysis of the correlation between cervical HPV infection, cervical lesions and vaginal microecology

BackgroundVaginal microbiota is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, and the specific changes in vaginal microbial composition during this process remains uncertain.ObjectiveThis study aimed to observe the changes in the specific composition of vaginal microorganisms in different cervical lesions and identify biomarkers at different stages of lesions.MethodsIn this study we used the illumina high-throughput gene sequencing technology to determine the V4 region of 16SrRNA and observed the vaginal microbial composition in different cervical lesions.ResultsThe vaginal microbiota of patients with high-risk HPV infection and cervical lesions is significantly different from that of the normal population, but there is no significant difference in the richness of vaginal microbes. The diversity of vaginal species in CC patients is higher than that in high-risk HPV infection or CIN patients. The main manifestation is an increase in the diversity of vaginal microbes, a decrease in the relative abundance of cyanobacteria and Lactobacillus, and an increase in the relative abundance of dialister, peptonephila and other miscellaneous bacteria. There are characteristic vaginal biomarker in normal women, high risk HPV patients and CC patients. In detail, the biomarker in the normal group was varibaculum, the biomarker in the high-risk HPV group was saccharopolyspora, the biomarker of the CC group was the Proteobacteria, Corynebacterium, Coprococcus, Peptococcus and Ruminococcus.ConclusionsThe study indicated that the compositions of vaginal microbes in different cervical lesions is different. The vaginal microbial composition has a certain diagnostic effect on healthy women, patients with high-risk HPV infection and cervical lesions. These microbes may serve as potential biomarkers for CC. It also provided an effective way for the treatment of HPV infections and cervical lesions

A Comprehensive Dataset and Automated Pipeline for Nailfold Capillary Analysis

Nailfold capillaroscopy is widely used in assessing health conditions, highlighting the pressing need for an automated nailfold capillary analysis system. In this study, we present a pioneering effort in constructing a comprehensive nailfold capillary dataset-321 images, 219 videos from 68 subjects, with clinic reports and expert annotations-that serves as a crucial resource for training deep-learning models. Leveraging this dataset, we finetuned three deep learning models with expert annotations as supervised labels and integrated them into a novel end-to-end nailfold capillary analysis pipeline. This pipeline excels in automatically detecting and measuring a wide range of size factors, morphological features, and dynamic aspects of nailfold capillaries. We compared our outcomes with clinical reports. Experiment results showed that our automated pipeline achieves an average of sub-pixel level precision in measurements and 89.9% accuracy in identifying morphological abnormalities. These results underscore its potential for advancing quantitative medical research and enabling pervasive computing in healthcare. Our data and code are available at https://github.com/THU-CS-PI-LAB/ANFC-Automated-Nailfold-Capillary.Comment: Dataset, code, pretrained models: https://github.com/THU-CS-PI-LAB/ANFC-Automated-Nailfold-Capillar

Mechanism of Litchi Semen Extract in Preventing Exercise-induced Muscle Damage Based on Network Pharmacology and in Vivo and in Vitro Experiments

Objective: Based on network pharmacology combined with the GEO database and in vivo and in vitro experiments to explore the potential mechanisms of litchi semen extract (LZH) for preventing exercise-induced muscle damage (EIMD). Methods: Hematoxylin-eosin (HE) staining and comparison of the levels of indicators of skeletal muscle damage in serum were performed to detect the effectiveness of LZH in preventing EIMD. The main active ingredients of LZH were searched through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database in conjunction with the published literature, and the targets corresponding to the active ingredients were found through the relevant websites, which were intersected with the EIMD-related targets obtained from the GEO database. The STRING database screened the intersected targets and finally enriched them for analysis. The results of the network pharmacology predictions were validated in vivo using the centrifugal exercise-induced EIMD mouse model and in vitro using the H2O2-induced C2C12 cell model. Results: In vivo experiments showed that skeletal muscle fiber cross-sectional area (P<0.05), creatine kinase (CK) (P<0.001) and lactate dehydrogenase (LDH) (P<0.01) were significantly reduced after the intervention of LZH. The results of network pharmacology showed that LZH had 14 active ingredients, corresponding to 367 targets. The GEO database obtained 1015 targets related to EIMD. The intersection of the two yielded 37 intersecting targets. The enrichment analysis demonstrated p53-mediated cell cycle arrest as the primary target for validation. In vivo experiments showed that LZH significantly reduced the expression of p53 (P<0.01), p21 (P<0.001), BCL2-associated X (Bax) (P<0.05), and the expression of Cyclin D1 (P<0.05), B-cell lymphoma-2 (Bcl-2) (P<0.05) expression was significantly increased. In vitro experiments showed that low and high dose pretreatment of LZH significantly decreased the expression of apoptosis (P<0.001), p53 (P<0.05), p21 (P<0.01, P<0.001) and increased the expression of Cyclin D1 (P<0.05, P<0.001). Conclusion: LZH attenuates EIMD, and its mechanism is closely related to the activation of G1 phase arrest and attenuation of apoptosis in skeletal muscle cells. The results suggest that LZH can be used as a nutritional supplement to prevent EIMD

Optimized data-driven prescribed performance attitude control for actuator saturated spacecraft

This article addresses the crucial requirements in spacecraft attitude control: prescribed performance guarantees under actuator saturation and real-time cost optimization. As an application-oriented study, an approximate optimal prescribed performance attitude control scheme is proposed for this objective. To be specific, the prescribed performance constraint is converted into the system dynamics and merged into the adaptive dynamic programming design philosophy. Subsequently, the online learning law is designed based on a special saturated HJB error, in which a dynamical scale is introduced to adjust the learning gain by measured data. It enhances learning efficiency and applicability. Then, uniformly ultimately bounded stability of the whole system is achieved with guaranteed convergence of optimization by the Lyapunov-based stability analysis. Finally, both numerical simulation and hardware-in-the-loop experiments demonstrate the superiority and effectiveness of the proposed method. These attributes and outcomes attained will promote the development of practical space missions