Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function.

Zinc Finger MIZ-Type Containing 1 (Zmiz1), also known as ZIMP10 or RAI17, is a transcription cofactor and member of the Protein Inhibitor of Activated STAT (PIAS) family of proteins. Zmiz1 is critical for a variety of biological processes including vascular development. However, its role in the lymphatic vasculature is unknown. In this study, we utilized human dermal lymphatic endothelial cells (HDLECs) and an inducible, lymphatic endothelial cell (LEC)-specific Zmiz1 knockout mouse model to investigate the role of Zmiz1 in LECs. Transcriptional profiling of ZMIZ1-deficient HDLECs revealed downregulation of genes crucial for lymphatic vessel development. Additionally, our findings demonstrated that loss of Zmiz1 results in reduced expression of proliferation and migration genes in HDLECs and reduced proliferation and migration in vitro. We also presented evidence that Zmiz1 regulates Prox1 expression in vitro and in vivo by modulating chromatin accessibility at Prox1 regulatory regions. Furthermore, we observed that loss of Zmiz1 in mesenteric lymphatic vessels significantly reduced valve density. Collectively, our results highlight a novel role of Zmiz1 in LECs and as a transcriptional regulator of Prox1, shedding light on a previously unknown regulatory factor in lymphatic vascular biology.

Zmiz1 is a novel regulator of brain development associated with autism and intellectual disability.

Neurodevelopmental disorders (NDDs) are a class of pathologies arising from perturbations in brain circuit formation and maturation with complex etiological triggers often classified as environmental and genetic. Neuropsychiatric conditions such as autism spectrum disorders (ASD), intellectual disability (ID), and attention deficit hyperactivity disorders (ADHD) are common NDDs characterized by their hereditary underpinnings and inherent heterogeneity. Genetic risk factors for NDDs are increasingly being identified in non-coding regions and proteins bound to them, including transcriptional regulators and chromatin remodelers. Importantly, de novo mutations are emerging as important contributors to NDDs and neuropsychiatric disorders. Recently, de novo mutations in transcriptional co-factor Zmiz1 or its regulatory regions have been identified in unrelated patients with syndromic ID and ASD. However, the role of Zmiz1 in brain development is unknown. Here, using publicly available databases and a Zmiz1 mutant mouse model, we reveal that Zmiz1 is highly expressed during embryonic brain development in mice and humans, and though broadly expressed across the brain, Zmiz1 is enriched in areas prominently impacted in ID and ASD such as cortex, hippocampus, and cerebellum. We investigated the relationship between Zmiz1 structure and pathogenicity of protein variants, the epigenetic marks associated with Zmiz1 regulation, and protein interactions and signaling pathways regulated by Zmiz1. Our analysis reveals that Zmiz1 regulates multiple developmental processes, including neurogenesis, neuron connectivity, and synaptic signaling. This work paves the way for future studies on the functions of Zmiz1 and highlights the importance of combining analysis of mouse models and human data.

Self-directed learning for medical graduates: A boon or bane in disguise? A cross-sectional study in Chennai.

BACKGROUND: Self-directed learning (SDL) is an essential aspect of adult education or andragogy, gaining significance in medical education with the introduction of competency-based medical education. The primary objective of this study is to assess the self-directed learning abilities of second-year medical undergraduates in Chennai, South India, and to identify potential challenges and gaps in their learning process. MATERIALS AND METHODS: A cross-sectional study was conducted among 82 second-year medical students attending self-directed learning sessions at a medical college in Chennai. Data were collected using the self-directed learning instrument (SDLI), a standardized questionnaire, administered through Google Forms. Participants' identities were maintained confidential. Data were analyzed using SPSS version 22.0. Descriptive data were presented as proportions and percentages. Normally distributed quantitative data were expressed as mean and standard deviation. Non-normal continuous data were expressed as median and interquartile range (IQR). RESULTS: The majority of the students (61%) demonstrated a high level of SDL ability, with a median score of 76. Students exhibited strong learning motivation (mean score 4.11) but struggled with planning and implementation (mean score 3.07). The maximum mean score was 4.11 for item 3 (constant improvement and excelling in learning), and the minimum mean score was 3.07 for item 11 (arranging and controlling learning time). The students showed high self-monitoring (mean score 3.76) and interpersonal communication skills (mean score 4.00). CONCLUSIONS: SDL emerges as a boon for medical undergraduates in this study. By providing adequate training to faculty members on SDL implementation and guidance to students on planning and time management, SDL can play a pivotal role in enhancing medical education quality and fostering life-long learning among future medical professionals.

Endothelial cell polarity and extracellular matrix composition require functional ATP6AP2 during developmental and pathological angiogenesis.

The (Pro)renin receptor ([P]RR), also known as ATP6AP2, is a single-transmembrane protein that is implicated in a multitude of biological processes. However, the exact role of ATP6AP2 during blood vessel development remains largely undefined. Here, we use an inducible endothelial cell-specific (EC-specific) Atp6ap2-KO mouse model to investigate the role of ATP6AP2 during both physiological and pathological angiogenesis in vivo. We observed that postnatal deletion of Atp6ap2 in ECs results in cell migration defects, loss of tip cell polarity, and subsequent impairment of retinal angiogenesis. In vitro, Atp6ap2-deficient ECs similarly displayed reduced cell migration, impaired sprouting, and defective cell polarity. Transcriptional profiling of ECs isolated from Atp6ap2 mutant mice further indicated regulatory roles in angiogenesis, cell migration, and extracellular matrix composition. Mechanistically, we provided evidence that expression of various extracellular matrix components is controlled by ATP6AP2 via the ERK pathway. Furthermore, Atp6ap2-deficient retinas exhibited reduced revascularization in an oxygen-induced retinopathy model. Collectively, our results demonstrate a critical role of ATP6AP2 as a regulator of developmental and pathological angiogenesis.

Boehmite-An Efficient and Recyclable Acid-Base Bifunctional Catalyst for Aldol Condensation Reaction.

In this work boehmite was used as an acid-base bifunctional catalyst for aldol condensation reactions of aromatic aldehydes and ketones. The catalyst was prepared by simple sol-gel method using Al(NO3)3·9H2O and NH4OH as precursors. The catalyst has been characterized by X-ray diffraction (XRD), Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), UV-visible spectroscopy (DRS), BET surface area analyses. Boehmite is successfully applied as catalyst for the condensation reaction between 4-nitrobenzaldehyde and acetone as a model substrate giving α, ß-unsaturated ketones without any side product. The scope of the reaction is extended for various substituted aldehydes. A probable mechanism has been suggested to explain the cooperative behavior of the acidic and basic sites. The catalyst is environmentally friendly and easily recovered from the reaction mixture. Also the catalyst is reusable up to 3 catalytic cycles.

Automatic Classification on Bio Medical Prognosisof Invasive Breast Cancer

Breast Cancer one of the appalling diseases among the middle-aged women and it is a foremost threatening death possibility cancer in women throughout the world. Earlier prognosis and preclusion reduces the conceivability of death. The proposed system beseech various data mining techniques together with a real-time input data from a biosensor device to determine the disease development proportion. Surface acoustic waves (SAW) biosensor empowers a label-free, worthwhile and straight detection of HER-2/neu cancer biomarker. The output from the biosensor is fed into the proposed system as an input along with data collected from Winconsin dataset. The complete dataset are processed using data mining classification algorithms to predict the accuracy. The exactness of the proposed model is improved by ranking attributes by Ranker algorithm. The results of the proposed model are highly gifted with an accuracy of 79.25% with SVM classifier and an ROC area of 0.754 which is better than other existing systems. The results are used in designing the proper drug thereby improving the survivability of the patients.

Heuristic Classifier for Observe Accuracy of Cancer Polyp Using Video Capsule Endoscopy

Methods: Colonoscopy is a technique for examine colon cancer, polyps. In endoscopy, video capsule is universally used mechanism for finding gastrointestinal stages. But both the mechanisms are used to find the colon cancer or colorectal polyp. The Automatic Polyp Detection sub-challenge conducted as part of the Endoscopic Vision Challenge (http://endovis.grand-challenge.org). Method: Colonoscopy may be primary way of improve the ability of colon cancer detection especially flat lesions. Which otherwise may be difficult to detect. Recently, automatic polyp detection algorithms have been proposed with various degrees of success. Though polyp detection in colonoscopy and other traditional endoscopy procedure based images is becoming a mature field, due to its unique imaging characteristics, detecting polyps automatically in colonoscopy is a hard problem. So the proposed video capsule cam supports to diagnose the polyps accurate and easy to identify its pattern. Existing methodology mainly concentrated on high accuracy and less time consumption and it uses many different types of data mining techniques. To analyse these high resolution video scale image we have to take segmentation of image in pixel level binary pattern with the help of a mid-pass filter and relative gray level of neighbours. This work consists of three major steps to improve the accuracy of video capsule endoscopy such as missing data imputation, high dimensionality reduction or feature selection and classification. The above steps are performed using a dataset called endoscopy polyp disease dataset with 500 patients. Our binary classification algorithm relieves human analyses using the video frames. SVM has given major contribution to process the dataset. Results: In this paper the key aspect of proposed results provide segmentation, binary pattern approach with Genetic Fuzzy based Improved Kernel Support Vector machine (GF-IKSVM) classifier. The segmented images all are mostly round shape. The result is refined via smooth filtering, computer vision methods and thresholding steps. Conclusion: Our experimental result produces 94.4% accuracy in that the proposed fuzzy system and genetic Fuzzy, which is higher than the methods, used in the literature. The GF-IKSVM classifier is well-organized and provides good accuracy results for patched VCE polyp disease diagnosis.

Automatic Colorectal Polyp Detection in Colonoscopy Video Frames

Colonoscopy is currently the best technique available for the detection of colon cancer or colorectal polyps or other precursor lesions. Computer aided detection (CAD) is based on very complex pattern recognition. Local binary patterns (LBPs) are strong illumination invariant texture primitives. Histograms of binary patterns computed across regions are used to describe textures. Every pixel is contrasted relative to gray levels of neighbourhood pixels. In this study, colorectal polyp detection was performed with colonoscopy video frames, with classification via J48 and Fuzzy. Features such as color, discrete cosine transform (DCT) and LBP were used in confirming the superiority of the proposed method in colorectal polyp detection. The performance was better than with other current methods.