Reader Module Research Articles

IGF2BP1-Mediated Regulation of CCN1 Expression by Specific Binding to G-Quadruplex Structure in Its 3'UTR.

The intricate regulation of gene expression is fundamental to the biological complexity of higher organisms, and is primarily governed by transcriptional and post-transcriptional mechanisms. The 3'-untranslated region (3'UTR) of mRNA is rich in cis-regulatory elements like G-quadruplexes (G4s), and plays a crucial role in post-transcriptional regulation. G4s have emerged as significant gene regulators, impacting mRNA stability, translation, and localization. In this study, we investigate the role of a robust parallel G4 structure situated within the 3'UTR of CCN1 mRNA in post-transcriptional regulation. This G4 structure is proximal to the stop codon of human CCN1, and evolutionarily conserved. We elucidated its interaction with the insulin-like growth factor 2 binding protein 1 (IGF2BP1), a noncanonical RNA N6-methyladenosine (m6A) modification reader, revealing a novel interplay between RNA modifications and G-quadruplex structures. Knockdown experiments and mutagenesis studies demonstrate that IGF2BP1 binds specifically to the G4 structure, modulating CCN1 mRNA stability. Additionally, we unveil the role of IGF2BP1's RNA recognition motifs in G4 recognition, highlighting this enthalpically driven interaction. Our findings offer fresh perspectives on the complex mechanisms of post-transcriptional gene regulation mediated by G4 RNA secondary structures.

Face Recognition Based Attendance System using ESP 32CAM

Abstract: In the modern industrial system, attendance logging is essential to raising system quality. Thus, it is necessary to have a robust computerized Face detection attendance recording system that uses an ESP32 camera. Each and every organization has strict attendance policies. It takes time and effort to manually maintain an attendance register. For example, RFID and biometric technology are two ways of solving the same issue. This research outlines a creative and efficient method for determining presence and verifying attendance. The ESP32 microcontroller family features integrated Wi-Fi and dual-mode Bluetooth. This facial detection-based technology does not require a person to be in close proximity to the fingerprint reader module, in contrast to biometric attendance systems. The biometric device becomes contaminated when the same employee or student records their attendance using the same biometric system. Furthermore, the likelihood of a proxy in RFID is considerable. This forecast will track student or employee attendance using facial recognition technology.

Phase separation of SPIN1 through its IDR facilitates histone methylation readout and tumorigenesis.

Spindlin1 (SPIN1) is a unique multivalent histone modification reader that plays a role in ribosomal RNA transcription, chromosome segregation, and tumorigenesis. However, the function of the extended N-terminal region of SPIN1 has remained unclear. Here, we discovered that SPIN1 can form phase-separated and liquid-like condensates both in vitro and in vivo through its N-terminal intrinsically disordered region (IDR). The phase separation of SPIN1 recruits the histone methyltransferase MLL1 to the same condensates and enriches the H3K4 methylation marks. This process also facilitates the binding of SPIN1 to H3K4me3 and activates tumorigenesis-related genes. Moreover, SPIN1-IDR enhances the genome-wide chromatin binding of SPIN1 and facilitates its localization to genes associated with the MAPK signaling pathway. These findings provide new insights into the biological function of the IDR in regulating SPIN1 activity and reveal a previously unrecognized role of SPIN1-IDR in histone methylation readout. Our study uncovers the crucial role of appropriate biophysical properties of SPIN1 in facilitating gene expression and links phase separation to tumorigenesis, which provides a new perspective for understanding the function of SPIN1.

UniGen: A Unified Generative Framework for Retrieval and Question Answering with Large Language Models

Generative information retrieval, encompassing two major tasks of Generative Document Retrieval (GDR) and Grounded Answer Generation (GAR), has gained significant attention in natural language processing. Existing methods for GDR and GAR rely on separate retrieval and reader modules, which hinder simultaneous optimization. To overcome this, we present UniGen, a Unified Generative framework for retrieval and question answering that integrates both tasks into a single generative model leveraging the capabilities of large language models. UniGen employs a shared encoder and two distinct decoders for generative retrieval and question answering. To facilitate the learning of both tasks, we introduce connectors, generated by large language models, to bridge the gaps between query inputs and generation targets, as well as between document identifiers and answers. Furthermore, we propose an iterative enhancement strategy that leverages generated answers and retrieved documents to iteratively improve both tasks. Through extensive experiments on the MS MARCO and NQ datasets, we demonstrate the effectiveness of UniGen, showcasing its superior performance in both retrieval and question answering tasks.

Depletion of the N6-Methyladenosine (m6A) reader protein IGF2BP3 induces ferroptosis in glioma by modulating the expression of GPX4

Emerging evidence highlights the multifaceted contributions of m6A modifications to glioma. IGF2BP3, a m6A modification reader protein, plays a crucial role in post-transcriptional gene regulation. Though several studies have identified IGF2BP3 as a poor prognostic marker in glioma, the underlying mechanism remains unclear. In this study, we demonstrated that IGF2BP3 knockdown is detrimental to cell growth and survival in glioma cells. Notably, we discovered that IGF2BP3 regulated ferroptosis by modulating the protein expression level of GPX4 through direct binding to a specific motif on GPX4 mRNA. Strikingly, the m6A modification at this motif was found to be critical for GPX4 mRNA stability and translation. Furthermore, IGF2BP3 knockdown glioma cells were incapable of forming tumors in a mouse xenograft model and were more susceptible to phagocytosis by microglia. Our findings shed light on an unrecognized regulatory function of IGF2BP3 in ferroptosis. The identification of a critical m6A site within the GPX4 transcript elucidates the significance of post-transcriptional control in ferroptosis.

Office Access System using RFID and Smart Lock

The RFID Door Access Control System ensures the security and dependability of numerous secure medical and scientific facilities, official premises, and locker rooms that house confidential files, granting access only to restricted individuals. The system combines various access methods and fortified security measures, ensuring convenient user access while remaining in-penetrable to unauthorized individuals. This research paper aimed to design a prototype of 3-layer authentication security system based on a solenoid door lock, 4x4 Keypad, RFID cards, Relay Module, 16x2 LCD, ESP32 micro-controller, RC-522 Reader module, and Blynk application. The project focuses on designing and implementing a robust system that integrates RFID technology with smart locks to grant authorized personnel access to numerous sections within the office premises.

Genetically encoded bioorthogonal tryptophan decaging in living cells.

Tryptophan (Trp) plays a critical role in the regulation of protein structure, interactions and functions through its π system and indole N-H group. A generalizable method for blocking and rescuing Trp interactions would enable the gain-of-function manipulation of various Trp-containing proteins in vivo, but generating such a platform remains challenging. Here we develop a genetically encoded N1-vinyl-caged Trp capable of rapid and bioorthogonal decaging through an optimized inverse electron-demand Diels-Alder reaction, allowing site-specific activation of Trp on a protein of interest in living cells. This chemical activation of a genetically encoded caged-tryptophan (Trp-CAGE) strategy enables precise activation of the Trp of interest underlying diverse important molecular interactions. We demonstrate the utility of Trp-CAGE across various protein families, such as catalase-peroxidases and kinases, as translation initiators and posttranslational modification readers, allowing the modulation of epigenetic signalling in a temporally controlled manner. Coupled with computer-aided prediction, our strategy paves the way for bioorthogonal Trp activation on more than 28,000 candidate proteins within their native cellular settings.

Revolutionizing Home Security: A Comprehensive Overview of an Advanced RFID Door Lock System for Keyless Access and Smart Home Protection

The abstract presents a cutting-edge RFID door lock system that does away with traditional physical keys to improve home security. The system uses state-of-the-art components, such as an RFID (Radio-Frequency Identification) reader and an Arduino microcontroller, to provide a safe, keyless access option for homes. This technology provides homes with more protection and convenience, which is a comfort in a world where theft and unwanted access are ongoing issues. Conventional keys are not the best option for home security because they can be stolen, lost, or duplicated. By using customized RFID cards or key fobs, the RFID door lock system, on the other hand, streamlines the entry procedure while significantly lowering the possibility of unwanted access. An RFID reader module, an Arduino microcontroller, and an electronic locking mechanism are the three most crucial parts of the system. Once the authenticity of the card has been confirmed by the RFID reader, the Arduino microcontroller will utilize the obtained data to initiate the lock. Additionally, the system can be improved with features like smartphone applications for remote access control, which let homeowners monitor and grant access from a distance. This RFID door lock system has many advantages for homeowners, including strong security features, user-friendliness, and the capacity to monitor access events. These features provide homeowners with convenience and peace of mind. RFID-based security systems are an important development in the rapidly developing field of smart home technology.

Use of RFID Technology to Enhance Electoral Integrity

As the first democratic nation in South Asia, Sri Lanka continues to conduct elections using the traditional paper-based process. The main disadvantages of this procedure are its dependence on human resources, high printing costs, and inefficient vote counting. This research proposes the implementation of an RFID – based voting system to replace the current paper-based election system with paperless electronic voting systems. Radio frequency identification (RFID) is a popular method for automatic identification and data capture that uses electromagnetic fields to automatically identify, and track tags attached to objects. In this system, each registered voter will have a separate voter identity card with an RFID tag printed on it. During the election, the RFID reader module senses the RFID tags with voter ID. After receiving the voter ID from the RFID reader, the IC compares the ID, and if the data matches the already stored information, the voter is allowed to cast his vote. The admin panel has a different ID, and they have authority to see the results, reset the voting results, add a new registered user, remove a registered user, reset all users, and reset all results. If the voter is not authorized the buzzer alarm will ring to inform them that the person is not allowed to vote. The implementation of this system helps to minimize the possibility of rigging in elections, reduce the probability of causing human error, and eliminate the need to do manual work.

Uncovering the non-histone interactome of the BRPF1 bromodomain using site-specific azide-acetyllysine photochemistry

Bromodomain-PHD finger protein 1 (BRPF1) belongs to the BRPF family of bromodomain-containing proteins. Bromodomains are exclusive reader modules that recognize and bind acetylated histones and non-histone transcription factors to regulate gene expression. The biological functions of acetylated histone recognition by BRPF1 bromodomain are well characterized; however, the function of BRPF1 regulation via non-histone acetylation is still unexplored. Therefore, identifying the non-histone interactome of BRPF1 is pivotal in deciphering its role in diverse cellular processes, including its misregulation in diseases like cancer. Herein, we identified the non-histone interacting partners of BRPF1 utilizing a protein engineering-based approach. We site-specifically introduced the unnatural photo-cross-linkable amino acid 4-azido-L-phenylalanine (AzF) into the bromodomain of BRPF1 without altering its ability to recognize acetylated histone proteins. Upon photo-irradiation, the engineered BRPF1 generates a reactive nitrene species, cross-linking interacting partners with spatio-temporal precision. We demonstrated the robust cross-linking efficiency of the engineered variant with reported histone ligands of BRPF1 and further used the variant reader to cross-link its interactome. We also characterized novel interacting partners by proteomics, suggesting roles for BRPF1 in diverse cellular processes. BRPF1 interaction with ILF3, one of these novel interacting partners, was further validated by ITC and co-IP. Lastly, we used publicly available ChIP-seq and RNA-seq datasets to understand the colocalization of BRPF1 and ILF3 in regulating gene expression in the context of hepatocellular carcinoma. Together, these results will be crucial for full understanding of the roles of BRPF1 in transcriptional regulation and in the design of small-molecule inhibitors for cancer treatment.

Analisis Sharing Data Wemos D1 R32 Menggunakan Web

The advancement of technology has increased the demand for media file storage. One common storage system used today involves the use of cables or devices that need to be connected to other devices. However, this method is not efficient for simultaneous file sharing, especially when many people want to access the same files. This research utilizes the Naive Bayes algorithm and Quality of Service method for testing and SPI (Serial Peripheral Interface) as the serial communication on Wemos D1 R32 with its sensors, in order to address this issue. The research is conducted through stages of literature review, design, testing, implementation, and testing using Wemos D1 R32 as the main platform along with supporting components such as a micro SD card reader module, an LCD OLED display, a micro SD card, and a battery. In the testing phase, conducted three times with each tested file format using the Naive Bayes algorithm in our system, the evaluation results are as follows: Very Good 86.66%, Good 13.33%, Moderate 0%, and Poor 0%.

Memory Network With Pixel-Level Spatio-Temporal Learning for Visual Object Tracking

Making full use of temporal and spatial information is critical to cope with the appearance changes of objects in visual object tracking. However, existing methods in the tracking field, which employ a memory network at frame level to learn this information, bring redundancy and cannot build long-term relationships among historical frames due to the limited memory size. In this paper, we propose a novel memory network, Pixel-level Spatio-Temporal Memory (PSTM), which organizes object features in an efficient way to leverage temporal and spatial context information. Specifically, PSTM is constructed and updated by a memory writer, which includes a pixel-level updating strategy to maintain the temporal consistency and dynamically memorize the noteworthy variations. Furthermore, in order to exploit relationships between the object and search region and precisely estimate the state of the object, we propose a memory reader, Pixel-wise Matching and Refinement module (PMR), and model spatial context without a complex manual-designed mechanism. Comprehensive experiments and comparisons on challenging large-scale benchmarks, including GOT-10k, TrackingNet, LaSOT, OTB2015, VOT2020, and NfS, have demonstrated the effectiveness of our proposed method, which performs favorably against state-of-the-art trackers.

A Fully Integrated RFID Reader SoC.

The traditional RFID reader module relies on a discrete original design. This design integrates a microcontroller, high-frequency RFID reader IC and other multiple chips onto a PCB board, leading to bottlenecks in cost, power consumption, stability and reliability. To align with the trend towards high integration, miniaturization and low power consumption in RFID reader, this paper introduces a fully integrated RFID Reader SoC. The SoC employs the open-source Cortex-M0 core to integrate the RF transceiver, analog circuits, baseband protocol processing, memory and interface circuits into one chip. It's compatible with ISO/IEC 14443 A-type and B-type and ISO/IEC 15693 transmission protocols and rates. Manufactured using a 0.18 μm process, the chip is compatible with multiple standards. The optimized design of the digital baseband control circuit results in a chip area of only 11.95 mm2 offering clear advantages in both area and integration compared to similar work.

Multivalency of nucleosome recognition by LEDGF.

Eukaryotic transcription is dependent on specific histone modifications. Their recognition by chromatin readers triggers complex processes relying on the coordinated association of transcription regulatory factors. Although various modification states of a particular histone residue often lead to differential outcomes, it is not entirely clear how they are discriminated. Moreover, the contribution of intrinsically disordered regions outside of the specialized reader domains to nucleosome binding remains unexplored. Here, we report the structures of a PWWP domain from transcriptional coactivator LEDGF in complex with the H3K36 di- and trimethylated nucleosome, indicating that both methylation marks are recognized by PWWP in a highly conserved manner. We identify a unique secondary interaction site for the PWWP domain at the interface between the acidic patch and nucleosomal DNA that might contribute to an H3K36-methylation independent role of LEDGF. We reveal DNA interacting motifs in the intrinsically disordered region of LEDGF that discriminate between the intra- or extranucleosomal DNA but remain dynamic in the context of dinucleosomes. The interplay between the LEDGF H3K36-methylation reader and protein binding module mediated by multivalent interactions of the intrinsically disordered linker with chromatin might help direct the elongation machinery to the vicinity of RNA polymerase II, thereby facilitating productive elongation.

Radio Frequency Identification (RFID) Based Library Management System

Purpose: The aim of this project is to design and build a library management system based on radio frequency identification that will help the librarian manage the shelves with less human involvement.
 Methodology: A dc supply at +5volts was connected to the microcontroller, with a voltage of +12volts dc connected to the buzzer, and a step-down transformer was used to convert 220volts to 5volts in this system. This power supply was connected to the switch, and by pressing a switch button, the current passed through the entire circuit. RFID collects all the data from the RFID tag. Using a UART module, the EM-18 RFID reader module was connected to 5v pic microcontrollers. The EM-1 RFID reader will read the tag number from an RFID tag when it is placed in its field of operation and output the information via a TX terminal. In order to signal successful tag detection, the beep terminal will turn low. Once the card is in front of the RFID reader, the student extracts the data from it and compares it to the data that is stored in the microprocessor, which is coded using embedded c language. If the data matches, the information is shown on the LCD.
 Finding: A library management system based on radio frequency identification and detection (RFID) was developed in this study to improve library use and management. To efficiently identify and manage the books, it will make use of the RFID reader. The student can search the database and, if the book is available, pick it up from the library because the database displays the book's availability at the library. The main advantages of this project in libraries include time savings, quick access to books, and the elimination of manual errors.
 Unique Contribution to Theory, Practice and policy: Every inventive technical design has its limits. This passive RFID-based library management system has some limitations as a technology for precise data collection. This study recommend that the RFID reader should be improved so that it has finger and thumb print access, which is needed to access student data and details. However, it should also include a facial recognition application, which would further strengthen the biometric security of the system and protect it from impersonation by careless students.

The bromo-adjacent homology domains of PBRM1 associate with histone tails and contribute to PBAF-mediated gene regulation

A critical component of gene regulation is recognition of histones and their post-translational modifications by transcription-associated proteins or complexes. Although many histone-binding reader modules have been characterized, the bromo-adjacent homology (BAH) domain family of readers is still poorly characterized. A pre-eminent member of this family is PBRM1 (BAF180), a component of the PBAF chromatin-remodeling complex. PBRM1 contains two adjacent BAH domains of unknown histone-binding potential. We evaluated the tandem BAH domains for their capacity to associate with histones and to contribute to PBAF-mediated gene regulation. The BAH1 and BAH2 domains of human PBRM1 broadly interacted with histone tails, but they showed a preference for unmodified N-termini of histones H3 and H4. Molecular modeling and comparison of the BAH1 and BAH2 domains with other BAH readers pointed to a conserved binding mode via an extended open pocket and, in general, an aromatic cage for histone lysine binding. Point mutants that were predicted to disrupt the interaction between the BAH domains and histones reduced histone binding invitro and resulted in dysregulation of genes targeted by PBAF in cellulo. Although the BAH domains in PBRM1 were important for PBAF-mediated gene regulation, we found that overall chromatin targeting of PBRM1 was not dependent on BAH-histone interaction. Our findings identify a function of the PBRM1 BAH domains in PBAF activity that is likely mediated by histone tail interaction.

RINK: Reader-Inherited Evidence Reranker for Table-and-Text Open Domain Question Answering

Most approaches used in open-domain question answering on hybrid data that comprises both tabular-and-textual contents are based on a Retrieval-Reader pipeline in which the retrieval module finds relevant “heterogenous” evidence for a given question and the reader module generates an answer from the retrieved evidence. In this paper, we present a Retriever-Reranker-Reader framework by newly proposing a Reader-INherited evidence reranKer (RINK) where a reranker module is designed by finetuning the reader’s neural architecture based on a simple prompting method. Our underlying assumption of reusing the reader’s module for the reranker is that the reader’s ability to generating an answer from evidence contains the knowledge required for the reranking, because the reranker needs to “read” in-depth a question and evidences more carefully and elaborately than a baseline retriever. Furthermore, we present a simple and effective pretraining method by extensively deploying the commonly used data augmentation methods of cell corruption and cell reordering based on the pretraining tasks - tabular-and-textual entailment and cross-modal masked language modeling. Experimental results on OTT-QA, a large-scale table-and-text open-domain question answering dataset, show that the proposed RINK armed with our pretraining procedure makes improvements over the baseline reranking method and leads to state-of-the-art performance.

Exploring the chemical space of functionalized [1,2,4]triazolo[4,3-a]quinoxaline-based compounds targeting the bromodomain of BRD9

Here we report a detailed structure–activity relationship (SAR) study related to [1,2,4]triazolo[4,3-a]quinoxaline-based compounds targeting the reader module of bromodomain containing-protein 9 (BRD9). 3D structure-based pharmacophore models, previously introduced by us, were here employed to evaluate a second generation of compounds, exploring different substitution patterns on the heterocyclic core. Starting from the promising data obtained from our previously identified [1,2,4]triazolo[4,3-a]quinoxaline-based compounds 1–4, the combination of in silico studies, chemical synthesis, biophysical and in vitro assays led to the identification of a new set of derivatives, selected for thoroughly exploring the chemical space of the bromodomain binding site. In more details, the investigation of different linkers at C-4 position highlighted the amine spacer as mandatory for the binding with the protein counterpart and the crucial role of the alkyl substituents at C-1 for increasing the selectivity toward BRD9. Additionally, the importance of a hydrogen bond donor group, critical to anchor the ZA region and required for the interaction with Ile53 residue, was inferred from the analysis of our collected results. Herein we also propose an optimization and an update of our previously reported “pharm-druglike2” 3D structure-based pharmacophore model, introducing it as “pharm-druglike2.1”. Compounds 24-26, 32, 34 and 36 were identified as new valuable BRD9 binders featuring IC50 values in the low micromolar range. Among them, 24 and 36 displayed an excellent selectivity towards BRD9 and a good antiproliferative effect on a panel of leukemia models, especially toward CCRF-CEM cell line, with no cytotoxicity on healthy cells. Notably, the interaction of 24 and 36 with the bromodomain and PHD finger-containing protein 1 (BRPF1) also emerged, disclosing them as new and unexplored dual inhibitors for these two proteins highly involved in leukemia. These findings highlight the potential for the identification of new attractive dual epidrugs as well as a promising starting point for the development of chemical degraders endowed with anticancer activities.

The cancer-testis lncRNA LINC01977 promotes HCC progression by interacting with RBM39 to prevent Notch2 ubiquitination

Cancer-testis genes are involved in the occurrence and development of cancer, but the role of cancer-testis-associated lncRNAs (CT-lncRNAs) in hepatocellular carcinoma (HCC) remains to be explored. Here, we discovered a novel CT-lncRNA, LINC01977, based on the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. LINC01977 was exclusively expressed in testes and highly expressed in HCC. High LINC01977 levels correlated with poorer overall survival (OS) in individuals with HCC. Functional assays showed that LINC01977 promoted HCC growth and metastasis in vitro and in vivo. Mechanistically, LINC01977 directly bound to RBM39 to promote the further entry of Notch2 into the nucleus, thereby preventing the ubiquitination and degradation of Notch2. Furthermore, the RNA binding protein IGF2BP2, one of the m6A modification readers, enhanced the stability of LINC01977, resulting in its high level in HCC. Therefore, the data suggest that LINC01977 interacts with RBM39 and promotes the progression of HCC by inhibiting Notch2 ubiquitination and degradation, indicating that LINC01977 may be a potential biomarker and therapeutic target for HCC patients.

FACE RECOGNITION BASED ATTENDANCE SYSTEM USING ESP 32CAM

Attendance recording is critical in current environment for increasing the quality of any industrial system. Accordingly, a strong computerised Face detection attendance recording system using an ESP32 camera is required. Every organisation has a stringent policy requiring attendance. Maintaining an attendance register manually involves effort and time. RFID and biometric technology, for instance, are two approaches to the same problem. This analysis describes an effective and inventive technique for validating attendance and detecting presence. The ESP32 microcontroller family has dual-mode Bluetooth and built-in Wi-Fi. In contrast to biometric attendance systems, this facial detectionbased technology does not require someone to be close to the fingerprint reader module. When the same student or employee uses the biometric attendance system to record their attendance, the biometric device becomes contaminated. And in case of RFID chances of proxy is high. Using facial recognition technology, this forecast will track employee or student attendance.