scholarly journals DTL-DephosSite: Deep Transfer Learning Based Approach to Predict Dephosphorylation Sites

2021 ◽  
Vol 9 ◽  
Author(s):  
Meenal Chaudhari ◽  
Niraj Thapa ◽  
Hamid Ismail ◽  
Sandhya Chopade ◽  
Doina Caragea ◽  
...  
Keyword(s):  
Transfer Learning ◽  
Learning Strategy ◽  
Test Results ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Cellular Physiology ◽  
Cellular Processes ◽  
Independent Test ◽  
Primary Amino ◽  
Matthew’S Correlation Coefficient

Phosphorylation, which is mediated by protein kinases and opposed by protein phosphatases, is an important post-translational modification that regulates many cellular processes, including cellular metabolism, cell migration, and cell division. Due to its essential role in cellular physiology, a great deal of attention has been devoted to identifying sites of phosphorylation on cellular proteins and understanding how modification of these sites affects their cellular functions. This has led to the development of several computational methods designed to predict sites of phosphorylation based on a protein’s primary amino acid sequence. In contrast, much less attention has been paid to dephosphorylation and its role in regulating the phosphorylation status of proteins inside cells. Indeed, to date, dephosphorylation site prediction tools have been restricted to a few tyrosine phosphatases. To fill this knowledge gap, we have employed a transfer learning strategy to develop a deep learning-based model to predict sites that are likely to be dephosphorylated. Based on independent test results, our model, which we termed DTL-DephosSite, achieved efficiency scores for phosphoserine/phosphothreonine residues of 84%, 84% and 0.68 with respect to sensitivity (SN), specificity (SP) and Matthew’s correlation coefficient (MCC). Similarly, DTL-DephosSite exhibited efficiency scores of 75%, 88% and 0.64 for phosphotyrosine residues with respect to SN, SP, and MCC.

scholarly journals Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes

2021 ◽  
Vol 14 (9) ◽  
pp. 848
Author(s):  
Lucas Cruz ◽  
Paula Soares ◽  
Marcelo Correia
Keyword(s):  
Protein Function ◽  
Deubiquitinating Enzymes ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Cellular Targets ◽  
Cellular Processes ◽  
Protein Ubiquitination ◽  
Damage Repair ◽  
Ubiquitin Molecule

Ubiquitination represents a post-translational modification (PTM) essential for the maintenance of cellular homeostasis. Ubiquitination is involved in the regulation of protein function, localization and turnover through the attachment of a ubiquitin molecule(s) to a target protein. Ubiquitination can be reversed through the action of deubiquitinating enzymes (DUBs). The DUB enzymes have the ability to remove the mono- or poly-ubiquitination signals and are involved in the maturation, recycling, editing and rearrangement of ubiquitin(s). Ubiquitin-specific proteases (USPs) are the biggest family of DUBs, responsible for numerous cellular functions through interactions with different cellular targets. Over the past few years, several studies have focused on the role of USPs in carcinogenesis, which has led to an increasing development of therapies based on USP inhibitors. In this review, we intend to describe different cellular functions, such as the cell cycle, DNA damage repair, chromatin remodeling and several signaling pathways, in which USPs are involved in the development or progression of cancer. In addition, we describe existing therapies that target the inhibition of USPs.

Citrullination Site Prediction by Incorporating Sequence Coupled Effects into PseAAC and Resolving Data Imbalance Issue

2020 ◽  
Vol 15 (3) ◽  
pp. 235-245 ◽  
Author(s):  
Md. Al Mehedi Hasan ◽  
Md Khaled Ben Islam ◽  
Julia Rahman ◽  
Shamim Ahmad
Keyword(s):  
Molecular Mechanisms ◽  
Performance Metrics ◽  
Arginine Residue ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Arginine Residues ◽  
Living Organisms ◽  
Matthew’S Correlation Coefficient ◽  
User Friendly ◽  
Fold Cross Validation

Background: Post-translational modification is one of the bio-molecular mechanisms in living organisms, which incorporate functional diversity in proteins as well as regulate cellular processes. Transformation of arginine residue to citrulline in protein is such a modification. Objective: Our objective is to identify citrullinated arginine residue sites quickly and accurately. Methods: In this study, a novel computational tool, abbreviated as predCitru-Site, has been developed to predict citrullination sites. This technique effectively has incorporated the sequencecoupling effect of surrounding amino acids of arginine residues as well as optimizes skewed training citrullination dataset for prediction quality improvement. The performance of predCitru- Site has been measured from the average of 5 complete runs of the 10-fold cross-validation test to comply with existing tools. Results and Conclusion: predCitru-Site has achieved 97.6% sensitivity, 98.9% specificity, and overall accuracy of 98.5%. With Matthew’s correlation coefficient of 0.967, it has also shown an area under the receiver operator characteristics curve of 0.997. Compared with existing tools, predCitru-Site significantly outperforms on the same benchmark dataset. It also shows significant improvement in the case of independent tests in all performance metrics (around 50% higher in AUC). These results suggest that our method is promising and can be used as a complementary technique for fast exploration of citrullination in arginine residue. A user-friendly web server has also been deployed at http://research.ru.ac.bd/predCitru-Site/ for the convenience of experimental scientists.

scholarly journals Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1960
Author(s):  
K. Tanuj Sapra ◽  
Ohad Medalia
Keyword(s):  
Intermediate Filaments ◽  
Eukaryotic Cell ◽  
Coiled Coils ◽  
Cellular Functions ◽  
Mechanical Pressure ◽  
Mechanical Feature ◽  
Cellular Processes ◽  
Nuclear Lamins ◽  
Filament Networks ◽  
And Function

The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm and the nucleus, thereby maintaining cellular function while under mechanical pressure. Intermediate filaments (IFs) are imperative to a plethora of regulatory and signaling functions in mechanotransduction. Mutations in all types of IF proteins are known to affect the architectural integrity and function of cellular processes, leading to debilitating diseases. The basic building block of all IFs are elongated α-helical coiled-coils that assemble hierarchically into complex meshworks. A remarkable mechanical feature of IFs is the capability of coiled-coils to metamorphize into β-sheets under stress, making them one of the strongest and most resilient mechanical entities in nature. Here, we discuss structural and mechanical aspects of IFs with a focus on nuclear lamins and vimentin.

scholarly journals TFEB Signalling-Related MicroRNAs and Autophagy

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 985
Author(s):  
Davide Corà ◽  
Federico Bussolino ◽  
Gabriella Doronzo
Keyword(s):  
Transcriptional Regulation ◽  
Stress Factors ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Factor Deficiency ◽  
Transcription Factor Eb ◽  
Important Regulator ◽  
Response To Stress ◽  
Post Transcriptional Regulation

The oncogenic Transcription Factor EB (TFEB), a member of MITF-TFE family, is known to be the most important regulator of the transcription of genes responsible for the control of lysosomal biogenesis and functions, autophagy, and vesicles flux. TFEB activation occurs in response to stress factors such as nutrient and growth factor deficiency, hypoxia, lysosomal stress, and mitochondrial damage. To reach the final functional status, TFEB is regulated in multimodal ways, including transcriptional rate, post-transcriptional regulation, and post-translational modifications. Post-transcriptional regulation is in part mediated by miRNAs. miRNAs have been linked to many cellular processes involved both in physiology and pathology, such as cell migration, proliferation, differentiation, and apoptosis. miRNAs also play a significant role in autophagy, which exerts a crucial role in cell behaviour during stress or survival responses. In particular, several miRNAs directly recognise TFEB transcript or indirectly regulate its function by targeting accessory molecules or enzymes involved in its post-translational modifications. Moreover, the transcriptional programs triggered by TFEB may be influenced by the miRNA-mediated regulation of TFEB targets. Finally, recent important studies indicate that the transcription of many miRNAs is regulated by TFEB itself. In this review, we describe the interplay between miRNAs with TFEB and focus on how these types of crosstalk affect TFEB activation and cellular functions.

scholarly journals Deep Transfer Learning for Improved Detection of Keratoconus using Corneal Topographic Maps

2021 ◽  
Author(s):  
Ali H. Al-Timemy ◽  
Nebras H. Ghaeb ◽  
Zahraa M. Mosa ◽  
Javier Escudero
Keyword(s):  
Transfer Learning ◽  
Learning Strategy ◽  
Clinical Decision ◽  
Topographic Maps ◽  
Computer Assisted ◽  
Clinical Knowledge ◽  
Average Accuracy ◽  
Assisted Diagnosis ◽  
Improved Accuracy ◽  
Fine Tune

Abstract Clinical keratoconus (KCN) detection is a challenging and time-consuming task. In the diagnosis process, ophthalmologists must revise demographic and clinical ophthalmic examinations. The latter include slit-lamb, corneal topographic maps, and Pentacam indices (PI). We propose an Ensemble of Deep Transfer Learning (EDTL) based on corneal topographic maps. We consider four pretrained networks, SqueezeNet (SqN), AlexNet (AN), ShuffleNet (SfN), and MobileNet-v2 (MN), and fine-tune them on a dataset of KCN and normal cases, each including four topographic maps. We also consider a PI classifier. Then, our EDTL method combines the output probabilities of each of the five classifiers to obtain a decision based on the fusion of probabilities. Individually, the classifier based on PI achieved 93.1% accuracy, whereas the deep classifiers reached classification accuracies over 90% only in isolated cases. Overall, the average accuracy of the deep networks over the four corneal maps ranged from 86% (SfN) to 89.9% (AN). The classifier ensemble increased the accuracy of the deep classifiers based on corneal maps to values ranging (92.2% to 93.1%) for SqN and (93.1% to 94.8%) for AN. Including in the ensemble-specific combinations of corneal maps’ classifiers and PI increased the accuracy to 98.3%. Moreover, visualization of first learner filters in the networks and Grad-CAMs confirmed that the networks had learned relevant clinical features. This study shows the potential of creating ensembles of deep classifiers fine-tuned with a transfer learning strategy as it resulted in an improved accuracy while showing learnable filters and Grad-CAMs that agree with clinical knowledge. This is a step further towards the potential clinical deployment of an improved computer-assisted diagnosis system for KCN detection to help ophthalmologists to confirm the clinical decision and to perform fast and accurate KCN treatment.

scholarly journals Targeting Hedgehog Signalling through the Ubiquitylation Process: The Multiple Roles of the HECT-E3 Ligase Itch

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 98 ◽  
Author(s):  
Paola Infante ◽  
Ludovica Lospinoso Severini ◽  
Flavia Bernardi ◽  
Francesca Bufalieri ◽  
Lucia Di Marcotullio
Keyword(s):  
E3 Ligase ◽  
Multiple Roles ◽  
Post Translational Modification ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Hedgehog Signalling ◽  
Promising Target ◽  
Important Pathway ◽  
Multiple Levels

Hedgehog signalling (Hh) is a developmental conserved pathway strongly involved in cancers when deregulated. This important pathway is orchestrated by numerous regulators, transduces through distinct routes and is finely tuned at multiple levels. In this regard, ubiquitylation processes stand as essential for controlling Hh pathway output. Although this post-translational modification governs proteins turnover, it is also implicated in non-proteolytic events, thereby regulating the most important cellular functions. The HECT E3 ligase Itch, well known to control immune response, is emerging to have a pivotal role in tumorigenesis. By illustrating Itch specificities on Hh signalling key components, here we review the role of this HECT E3 ubiquitin ligase in suppressing Hh-dependent tumours and explore its potential as promising target for innovative therapeutic approaches.

scholarly journals BeautyNet: Joint Multiscale CNN and Transfer Learning Method for Unconstrained Facial Beauty Prediction

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yikui Zhai ◽  
He Cao ◽  
Wenbo Deng ◽  
Junying Gan ◽  
Vincenzo Piuri ◽  
...  
Keyword(s):  
Transfer Learning ◽  
Classification Accuracy ◽  
Learning Strategy ◽  
State Of The Art ◽  
Activation Function ◽  
Training Data ◽  
Fine Grained ◽  
Pattern Recognition Problem ◽  
Face Features ◽  
Facial Beauty

Because of the lack of discriminative face representations and scarcity of labeled training data, facial beauty prediction (FBP), which aims at assessing facial attractiveness automatically, has become a challenging pattern recognition problem. Inspired by recent promising work on fine-grained image classification using the multiscale architecture to extend the diversity of deep features, BeautyNet for unconstrained facial beauty prediction is proposed in this paper. Firstly, a multiscale network is adopted to improve the discriminative of face features. Secondly, to alleviate the computational burden of the multiscale architecture, MFM (max-feature-map) is utilized as an activation function which can not only lighten the network and speed network convergence but also benefit the performance. Finally, transfer learning strategy is introduced here to mitigate the overfitting phenomenon which is caused by the scarcity of labeled facial beauty samples and improves the proposed BeautyNet’s performance. Extensive experiments performed on LSFBD demonstrate that the proposed scheme outperforms the state-of-the-art methods, which can achieve 67.48% classification accuracy.

scholarly journals Dynein Light Chain 1 Regulates Dynamin-mediated F-Actin Assembly during Sperm Individualization in Drosophila

2005 ◽  
Vol 16 (7) ◽  
pp. 3107-3116 ◽  
Author(s):  
Anindya Ghosh-Roy ◽  
Bela S. Desai ◽  
Krishanu Ray
Keyword(s):  
Light Chain ◽  
Cytoplasmic Dynein ◽  
Actin Dynamics ◽  
Dynein Light Chain ◽  
Actin Assembly ◽  
Cellular Functions ◽  
Directed Movement ◽  
Cellular Processes ◽  
Dynactin Complex

Toward the end of spermiogenesis, spermatid nuclei are compacted and the clonally related spermatids individualize to become mature and active sperm. Studies in Drosophila showed that caudal end-directed movement of a microfilament-rich structure, called investment cone, expels the cytoplasmic contents of individual spermatids. F-actin dynamics plays an important role in this process. Here we report that the dynein light chain 1 (DLC1) of Drosophila is involved in two separate cellular processes during sperm individualization. It is enriched around spermatid nuclei during postelongation stages and plays an important role in the dynein-dynactin–dependent rostral retention of the nuclei during this period. In addition, DDLC1 colocalizes with dynamin along investment cones and regulates F-actin assembly at this organelle by retaining dynamin along the cones. Interestingly, we found that this process does not require the other subunits of cytoplasmic dynein-dynactin complex. Altogether, these observations suggest that DLC1 could independently regulate multiple cellular functions and established a novel role of this protein in F-actin assembly in Drosophila.

CVID-Associated B Cell Activating Factor Receptor Variants Change Receptor Oligomerization, Ligand Binding and Signaling Responses

2021 ◽  
Author(s):  
Violeta Block ◽  
Eirini Sevdali ◽  
Mike Recher ◽  
Hassan Abolhassani ◽  
Lennart Hammarstrom ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
Ectodomain Shedding ◽  
Cellular Functions ◽  
Single Nucleotide Variants ◽  
B Cell Activating Factor ◽  
Human B Cells ◽  
Receptor Component ◽  
Primary Amino

Abstract Purpose B cell activating factor (BAFF) binding to BAFF-receptor(BAFFR) activates essential cellular functions required forthe survival of mature, human B cells. Thus,deletion ofthe BAFFR gene blocks the development of B cells at the transition from immature to mature B cells resulting in B lymphopenia and hypogammaglobulinemia. In addition to complete BAFFR deficiency, single nucleotide variants changing the primary amino acid sequence of BAFFR gene exist. Some of these variants were foundin patients suffering from immunodeficiency, autoimmunity, or B cell lymphomas. However, it remains unclearto which extent such variants disturb the activity of BAFFR. Methods Since individual differences and genetic/environmental modifiers change the expression and activity of BAFFR, we developed a cellular system that allows the unbiased analysis of BAFFR variants P21R, A52T, G64V, Dup92-95, P146S, and H159Y regarding oligomerization, signaling, and ectodomain shedding.Results Here we show that several of these variants impair BAFFR oligomerization, direct interactions between BAFFR and the B cell receptor component CD79B, BAFFR ectodomain shedding and the activation of AKT and ERK1/2. Conclusion All of these variants are pathogenic and have the potential to contribute to the development of primary antibody deficiencies, autoimmunity and lymphoma, but they most likely do not cause B lymphopenia and agammaglobulinemia like complete BAFFR deficiency.

Semisynthetic triazoles as an approach in the discovery of Novel Lead Compounds

2021 ◽  
Vol 25 ◽  
Author(s):  
Pedro Alves Bezerra Morais ◽  
Carla Santana Francisco ◽  
Heberth de Paula ◽  
Rayssa Ribeiro ◽  
Mariana Alves Eloy ◽  
...  
Keyword(s):  
Natural Products ◽  
Medicinal Chemistry ◽  
Chemical Space ◽  
Biological Activities ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Modern Drug ◽  
New Chemical Entities ◽  
Almost All ◽  
The 19Th Century

: Historically, the medicinal chemistry is concerned with the approach of organic chemistry to new drug synthesis. Considering the fruitful collections of new molecular entities, the dedicated efforts for medicinal chemistry are rewarding. Planning and search of new and applicable pharmacologic therapies involve the altruistic nature of the scientists. Since the 19th century, notoriously the application of isolated and characterized plant-derived compounds in modern drug discovery and in various stages of clinical development highlight its viability and significance. Natural products influence a broad range of biological processes, covering transcription, translation, and post-translational modification and being effective modulators of almost all basic cellular processes. The research of new chemical entities through “click chemistry” continuously opens up a map for the remarkable exploration of chemical space in towards leading natural products optimization by structure-activity relationship. Finally, here in this review, we expect to gather a broad knowledge involving triazolic natural products derivatives, synthetic routes, structures, and their biological activities.

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