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Topic Review
DSResSol
Protein solubility is an important thermodynamic parameter that is critical for the characterization of a protein’s function, and a key determinant for the production yield of a protein in both the research setting and within industrial (e.g., pharmaceutical) applications. Experimental approaches to predict protein solubility are costly, time-consuming, and frequently offer only low success rates. To reduce cost and expedite the development of therapeutic and industrially relevant proteins, a highly accurate computational tool for predicting protein solubility from protein sequence is sought. While a number of in silico prediction tools exist, they suffer from relatively low prediction accuracy, bias toward the soluble proteins, and limited applicability for various classes of proteins. In this study, researchers developed a novel deep learning sequence-based solubility predictor, DSResSol, that takes advantage of the integration of squeeze excitation residual networks with dilated convolutional neural networks and outperforms all existing protein solubility prediction models. This model captures the frequently occurring amino acid k-mers and their local and global interactions and highlights the importance of identifying long-range interaction information between amino acid k-mers to achieve improved accuracy, using only protein sequence as input. DSResSol outperforms all available sequence-based solubility predictors by at least 5% in terms of accuracy when evaluated by two different independent test sets. Compared to existing predictors, DSResSol not only reduces prediction bias for insoluble proteins but also predicts soluble proteins within the test sets with an accuracy that is at least 13% higher than existing models. Researchers derive the key amino acids, dipeptides, and tripeptides contributing to protein solubility, identifying glutamic acid and serine as critical amino acids for protein solubility prediction. Overall, DSResSol can be used for the fast, reliable, and inexpensive prediction of a protein’s solubility to guide experimental design.
  • 1.0K
  • 14 Jan 2022
Topic Review
Angiotensin II-Induced Long Non-Coding RNA Alivec Regulates Chondrogenesis
Angiotensin II (AngII)-regulated Long non-coding RNAs (lncRNAs) Alivec functions, at least in part, to mediate the AngII-induced chondrogenic transformation of vascular smooth muscle cells (VSMCs) implicated in vascular dysfunction and hypertension. 
  • 1.0K
  • 10 Mar 2023
Topic Review
Entrectinib—An Inhibitor of SARS-CoV-2 Cell Entry
This entry describes entrectinib as an antiviral drug.
  • 1.0K
  • 20 Jan 2022
Topic Review
Natural Resistance of Plants
The over-reliance on herbicides to reduce weed infestation in crops has led to the rapid evolution of herbicide-resistant (HR) weeds. Weed resistance to herbicides should be minimized, as this can lead to serious limitations in the food security for people around the world. Landing page resistance can occur as a result of changes in the biochemical sites of the action of one herbicide. Inappropriate resistance occurs through mechanisms that reduce the number of herbicide molecules and reach their target site. In major field crops, synthetic herbicides are used to control weeds worldwide. Cross-resistance can occur with herbicides from the same or different herbicide families, and with the same or different sites of action. Multiple resistance refers to the evolved mechanisms of resistance to more than one herbicide (e.g., resistance to inhibitors (ALS) and (ACC), and this resistance has resulted from separate selection processes). Currently, weed re-sistance has been transferred to 161 different herbicides, covering twenty-three of the twenty-six known herbicide sites. We can protect crops that are associated with herbicide tolerant weeds through biochemical, genetic and crop control strategies. The “European Green Deal” forces producers to change their approaches to plant protection. The emphasizes the importance and advantages of enhancing the natural resistance of plants to pests, with particular emphasis on the importance of oxylipins in plant protection. The summarize the latest research on the reaction of plants to pesticides, including herbicides, in order to assess the possibility of using jasmonates and brassinosteroids to stimulate the natural, induced systemic immunity of plants, as well as investigate the possibility of the interaction of oxylipins with ethylene, salicylates and other compounds.
  • 1.0K
  • 16 Nov 2022
Topic Review
PLXNA4 Gene
PLXNA4 gene, is known to play a role as a guide for axons in the development of the nervous system. When the PLXNA4 recombinant protein was added, neuron-related genes were increased. In the PLXNA4 gene knockdown experiment, the expression of neuron-related genes was not changed by LISSV exposure. The PLXNA4 gene is activated by sema family ligands. 
  • 1.0K
  • 08 Mar 2022
Topic Review
Timing of Metastatic Colorectal Cancer
Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, where ~50% of patients develop metastasis, despite current improved management. Genomic characterisation of metastatic CRC, and elucidating the effects of therapy on the metastatic process, are essential to help guide precision medicine. Multi-region whole-exome sequencing was performed on 191 sampled tumour regions of patient-matched therapy-naïve and treated CRC primary tumours (n = 92 tumour regions) and metastases (n = 99 tumour regions), in 30 patients. Somatic variants were analysed to define the origin, composition, and timing of seeding in the metastatic progression of therapy-naïve and treated metastatic CRC. High concordance, with few genomic differences, was observed between primary CRC and metastases. Most cases supported a late dissemination model, via either monoclonal or polyclonal seeding. Polyclonal seeding appeared more common in therapy-naïve metastases than in treated metastases. Whereby, treatment prompted for the selection of distinct resistant clones, through monoclonal seeding to distant metastatic sites. Overall, this study reinforces the importance of early clinical detection and surgical excision of the CRC tumour, whilst further highlighting the clinical challenges for metastatic CRC with increased intratumour heterogeneity (either due to early dissemination or polyclonal metastatic spread) and the underlying risk of future therapeutic resistance in treated patients.
  • 1.0K
  • 20 Oct 2020
Topic Review
Human Mitochondrial Pyruvate Carrier
Human mitochondrial pyruvate carriers (hMPCs), which are required for the uptake of pyruvate into mitochondria, are associated with several metabolic diseases, including type 2 diabetes and various cancers. Yeast MPC was recently demonstrated to form a functional unit of heterodimers. However, human MPC-1 (hMPC-1) and MPC-2 (hMPC-2) have not yet been individually isolated for their detailed characterization, in particular in terms of their structural and functional properties, namely, whether they exist as homo- or heterodimers. In this study, hMPC-1 and hMPC-2 were successfully isolated in micelles and they formed stable homodimers. However, the heterodimer state was found to be dominant when both hMPC-1 and hMPC-2 were present. In addition, as heterodimers, the molecules exhibited a higher binding capacity to both substrates and inhibitors, together with a larger structural stability than when they existed as homodimers. Taken together, our results demonstrated that the hetero-dimerization of hMPCs is the main functional unit of the pyruvate metabolism, providing a structural insight into the transport mechanisms of hMPCs.
  • 1.0K
  • 24 Mar 2021
Topic Review
COVID-19 Vaccine Approved for Public Use
Coronavirus disease 2019 (COVID-19) outbreak was first reported in Wuhan, China in December 2019, and was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel pleomorphic, positive-stranded RNA virus belonging to the Coronaviridae family. Quickly, it has become a global pandemic, infecting more than 176 million people and causing the death of more than 3.8 million individuals, that we are yet to recover from. Thus, an ongoing quest is being carried out for prophylaxis/therapy to prevent the transition from infection into serious forms of COVID-19.
  • 1.0K
  • 30 Nov 2021
Topic Review
MS-Based Proteomics for Bipolar Disorder Potential Biomarkers Assessment
Bipolar disorder (BD) is a clinically heterogeneous condition, presenting a complex underlying etiopathogenesis that is not sufficiently characterized. Without molecular biomarkers being used in the clinical environment, several large screen proteomics studies have been conducted to provide valuable molecular information. Mass spectrometry (MS)-based techniques can be a powerful tool for the identification of disease biomarkers, improving prediction and diagnosis ability.
  • 1.0K
  • 27 May 2022
Topic Review
Hippophae rhamnoides/Cassia fistula Extracts
The work deals with the in vitro evaluations of the pod extracts of C. fistula which are shown to exert better antioxidant and enzymatic properties than those exhibited by the fruit extract of H. rhamnoides.
  • 1.0K
  • 03 Nov 2020
Topic Review
GSK-3 in Neurodegeneration
Glycogen synthase kinase-3 (GSK-3) is a central player in regulating mood behavior, cognitive functions, and neuron viability. Indeed, many targets controlled by GSK-3 are critically involved in progressing neuron deterioration and disease pathogenesis. 
  • 1.0K
  • 06 Mar 2021
Topic Review
3D Tissue and Organ Reconstruction
Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. 
  • 1.0K
  • 24 Feb 2021
Topic Review
Antibodies induced by Glycosphingolipids
Glycosphingolipids containing very-long-chain fatty acids (VLCFAs) regulate several immune responses, such as cytokine production, immune signaling, and antibody induction. Here, we report that immunization with glycosphingolipids containing-VLCFAs can efficiently induce the production of anti-glycan antibodies by B cells.
  • 1.0K
  • 30 Oct 2020
Topic Review
Skeletal Muscle and Stress Proteins
All organisms and cells respond to various stress conditions by up-regulating the expression and/or activation of a group of proteins called heat shock proteins (HSPs). Although their expression is induced by several stimuli, they are commonly recognized as HSPs due to the first experiments showing their increased transcription after application of heat shock. These proteins are molecular chaperones mainly involved in assisting protein transport and folding, assembling multimolecular complexes, and triggering protein degradation by proteasome. In addition, they play a crucial role in gene expression regulation, DNA replication, signal transduction, cell differentiation, apoptosis, cellular senescence or immortalization, and intercellular communications. Heat shock proteins are classified according to their molecular weight in super heavy, 100, 90, 70, 60, 40, and small HSPs. Although they are the most highly conserved, ubiquitous, and abundant proteins in all organisms, their cellular stress response can depend on the class and stimulus.
  • 1.0K
  • 16 Apr 2021
Topic Review
Extracellular Vesicles in Tumour Microenvironment
The tumour microenvironment (TME) contains cells of different origin, including cancer, immune, endothelial, and stromal cells. In the last decades extracellular vesicles (EV) released by these cells have gained attention as drivers of the TME diversity and tumour behaviour. In the TME, EV can switch tumour growth, immune-escape and metastatic spread or exert anti-tumour activity depending on their cell of origin and cargo. Moreover, since potentially detectable in different biological fluids, EV have been proposed as diagnostic and therapeutic, or “theragnostic” tools. Specifically, EV cargo has been considered a tumour “fingerprint”, and differentially expressed proteins and genetic materials proposed as potential targets for anti-cancer based therapies. Approaches using engineered EV or EV as naturally delivery system for “therapeutics” have been explored in preclinical models and their effectiveness, in targeting the TME, proven in primary and metastatic tumours. More recently, CAR-T cells and CAR EV combo platform have been proposed to improve the CAR-based anti-cancer approach. Likewise, their potential application for immune cell targeting has provide significant insights to move towards anti-cancer immunotherapeutic approaches. On these bases, a number of clinical trials aimed to deeply explore EV clinical application as anti-tumour based approach or “theragnostics” are on-going. Should validated as diagnostic/prognostic/anti-cancer tools the still open questions would be hopefully addressed and their clinical application would become the on-coming challenge against cancer. However, to move towards EV clinical application several hurdles including potency tests, scalability and full characterization in agreement with the regulatory agency should be solved.
  • 1.0K
  • 09 Nov 2020
Topic Review
MSC Senescence
Mesenchymal stromal cells (MSCs) are a heterogeneous population of stromal cells capable of self-renewal and multi-lineage differentiation into various tissues of mesodermal origin.
  • 1.0K
  • 02 Sep 2021
Topic Review
Microglial Phagocytosis
       Multiple sclerosis (MS) is the most common autoimmune and demyelinating disease of the central nervous system (CNS), characterized, in the majority of cases, by initial relapses that later evolve into progressive neurodegeneration, severely impacting patients’ motor and cognitive functions. Despite the availability of immunomodulatory therapies effective to reduce relapse rate and slow disease progression, they all failed to restore CNS myelin that is necessary for MS full recovery. Microglia are the primary inflammatory cells present in MS lesions, therefore strongly contributing to demyelination and lesion extension. Thus, many microglial-based therapeutic strategies have been focused on the suppression of microglial pro-inflammatory phenotype and neurodegenerative state to reduce disease severity.
  • 1.0K
  • 25 Aug 2020
Topic Review
Central Type-1 Cannabinoid Receptor Gene
Different neuromodulatory systems are involved in long-term energy balance and body weight and, among these, evidence shows that the endocannabinoid system, in particular the activation of type-1 cannabinoid receptor, plays a key role.
  • 1.0K
  • 18 Jan 2021
Topic Review
TGR5
Takeda G protein-coupled receptor (TGR5) is a metabolic regulator, which is also involved in inflammatory responses. TGR5 belongs to the G protein-coupled receptor (GPCR) superfamily.
  • 1.0K
  • 02 Aug 2021
Topic Review
Effects of Ellagic Acid in Neurological Diseases
Aging is associated with several diseases that threaten the health of older people, such as neurodegenerative diseases, which cause indelible and irreversible damage to both the physical and psychological well-being of older people and impose a heavy burden on their families and society. In recent years, a large number of studies have focused on the therapeutic effects of Ellagic Acid, demonstrating the health benefits of EA for neurodegenerative diseases. Three common neurological diseases are described here: AD, PD, and cerebral ischemia as well as the antioxidative and anti-inflammatory protective effects of EA.
  • 1.0K
  • 26 Oct 2022
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