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Topic Review
Protein Arginine Methyltransferase PRMT7
PRMT7 is a member of the protein arginine methyltransferase (PRMT) family, which methylates a diverse set of substrates. Arginine methylation as a posttranslational modification regulates protein–protein and protein–nucleic acid interactions, and as such, has been implicated in various biological functions. PRMT7 is a unique, evolutionarily conserved PRMT family member that catalyzes the mono-methylation of arginine. The structural features, functional aspects, and compounds that inhibit PRMT7 are discussed here. Several studies have identified physiological substrates of PRMT7 and investigated the substrate methylation outcomes which link PRMT7 activity to the stress response and RNA biology. PRMT7-driven substrate methylation further leads to the biological outcomes of gene expression regulation, cell stemness, stress response, and cancer-associated phenotypes such as cell migration. Furthermore, organismal level phenotypes of PRMT7 deficiency have uncovered roles in muscle cell physiology, B cell biology, immunity, and brain function. 
  • 1.3K
  • 10 Aug 2021
Topic Review
Omega-3 LCPUFAs against Age-Related Cognitive Impairment
Among nutrients to cope with aging in special cognitive decline, the long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as very promising ones. Due to their neuroinflammatory resolving effects, an increased status of DHA and EPA in the elderly has been linked to better cognitive function and a lower risk of dementia. Recently, supplementation with structured forms of EPA and DHA, which can be derived natural forms or targeted structures, have proven enhanced bioavailability and powerful benefits. 
  • 1.3K
  • 31 Mar 2022
Topic Review
Biotechnological Tools to Develop Abiotic Stress-Tolerant Plants
Biotechnological tools include several methods used for plants to develop tolerance to abiotic stress. The genetic transformation of tomato relies highly on the tissue culture technique. Advances in the field of plant genetic transformation have enabled the identification of genes that are responsible for tolerance to different environmental stresses. Various biotechnological tools can be used to alter the tomato genes so that this species can more rapidly or better adapt to abiotic stress. Further advancement in understanding the genomics of wild relatives of tomatoes and other Solanaceae has facilitated their exploitation in various breeding programs aiming to introgress genes responsible for abiotic stress resistance in cultivars.
  • 1.3K
  • 06 Jan 2023
Topic Review
Extracellular Vesicles in Helicobacter pylori-Infection
Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived, as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. 
  • 1.3K
  • 13 May 2021
Topic Review
Apoptosis-Associated Protein Domains
There are proteins or families of proteins that regulate the caspase activation pathways, namely, the extrinsic or intrinsic pathways, and they are identified depending on their amino acid sequence or homologue. The interactions facilitated by these protein families are driven through protein domains that are linked with the regulation of apoptosis, such as death domains (DDs), caspase recruitment domains (CARDs), death effector domains (DEDs), BCL-2 family proteins and of IAP-family proteins.
  • 1.3K
  • 27 Apr 2022
Topic Review
YAP-TEAD Interaction Disruptors
This a entry that comprehensively covers the modalities that act as disruptors of the YAP-TEAD interaction. The transcriptional co-activator YAP (Yes-associated protein) by pairing with the transcription factor TEAD (TEA domain) orchestrates the expression of several oncogenic transcriptional programs. These programs are seen in a proportion of all solid tumors. Therefore, the disruption of YAP-TEAD interaction is proposed as an attractive option to target cancers.
  • 1.3K
  • 11 Jan 2021
Topic Review
Dictyostelium discoideum
Dictyostelium discoideum has provided a useful, simple model to aid in unraveling the complex pathological characteristics of neurological disorders including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, neuronal ceroid lipofuscinoses and lissencephaly. 
  • 1.3K
  • 06 May 2022
Topic Review
Chitosan-Based Delivery Systems for Carotenoids
Carotenoids are secondary metabolites present in microorganisms (bacteria, yeast, fungi, and microalgae) and higher plants. They cannot be produced by the human organism. In nature, their principal role is to attract different light wavelengths and transfer their energy to chlorophylls, a function occurring mainly in photosynthetic organisms. Moreover, they can act as photo-protectors, precursors of hormonal substances, antistress secondary metabolites, and attractive agents in plant–insect interaction.
  • 1.3K
  • 27 Sep 2023
Topic Review
Electrochemical Methods for Liquid Biopsy
The screening and early diagnosis of diseases are crucial for a patient’s treatment to be successful and to improve their survival rate, especially for cancer. The development of non-invasive analytical methods able to detect the biomarkers of pathologies is a critical point to define a successful treatment and a good outcome. A biopsy is a technique in which tissue samples are taken from the body and examined under a microscope to see if cancer (though the concept is applicable to many other diseases) or abnormal cells are present. Electrochemical methods, such as electrochemical impedance spectroscopy (EIS), differential pulse voltammetry (DPV), and cyclic voltammetry (CV), play a crucial role in both the development of biosensors and the evaluation of their performance. These methods are highly valuable approaches in the field of liquid biopsy.
  • 1.3K
  • 18 Oct 2023
Topic Review
Lactoferrin and Its Derived Peptides
Lf is bacteriostatic and/or bactericidal, can stimulate cell proliferation and differentiation, facilitate iron absorption, improve neural development and cognition, promote bone growth, prevent cancer and exert anti-inflammatory and immunoregulatory effects.
  • 1.3K
  • 29 Dec 2020
Topic Review
Peptide Hormones and Adipose Tissue
Peptide hormones play a prominent role in controlling energy homeostasis and metabolism. They have been implicated in controlling appetite, the function of the gastrointestinal and cardiovascular systems, energy expenditure, and reproduction. Furthermore, there is growing evidence indicating that peptide hormones and their receptors contribute to energy homeostasis regulation by interacting with white and brown adipose tissue.
  • 1.3K
  • 06 Jun 2021
Topic Review
Type 2 Transglutaminase in Coeliac Disease
Coeliac disease (CD) is a multifactiorial enteropathy that affects the small intestine of genetically predisposed individuals. A condition of partial to total atrophy, together with crypt hyperplasia and consistent lymphocytic infiltration, characterises the intestinal mucosa of affected patients. The main environmental trigger is a heterogenic proteic component of some dietary cereals, commonly known as gluten. A strong immune response against gluten, both cellular and humoral, is mounted in CD, accompanied by a humoral autoimmune response against self-proteins, in particular type 2 transglutaminase (TG2).
  • 1.3K
  • 22 Jul 2022
Topic Review
Choroid Plexus
Cerebrospinal fluid (CSF) is the liquid that fills the brain ventricles. CSF represents not only a mechanical brain protection but also a rich source of signalling factors modulating diverse processes during brain development and adulthood. The choroid plexus (CP) is a major source of CSF and as such it has recently emerged as an important mediator of extracellular signalling within the brain. Growing interest in the CP revealed its capacity to release a broad variety of bioactive molecules that, via CSF, regulate processes across the whole central nervous system (CNS). Moreover, CP has been also recognized as a sensor, responding to altered composition of CSF associated with changes in the patterns of CNS activity. In this review, we summarize the recent advances in our understanding of the CP as a signalling centre that mediates long-range communication in the CNS. By providing a detailed account of the CP secretory repertoire, we describe how the CP contributes to the regulation of the extracellular environment—in the context of both the embryonal as well as the adult CNS. We highlight the role of the CP as an important regulator of CNS function that acts via CSF-mediated signalling. Further studies of CP–CSF signalling hold the potential to provide key insights into the biology of the CNS, with implications for better understanding and treatment of neuropathological conditions.
  • 1.3K
  • 06 Nov 2020
Topic Review
Aberrant BMP2 Signaling
The most common bone disease in humans is osteoporosis (OP). Current therapeutics targeting OP have several negative side effects. Bone morphogenetic protein 2 (BMP2) is a potent growth factor that is known to activate both osteoblasts and osteoclasts. It completes these actions through both SMAD-dependent and SMAD-independent signaling. A novel interaction between the BMP type Ia receptor (BMPRIa) and casein kinase II (CK2) was discovered, and several CK2 phosphorylation sites were identified. A corresponding blocking peptide (named CK2.3) was designed to further elucidate the phosphorylation site’s function. Previously, CK2.3 demonstrated an increased osteoblast activity and decreased osteoclast activity in a variety of animal models, cell lines, and isolated human osteoblasts. It is hypothesized that CK2.3 completes these actions through the BMP signaling pathway. Furthermore, it was recently discovered that BMP2 did not elicit an osteogenic response in osteoblasts from patients diagnosed with OP, while CK2.3 did.
  • 1.3K
  • 26 Oct 2020
Topic Review
Protein Tertiary Structure Prediction
The prediction of three-dimensional (3D) protein structure from amino acid sequences has stood as a significant challenge in computational and structural bioinformatics for decades. The widespread integration of artificial intelligence (AI) algorithms has substantially expedited advancements in protein structure prediction, yielding numerous significant milestones. In particular, the end-to-end deep learning method AlphaFold2 has facilitated the rise of structure prediction performance to new heights, regularly competitive with experimental structures in the 14th Critical Assessment of Protein Structure Prediction (CASP14). 
  • 1.3K
  • 26 Feb 2024
Topic Review
BAZ1B the Protean Protein
The bromodomain adjacent to the zinc finger domain 1B (BAZ1B) or Williams syndrome transcription factor (WSTF) are just two of the names referring the same protein that is encoded by the WBSCR9 gene and is among the 26–28 genes that are lost from one copy of 7q11.23 in Williams syndrome (WS: OMIM 194050). Patients afflicted by this contiguous gene deletion disorder present with a range of symptoms including cardiovascular complications, developmental defects as well as a characteristic cognitive and behavioral profile. Studies in patients with atypical deletions and mouse models support BAZ1B hemizygosity as a contributing factor to some of the phenotypes. Focused analysis on BAZ1B has revealed this to be a versatile nuclear protein with a central role in chromatin remodeling through two distinct complexes as well as being involved in the replication and repair of DNA, transcriptional processes involving RNA Polymerases I, II, and III as well as possessing kinase activity. 
  • 1.3K
  • 22 Oct 2021
Topic Review
Gap Junction Channel
In most tissues, cells in contact with each other exchange cytosolic molecules of low molecular weight via channels aggregated at gap junctions. Gap junction mediated cell-to-cell communication allows neighboring cells to coordinate and regulate many functional activities in mature and developing organs. A gap junction channel is made of the interaction of two hemichannels (connexons/innexons) that form a hydrophilic pathway across the two apposed plasma membranes and the extracellular space (gap). Each connexon/innexon is an oligomer of six proteins (connexins/innexins) that span the plasma membrane and create a hydrophilic pore insulated from lipid bilayer and extracellular medium (Rev. in: Peracchia, C., Gap junction stucture and chemical regulation. Direct calmodulin role in cell-to-cell channel gating. Academic Press. An imprint of Elsevier: London, UK, 2019). Gap junction channels have been thought to possess as many as four types of gates: fast transjunctional voltage (Vj) gate, slow Vj-gate, chemical gate and gate sensitive to membrane potential (Vm). However, since the behavior of the slow Vj-gate and the Vm-sensitive is the same as that of the chemical gate, most likely these gates are the same. We have named this gate “chemical/slow gate” (Peracchia, C. Calmodulin-mediated regulation of gap junction channels. Int. J. Mol. Sci. 2020, 21, 485). In 2000, we proposed a calmodulin (CaM)-mediated “cork-type” gating model. The model proposes two mechanisms. One, “Ca-CaM-Cork”, envisions physical blockage of the channel’s mouth by a CaM lobe (N-lobe?), likely to be combined with conformational connexin changes induced by Ca2+-CaM binding to connexin sites. The other, “CaM-Cork”, also proposes a physical blockage of the channel’s mouth by a CaM lobe, but without calcium-ctivation. The first is only reversed by the return of intracellular Ca2+ concentration ([Ca2+]i) to resting values. The latter is reversed by Vj positive at the gated side (Peracchia, C. Calmodulin-Cork model of gap junction channel gating. - One molecule, two mechanisms. Int. J. Mol. Sci. 2020, 21, 4938). Evidence that gap junction mediated cell communication is finely regulated by nanomolar [Ca2+]i via the direct action of Ca2+-CaM indicates that gap junction channel gating is not just a safety mechanism for protecting cells from damaged/dead neighbors (healing-over). Rather, it is also a mechanism designed to finely modulate cell–cell exchange of small molecules. In summary: At resting [Ca2+]i, (<50nM) some channels are spontaneously closed by the CaM-Cork gating mechanism. With moderate [Ca2+]i rise (50–100 nM, the CaMKII cascade may be activated causing channels closed by the CaM-Cork mechanism to open. With greater [Ca2+]i rise (>100 nM), the channels start closing by the Ca-CaM-Cork mechanism. CaM lobe channel mouth plugging is likely to include connexin conformational changes. CaM-Cork gated channels could be reopened by Vj positive at gated side, but since they would close at the negative side no Gj change would occur. This is not the case with heterotypic channels between wild-type connexins paired with more gating-sensitive mutants. Most Ca-CaM-Cork gated channels reopen with a drop in [Ca2+]i to resting values (<50 nM). However, with prolonged exposure to high [Ca2+]i, channel gating may not be reversible. Many questions still need to be answered in terms of molecular details, such as: Is CaM anchored to the NT or the CL2 domain? Is CaM anchored to connexins by the C-lobe or the N-lobe? Is the gating lobe the N-lobe or the C-lobe? Does the gating lobe bind to the CL2 or the NT CaM binding site? Are all of the CaMs anchored to a connexon Ca2+-activated? If so, how many lobes gate the channel? Does CaM activation cause connexin conformational changes?
  • 1.3K
  • 17 Jul 2020
Topic Review
Large Rab GTPases
Rab GTPases are major coordinators of intracellular membrane trafficking, including vesicle transport, membrane fission, tethering, docking, and fusion events. Rab GTPases are roughly divided into two groups: conventional “small” Rab GTPases and atypical “large” Rab GTPases that have been recently reported. Some members of large Rab GTPases in mammals include Rab44, Rab45/RASEF, and Rab46. The genes of these large Rab GTPases commonly encode an amino-terminal EF-hand domain, coiled-coil domain, and the carboxyl-terminal Rab GTPase domain. A common feature of large Rab GTPases is that they express several isoforms in cells. For instance, Rab44’s two isoforms have similar functions, but exhibit differential localization. The long form of Rab45 (Rab45-L) is abundantly distributed in epithelial cells. The short form of Rab45 (Rab45-S) is predominantly present in the testes. Both Rab46 (CRACR2A-L) and the short isoform lacking the Rab domain (CRACR2A-S) are expressed in T cells, whereas Rab46 is only distributed in endothelial cells. Although evidence regarding the function of large Rab GTPases has been accumulating recently, there are only a limited number of studies. Here, we report the recent findings on the large Rab GTPase family concerning their function in membrane trafficking, cell differentiation, related diseases, and knockout mouse phenotypes.
  • 1.3K
  • 16 Aug 2021
Topic Review
Bile Salt Hydrolases
Bile salt hydrolase (BSH; EC 3.5.1.24) is an enzyme produced by the intestinal microbiota that catalyzes the hydrolysis of amide bonds in conjugated BAs, resulting in the release of free amino acids. These enzymes belong to the N-terminal nucleophilic (Ntn) hydrolase superfamily and share a similar αββα-core structure to an N-terminal catalytic cysteine residue. This residue is critical to the catalysis mechanism and acts both as a nucleophile and a proton donor. The N-terminal amino group serves as the proton acceptor and activates the nucleophilic thiol group of the cysteine side chain. Besides the cysteine residue, other amino acids conserved in most BSHs are also relevant to the catalytic reaction, including Arg18, Asp21, Asn82, Asn175, and Arg228.
  • 1.3K
  • 27 May 2021
Topic Review
PPAR Alpha
Peroxisome proliferator-activated receptor α is a potent regulator of systemic and cellular metabolism and energy homeostasis, but it also suppresses various inflammatory reactions.
  • 1.3K
  • 19 Oct 2021
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