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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
Alternative Splicing and Isoforms
Alternative splicing of pre-mRNA is a key mechanism for increasing the complexity of proteins in humans, causing a diversity of expression of transcriptomes and proteomes in a tissue-specific manner. Alternative splicing is an essential process in post-transcriptional mRNA processing, and produces various mature mRNAs with different structures and functions.
  • 1.3K
  • 10 Mar 2022
Topic Review
Talazoparib and Niraparib
Niraparib (MK-4827) inhibits PARP1 and PARP2. It was approved by the U.S. Food and Drug Administration (FDA) in March 2017 indicated for the therapy of adult patients with ovarian, fallopian tube and peritoneal neoplasms. Talazoparib (BMN 673) is a potent and selective inhibitor of PARP1 and PARP2 used at lower concentrations than previous generations of PARP inhibitors. The FDA approved Talazoparib in October 2018 for patients with germline BRCA-mutated, HER2-negative breast cancer. Poly (ADP-ribose) polymerases (PARP) play an essential role in different cellular processes, including several pathways of DNA repair. PARP inhibitors (PARPi) are able to impair DNA damage repair by non-homologous end joining (NHEJ). This effect depends on the cell´s ability to compensate for the inhibition of PARP-mediated pathways by other repair pathways. PARPi especially induce cell death in cancer cells with a lack of PARP-independent DNA repair pathways.
  • 1.3K
  • 25 Jun 2021
Topic Review
FTO Dioxygenase
The FTO (FaT mass and Obesity-associated) protein is an alpha-ketoglutarate and iron dependent dioxygenase, a member of ALKBH family proteins. FTO removes the methyl groups from modified nucleotides on single stranded DNA or RNA with N6-methyladenozine in the mRNA removed most efficiently. It is engaged in wide range of key physiological processes such as adipogenesis, cell cycle progression, heart remodelling, neural development and osteogenesis. Impairments of FTO activity is lethal or leads to serious developmental disorders. It is also one of the factors responsible for development and maintenance of many type of cancers. FTO acts in cooperation with other proteins e.g. CaMKII, MRS, SFPQ or XPO2. Similarly to other dioxygenases, it shows ability to form homodimer. Recently, it was shown that FTO interacts with the calmodulin (CaM) in Ca2+ dependent manner.
  • 1.3K
  • 26 Oct 2021
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
LncRNAs
Chemo and radiation therapies are the most commonly used therapies for cancer, but they can induce DNA damage, resulting in the apoptosis of host cells. DNA double-stranded breaks (DSBs) are the most lethal form of DNA damage in cells, which are constantly caused by a wide variety of genotoxic agents, both environmentally and endogenously. To maintain genomic integrity, eukaryotic organisms have developed a complex mechanism for the repair of DNA damage. Researches reported that many cellular long noncoding RNAs (lncRNAs) were involved in the response of DNA damage. The roles of lncRNAs in DNA damage response can be regulated by the dynamic modification of N6-adenosine methylation (m6A). The cellular accumulation of DNA damage can result in various diseases, including cancers. Additionally, lncRNAs also play roles in controlling the gene expression and regulation of autophagy, which are indirectly involved with individual development. The dysregulation of these functions can facilitate human tumorigenesis. In this review, we summarized the origin and overview function of lncRNAs and highlighted the roles of lncRNAs involved in the repair of DNA damage.
  • 1.3K
  • 03 Feb 2021
Topic Review
Calcium Dyshomeostasis in Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder that is characterized by amyloid β-protein deposition in senile plaques, neurofibrillary tangles consisting of abnormally phosphorylated tau protein, and neuronal loss leading to cognitive decline and dementia. Despite extensive research, the exact mechanisms underlying AD remain unknown and effective treatment is not available. Many hypotheses have been proposed to explain AD pathophysiology; however, there is general consensus that the abnormal aggregation of the amyloid β peptide (Aβ) is the initial event triggering a pathogenic cascade of degenerating events in cholinergic neurons. The dysregulation of calcium homeostasis has been studied considerably to clarify the mechanisms of neurodegeneration induced by Aβ. Intracellular calcium acts as a second messenger and plays a key role in the regulation of neuronal functions, such as neural growth and differentiation, action potential, and synaptic plasticity. The calcium hypothesis of AD posits that activation of the amyloidogenic pathway affects neuronal Ca2+ homeostasis and the mechanisms responsible for learning and memory. Aβ can disrupt Ca2+ signaling through several mechanisms, by increasing the influx of Ca2+ from the extracellular space and by activating its release from intracellular stores. Here, we review the different molecular mechanisms and receptors involved in calcium dysregulation in AD and possible therapeutic strategies for improving the treatment.
  • 1.3K
  • 11 Oct 2021
Topic Review
Topical Insulin Delivery
Insulin is one of the cheapest growth factors in the market able to accelerate the re-epithelialization and stimulate angiogenesis and cell migration. However, the effectiveness of topical insulin in wound healing is hampered by the proteases in the wound bed. The encapsulation into nanoparticles improves its stability in the wound, providing adhesion to the mucosal surface and allowing its sustained release. 
  • 1.3K
  • 13 Sep 2021
Topic Review
Vitamin D and Primary Ciliary Dyskinesia
Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. Low plasmatic level of this vitamin is present in the PCD population. The utility of vitamin D supplementation may be essential in this group of individuals.
  • 1.3K
  • 04 Nov 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
Irisin and Autophagy: First Update
Aging and sedentary life style are considered independent risk factors for many disorders. Under these conditions, accumulation of dysfunctional and damaged cellular proteins and organelles occurs, resulting in a cellular degeneration and cell death. Autophagy is a conserved recycling pathway responsible for the degradation, then turnover of cellular proteins and organelles. This process is a part of the molecular underpinnings by which exercise promotes healthy aging and mitigate age-related pathologies. Irisin is a myokine released during physical activity and acts as a link between muscles and other tissues and organs. Its main beneficial function is the change of subcutaneous and visceral adipose tissue into brown adipose tissue, with a consequential increase in thermogenesis. Irisin modulates metabolic processes, acting on glucose homeostasis, reduces systemic inflammation, maintains the balance between resorption and bone formation, and regulates the functioning of the nervous system. Recently, some of its pleiotropic and favorable properties have been attributed to autophagy induction, posing irisin as an important regulator of autophagy by exercise.
  • 1.3K
  • 29 Oct 2020
Topic Review
Polyphenoloxidase (PPO)
Fresh-cut produce are quite popular among consumers due to their eating ease, high quality and functional content. However, some of the processing steps taking place during minimal processing (such as cutting, peeling, draining, etc.) might speed up decay, e.g., microbial growth, dehydration or browning. When it comes to the latter, polyphenol oxidase (PPO) plays an important role, being the center of many works focused on the understanding of its reaction mechanism and the application of conservative techniques. The aim of this review study was to compare recent research about the effect of PPO on minimally processed fruits and vegetables, trying to understand the way it acts, the measurement of its activity and current treatments, such as modified atmosphere packaging, washing treatments or edible coatings, among others. In conclusion, the combination of conservation techniques (that is, hurdle technology) is vital to guarantee global quality in minimally processed fruits and vegetables, including synergistic effects which will allow the use of mild treatment conditions to decrease PPO activity. However, further research is required to clearly understand PPO inhibition in trendy techniques such as irradiation. 
  • 1.3K
  • 10 Sep 2021
Topic Review
Marine Algae Polysaccharide in Gut Microbiota
Cardiovascular disease (CVD) is the number one cause of death worldwide. Evidence has demonstrated an association between the gut microbiota and CVD, including heart failure, cerebrovascular illness, hypertension, and stroke. Marine algal polysaccharides (MAPs) are valuable natural sources of diverse bioactive compounds. MAPs have many pharmaceutical activities, including antioxidant, anti-inflammatory, immunomodulatory, and antidiabetic effects. 
  • 1.3K
  • 28 Nov 2022
Topic Review
Deep Learning Architectures from A Genomic Perspective
The data explosion driven by advancements in genomic research, such as high-throughput sequencing techniques, is constantly challenging conventional methods used in genomics. In parallel with the urgent demand for robust algorithms, deep learning has succeeded in various fields such as vision, speech, and text processing.
  • 1.3K
  • 08 Nov 2023
Topic Review
CLMS application for protein interfaces
The fundamentals of how protein–protein/RNA/DNA interactions influence the structures and functions of the workhorses from the cells have been well documented in the 20th century. A diverse set of methods exist to determine such interactions between different components, particularly, the mass spectrometry (MS) methods, with its advanced instrumentation, has become a significant approach to analyze a diverse range of biomolecules, as well as bring insights to their biomolecular processes. Cross-linking mass spectrometry (CLMS) holds promise to identify interaction sites in larger and more complex biological systems.
  • 1.3K
  • 16 Mar 2021
Topic Review
Polyphenols Nano Formulations
Polyphenols are phytochemical with potent antioxidant and antiinflammatory activities which are tremendously of important to fight premature aging, infections, cancers and other related chronic inflammatory diseases. Nanoencapsulation of these natural and functional biocompounds is useful to increase the bioavailability and efficiency of polyphenols, which can be further used as adjuvant therapeutics.
  • 1.3K
  • 26 Nov 2020
Topic Review
The Zinc-Sensing Receptor GPR39
GPR39, also known as ZnR (zinc sensing receptor), is a member of a large family A of 7-transmembrane (7-TM) containing G protein-coupled receptors (GPCRs).
  • 1.3K
  • 05 May 2021
Topic Review
Evaluating Enzymatic Productivity
Kinetic productivity analysis is critical to the characterization of enzyme catalytic performance and capacity. Enzymatic productivity is a measure of product formation or substrate disappearance over time, at a prescribed temperature under specified reaction conditions. It is the only measure which reliably summarizes the durability and reaction yield (a measure of the conversion of substrate) of an enzymatic process. Kinetic productivity analysis can be employed to assess the catalytic capacity of genetically and chemically modified variants, whole cells, the effect of immobilization carriers on productivity, difference between isoforms isolated from a range of organisms or tissues, and the effect of reaction solution additives.
  • 1.3K
  • 08 Jul 2022
Topic Review
SRC-3
Steroid receptor coactivator-3 (SRC-3), also known as amplified in breast cancer 1 (AIB1), is a member of the SRC family. SRC-3 regulates not only the transcriptional activity of nuclear receptors but also many other transcription factors. Besides the essential role of SRC-3 in physiological functions, it also acts as an oncogene to promote multiple aspects of cancer.
  • 1.3K
  • 25 May 2021
Topic Review
Impact of TRAP1 on Cancer Metabolism
The Hsp90 chaperone TNF-receptor-associated protein-1 (TRAP1) is primarily localized to the mitochondria and controls both cellular metabolic reprogramming and mitochondrial apoptosis. TRAP1 upregulation facilitates the growth and progression of many cancers by promoting glycolytic metabolism and antagonizing the mitochondrial permeability transition that precedes multiple cell death pathways. TRAP1 attenuation induces apoptosis in cellular models of cancer, identifying TRAP1 as a potential therapeutic target in cancer. Similar to cytosolic Hsp90 proteins, TRAP1 is also subject to post-translational modifications (PTM) that regulate its function and mediate its impact on downstream effectors, or ‘clients’.
  • 1.3K
  • 08 Jun 2022
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