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Topic Review
CRISPR FokI Dead Cas9 System
FokI–dCas9 (fdCas9) or RNA-guided FokI nuclease (RFN) is a genome editing tool engineered by fusing  the catalytic domain of the FokI endonuclease to the N-terminal catalytic inactive Cas9 protein. The fdCas9 system is active only as a heterodimer, requiring the simultaneous binding of two fdCas9/sgRNAs monomers at adjacent target sites in a PAM-out orientation, and a specific spacer distance separating the two binding sites of the two sgRNAs. The five engineered and published constructs induce significant gene editing activities and specificities, as tested on various gene targets and overcome the off-target effects associated with other genome editing tools, including ZFNs, TALENs, and CRISPR/Cas systems.
  • 2.0K
  • 30 Nov 2020
Topic Review
TGF-β Signaling in Tumor Microenvironment
Transforming growth factor-β (TGF-β) signaling triggers diverse biological actions in inflammatory diseases. In tissue fibrosis, it acts as a key pathogenic regulator for promoting immunoregulation via controlling the activation, proliferation, and apoptosis of immunocytes. In cancer, it plays a critical role in tumor microenvironment (TME) for accelerating invasion, metastasis, angiogenesis, and immunosuppression. Increasing evidence suggest a pleiotropic nature of TGF-β signaling as a critical pathway for generating fibrotic TME, which contains numerous cancer-associated fibroblasts, extracellular matrix proteins, and remodeling enzymes. Better understanding the underlying mechanisms may uncover novel therapeutic targets for cancer.
  • 1.9K
  • 28 Jul 2021
Topic Review
Histone deacetylase (HDAC)
Histone deacetylase (HDAC) enzymes play crucial roles in epigenetic gene expression and are an attractive therapeutic target. Five HDAC inhibitors have been approved for cancer treatment to date, however clinical applications have been limited due to poor single agent drug efficacy and side effects associated with a lack of HDAC isoform or complex selectivity. An emerging strategy aiming to address these limitations is the development of bifunctional HDAC therapeutics – single molecules comprising a HDAC inhibitor conjugated to another specificity targeting moiety. There has been many recent advancements in novel types of dual-targeting HDAC modulators, including PROTACs, often achieving high HDAC isoform selectivity, as well as some dual inhibitor examples affording HDAC complex selectivity. Such bifunctional molecules have future potential in achieving enhanced drug efficacy and therapeutic benefits in treating disease.
  • 1.9K
  • 12 Oct 2020
Topic Review
PAX5 Expression and Regulation
PAX5, a member of the Paired Box (PAX) transcription factor family, is an essential factor for B-lineage identity during lymphoid differentiation. Mechanistically, PAX5 controls gene expression profiles, pivotal to cellular processes such as viability, proliferation, and differentiation. Given its crucial function in B-cell development, PAX5 aberrant expression also correlates with hallmark cancer processes leading to hematological and other types of cancer lesion.
  • 1.9K
  • 26 Sep 2022
Topic Review
HSP90 inhibitors for IPF/COVID-19
Heat shock protein 90 (HSP90) is an important chaperone that assists the late stage folding of several proteins involved in cell survival in response to environmental stressors. The inhibition of HSP90 is followed by a complex modulation of the proteome and the kinome, that has proved beneficial in cancer and various neurodegenerative diseases. Additionally, accumulating literature suggests that HSP90 may be a key target during the development of pulmonary fibrosis and that its inhibition could serve as a new and exciting therapeutic approach. We have summarized the current evidence about HSP90’s role in Idiopathic Pulmonary Fibrosis (IPF), the results from preclinical studies on its inhibition and the intracellular signaling pathways involved, in a recent review article (Review). In this Article entry, we will introduce the main findings discussed in the review and focus on its translation and possible significance in the era of the SARS-CoV-2 pandemic.
  • 1.9K
  • 07 Aug 2020
Topic Review
Development of Rudimentary Structure of Mammary Gland
The mammary gland is a compound, branched tubuloalveolar structure and a major characteristic of mammals. The mammary gland has evolved from epidermal apocrine glands, the skin glands as an accessory reproductive organ to support postnatal survival of offspring by producing milk as a source of nutrition. The mammary gland development begins during embryogenesis as a rudimentary structure that grows into an elementary branched ductal tree and is embedded in one end of a larger mammary fat pad at birth. At the onset of ovarian function at puberty, the rudimentary ductal system undergoes dramatic morphogenetic change with ductal elongation and branching. During pregnancy, the alveolar differentiation and tertiary branching are completed, and during lactation, the mature milk-producing glands eventually develop. The early stages of mammary development are hormonal independent, whereas during puberty and pregnancy, mammary gland development is hormonal dependent. The mammary gland develops as a rudimentary structure from a thickening under the ventral skin during embryogenesis. This rudimentary structure grows into a rudimentary branched ductal tree embedded in one end of a larger mammary fat pad at birth. The embryonic development of the mammary gland is a series of several hormone-independent specialized events.
  • 1.9K
  • 18 Apr 2022
Topic Review
Aldose Reductase
Aldose reductase (AR) is a member of the reduced nicotinamide adenosine dinucleotide phosphate (NADPH)-dependent aldo-keto reductase superfamily. It is also the rate-limiting enzyme of the polyol pathway, catalyzing the conversion of glucose to sorbitol, which is subsequently converted to fructose by sorbitol dehydrogenase. AR is highly expressed by Schwann cells in the peripheral nervous system (PNS). The excess glucose flux through AR of the polyol pathway under hyperglycemic conditions has been suggested to play a critical role in the development and progression of diabetic peripheral neuropathy (DPN).
  • 1.9K
  • 09 Feb 2021
Topic Review
COP9 Signalosome
The COP9 signalosome (CSN) is a regulator of the ubiquitin proteasome system (UPS). In mammalian cells it occurs as an eight-subunit protein complex, six Proteasome-COP9 signalosome-Initiation factor eIF3 (PCI)-domain subunits including CSN1-4, CSN7 and CSN8 and two MOV34-Pad1-N-terminal (MPN)-domain subunits called CSN5 and CSN6. The CSN regulates cullin-RING-ubiquitin ligases (CRLs) by specifically removing NEDD8 from cullins. In cooperation with CAND1 it controls the adaptation of the CRL network to fluctuations in substrate availability. The CSN complex belongs to the JAMM family of deubiquitylating enzymes (DUBs). In addition, it interacts with other deubiquitylating enzymes including USP15 and USP48 coordinating ubiquitylation and deubiquitylation activities.
  • 1.9K
  • 26 Oct 2020
Topic Review
Effect of Oral l-Carnitine Supplementation on Exercise Performance
l-Carnitine (l-C) and any of its forms (glycine-propionyl l-Carnitine (GPL-C) or l-Carnitine l-tartrate (l-CLT)) has been frequently recommended as a supplement to improve sports performance due to, among others, its role in fat metabolism and in maintaining the mitochondrial acetyl-CoA/CoA ratio. 
  • 1.9K
  • 15 Dec 2021
Topic Review
Autothermal Thermophilic Aerobic Digestion
Pembroke JT and MP Ryan.  Autothermal thermophilic aerobic digestion (ATAD) is a microbial fermentation process characterized as a tertiary treatment of waste material carried out in jacketed reactors. Heat is generated which selects a thermoduric microbial population. The process results in a stabilised, pasteurised sludge suitable for land application as a fertiliser. The microbial population biodegrades sludge contents, are unique in terms of diversity and have biotechnological potential as enzymes and proteins associated with the microbial population are thermostable. 
  • 1.9K
  • 24 Dec 2021
Topic Review
BH3-Only Proteins Noxa and Puma in Apoptosis Regulation
Apoptosis is an evolutionarily conserved and tightly regulated cell death pathway. Physiological cell death is important for maintaining homeostasis and optimal biological conditions by continuous elimination of undesired or superfluous cells. The BH3-only pro-apoptotic members are strong inducers of apoptosis. The pro-apoptotic BH3-only protein Noxa activates multiple death pathways by inhibiting the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family protein, Mcl-1, and other protein members leading to Bax and Bak activation and mitochondrial outer membrane permeabilization (MOMP). On the other hand, Puma is induced by p53-dependent and p53-independent apoptotic stimuli in several cancer cell lines. Moreover, this protein is involved in several physiological and pathological processes, such as immunity, cancer, and neurodegenerative diseases. Future heat shock research could disclose the effect of hyperthermia on both Noxa and BH3-only proteins. This suggests post-transcriptional mechanisms controlling the translation of both Puma and Noxa mRNA in heat-shocked cells. 
  • 1.9K
  • 10 Mar 2022
Topic Review
Carbohydrate-Binding Modules of Potential Resources
Carbohydrate-binding modules (CBMs) are a class of multi-module enzyme proteins and their function is to respond to bind to the carbohydrate substrate. Cellulose-binding domains (CBDs) are the earliest-discovered CBMs which were used to be catergozied based on their sequence homology. However, with the in-depth study of carbohydrate hydrolases, more modules in carbohydrate-active enzymes were discovered that could bind, in addition to cellulose, to other types of carbohydrates such as chitin, glucan, xylan, or starch. 
  • 1.9K
  • 07 May 2022
Topic Review
IP6K
Inositol and its phosphate metabolites play a pivotal role in several biochemical pathways and gene expression regulation: inositol pyrophosphates (PP-IPs) have been increasingly appreciated as key signaling modulators. Fluctuations in their intracellular levels hugely impact the transfer of phosphates and the phosphorylation status of several target proteins. Pharmacological modulation of the proteins associated with PP-IP activities has proved to be beneficial in various pathological settings. IP7 has been extensively studied and found to play a key role in pathways associated with PP-IP activities. Three inositol hexakisphosphate kinase (IP6K) isoforms regulate IP7 synthesis in mammals. Genomic deletion or enzymic inhibition of IP6K1 has been shown to reduce cell invasiveness and migration capacity, protecting against chemical-induced carcinogenesis. IP6K1 could therefore be a useful target in anticancer treatment.
  • 1.9K
  • 14 Oct 2020
Topic Review
D2 Dopamine Receptor (D2-R)
The type 2 dopamine receptor D2 (D2-R), member of the G protein-coupled receptor (GPCR) superfamily, exists in two isoforms, short (D2S-R) and long (D2L-R). They differ by an additional 29 amino acids (AA) in the third cytoplasmic loop (ICL3) of the D2L-R. These isoforms differ in their intracellular localization and trafficking functionality, as D2L-R possesses a larger intracellular pool, mostly in the endoplasmic reticulum (ER). 
  • 1.9K
  • 26 Oct 2020
Topic Review
Methods for Characterizing Protein S-Glutathionylation
Protein S-glutathionylation (SSG) is a reversible post-translational modification (PTM) featuring the conjugation of glutathione to a protein cysteine thiol. SSG can alter protein structure, activity, subcellular localization, and interaction with small molecules and other proteins. Thus, it plays a critical role in redox signaling and regulation in various physiological activities and pathological events. Many approaches have been developed for the detection of SSG, including direct detection, selective reduction and tagging approaches, and chemoselective probe-based approaches. Utilization of these methods in profiling the SSG proteome had been reported in various biological systems. 
  • 1.9K
  • 07 Dec 2022
Topic Review
Plant Synthetic Promoters Structure and Function
A promoter is the region of genomic DNA located upstream of a gene that initiates the process of transcription under specific cellular conditions. Structurally, it is modular in nature and comprises a core promoter that includes a TATA box and a CAAT box, as well as proximal and distal regions.
  • 1.9K
  • 28 Apr 2023
Topic Review
Extreme Microorganisms in the Context of Biogeochemical Nitrogen Cycle
Extreme microorganisms (extremophile) are organisms that inhabit environments characterized by inhospitable parameters for most live beings (extreme temperatures and pH values, high or low ionic strength, pressure, or scarcity of nutrients). To grow optimally under these conditions, extremophiles have evolved molecular adaptations affecting their physiology, metabolism, cell signaling, etc. Due to their peculiarities in terms of physiology and metabolism, they have become good models for (i) understanding the limits of life on Earth, (ii) exploring the possible existence of extraterrestrial life (Astrobiology), or (iii) to look for potential applications in biotechnology. Recent research has revealed that extremophilic microbes play key roles in all biogeochemical cycles on Earth. Nitrogen cycle (N-cycle) is one of the most important biogeochemical cycles in nature; thanks to it, nitrogen is converted into multiple chemical forms, which circulate among atmospheric, terrestrial and aquatic ecosystems. This review summarizes recent knowledge on the role of extreme microorganisms in the N-cycle in extremophilic ecosystems, with special emphasis on members of the Archaea domain. Potential implications of these microbes in global warming and nitrogen balance, as well as their biotechnological applications are also discussed.
  • 1.9K
  • 17 Jun 2020
Topic Review
Nuclear domains 10 (ND10)
Nuclear domains 10 (ND10), a.k.a. promyelocytic leukemia nuclear bodies (PML-NBs), are membraneless subnuclear domains that are highly dynamic in their protein composition in response to cellular cues. They are known to be involved in many key cellular processes including DNA damage response, transcription regulation, apoptosis, oncogenesis, and antiviral defenses.
  • 1.9K
  • 25 Mar 2021
Topic Review
Calcium Indicator NCaMP7
Green fluorescent genetically encoded calcium indicators (GECIs) are the most popular tool for visualization of calcium dynamics in vivo. However, most of them are based on the EGFP protein and have similar molecular brightnesses. The NTnC indicator, which is composed of the mNeonGreen fluorescent protein with the insertion of troponin C, has higher brightness as compared to EGFP-based GECIs, but shows a limited inverted response with an ΔF/F of 1. By insertion of a calmodulin/M13-peptide pair into the mNeonGreen protein, we developed a green GECI called NCaMP7. In vitro, NCaMP7 showed positive response with an ΔF/F of 27 and high affinity (Kd of 125 nM) to calcium ions. NCaMP7 demonstrated a 1.7-fold higher brightness and similar calcium-association/dissociation dynamics compared to the standard GCaMP6s GECI in vitro. According to fluorescence recovery after photobleaching (FRAP) experiments, the NCaMP7 design partially prevented interactions of NCaMP7 with the intracellular environment. The NCaMP7 crystal structure was obtained at 1.75Å resolution to uncover the molecular basis of its calcium ions sensitivity.The NCaMP7 indicator retained a high and fast response when expressed in cultured HeLa and neuronal cells. Finally, we successfully utilized the NCaMP7 indicator for in vivo visualization of grating-evoked and place-dependent neuronal activity in the visual cortex and the hippocampus of mice using a two-photon microscope and an NVista miniscope, respectively.
  • 1.9K
  • 26 Oct 2020
Topic Review
cAMP-Response Element Modulator in Spermatogenesis and Male Fertility
Spermatogenesis is a very complex process with an intricate transcriptional regulation. The transition from the diploid to the haploid state requires the involvement of specialized genes in meiosis, among other specific functions for the formation of the spermatozoon. The transcription factor cAMP-response element modulator (CREM) is a key modulator that triggers the differentiation of the germ cell into the spermatozoon through the modification of gene expression. CREM has multiple repressor and activator isoforms whose expression is tissue-cell-type specific and tightly regulated by various factors at the transcriptional, post-transcriptional and post-translational level. The activator isoform CREMτ controls the expression of several relevant genes in post-meiotic stages of spermatogenesis. In addition, exposure to xenobiotics negatively affects CREMτ expression, which is linked to male infertility. On the other hand, antioxidants could have a positive effect on CREMτ expression and improve sperm parameters in idiopathically infertile men.
  • 1.9K
  • 01 Nov 2023
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