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Topic Review
ClC-1 Chloride Channel Structure and Myotonia-Causing Mutations Update
Myotonia congenita is a hereditary muscle disease mainly characterized by muscle hyperexcitability, which leads to a sustained burst of discharges that correlates with the magnitude and duration of involuntary aftercontractions, muscle stiffness, and hypertrophy. Mutations in the chloride voltage-gated channel 1 (CLCN1) gene that encodes the skeletal muscle chloride channel (ClC-1) are responsible for this disease, which is commonly known as myotonic chloride channelopathy. The structure of the channel has been updated and the biophysical properties of the mutated channel have been explored and analyzed, providing important clues to the general function/dysfunction of the wild-type and mutated channels.
  • 866
  • 02 Nov 2023
Topic Review
Optical Biosensors for COVID-19 and Other Viruses Diagnosis
The sudden outbreak of the COVID-19 pandemic led to a huge concern globally because of the astounding increase in mortality rates worldwide. The medical imaging computed tomography technique, whole-genome sequencing, and electron microscopy are the methods generally used for the screening and identification of the SARS-CoV-2 virus.
  • 862
  • 28 Sep 2023
Topic Review
Metal-Based Nanoparticle-Mediated Biological Effects in Arabidopsis thaliana
The widespread application of metal-based nanoparticles (MNPs) has prompted great interest in nano-biosafety. Consequently, as more and more MNPs are released into the environment and eventually sink into the soil, plants, as an essential component of the ecosystem, are at greater risk of exposure and response to these MNPs. Therefore, to understand the potential impact of nanoparticles on the environment, their effects should be thoroughly investigated. Arabidopsis (Arabidopsis thaliana L.) is an ideal model plant for studying the impact of environmental stress on plants’ growth and development because the ways in which Arabidopsis adapt to these stresses resemble those of many plants, and therefore, conclusions obtained from these scientific studies have often been used as the universal reference for other plants.
  • 861
  • 11 Jul 2022
Topic Review
Elucidating Selenoprotein M Function from Structure
Selenocysteine (Sec), the 21st amino acid, is structurally similar to cysteine but with a sulfur to selenium replacement. This single change retains many of the chemical properties of cysteine but often with enhanced catalytic and redox activity. Incorporation of Sec into proteins is unique, requiring additional translation factors and multiple steps to insert Sec at stop (UGA) codons. These Sec-containing proteins (selenoproteins) are found in all three domains of life where they often are involved in cellular homeostasis (e.g., reducing reactive oxygen species). The essential role of selenoproteins in humans requires us to maintain appropriate levels of selenium, the precursor for Sec, in our diet. Too much selenium is also problematic due to its toxic effects. Deciphering the role of Sec in selenoproteins is challenging for many reasons, one of which is due to their complicated biosynthesis pathway. However, clever strategies are surfacing to overcome this and facilitate production of selenoproteins.
  • 855
  • 01 Nov 2023
Topic Review
The DNA Alkyltransferase Family of DNA Repair Proteins
DNA alkyltransferase and alkyltransferase-like family proteins are responsible for the repair of highly mutagenic and cytotoxic O6-alkylguanine and O4-alkylthymine bases in DNA. Their mechanism involves binding to the damaged DNA and flipping the base out of the DNA helix into the active site pocket in the protein. Alkyltransferases then directly and irreversibly transfer the alkyl group from the base to the active site cysteine residue. In contrast, alkyltransferase-like proteins recruit nucleotide excision repair components for O6-alkylguanine elimination. One or more of these proteins are found in all kingdoms of life, and where this has been determined, their overall DNA repair mechanism is strictly conserved between organisms.
  • 850
  • 19 Jan 2024
Topic Review
Amyloid Oligomers
Amyloid oligomers are considered to be potential targets for the development of therapeutic strategies for a wide range of neurodegenerative diseases. However, due to the low-populated, transient, and heterogeneous nature of amyloid oligomers, they are hard to characterize by conventional bulk methods. The development of single molecule approaches provides a powerful toolkit for investigating these oligomeric intermediates as well as the complex process of amyloid aggregation at molecular resolution.
  • 840
  • 21 Apr 2021
Topic Review
A New Paradigm for KIM-PTP Drug Discovery
The kinase interaction motif protein tyrosine phosphatases (KIM-PTPs), HePTP, PTPSL and STEP, are involved in the negative regulation of mitogen-activated protein kinase (MAPK) signalling pathways and are important therapeutic targets for a number of diseases. 
  • 839
  • 29 Mar 2022
Topic Review
Disruption of Claudin-Made Tight Junction Barriers by CpE
Claudins are a family of integral membrane proteins that enable epithelial cell/cell interactions by localizing to and driving the formation of tight junctions. Via claudin self-assembly within the membranes of adjoining cells, their extracellular domains interact, forming barriers to the paracellular transport of small molecules and ions. The bacterium Clostridium perfringens causes prevalent gastrointestinal disorders in mammals by employing an enterotoxin (CpE) that targets claudins. CpE binds to claudins at or near tight junctions in the gut and disrupts their barrier function, potentially by disabling their assembly or via cell signaling means—the mechanism(s) remain unclear.
  • 837
  • 10 Mar 2022
Topic Review
25-Hydroxycholesterol Effect on Membrane Properties
Cholesterol is responsible for the plasticity of plasma membranes and is involved in physiological and pathophysiological responses. Cholesterol homeostasis is regulated by oxysterols, such as 25-hydroxycholesterol. The presence of 25-hydroxycholesterol at the membrane level has been shown to interfere with several viruses’ entry into their target cells. We used atomic force microscopy to assess the effect of 25-hydroxycholesterol on different properties of supported lipid bilayers with controlled lipid compositions. In particular, we showed that 25-hydroxycholesterol inhibits the lipid-condensing effects of cholesterol, rendering the bilayers less rigid. This study indicates that the inclusion of 25-hydroxycholesterol in plasma membranes or the conversion of part of their cholesterol content into 25-hydroxycholesterol leads to morphological alterations of the sphingomyelin (SM)-enriched domains and promotes lipid packing inhomogeneities. These changes culminate in membrane stiffness variations.
  • 832
  • 17 Mar 2021
Topic Review
Functional Near-Infrared Spectrometry
Functional Near-Infrared Spectroscopy (fNIRS) has emerged as a promising tool for understanding the human brain’s complex workings due to its ability to measure changes in oxygenated and deoxygenated hemoglobin levels, thus providing insights into neural activity and functional connectivity. fNIRS technology offers a novel approach to studying brain function, especially visual processing and perception. fNIRS offers unique advantages, such as portability, cost-effectiveness and safety, making it suitable for clinical and research applications. Additionally, the combination of fNIRS with emerging technologies like virtual reality (VR), augmented reality (AR) and artificial intelligence (AI) opens new avenues for immersive investigations into brain function.
  • 832
  • 29 Jan 2024
Topic Review
Biological Activity of C60,70 Fullerenols
The simplest bioassay based on a bioluminescent system of coupled enzyme reactions was used to study toxic and antioxidant effects of a water-soluble fullerene derivative, fullerenol, with 10-12 oxygen groups (F10-12) at the enzymatic level. Toxic and antioxidant characteristics of F10-12 were compared to those of homologous fullerenols with a higher number of oxygen groups: F24-28 and F40-42. An active role of reactive oxygen species (ROS) in the bioeffects of F10-12 was demonstrated.
  • 820
  • 11 Aug 2021
Topic Review
DGKα
Cancer immunotherapy has revolutionized the oncology field. Despite the success, new molecular targets are needed to increase the percentage of patients that benefits from this therapy. Diacylglycerol kinase α (DGKα) has gathered great attention as a potential molecular target in immunotherapy because of its role in cancer proliferation and immunosuppression. DGKα catalyzes the ATP-dependent phosphorylation of diacylglycerol (DAG) to produce phosphatidic acid (PA). Since both lipids are potent signaling messengers, DGKα acts as a switch between different signaling pathways. Its role in cancer and immunosuppression has long been ascribed to the regulation of DAG/PA levels. However, this paradigm has been challenged with the identification of DGKα substrate acyl chain specificity, which suggests its role in signaling could be specific to DAG/PA molecular species. In several biological processes where DGKα plays a role, large membrane morphological changes take place. DGKα substrate specificity depends on the shape of the membrane that the enzyme binds to. 
  • 820
  • 15 Nov 2022
Topic Review
Nuclear Magnetic Resonance Applications on Bovine Milk
Nuclear magnetic resonance (NMR) spectroscopy is emerging as a promising technique for the analysis of bovine milk, primarily due to its non-destructive nature, minimal sample preparation requirements, and comprehensive approach to untargeted milk analysis. These inherent strengths of NMR make it a formidable complementary tool to mass spectrometry-based techniques in milk metabolomic studies.
  • 819
  • 15 Sep 2023
Topic Review
The Cell Nucleus as a Multiscale Porous Medium
Chromatin regulatory processes physically take place in the environment of the cell nucleus, which is filled with the chromosomes and a plethora of smaller biomolecules. The nucleus contains macromolecular assemblies of different sizes, from nanometer-sized protein complexes to micrometer-sized biomolecular condensates, chromosome territories, and nuclear bodies. This multiscale organization impacts the transport processes within the nuclear interior, the global mechanical properties of the nucleus, and the way the nucleus senses and reacts to mechanical stimuli. 
  • 814
  • 10 Aug 2023
Topic Review
Circulating Tumour Cells
Cancer is one of the dreaded diseases to which a sizeable proportion of the population succumbs every year. Circulating tumour cells (CTCs) have grabbed the attention of researchers in the detection of metastasis and there has been a huge surge in the surrounding research activities. Acting as a biomarker, CTCs prove beneficial in a variety of aspects. Nanomaterial-based strategies have been devised to have a tremendous impact on the early and rapid examination of tumor cells.
  • 810
  • 01 Feb 2023
Topic Review
Tetraoctylammonium
Alkylammonium salts have been used extensively to study the structure and function of potassium channels. Here, we use the long-chain, hydrophobic tetraoctylammonium (TOA+) to shed light on the structure of the inactivated state of KcsA, a tetrameric prokaryotic potassium channel. By the combined use of a thermal denaturation assay and the analysis of homo-Förster resonance energy transfer in a mutant channel containing a single tryptophan (W67) per subunit, we found that TOA+ binds the channel cavity with high affinity, either with the inner gate open or closed. Moreover, bound TOA+ induces a decrease in the affinity for K+ in the two characteristic K+ binding events to the channel selectivity filter at pH 7.0, when the channel inner gate is in the closed conformation. This is similar to that observed in the absence of TOA+ upon acidic-pH-induced channel inactivation. Therefore, this suggests that TOA+ binding by itself causes inactivation at pH 7.0 when the inner gate is closed. Furthermore, in apparent agreement with such conclusion, the presence of bound TOA+ in the pH 4.0 samples has only modest effects on the affinity of the two binding events for K+, likely because the channel is already inactivated. Finally, we also observed that TOA+ bound at the cavity, allosterically modifies the conformation of the pore helices, leading to longer W67-W67 intersubunit distances at any K+ concentration and both at pH 7.0 and pH 4.0. The changes in the pore helix conformation, along with the decreased affinity for K+ at pH 7.0 caused by TOA+, seen in both homo-FRET and thermal denaturation experiments, are very similar to those effects caused by inactivation at pH 4.0.
  • 809
  • 30 Apr 2021
Topic Review
The Gene Family of Voltage-Gated ChLoride Channels
Endosomes and lysosomes are intracellular vesicular organelles with important roles in cell functions such as protein homeostasis, clearance of extracellular material, and autophagy. Endolysosomes are characterized by an acidic luminal pH that is critical for proper function. Five members of the gene family of voltage-gated ChLoride Channels (CLC proteins) are localized to endolysosomal membranes, carrying out anion/proton exchange activity and thereby regulating pH and chloride concentration. Mutations in these vesicular CLCs cause global developmental delay, intellectual disability, various psychiatric conditions, lysosomal storage diseases, and neurodegeneration, resulting in severe pathologies or even death. 
  • 808
  • 14 Jun 2023
Topic Review
Nanoscale Sub-Compartmentalization of the Dendritic Spine Compartment
Compartmentalization of the membrane is essential for cells to perform highly specific tasks and spatially constrained biochemical functions in topographically defined areas. These membrane lateral heterogeneities range from nanoscopic dimensions, often involving only a few molecular constituents, to micron-sized mesoscopic domains resulting from the coalescence of nanodomains. Short-lived domains lasting for a few milliseconds coexist with more stable platforms lasting from minutes to days. This panoply of lateral domains subserves the great variety of demands of cell physiology, particularly high for those implicated in signaling. The dendritic spine, a subcellular structure of neurons at the receiving (postsynaptic) end of central nervous system excitatory synapses, exploits this compartmentalization principle. In its most frequent adult morphology, the mushroom-shaped spine harbors neurotransmitter receptors, enzymes, and scaffolding proteins tightly packed in a volume of a few femtoliters. In addition to constituting a mesoscopic lateral heterogeneity of the dendritic arborization, the dendritic spine postsynaptic membrane is further compartmentalized into spatially delimited nanodomains that execute separate functions in the synapse. 
  • 805
  • 30 Nov 2021
Topic Review
Amyloid Pathologies
Protein aggregation into amyloid fibrils affects many proteins in a variety of diseases, including neurodegenerative disorders, diabetes, and cancer. Physicochemically, amyloid formation is a phase transition process, where soluble proteins are transformed into solid fibrils with the characteristic cross-β conformation responsible for their fibrillar morphology.
  • 804
  • 11 Apr 2022
Topic Review
Protein Ser/Thr Phosphatase Folding
Post-translational modification (PTM) is a key mechanism providing the functional diversity of proteins in cellular signaling and physiology and changing the functions or stability of proteins. 
  • 800
  • 25 Jul 2023
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