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Small-conductance Ca2+-activated K+ channels (SK, KCa2) are gated solely by intracellular microdomain Ca2+. The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin (CaM) interacts with the CaM binding domain (CaMBD) of the SK channels, serving as the obligatory Ca2+ sensor to gate the channels. In heterologous expression systems, phosphatidylinositol 4,5-bisphosphate (PIP2) coordinates with CaM in regulating SK channels. However, the roles and mechanisms of PIP2 in regulating SK channels in cardiomyocytes remain unknown. Here, optogenetics, magnetic nanoparticles, combined with Rosetta structural modeling, and molecular dynamics (MD) simulations revealed the atomistic mechanisms of how PIP2 works in concert with Ca2+-CaM in the SK channel activation. Our computational study affords evidence for the critical role of the amino acid residue R395 in the S6 transmembrane segment, which is localized in propinquity to the intracellular hydrophobic gate. This residue forms a salt bridge with residue E398 in the S6 transmembrane segment from the adjacent subunit. Both R395 and E398 are conserved in all known isoforms of SK channels. Our findings suggest that the binding of PIP2 to R395 residue disrupts the R395:E398 salt bridge, increasing the flexibility of the transmembrane segment S6 and the activation of the channel. Importantly, our findings serve as a platform for testing of structural-based drug designs for therapeutic inhibitors and activators of the SK channel family. The study is timely since inhibitors of SK channels are currently in clinical trials to treat atrial arrhythmias.

Human voltage-gated sodium (hNaV) channels are responsible for initiating and propagating action potentials in excitable cells, and mutations have been associated with numerous cardiac and neurological disorders. hNaV1.7 channels are expressed in peripheral neurons and are promising targets for pain therapy. The tarantula venom peptide protoxin-II (PTx2) has high selectivity for hNaV1.7 and is a valuable scaffold for designing novel therapeutics to treat pain. Here, we used computational modeling to study the molecular mechanisms of the state-dependent binding of PTx2 to hNaV1.7 voltage-sensing domains (VSDs). Using Rosetta structural modeling methods, we constructed atomistic models of the hNaV1.7 VSD II and IV in the activated and deactivated states with docked PTx2. We then performed microsecond-long all-atom molecular dynamics (MD) simulations of the systems in hydrated lipid bilayers. Our simulations revealed that PTx2 binds most favorably to the deactivated VSD II and activated VSD IV. These state-specific interactions are mediated primarily by PTx2's residues R22, K26, K27, K28, and W30 with VSD and the surrounding membrane lipids. Our work revealed important protein-protein and protein-lipid contacts that contribute to high-affinity state-dependent toxin interaction with the channel. The workflow presented will prove useful for designing novel peptides with improved selectivity and potency for more effective and safe treatment of pain.

This article describes a simple setup of electrospinning using widely available resources. The Arduino board, an electronic platform that is commonly accessible was adapted for a controller. Specifically, recycled parts consisting of plastic gears and a lipstick case were incorporated for the construction of a syringe pump. A cheap DC-DC converter was utilized to provide a high voltage supply for stretching of a polymer solution. In order to test the performance of the setup, we obtained the electrospinning fibres with cigarette filter tips dissolved in acetone and liquid glue. The analysis results indicated the average diameter of fibres ~3.7 ± 0.5 [mu]m and ~2.8 ± 0.3 [mu]m, respectively. The whole process of controlling can be automatically conducted by a simple application written in DELPHI 7.0 language. It could serve as a form of research project to improve students' lab experience.

This article describes a simple way to introduce nanomaterials using the presence of carbon nanodots (CNDs) in widely available food. Budweiser® beer and Coca-Cola®, commercial foods that are commonly accessible, were utilized to demonstrate the optical property of nanoparticles. Specifically, green and violet laser pointers were employed for the observation of excitation-dependent photoluminescence of CNDs. To represent the application of CNDs, we obtained multiple-color emissions in onion cells that were imaged by using Budweiser beer and Coca-Cola as a dye. The demonstration could offer a perspective on the use of food in teaching nanomaterials at the high school and undergraduate levels.

The article aims to compare the properties and quality of two types of organic Japanese soy sauce from the market, declared by manufacturers as koikuchi, and tamari, both conventional and organic, along with an attempt to determine the differentiating factors using modern statistical methods. The amino acid profile showed the highest proportions were glutamic acid and aspartic acid. Tamari sauces could be distinguished from koikuchi by an elevated content of glutamic acid and alanine, while conventional and organic products differed the most in the shares of arginine, aspartic acid, and serine. The total polyphenol content was higher in conventional soy sauces and better antioxidant properties were found in koikuchi. Organic tamari sauces were characterized by higher antioxidant capacities and total flavonoid content. The volatile profile showed a significant difference between organic and conventional sauces. The research did not confirm that the quality of sauces declared as organic was significantly enhanced, and the overall quality of all tested sauces was high, both in terms of microbiological safety and physicochemical parameters.

Trong nghiên cứu này, chúng tôi tiến hành chế tạo vật liệu hạt cacbon nano (CDs) từ hạt đậu xanh bằng phương pháp thủy nhiệt. Vật liệu CDs chế tạo được có đường kính trung bình d = 13,8 nm. Kết quả khảo sát phổ hấp thụ cho thấy đỉnh đặc trưng ở bước sóng l = 280 nm, ứng với chuyển dịch n → π* của liên kết C=O. Các hạt CDs phát bức xạ dạng phổ rộng trong vùng 320–460 nm khi thay đổi bước sóng kích thích. Hơn nữa, sử dụng quinine sulfate làm dung dịch đối chứng và áp dụng phương pháp so sánh, chúng tôi đã bước đầu tính được giá trị hiệu suất lượng tử của dung dịch cacbon nano (12,18%). Đây là giá trị hiệu suất lượng tử khá cao khi so sánh với hạt cacbon nano chế tạo từ các nguồn nguyên liệu khác.

Small-conductance Ca2+-activated K+ channels (SK, KCa²) are gated solely by intracellular microdomain Ca2+. The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin (CaM) interacts with the CaM binding domain (CaMBD) of the SK channels, serving as the obligatory Ca2+ sensor to gate the channels. In heterologous expression systems, phosphatidylinositol 4,5-bisphosphate (PIP2) coordinates with CaM in regulating SK channels. However, the roles and mechanisms of PIP2 in regulating SK channels in cardiomyocytes remain unknown. Here, optogenetics, magnetic nanoparticles, combined with Rosetta structural modeling, and molecular dynamics (MD) simulations revealed the atomistic mechanisms of how PIP2 works in concert with Ca2+-CaM in the SK channel activation. Our computational study affords evidence for the critical role of the amino acid residue R395 in the S6 transmembrane segment, which is localized in propinquity to the intracellular hydrophobic gate. This residue forms a salt bridge with residue E398 in the S6 transmembrane segment from the adjacent subunit. Both R395 and E398 are conserved in all known isoforms of SK channels. Our findings suggest that the binding of PIP2 to R395 residue disrupts the R395:E398 salt bridge, increasing the flexibility of the transmembrane segment S6 and the activation of the channel. Importantly, our findings serve as a platform for testing of structural-based drug designs for therapeutic inhibitors and activators of the SK channel family. The study is timely since inhibitors of SK channels are currently in clinical trials to treat atrial arrhythmias. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of medium and large arteries leading to cranial and extracranial manifestations. Temporal artery biopsy is considered the gold standard; however, its sensitivity is low at 47%. We report a unique case of Bing–Neel Syndrome (BNS) presenting as biopsy‐proven GCA. BNS is a rare complication (1%) of Waldenstrom Macroglobulinemia (WM), which results from infiltration of lymph plasmacytoid cells and plasma cells into the central nervous system. A 77‐year‐old female with a past medical history of glaucoma, hypertension, diabetes, and chronic ocular ischemic syndrome in her right eye presented with progressive left eye vision loss for 5 days. Fundoscopic examination was notable for pseudophakic pseudopallor but no optic disc edema. Intraocular pressure was >40 and normalized after acetazolamide. The patient was started on pulse dose steroids by her neuro‐ophthalmologist. She was discharged home on 60 mg of prednisone. At follow up with her neuro‐ophthalmologist, new dot blot hemorrhages in the left eye were noted and she was readmitted for pulse dose of intravenous methylprednisolone. Temporal artery biopsy was consistent with GCA spectrum. Work up revealed paraproteinemia and subsequent bone marrow biopsy demonstrated WM. The patient was treated for her WM and her ophthalmic complications stabilized. [ABSTRACT FROM AUTHOR]

In this study, we describe a method to employ a conventional compound light microscope, usually available in laboratories, to obtain fluorescence. In particular, two pieces of colored acrylic plastic were utilized to assist the microscope in filter performance. We also attempted to examine the applicability of the setup by staining onion cells with highlighter ink. This activity is intended to serve as an experiment for life sciences courses using physics-based methods in a biological context. This setup has the advantages of ease of use and low cost.

The article aims to compare the properties and quality of two types of organic Japanese soy sauce from the market, declared by manufacturers as koikuchi, and tamari, both conventional and organic, along with an attempt to determine the differentiating factors using modern statistical methods. The amino acid profile showed the highest proportions were glutamic acid and aspartic acid. Tamari sauces could be distinguished from koikuchi by an elevated content of glutamic acid and alanine, while conventional and organic products differed the most in the shares of arginine, aspartic acid, and serine. The total polyphenol content was higher in conventional soy sauces and better antioxidant properties were found in koikuchi. Organic tamari sauces were characterized by higher antioxidant capacities and total flavonoid content. The volatile profile showed a significant difference between organic and conventional sauces. The research did not confirm that the quality of sauces declared as organic was significantly enhanced, and the overall quality of all tested sauces was high, both in terms of microbiological safety and physicochemical parameters. [ABSTRACT FROM AUTHOR]