Transient receptor potential vanilloid 1 (TRPV1) channels mediate several types of physiological responses. Despite the importance of these channels in pain detection and inflammation, little is known about how their structural components convert different types of stimuli into channel activity. To localize the activation gate of these channels, we inserted cysteines along the S6 segment of mutant TRPV1 channels and assessed their accessibility to thiol-modifying agents. We show that access to the pore of TRPV1 is gated by S6 in response to both capsaicin binding and increases in temperature, that the pore-forming S6 segments are helical structures and that two constrictions are present in the pore: one that impedes the access of large molecules and the other that hampers the access of smaller ions and constitutes an activation gate of these channels.

BackgroundThe Cavβ subunits of high voltage-activated Ca2+ channels control the trafficking and biophysical properties of the α1 subunit. The Cavβ-α1 interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that βs regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the α-interaction domain (AID) be a rigid structure.Methodology/Principal FindingsThe present study tests this hypothesis by altering the flexibility and orientation of this region in α12.2, then testing for Cavβ regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6). This mutation abolished β2a and β3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of β2a to produce non-inactivating currents. Orientation of Cavβ with respect to α12.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively). Again, the ability of Cavβ subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Cavβ subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms β-sheet. The orientation of β with respect to α was confirmed by the bimolecular fluorescence complementation assay.Conclusions/SignificanceThese results show that the orientation of the Cavβ subunit relative to the α12.2 subunit is critical, and suggests additional points of contact between these subunits are required for Cavβ to regulate channel activity.

Mutations in the I-II loop of Ca v 3.2 channels were discovered in patients with childhood absence epilepsy. All of these mutations increased the surface expression of the channel, whereas some mutations, and in particular C456S, altered the biophysical properties of channels. Deletions around C456S were found to produce channels that opened at even more negative potentials than control, suggesting the presence of a gating brake that normally prevents channel opening. The goal of the present study was to identify the minimal sequence of this brake and to provide insights into its structure. A peptide fragment of the I-II loop was purified from bacteria, and its structure was analyzed by circular dichroism. These results indicated that the peptide had a high ␣-helical content, as predicted from secondary structure algorithms. Based on homology modeling, we hypothesized that the proximal region of the I-II loop may form a helix-loophelix structure. This model was tested by mutagenesis followed by electrophysiological measurement of channel gating. Mutations that disrupted the helices, or the loop region, had profound effects on channel gating, shifting both steady state activation and inactivation curves, as well as accelerating channel kinetics. Mutations designed to preserve the helical structure had more modest effects. Taken together, these studies showed that any mutations in the brake, including C456S, disrupted the structural integrity of the brake and its function to maintain these low voltage-activated channels closed at resting membrane potentials.

In the actuality, there is an increasing trend to consume healthy/ super foods, such as Amaranth: a super crop of this millennium with high nutraceutical values. Amaranth can be considered as a "super food" because it is a gluten-free pseudo cereal that besides being a relevant source of vegetable protein, provides to the human diet, a balanced content of essential amino acids, significant amounts of calcium, dietary fiber, omega-3, omega-6, vitamins, minerals and antioxidants. The aim of this mini review is to provide insights into Amaranth´s health benefits such as helps to improve nutrition and health as it is a powerful vegetable protein source adequate to fight high cholesterol, avoids chronic inflammation, oxidative stress, osteoporosis, gastric problems, bad nutrition due to gluten intolerance, diabetes among others relevant diseases. Amaranth´s brief history This pseudo cereal "Amaranthus spp." is commonly called Amaranth, its name comes from the Greek word Amaranthus that means eternal flower and it is considered as an important nutritional crop. 1 Amaranth has been included in the human diet since long time ago by the pre-Columbian Mesoamerican among other ancient civilizations. 2 The Aztecs called Amaranth "Huautli" and the Mayas named it "Xtes". In the actuality, Mexicans make Amaranth sweets calling them "Alegría" meaning happiness. Now, around the World, Amaranth is being considered as a "super crop" as more evidence comes out demonstrating that is a rich nutrient pseudo cereal as shown herein. Around the 80's, Amaranth was considered by the U.S. National Academy of Sciences like an "underexploited tropical plant with promising economic value" 3 since then, research to know more about Amaranth properties has increased in order to gain insights into its nutritional and agronomic values. 4 Amaranth can be easily recognized among other crops as each plant has an "immortal colorful flower" that based in our own experience, contains around 1Kg of seeds as shown in Figure 1. Figure 1 (A) Amaranthus hypochondriacus plant and (B) Amaranth seeds. Nutritional properties: Amaranth is becoming to be a super food as its composition includes high quality of carbohydrates, dietary fiber, lipids as omega-3 and omega-6, essential amino acids and other important constituents, such as squalene, tocopherols, phenolic compounds, flavonoids, phytates, vitamins and minerals. Amaranth´s nutritional composition: Amaranthus spp. belongs to Amaranthaceae family and produces a pseudo-cereal grain. Amaranth seeds contain significant amounts of high-quality proteins, lipids, carbohydrates, dietary fiber, vitamins and minerals, as shown in Figure 2 & Table 1. An important nutritional fact is that besides containing a high amount of protein, Amaranth´s seeds help to have a balanced protein

Microalgae have demonstrated a large potential in biotechnology as a source of various macromolecules (proteins, carbohydrates, and lipids) and high-added value products (pigments, poly-unsaturated fatty acids, peptides, exo-polysaccharides, etc.). The production of biomass at a large scale becomes more economically feasible when it is part of a biorefinery designed within the circular economy concept. Thus, the aim of this critical review is to highlight and discuss challenges and future trends related to the multi-product microalgae-based biorefineries, including both phototrophic and mixotrophic cultures treating wastewater and the recovery of biomass as a source of valuable macromolecules and high-added and low-value products (biofertilizers and biostimulants). The therapeutic properties of some microalgae-bioactive compounds are also discussed. Novel trends such as the screening of species for antimicrobial compounds, the production of bioplastics using wastewater, the circular economy strategy, and the need for more Life Cycle Assessment studies (LCA) are suggested as some of the future research lines.

The Arc two-component system modulates the expression of numerous genes in response to respiratory growth conditions. This system comprises ArcA as the response regulator and ArcB as the sensor kinase. ArcB is a tripartite histidine kinase whose activity is regulated by the oxidation of two cytosol-located redox-active cysteine residues that participate in intermolecular disulfide bond formation. Here, we report that the ArcB protein segment covering residues 70–121, fulfills the molecular characteristics of a leucine zipper containing coiled coil structure. Also, mutational analyses of this segment reveal three different phenotypical effects to be distributed along the coiled coil structure of ArcB, demonstrating that this motif is essential for proper ArcB signaling.

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-Lagunas (2011) Induction of a fast inactivation gating on delayed rectifier Shab K + channels by the anti-inflammatory drug celecoxib , Channels, 5:1, 56-64,