Effective pore size and radius of capture for K+ ions in K-channels

Indexación: Web of Science; Scopus.Reconciling protein functional data with crystal structure is arduous because rare conformations or crystallization artifacts occur. Here we present a tool to validate the dimensions of open pore structures of potassium-selective ion channels. We used freely available algorithms to calculate the molecular contour of the pore to determine the effective internal pore radius (r(E)) in several K-channel crystal structurss. r(E) was operationally defined as the radius of the biggest sphere able to enter the pore from the cytosolic side. We obtained consistent r(E) estimates for MthK and Kv1.2/2.1 structures, with r(E) = 5.3-5.9 angstrom and r(E) = 4.5-5.2 angstrom, respectively. We compared these structural estimates with functional assessments of the internal mouth radii of capture (r(C)) for two electrophysiological counterparts, the large conductance calcium activated K-channel (r(C) = 2.2 angstrom) and the Shaker K-v-channel (r(C) = 0.8 angstrom), for MthK and Kv1.2/2.1 structures, respectively. Calculating the difference between r(E) and r(C), produced consistent size radii of 3.1-3.7 angstrom and 3.6-4.4 angstrom for hydrated K+ ions. These hydrated K+ estimates harmonize with others obtained with diverse experimental and theoretical methods. Thus, these findings validate MthK and the Kv1.2/2.1 structures as templates for open BK and Kv-channels, respectively.http://recursosbiblioteca.unab.cl:2226/articles/srep1989

Carbohydrate sources and maximizing the use of supplemental amino acids in diets for weanling pigs

The objectives of this research were 1) to determine the effect of replacing dried whey (DW) with milk chocolate product (MCP), dried whey permeate (DWP) with candy oats (CO), and spray-dried plasma protein (SDPP) with a novel swine nutritional supplement (SNS) on growth performance of weanling pigs, and 2) to determine the maximum level of supplemental L-Lys, along with DL-Met, L-Thr, and L-Trp that can be added in diets for 6- to 12 and 13- to 23-kg pigs. Three experiments were conducted to compare the feeding value of MCP (20% lactose and 60% sugars) and DW (70% lactose). Results from these experiments indicate that partial or total replacement of DW with MCP did not affect wk-1 feed intake or growth performance of weanling pigs. A similar experiment was conducted to compare the feeding value of CO (60% total sugars and 25% cooked oat-based cereals) and DWP (80% lactose). Results from this experiment indicate that a combination of DWP and CO increased wk-1 feed intake and growth performance of weanling pigs. Thus, MCP or CO could be considered as a formulation alternative to DW or DWP, respectively. Two experiments were conducted to determine the effect of replacing SDPP with SNS (concentrated plasma fraction). Results from these experiments indicate that the inclusion of SDPP or its replacement with SNS did not affect growth performance of weanling pigs. Eight experiments were conducted to determine the maximum level of supplemental L-Lys, along with DL-Met, L-Thr, and L-Trp that can be added in diets for 6- to 12-kg and 13- to 23-kg pigs without negatively affecting growth performance. Results from these experiments indicate that supplemental L-Lys levels of 0.198 and 0.298% or 0.331 and 0.423% can be added in diets for 6- to 12 or 13- to 23-kg pigs without negatively affecting G:F or ADG, respectively. The optimum SID Ile:Lys may not be greater than 0.55 in diets for 6- to 12-kg pigs containing low levels of red blood cells. The optimum SID Ile:Lys and SID Val:Lys may not be greater than 0.56 or 0.62, respectively, in corn-SBM diets for 13- to 23-kg pigs

Evaluation of novel dietary feed additives for nursery and growing/finishing pigs

The objectives of this research were: 1) to compare the effect of source and level of inclusion of dried whey permeate (DWP) and a carbohydrate product (CHO) on growth performance of nursery pigs, 2) to evaluate the effect of a fortified nutrient pack (FNP) on growth performance and total tract nutrient digestibility in growing/finishing pigs, and 3) to compare chromic oxide (Cr2O3) and acid insoluble ash (AIA) as digestibility markers for total tract digestibility determination in growing/finishing pigs. Three experiments were conducted to compare the feeding value of DWP (80% lactose) and CHO (40% lactose, 30% sucrose, and 10% glucose) in diets for nursery pigs. Results from these experiments indicate that the inclusion of DWP and CHO improved ADG and ADFI compared with pigs fed a diet without lactose. However, the importance of including a highly digestible carbohydrate source in diets for nursery pigs is more evident as pigs are weaned lighter and younger. Two experiments were conducted to evaluate the effect of FNP (fumaric, malic, citric, phosphoric, and lactic acids, L-carnitine, chromium picolinate, inulin, d-pantothenic acid, and niacin) on growth performance and total tract nutrient digestibility in growing/finishing pigs. Results from these experiments indicate that the addition of 0.25 or 0.50% FNP to the diets did not improve ADG, ADFI, or G/F of growing/finishing pigs. Dry matter, CP, and GE digestibility were not improved (P \u3e 0.1) with the addition of FNP in 50-kg pigs. However, the addition of 0.25% FNP to the diets of 85-kg pigs during the last 14 d of growth, improved CP and GE digestibility. Two experiments were conducted to compare Cr2O3 and AIA as digestibility markers for total tract digestibility determination in growing/finishing pigs fed ad libitum. Results from these experiments indicate that Cr2O3 and AIA offer a rapid and reliable technique for digestibility determination in growing/finishing pigs. However, AIA showed superior characteristics compared with Cr2O3 as its analyzed values are more consistent, produce less environmental impact, and is more cost effective

Gating-induced large aqueous volumetric remodeling and aspartate tolerance in the voltage sensor domain of Shaker K+ channels

Indexación: Scopus.ACKNOWLEDGMENTS. We thank Chris Lingle and Yu Zhou (Washington University) for critical reading of the manuscript and Victoria Prado for Xenopus care and oocyte preparation. We also thank Millennium Scientific Initiative P029-022-F. This work was supported by Fondecyt Postdoctoral Grants 3170599 (to I.D.-F.) and 3160321 (to H.M.).Neurons encode electrical signals with critically tuned voltage-gated ion channels and enzymes. Dedicated voltage sensor domains (VSDs) in these membrane proteins activate coordinately with an unresolved structural change. Such change conveys the transmembrane translocation of four positively charged arginine side chains, the voltage-sensing residues (VSRs; R1–R4). Countercharges and lipid phosphohead groups likely stabilize these VSRs within the low-dielectric core of the protein. However, the role of hydration, a sign-independent charge stabilizer, remains unclear. We replaced all VSRs and their neighboring residues with negatively charged aspartates in a voltage-gated potassium channel. The ensuing mild functional effects indicate that hydration is also important in VSR stabilization. The voltage dependency of the VSR aspartate variants approached the expected arithmetic summation of charges at VSR positions, as if negative and positive side chains faced similar pathways. In contrast, aspartates introduced between R2 and R3 did not affect voltage dependence as if the side chains moved outside the electric field or together with it, undergoing a large displacement and volumetric remodeling. Accordingly, VSR performed osmotic work at both internal and external aqueous interfaces. Individual VSR contributions to volumetric works approached arithmetical additivity but were largely dissimilar. While R1 and R4 displaced small volumes, R2 and R3 volumetric works were massive and vectorially opposed, favoring large aqueous remodeling during VSD activation. These diverse volumetric works are, at least for R2 and R3, not compatible with VSR translocation across a unique stationary charge transfer center. Instead, VSRs may follow separated pathways across a fluctuating low-dielectric septum. © National Academy of Sciences. All rights reserved.https://www.pnas.org/content/115/32/820

Discrete breathers for understanding reconstructive mineral processes at low temperatures

Reconstructive transformations in layered silicates need a high tem- perature in order to be observed. However, very recently, some systems have been found where transformation can be studied at temperatures 600 C below the lowest experimental results previously reported, including sol-gel methods. We explore the possible relation with the existence of intrinsic localized modes, known as discrete breathers. We construct a model for nonlinear vibrations within the cation layer, obtain their parameters and calculate them numerically, obtaining their energies. Their statistics shows that although there are far less breathers than phonons, there are much more above the activation energy, being therefore a good candidate to explain the reconstructive transformations at low temperature.Comment: 27 pages, 11 figure

Multiple hybridization events, polyploidy and low postmating isolation entangle the evolution of neotropical species of Epidendrum (Orchidaceae)

Background: Hybridization and polyploidy are central processes in evolution and speciation. These mechanisms often lead to complex patterns of genetic variation and the creation of novel genotypes, which may establish if they become isolated from gene flow. However, in the absence of reproductive isolation, species boundaries might easily be disrupted. Here, we used a combination of AFLPs, chloroplast DNA markers and flow cytometry to investigate the evolutionary outcomes of hybridization between two endemic Ecuadorian species of Epidendrum (E. madsenii and E. rhopalostele) in three hybrid zones. Postmating isolation was also quantified to determine the role of this barrier in restraining gene flow between hybrids and the parental species. In addition, future ecological niche models were constructed to predict the outcomes of hybridization between these species. Results: Our results confirmed the presence of hybrids in all hybrid zones, but revealed that a third parental species (E. falcisepalum) has contributed to one of the hybrid zones studied. Backcross genotypes were frequent in all hybrid zones, which was in accordance with the absence of strong reproductive barriers. The process of hybridization was highly asymmetric and followed in some cases by polyploidy. The projection of future niche models predicted a severe reduction in the area suitable for the occurrence of these species, although favorable conditions will still occur for the existence of the current hybrid zones. Conclusions: The recurrent process of hybridization has compromised the genetic integrity of the parental species. Most individuals of the parental species can no longer be considered as pure-bred individuals because most were classified as backcrossed hybrids. Novel genetic lineages occur in all hybrid zones implying that hybrids are fertile and can compete with the parental species. These results, together with the prediction of suitable conditions for the future occurrence of these hybrid zones, highlight the importance of conserving these geographic areas as sources of novel taxonomic entities

Hypertriglyceridaemia‐induced pancreatitis prompted by acute corticosteroid treatment: caution for clinicians

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148397/1/imj14228.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148397/2/imj14228_am.pd