Impaired wound healing in diabetics usually leads to life-threatening complications. To develop a system for fastening skin wound healing efficiently and safely in diabetics, thermos-sensitive hydrogel containing the nanodrug, loaded in the form of gelatin microspheres (GMs), was designed to deliver curcumin (Cur) as a therapeutic drug. Cur is a naturally existing polyphenolic compound with a broad range of biological functions useful for potential therapies. Because Cur molecule has weakness in both bioavailability and in vivo stability, delivery of Cur requires assistance from other molecules to act as carrier vehicles in a sustained manner for therapeutic use. At first, self-assembly of Cur nanoparticles (CNPs) was done to improve bioavailability. The CNPs were further enclosed into GMs for responding to the matrix metalloproteinases (MMPs) that usually overexpress at diabetic nonhealing wound sites. The GMs containing CNPs were loaded into the thermos-sensitive hydrogel and were finally proved for the capacity of specially induced drug release at the wound bed, which promoted the efficacy in healing the standardized skin wounds in streptozotocin-induced diabetic mice. Our results indicated that the successfully developed CNP delivery system had the capacity to significantly promote skin wound healing, which suggested that it could have the potential to become a wound dressing with the properties of antioxidants and promotions of cell migration.

Unfavorable genetic correlations between growth and wood quality traits are one of the biggest challenges in advanced conifer breeding programs. To examine and deal with such correlation, increment cores were sampled at breast height from 5,618 trees in 524 open-pollinated families in two 21-year-old Norway spruce progeny trials in southern Sweden, and age trends of genetic variation, genetic correlation, and efficiency of selection were investigated. Wood quality traits were measured on 12-mm increment cores using SilviScan. Heritability was moderate (~0.4-0.5) for wood density and modulus of elasticity (MOE) but low (~0.2) for microfibril angle (MFA). Different age trends were observed for wood density, MFA, and MOE, and the lower heritability of MFA relative to wood density and MOE in Norway spruce contrasted with general trends of the three wood quality traits in pine. Genetic correlations among growth, wood density, MFA, and MOE increased to a considerably high value from pith to bark with unfavorable genetic correlations (−0.6 between growth and wood density, −0.74 between growth and MOE). Age-age genetic correlations reached 0.9 after ring 4 for diameter at breast height (DBH), wood density, MFA, and MOE traits. Early selections at ring 10 for diameter and at ring 6 or 7 for wood quality traits had similar effectiveness as selection conducted at reference ring 15. Selection based on diameter alone produced 19.0 % genetic gain in diameter but resulted in 4.8 % decrease in wood density, 9.4 % decrease in MOE, and 8.0 % increase in MFA. Index selection with a restriction of no change in wood density, MOE, and MFA, respectively, produced relatively lower genetic gains in diameter (16.4, 12.2, and 14.1 %, respectively), indicating such index selection could be implemented to maintain current wood density. Index selection using economic weights is, however, recommended for maximum economic efficiency.

Rapid progress in understanding the molecular mechanisms associated with cochlear and auditory nerve degenerative processes offers hope for the development of gene-transfer and molecular approaches to treat these diseases in patients. For therapies based on these discoveries to become clinically useful, it will be necessary to develop safe and reliable mechanisms for the delivery of drugs into the inner ear, bypassing the blood-labyrinthine barrier. Toward the goal of developing an inner ear perfusion device for human use, a reciprocating microfluidic system that allows perfusion of drugs into the cochlear perilymph through a single inlet hole in scala tympani of the basal turn was developed. The performance of a prototype, extracorporeal reciprocating perfusion system in guinea pigs is described. Analysis of the cochlear distribution of compounds after perfusion took advantage of the place-dependent generation of responses to tones along the length of the cochlea. Perfusion with a control artificial perilymph solution had no effect. Two drugs with wellcharacterized effects on cochlear physiology, salicylate (5 mM) and DNQX (6,7-Dinitroquinoxaline-2,3-dione; 100 and 300 μM), reversibly altered responses. The magnitude of drug effect decreased with distance from the perfusion pipette for up to 10 mm, and increased with dose and length of application.

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Summary Vast population movements induced by recurrent climatic cycles have shaped the genetic structure of plant species. During glacial periods species were confined to low‐latitude refugia from which they recolonized higher latitudes as the climate improved. This multipronged recolonization led to many lineages that later met and formed large contact zones. We utilize genomic data from 5000 Picea abies trees to test for the presence of natural selection during recolonization and establishment of a contact zone in Scandinavia. Scandinavian P. abies is today made up of a southern genetic cluster originating from the Baltics, and a northern one originating from Northern Russia. The contact zone delineating them closely matches the limit between two major climatic regions. We show that natural selection contributed to its establishment and maintenance. First, an isolation‐with‐migration model with genome‐wide linked selection fits the data better than a purely neutral one. Second, many loci show signatures of selection or are associated with environmental variables. These loci, regrouped in clusters on chromosomes, are often related to phenology. Altogether, our results illustrate how climatic cycles, recolonization and selection can establish strong local adaptation along contact zones and affect the genetic architecture of adaptive traits.

The purging of deleterious alleles has been hypothesized to mitigate inbreeding depression, but its effectiveness in endangered species remains debatable. To understand how deleterious alleles are purged during population contractions, we analyzed genomes of the endangered Chinese crocodile lizard (Shinisaurus crocodilurus), which is the only surviving species of its family and currently isolated into small populations. Population genomic analyses revealed four genetically distinct conservation units and sharp declines in both effective population size and genetic diversity. By comparing the relative genetic load across populations and conducting genomic simulations, we discovered that seriously deleterious alleles were effectively purged during population contractions in this relict species, although inbreeding generally enhanced the genetic burden. However, despite with the initial purging, our simulations also predicted that seriously deleterious alleles will gradually accumulate under prolonged bottlenecking. Therefore, we emphasize the importance of maintaining a minimum population capacity and increasing the functional genetic diversity in conservation efforts to preserve populations of the crocodile lizard and other endangered species.

A genomic selection study of growth and wood quality traits is reported based on control-pollinated Norway spruce families established in 2 Northern Swedish trials at 2 locations using exome capture as a genotyping platform. Nonadditive effects including dominance and first-order epistatic interactions (including additive-by-additive, dominance-by-dominance, and additive-by-dominance) and marker-by-environment interaction (M×E) effects were dissected in genomic and phenotypic selection models. Genomic selection models partitioned additive and nonadditive genetic variances more precisely than pedigree-based models. In addition, predictive ability in GS was substantially increased by including dominance and slightly increased by including M×E effects when these effects are significant. For velocity, response to genomic selection per year increased up to 78.9/80.8%, 86.9/82.9%, and 91.3/88.2% compared with response to phenotypic selection per year when genomic selection was based on 1) main marker effects (M), 2) M + M×E effects (A), and 3) A + dominance effects (AD) for sites 1 and 2, respectively. This indicates that including M×E and dominance effects not only improves genetic parameter estimates but also when they are significant may improve the genetic gain. For tree height, Pilodyn, and modulus of elasticity (MOE), response to genomic selection per year improved up to 68.9%, 91.3%, and 92.6% compared with response to phenotypic selection per year, respectively.Subject Area: Quantitative genetics and Mendelian inheritance

Norway spruce (Picea abies L. Karst) is one of the most important forest tree species with significant economic and ecological impact in Europe. For decades, genomic and genetic studies on Norway spruce have been challenging due to the large and repetitive genome (19.6 Gb with more than 70% being repetitive). To accelerate genomic studies, including population genetics, genome‐wide association studies (GWAS) and genomic selection (GS), in Norway spruce and related species, we here report on the design and performance of a 50K single nucleotide polymorphism (SNP) genotyping array for Norway spruce. The array is developed based on whole genome resequencing (WGS), making it the first WGS‐based SNP array in any conifer species so far. After identifying SNPs using genome resequencing data from 29 trees collected in northern Europe, we adopted a two‐step approach to design the array. First, we built a 450K screening array and used this to genotype a population of 480 trees sampled from both natural and breeding populations across the Norway spruce distribution range. These samples were then used to select high‐confidence probes that were put on the final 50K array. The SNPs selected are distributed over 45,552 scaffolds from the P. abies version 1.0 genome assembly and target 19,954 unique gene models with an even coverage of the 12 linkage groups in Norway spruce. We show that the array has a 99.5% probe specificity, >98% Mendelian allelic inheritance concordance, an average sample call rate of 96.30% and an SNP call rate of 98.90% in family trios and haploid tissues. We also observed that 23,797 probes (50%) could be identified with high confidence in three other spruce species (white spruce [Picea glauca], black spruce [P. mariana] and Sitka spruce [P. sitchensis]). The high‐quality genotyping array will be a valuable resource for genetic and genomic studies in Norway spruce as well as in other conifer species of the same genus.