Genetic Diversity for Effective Resistance in Wheat Landraces from Ethiopia and Eritrea to Fungal Diseases and Toxic Aluminum Ions.

To reveal genetic diversity for effective resistance to five foliar diseases and toxic aluminum ions, the entire collection of wheat species from the N.I. Vavilov All-Russian Institute of Plant Genetic Resources (VIR) originating from Ethiopia and Eritrea were studied regarding their traits. The collection contains 509 samples of four wheat species (Triticum aestivum-122 samples; T. aethiopicum-340 samples; T. polonicum-6 samples; and T. dicoccum-41 samples). The majority of accessions are new entries of landraces added to the Vavilov collection as a result of the Russian-Ethiopian expedition in 2012. Wheat seedlings were inoculated with causal agents of leaf rust (Pt), powdery mildew (Bgt), Septoria nodorum blotch (SNB), and dark-brown leaf spot blotch (HLB). The types of reaction and disease development were assessed to describe the levels of resistance. All samples of T. aethiopicum were also screened for seedling and adult resistance to Pt, Bgt, and yellow rust (Pst) under field conditions after double inoculation with the corresponding pathogens. To study tolerance to abiotic stress, seedlings were grown in a solution of Al3+ (185 µM, pH 4,0) and in water. The index of root length was used to characterize tolerance. Seedlings belonging to only two accessions out of those studied-k-68236 of T. aethiopicum and k-67397 of T. dicoccum-were resistant to Pt at 20 °C but susceptible at 25 °C. Specific molecular markers closely linked to the five genes for Pt resistance effective against populations of the pathogen from the northwestern region of Russia were not amplified in these two entries after PCR with corresponding primers. Four entries of T. dicoccum-k-18971, k-18975, k-19577, and k-67398-were highly resistant to Bgt. All samples under study were susceptible to HLB and SNB. Under field conditions, 15% of the T. aethiopicum samples were resistant to Pst, both at the seedling and the flag leaf stages, but all were susceptible to the other diseases under study. Among the evaluated samples, 20 entries of T. aestivum, 1 of T. polonicum (k-43765), and 2 of T. dicoccum (k-18971, k-67397) were tolerant to aluminum ions. The identified entries could be valuable sources for the breeding of T. aestivum and other wheats for resistance to biotic and abiotic stresses.

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population.

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10-6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10-10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.

Language development in rural and urban Russian-speaking children with and without developmental language disorder.

Using a newly developed Assessment of the Development of Russian Language (ORRIA), we investigated differences in language development between rural vs. urban Russian-speaking children (n = 100 with a mean age of 6.75) subdivided into groups with and without developmental language disorders. Using classical test theory and item response theory approaches, we found that while ORRIA displayed overall satisfactory psychometric properties, several of its items showed differential item functioning favoring rural children, and several others favoring urban children. After the removal of these items, rural children significantly underperformed on ORRIA compared to urban children. The urbanization factor did not significantly interact with language group. We discuss the latter finding in the context of the multiple additive risk factors for language development and emphasize the need for future studies of the mechanisms that underlie these influences and the implications of these findings for our understanding of the etiological architecture of children's language development.

Urokinase-type plasminogen activator (uPA) induces pulmonary microvascular endothelial permeability through low density lipoprotein receptor-related protein (LRP)-dependent activation of endothelial nitric-oxide synthase.

Urokinase plasminogen activator (uPA) and PA inhibitor type 1 (PAI-1) are elevated in acute lung injury, which is characterized by a loss of endothelial barrier function and the development of pulmonary edema. Two-chain uPA and uPA-PAI-1 complexes (1-20 nM) increased the permeability of monolayers of human pulmonary microvascular endothelial cells (PMVECs) in vitro and lung permeability in vivo. The effects of uPA-PAI-1 were abrogated by the nitric-oxide synthase (NOS) inhibitor L-NAME (N(D)-nitro-L-arginine methyl ester). Two-chain uPA (1-20 nM) and uPA-PAI-1 induced phosphorylation of endothelial NOS-Ser(1177) in PMVECs, which was followed by generation of NO and the nitrosylation and dissociation of ß-catenin from VE-cadherin. uPA-induced phosphorylation of eNOS was decreased by anti-low density lipoprotein receptor-related protein-1 (LRP) antibody and an LRP antagonist, receptor-associated protein (RAP), and when binding to the uPA receptor was blocked by the isolated growth factor-like domain of uPA. uPA-induced phosphorylation of eNOS was also inhibited by the protein kinase A (PKA) inhibitor, myristoylated PKI, but was not dependent on PI3K-Akt signaling. LRP blockade and inhibition of PKA prevented uPA- and uPA-PAI-1-induced permeability of PMVEC monolayers in vitro and uPA-induced lung permeability in vivo. These studies identify a novel pathway involved in regulating PMVEC permeability and suggest the utility of uPA-based approaches that attenuate untoward permeability following acute lung injury while preserving its salutary effects on fibrinolysis and airway remodeling.

Comprehensive approach to high-resolution KIR typing.

Multiple studies suggest that prospective KIR typing may be beneficial for the outcome of bone marrow transplants, but to date no practical high-resolution KIR typing system has been developed. Here we propose a comprehensive high-resolution typing approach that provides allele level KIR typing. Based on the low-resolution typing obtained by SSO, the 14 KIR loci are divided in groups according to the level of polymorphism in exons coding for extracellular Ig-like domains and cytoplasmic tail. The first group is typed by sequence-specific oligonucleotide only; the second is typed by sequence-based typing (SBT) based on the amplification of a fragment coding the Ig-like domains; and the third is typed by SBT based on amplification of a fragment coding the cytoplasmic tail. SBT for the fourth group includes both the Ig-like and cytoplasmic domains. Because of a considerable number of polymorphisms scattered throughout all nine KIR exons, SBT results may still produce a number of ambiguities, which can be resolved by sequence-specific primers. This combined high-resolution approach was applied to the complete KIR typing of 205 Caucasian hematopoietic stem cell donors in support of the National Marrow Donor Program High-resolution KIR Typing Pilot Project. High-resolution typing of several KIR loci produced numerous novel alleles, whereas some loci demonstrated very limited polymorphism. Several of the novel alleles appeared in more than four donors, suggesting that these alleles are not rare. Our results showed that the comprehensive KIR typing approach presented here provides the balance of high-resolution typing and cost effectiveness.