Single exon skipping can address a multi-exon duplication in the dystrophin gene

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease typically caused by protein-truncating mutations that preclude synthesis of a functional dystrophin. Exonic deletions are the most common type of DMD lesion, however, whole exon duplications account for between 10–15% of all reported mutations. Here, we describe in vitro evaluation of antisense oligonucleotide-induced splice switching strategies to re-frame the transcript disrupted by a multi-exon duplication within the DMD gene. Phosphorodiamidate morpholino oligomers and phosphorodiamidate morpholino oligomers coupled to a cell penetrating peptide were evaluated in a Duchenne muscular dystrophy patient cell strain carrying an exon 14–17 duplication. Two strategies were employed; the conventional approach was to remove both copies of exon 17 in addition to exon 18, and the second strategy was to remove only the first copy of exon 17. Both approaches result in a larger than normal but in-frame DMD transcript, but surprisingly, the removal of only the first exon 17 appeared to be more efficient in restoring dystrophin, as determined using western blotting. The emergence of a normal sized DMD mRNA transcript that was not apparent in untreated samples may have arisen from back splicing and could also account for some of the dystrophin protein being produced

Allelic variation of low molecular weight glutenin subunits composition and the revealed genetic diversity in durum wheat Triticum turgidum L. ssp. durum

Low molecular weight glutenin subunits (LMW-GS) play an important role in determining the bread-making characteristics of dough in the end-use quality of wheat. In this study, A total of 149 worldwide-originated durum wheat were used to analyze the composition of LMW-GS using MALDI-TOF-MS. Based on the allelic variation of glutenin subunits, the genetic diversity was evaluated for the 149 durum wheat. Five types of alleles were identified at the Glu-A3 locus with Glu-A3e, Glu-A3a/c, Glu-A3f, Glu-A3d and Glu-A3b accounting for 43.0%, 16.1%, 12.8%, 10.1% and 7.4 % of the accessions, respectively. Five types of alleles were identified at the Glu-B3 locus: Glu-B3d (60.4%), Glu-B3b (6.0%), Glu-B3c (6.0%), Glu-B3h (2.7%) and Glu-B3f (0.7%). Two novel alleles encoding abnormal subunits 40500 Da and 41260 Da were identified at the Glu-A3 and Glu-B3 loci, respectively. Further studies are needed to match these novel alleles to previously discovered novel alleles. Moreover, the genetic diversity analysis indicated that great genetic variation existed in durum wheat among encoding loci of glutenin subunits, released periods of varieties and different geographical origins. The results provide more important information of potential germplasm for the improvement of durum wheat and common wheat

Scorpion Biodiversity and Interslope Divergence at “Evolution Canyon”, Lower Nahal Oren Microsite, Mt. Carmel, Israel

BACKGROUND: Local natural laboratories, designated by us as the "Evolution Canyon" model, are excellent tools to study regional and global ecological dynamics across life. They present abiotic and biotic contrasts locally, permitting the pursuit of observations and experiments across diverse taxa sharing sharp microecological subdivisions. Higher solar radiation received by the "African savannah-like" south-facing slopes (AS) in canyons north of the equator than by the opposite "European maquis-like" north-facing slopes (ES) is associated with higher abiotic stress. Scorpions are a suitable taxon to study interslope biodiversity differences, associated with the differences in abiotic factors (climate, drought), due to their ability to adapt to dry environments. METHODOLOGY/PRINCIPAL FINDINGS: Scorpions were studied by the turning stone method and by UV light methods. The pattern observed in scorpions was contrasted with similar patterns in several other taxa at the same place. As expected, the AS proved to be significantly more speciose regarding scorpions, paralleling the interslope patterns in taxa such as lizards and snakes, butterflies (Rhopalocera), beetles (families Tenebrionidae, Dermestidae, Chrysomelidae), and grasshoppers (Orthoptera). CONCLUSIONS/SIGNIFICANCE: Our results support an earlier conclusion stating that the homogenizing effects of migration and stochasticity are not able to eliminate the interslope intra- and interspecific differences in biodiversity despite an interslope distance of only 100 m at the "EC" valley bottom. In our opinion, the interslope microclimate selection, driven mainly by differences in insolance, could be the primary factor responsible for the observed interslope pattern

Bacterial Distribution in the Rhizosphere of Wild Barley under Contrasting Microclimates

Background: All plants in nature harbor a diverse community of rhizosphere bacteria which can affect the plant growth. Our samples are isolated from the rhizosphere of wild barley Hordeum spontaneum at the Evolution Canyon (‘EC’), Israel. The bacteria which have been living in close relationship with the plant root under the stressful conditions over millennia are likely to have developed strategies to alleviate plant stress. Methodology/Principal Findings: We studied distribution of culturable bacteria in the rhizosphere of H. spontaneum and characterized the bacterial 1-aminocyclopropane-1-carboxylate deaminase (ACCd) production, biofilm production, phosphorus solubilization and halophilic behavior. We have shown that the H. spontaneum rhizosphere at the stressful South Facing Slope (SFS) harbors significantly higher population of ACCd producing biofilm forming phosphorus solubilizing osmotic stress tolerant bacteria. Conclusions/Significance: The long-lived natural laboratory ‘EC ’ facilitates the generation of theoretical testable and predictable models of biodiversity and genome evolution on the area of plant microbe interactions. It is likely that the bacteria isolated at the stressful SFS offer new opportunities for the biotechnological applications in our agro-ecologica

Natural Variation in Grain Selenium Concentration of Wild Barley, Hordeum spontaneum, Populations from Israel

Wild barley (Hordeum spontaneum), the progenitor of cultivated barley, is an important genetic resource for cereal improvement. Selenium (Se) is an essential trace mineral for humans and animals with antioxidant, anticancer, antiarthropathy, and antiviral effects. In the current study, the grain Se concentration (GSeC) of 92 H. spontaneum genotypes collected from nine populations representing different habitats in Israel was investigated in the central area of Guizhou Province, China. Remarkable variations in GSeC were found between and within populations, ranging from 0 to 0.387 mg kg−1 among the 92 genotypes with an average of 0.047 mg kg−1. Genotype 20_C from the Sede Boqer population had the highest GSeC, while genotype 25_1 from the Atlit population had the lowest. The mean value of GSeC in each population varied from 0.010 to 0.105 mg kg−1. The coefficient of variation for each population ranged from 12% to 163%. Significant correlations were found between GSeC and 12 ecogeographical factors out of 14 studied. Habitat soil type also significantly affected GSeC. The wild barley exhibited wider GSeC ranges and greater diversity than its cultivated counterparts. The higher Se grain concentrations found in H. spontaneum populations suggest that wild barley germplasm confer higher abilities for Se uptake and accumulation, which can be used for genetic studies of barley nutritional value and for further improvement of domesticated cereals

Random fields on model sets with localized dependency and their diffraction

For a random field on a general discrete set, we introduce a condition that the range of the correlation from each site is within a predefined compact set D. For such a random field omega defined on the model set Lambda that satisfies a natural geometric condition, we develop a method to calculate the diffraction measure of the random field. The method partitions the random field into a finite number of random fields, each being independent and admitting the law of large numbers. The diffraction measure of omega consists almost surely of a pure-point component and an absolutely continuous component. The former is the diffraction measure of the expectation E[omega], while the inverse Fourier transform of the absolutely continuous component of omega turns out to be a weighted Dirac comb which satisfies a simple formula. Moreover, the pure-point component will be understood quantitatively in a simple exact formula if the weights are continuous over the internal space of Lambda Then we provide a sufficient condition that the diffraction measure of a random field on a model set is still pure-point.Comment: 21 page

Lipid Profile and Serum Characteristics of the Blind Subterranean Mole Rat, Spalax

to underground life resulted in structural and molecular-genetic differences comparing to above-ground mammals. These differences include higher myocardial maximal oxygen consumption, increased lung diffusion capacity, increased blood vessels density, and unique expression patterns of cancer and angiogenesis related genes such as heparanase, vascular endothelial growth factor, and P53. revealed special features in this mammal. pursue underground, dietary components, and evolutionary genetic adaptations. Unfolding the genetic basis of these differences will probably result in unique treatments for a variety of human diseases such as dyslipedemias, inflammation and cancer

New insights into the evolution of wheat avenin-like proteins in wild emmer wheat (Triticum dicoccoides)

Fifteen full-length wheat grain avenin-like protein coding genes (TaALP) were identified on chromosome arms 7AS, 4AL, and 7DS of bread wheat with each containing five genes. Besides the a- and b-type ALPs, a c type was identified in the current paper. Both a and b types have two subunits, named x and y types. The five genes on each of the three chromosome arms consisted of two x-type genes, two y-type genes, and one c-type gene. The a-type genes were typically of 520 bp in length, whereas the b types were of 850 bp in length, and the c type was of 470 bp in length. The ALP gene transcript levels were significantly up-regulated in Blumeria graminis f. sp. tritici (Bgt)-infected wheat grain caryopsis at early grain filling. Wild emmer wheat [(WEW), Triticum dicoccoides] populations were focused on in our paper to identify allelic variations of ALP genes and to study the influence of natural selection on certain alleles. Consequently, 25 alleles were identified for TdALP-bx-7AS, 13 alleles were identified for TdALP-ax-7AS, 7 alleles were identified for TdALP-ay-7AS, and 4 alleles were identified for TdALP-ax-4AL. Correlation studies on TdALP gene diversity and ecological stresses suggested that environmental factors contribute to the ALP polymorphism formation in WEW. Many allelic variants of ALPs in the endosperm of WEW are not present in bread wheat and therefore could be utilized in breeding bread wheat varieties for better quality and elite plant defense characteristics

Is Evolution of Blind Mole Rats Determined by Climate Oscillations?

The concept of climate variability facilitating adaptive radiation supported by the ‘‘Court Jester’’ hypothesis is disputed by the ‘‘Red Queen’’ one, but the prevalence of one or the other might be scale-dependent. We report on a detailed, comprehensive phylo-geographic study on the ,4 kb mtDNA sequence in underground blind mole rats of the family Spalacidae (or subfamily Spalacinae) from the East Mediterranean steppes. Our study aimed at testing the presence of periodicities in branching patterns on a constructed phylogenetic tree and at searching for congruence between branching events, tectonic history and paleoclimates. In contrast to the strong support for the majority of the branching events on the tree, the absence of support in a few instances indicates that network-like evolution could exist in spalacids. In our tree, robust support was given, in concordance with paleontological data, for the separation of spalacids from muroid rodents during the first half of the Miocene when open, grass-dominated habitats were established. Marine barriers formed between Anatolia and the Balkans could have facilitated the separation of the lineage ‘‘Spalax’’ from the lineage ‘‘Nannospalax’’ and of the clade ‘‘leucodon’’ from the clade ‘‘xanthodon’’. The separation of the clade ‘‘ehrenbergi’’ occurred during the late stages of the tectonically induced uplift of the Anatolian high plateaus and mountains, whereas the separation of the clade ‘‘vasvarii’’ took place when the rapidly uplifting Taurus mountain range prevented the Mediterranean rainfalls from reaching the Central Anatolian Plateau. The separation of Spalax antiquus and S. graecus occurred when the southeastern Carpathians were uplifted. Despite the role played by tectonic events, branching events that show periodicity corresponding to 400-kyr and 100-kyr eccentricity bands illuminate the important role of orbital fluctuations on adaptive radiation in spalacids. At the given scale, our results supports the ‘‘Court Jester’’ hypothesis over the ‘‘Red Queen’’ one