Defective hematopoietic differentiation of immune aplastic anemia patient-derived iPSCs

In acquired immune aplastic anemia (AA), pathogenic cytotoxic Th1 cells are activated and expanded, driving an immune response against the hematopoietic stem and progenitor cells (HSPCs) that provokes cell depletion and causes bone marrow failure. However, additional HSPC defects may contribute to hematopoietic failure, reflecting on disease outcomes and response to immunosuppression. Here we derived induced pluripotent stem cells (iPSCs) from peripheral blood (PB) erythroblasts obtained from patients diagnosed with immune AA using non-integrating plasmids to model the disease. Erythroblasts were harvested after hematologic response to immunosuppression was achieved. Patients were screened for germline pathogenic variants in bone marrow failure-related genes and no variant was identified. Reprogramming was equally successful for erythroblasts collected from the three immune AA patients and the three healthy subjects. However, the hematopoietic differentiation potential of AA-iPSCs was significantly reduced both quantitatively and qualitatively as compared to healthy-iPSCs, reliably recapitulating disease: differentiation appeared to be more severely affected in cells from the two patients with partial response as compared to the one patient with complete response. Telomere elongation and the telomerase machinery were preserved during reprogramming and differentiation in all AA-iPSCs. Our results indicate that iPSCs are a reliable platform to model immune AA and recapitulate clinical phenotypes. We propose that the immune attack may cause specific epigenetic changes in the HSPCs that limit adequate proliferation and differentiation.Subject terms: Anaemia, Induced pluripotent stem cells     

Salmonella enterica strains belonging to O serogroup 1,3,19 induce chlorosis and wilting of Arabidopsis thaliana leaves

The number of outbreaks and illness linked to the consumption of contaminated salad leaves have increased dramatically in the last decade. Escherichia coli and Salmonella enterica are the most common food-borne pathogens linked to consumption of fresh produce. Different serovars of S. enterica subspecies enterica have been shown to bind the surface of salad leaves, to exhibit tropism towards the stomata and to invade leaves and reach the underlying mesophyll. However the consequences of leaf invasion are not known. Here we show that following infiltration, serovars Typhimurium, Enteritidis, Heidelberg and Agona, as well as strains of S. enterica subspecies arizonae and diarizonae, survive in the mesophyll of Arabidopsis thaliana leaves but induce neither leaf chlorosis nor wilting. In contrast, S. Senftenberg induced strong leaf wilting 4 days post infiltration in A. thaliana accession Col-0 but not in accession Ws-0. Dead S. Senftenberg and bacterial lysates also induced leaf wilting. We found that mutations in the Arabidopsis pathogen associated molecular pattern (PAMP) recognition receptors (PRRs) FLS2, which recognizes flagellin, and EFR, which recognizes the bacterial elongation factor EF-Tu, had no effect on the wilting response of A. thaliana to S. Senftenberg. Infiltration of A. thaliana leaves with serovars Cannstatt, Krefeld and Liverpool, which like Senftenberg belong to Salmonella serogroup E(4) (O:1,3,19), also resulted in rapid leaf wilting, while all tested rough S. Senftenberg strains (lacking the O antigen) failed to elicit leaf wilting. These results suggest that the Salmonella O antigen 1,3,19 specifically triggers leaf chlorosis and wilting in A. thaliana.     

Relative DNA content in diploid,polyploid, and multiploid species of <Emphasis Type="Italic">Paspalum</Emphasis> (Poaceae) with relation to reproductive mode and taxonomy

It is generally accepted that polyploids have downsized basic genomes rather than additive values with respect to their related diploids. Changes in genome size have been reported in correlation with several biological characteristics. About 75 % of around 350 species recognized for Paspalum (Poaceae) are polyploid and most polyploids are apomictic. Multiploid species are common with most of them bearing sexual diploid and apomictic tetraploid or other ploidy levels. DNA content in the embryo and the endosperm was measured by flow cytometry in a seed-by-seed analysis of 47 species including 77 different entities. The relative DNA content of the embryo informed the genome size of the accession while the embryo:endosperm ratio of DNA content revealed its reproductive mode. The genome sizes (2C-value) varied from 0.5 to 6.5 pg and for 29 species were measured for the first time. Flow cytometry provided new information on the reproductive mode for 12 species and one botanical variety and supplied new data for 10 species concerning cytotypes reported for the first time. There was no significant difference between the mean basic genome sizes (1Cx-values) of 32 sexual and 45 apomictic entities. Seventeen entities were diploid and 60 were polyploids with different degrees. There were no clear patterns of changes in 1Cx-values due to polyploidy or reproductive systems, and the existing variations are in concordance with subgeneric taxonomical grouping.     

Seed Rain and Seed Dispersal Agents in Pure and Mixed Plantations of Native Trees and Abandoned Pastures at La Selva Biological Station, Costa Rica

Lack of seed dispersal can be an important obstacle to natural regeneration (NR) of degraded pastures in the humid tropics. Tree plantations can facilitate secondary forest succession by attracting seed dispersal agents from nearby forests. We studied seed rain and seed dispersal agents in 12–13 years old pure and mixed native tree plantations at La Selva Biological Station, Costa Rica from July to December 2004. Plantations of Balizia elegans (5,522), Dipteryx panamensis (2,263), and Jacaranda copaia (2,091) had the greatest total seed abundance; treatments with the least total seed abundance were Calophyllum brasiliense (56), nonplanted abandoned pasture control 2 (353), Mixed Species 2 (389), and control 1 (836). Plantations of J. copaia and Hyeronima alchorneoides had the greatest seed species richness density, whereas the lowest seed species richness was found in the control treatments. The NR plots had more seeds dispersed by wind, whereas in the plantations, the most important dispersal agents were birds and mammals. The most abundant seeds were those of Miconia spp. (14,492), Psychotria bracheata (2,252), and the Poaceae family (1,346), all species from early successional stages. Plantations of native species are effective in attracting seed dispersal agents and thus facilitating regeneration of degraded pasturelands in the region.     

A comparative assessment of plant flammability through a functional approach: The case of woody species from Argentine Chaco region

Recent changes to fire regimes in many regions of the world have led to renewed interest in plant flammability experiments to understand and predict the consequences of such changes. These experiments require the development of practical and standardised flammability testing protocols. The research aims were (i) to compare plant flammability assessments carried out using two different approaches, namely functional trait analysis and testing with a shoot‐level device; and (ii) to evaluate the effect of disturbances and seasonal variability on flammability. The study area was located in the Western Chaco region, Argentina, and 11 species were selected based on their representativeness in forests. We studied six functional traits related to flammability, growth habit and foliar persistence, in forests without disturbances over the three last decades as well as in disturbed forests. The seasonal variation of these functional traits was evaluated over two consecutive years. Functional trait flammability index (FI) and shoot‐level measurements followed standard protocols. Sixty per cent of the species measured presented a high to very high FI. The results of both assessment methods were significantly correlated. Both methods identified the same species as having medium flammability, but differed in regards to the most flammable species. Senegalia gilliesii was identified as the most flammable species when using functional trait analysis, whereas shoot‐level assessments found Larrea divaricata and Schinus johnstonii to be the most flammable. There were no disturbance effects on the FI but there was seasonal variation. Our results validate the use of functional traits as a predictive method of flammability testing and represent the first global effort comparing flammability obtained through functional trait analysis with empirical measurements. The significant correlation between both methods allows the selection of the one that is more appropriate for the size of the area to be evaluated and for the availability of technical resources. Abstract in Spanish is available with online material.     

Allelic Analyses of the Arabidopsis YUC1 Locus Reveal Residues and Domains Essential for the Functions of YUC Family of Flavin Monooxygenases

Flavin monooxygenases(FMOs) play critical roles in plant growth and development by synthesizing auxin and other signaling molecules.However,the structure and function relationship within plant FMOs is not understood.Here we defined the important residues and domains of the Arabidopsis YUC1 FMO,a key enzyme in auxin biosynthesis.We previously showed that simultaneous inactivation of YUC1 and its homologue YUC4 caused severe defects in vascular and floral development.We mutagenized the yuc4 mutant and screene...     

Ecological photodynamic therapy: New trend to disrupt the intricate networks within tumor ecosystem

As with natural ecosystems, species within the tumor microenvironment are connected by pairwise interactions (e.g. mutualism, predation) leading to a strong interdependence of different populations on each other. In this review we have identified the ecological roles played by each non-neoplastic population (macrophages, endothelial cells, fibroblasts) and other abiotic components (oxygen, extracellular matrix) directly involved with neoplastic development. A way to alter an ecosystem is to affect other species within the environment that are supporting the growth and survival of the species of interest, here the tumor cells; thus, some features of ecological systems could be exploited for cancer therapy. We propose a well-known antitumor therapy called photodynamic therapy (PDT) as a novel modulator of ecological interactions. We refer to this as “ecological photodynamic therapy.” The main goal of this new strategy is the improvement of therapeutic efficiency through the disruption of ecological networks with the aim of destroying the tumor ecosystem. It is therefore necessary to identify those interactions from which tumor cells get benefit and those by which it is impaired, and then design multitargeted combined photodynamic regimes in order to orchestrate non-neoplastic populations against their neoplastic counterpart. Thus, conceiving the tumor as an ecological system opens avenues for novel approaches on treatment strategies.