Disease resistance genes encoding nucleotide-binding and leucine-rich repeat (NLR) intracellular immune receptor proteins detect pathogens by the presence of pathogen effectors. Plant genomes ...typically contain hundreds of NLR-encoding genes. The availability of the hexaploid wheat (
) cultivar Chinese Spring reference genome allows a detailed study of its NLR complement. However, low
expression and high intrafamily sequence homology hinder their accurate annotation. Here, we developed NLR-Annotator, a software tool for in silico NLR identification independent of transcript support. Although developed for wheat, we demonstrate the universal applicability of NLR-Annotator across diverse plant taxa. We applied our tool to wheat and combined it with a transcript-validated subset of genes from the reference gene annotation to characterize the structure, phylogeny, and expression profile of the
gene family. We detected 3,400 full-length NLR loci, of which 1,560 were confirmed as expressed genes with intact open reading frames. NLRs with integrated domains mostly group in specific subclades. Members of another subclade predominantly locate in close physical proximity to NLRs carrying integrated domains, suggesting a paired helper function. Most
(88%) display low basal expression (in the lower 10 percentile of transcripts). In young leaves subjected to biotic stress, we found up-regulation of 266 of the
To illustrate the utility of our tool for the positional cloning of resistance genes, we estimated the number of
genes within the intervals of mapped rust resistance genes. Our study will support the identification of functional resistance genes in wheat to accelerate the breeding and engineering of disease-resistant varieties.
When the sensory–motor integration system is malfunctioning provokes a wide variety of neurological disorders, which in many cases cannot be treated with conventional medication, or via existing ...therapeutic technology. A brain–computer interface (BCI) is a tool that permits to reintegrate the sensory–motor loop, accessing directly to brain information. A potential, promising and quite investigated application of BCI has been in the motor rehabilitation field. It is well-known that motor deficits are the major disability wherewith the worldwide population lives. Therefore, this paper aims to specify the foundation of motor rehabilitation BCIs, as well as to review the recent research conducted so far (specifically, from 2007 to date), in order to evaluate the suitability and reliability of this technology. Although BCI for post-stroke rehabilitation is still in its infancy, the tendency is towards the development of implantable devices that encompass a BCI module plus a stimulation system.
•BCIs permit to reintegrate the sensory–motor loop by accessing to brain information.•Motor imagery based BCIs seem to be an effective system for an early rehabilitation.•This technology does not need remaining motor activity and promotes neuroplasticity.•BCI for rehabilitation tends towards implantable devices plus stimulation systems.
SUMMARY
In maize (Zea mays ssp. mays), agriculturally damaging herbivores include lepidopteran insects, such as the European corn borer (Ostrinia nubilalis), and distantly related arthropods, like ...the two‐spotted spider mite (Tetranychus urticae). A small number of maize lines, including B96 and B75, are highly resistant to both herbivores, and B96 is also resistant to thrips. Using T. urticae as a representative pest that causes significant leaf tissue damage, we examined the gene expression responses of these lines to herbivory in comparison with each other and with the susceptible line B73. Upon herbivory, the most resistant line, B96, showed the strongest gene expression response, with a dramatic upregulation of genes associated with jasmonic acid biosynthesis and signaling, as well as the biosynthesis of specialized herbivore deterrent compounds, such as death acids and benzoxazinoids. Extending this work with allele‐specific expression analyses in F1 hybrids, we inferred that the concerted upregulation of many defense genes, including the majority of benzoxazinoid biosynthetic genes in B96, as compared with B73, for the herbivore treatment, resulted from an assemblage of trans control and multiple cis effects acting with similar directionality on gene expression. Further, at the level of individual and potentially rate limiting genes in several major defense pathways, cis and trans effects acted in a reinforcing manner to result in exceptionally high expression in B96. Our study provides a comprehensive resource of cis elements for maize lines important in breeding efforts for herbivore resistance, and reveals potential genetic underpinnings of the origins of multi‐herbivore resistance in plant populations.
Significance Statement
Upon herbivory by a generalist spider mite, transcriptome reprogramming varied among maize lines, with differences in the expression of genes involved in jasmonic acid synthesis and signaling and specialized compound production. As assessed using allelic expression, cis + trans reinforcing regulation led to the very high expression of key defense genes in the most herbivore‐resistant line.
The European Union has an ambitious plan to reduce energy use and emissions by the year 2030. The building and real estate sectors have a great potential to help reduce emissions by energy ...efficiency. However, different energy sources and environmental standards affect the decision making of these major renovations in the existing stock. This study investigates how different renovation strategies affect the energy rating of a selected Building Environmental Assessment Tool and analyses the consequences in terms of greenhouse gas emissions for the local district heating system. Both building energy simulations and energy systems cost optimization were used to determine the energy use and local emissions. The results of different renovation scenarios were used to evaluate the rating in the selected tool and the impact in the district heating local emissions. The used methodology illustrates how energy efficient renovation impacts on the district heating system's local emissions. However, a bias towards resource classification within the Swedish Building Environmental Tool, Miljöbyggnad, needs to be addressed in order to assess the impact of local emissions.
•How renovation affects energy rating in a Building Environmental Assessment Tool.•Analyse the consequences in terms of GHG emissions from the district heating system.•Similar improvements from different renovation strategies.•Biases in the Building Environmental Assessment Tool in emissions classification.•A clear picture of renovation impact on the local energy system.
Specific microbial signals induce the differentiation of a distinct pool of RORγ+ regulatory T (Treg) cells crucial for intestinal homeostasis. We discovered highly analogous populations of ...microbiota-dependent Treg cells that promoted tissue regeneration at extra-gut sites, notably acutely injured skeletal muscle and fatty liver. Inflammatory meditators elicited by tissue damage combined with MHC-class-II-dependent T cell activation to drive the accumulation of gut-derived RORγ+ Treg cells in injured muscle, wherein they regulated the dynamics and tenor of early inflammation and helped balance the proliferation vs. differentiation of local stem cells. Reining in IL-17A-producing T cells was a major mechanism underlying the rheostatic functions of RORγ+ Treg cells in compromised tissues. Our findings highlight the importance of gut-trained Treg cell emissaries in controlling the response to sterile injury of non-mucosal tissues.
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•Muscle injury induces local accumulation of RORγ+ Treg cells emanating from the gut•The microbiota regulates muscle repair via RORγ+ Treg cells•Muscle RORγ+ Treg cells shield differentiating muscle stem cells from IL-17A•RORγ+ Treg cell emissaries play a general role in the homeostasis of extra-gut tissues
Colonic RORγ+ Treg cells are a specialized microbiota-dependent population crucial for intestinal homeostasis, but their role in extra-gut tissues remains unexplored. Hanna et al. report that these cells seed non-mucosal tissues in response to injury wherein they can rein in IL-17A-driven inflammation, regulate stem cell activities, and promote tissue regeneration.
Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) arise from common progenitors. Tumor-derived factors redirect differentiation from immune-promoting DCs to tolerogenic MDSCs, an ...immunological hallmark of cancer. Indeed, in vitro differentiation of DCs from human primary monocytes results in the generation of MDSCs under tumor-associated conditions (PGE2 or tumor cell-conditioned media). Comparison of MDSC and DC DNA methylomes now reveals extensive demethylation with specific gains of DNA methylation and repression of immunogenic-associated genes occurring in MDSCs specifically, concomitant with increased DNA methyltransferase 3A (DNMT3A) levels. DNMT3A downregulation erases MDSC-specific hypermethylation, and it abolishes their immunosuppressive capacity. Primary MDSCs isolated from ovarian cancer patients display a similar hypermethylation signature in connection with PGE2-dependent DNMT3A overexpression. Our study links PGE2- and DNMT3A-dependent hypermethylation with immunosuppressive MDSC functions, providing a promising target for therapeutic intervention.
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•PGE2 induces specific upregulation of DNMT3A in MDSCs•MDSC-suppressive properties depend on DNMT3A and hypermethylation of myeloid genes•Specific DNMT3A-mediated changes in MDSCs suggest potential therapeutic targets•PGE2- and DNMT3A-dependent effects occur in in vitro models and primary samples
Rodríguez-Ubreva et al. find that inflammatory factors, such as prostaglandin E2, that are able to redirect the differentiation of precursor myeloid cells toward tolerogenic myeloid-derived suppressor cells (MDSCs) also impose a DNMT3A-dependent fingerprint in myeloid genes that leads to the acquisition of suppressive properties.
Biomedical single-cell atlases describe disease at the cellular level. However, analysis of this data commonly focuses on cell-type-centric pairwise cross-condition comparisons, disregarding the ...multicellular nature of disease processes. Here, we propose multicellular factor analysis for the unsupervised analysis of samples from cross-condition single-cell atlases and the identification of multicellular programs associated with disease. Our strategy, which repurposes group factor analysis as implemented in multi-omics factor analysis, incorporates the variation of patient samples across cell-types or other tissue-centric features, such as cell compositions or spatial relationships, and enables the joint analysis of multiple patient cohorts, facilitating the integration of atlases. We applied our framework to a collection of acute and chronic human heart failure atlases and described multicellular processes of cardiac remodeling, independent to cellular compositions and their local organization, that were conserved in independent spatial and bulk transcriptomics datasets. In sum, our framework serves as an exploratory tool for unsupervised analysis of cross-condition single-cell atlases and allows for the integration of the measurements of patient cohorts across distinct data modalities.
Slug (SNAI2), a member of the well-conserved Snail family of transcription factors, has multiple developmental roles, including in epithelial-to-mesenchymal transition (EMT). Here, we show that Slug ...is critical for the pathological angiogenesis needed to sustain tumor growth, and transiently necessary for normal developmental angiogenesis. We find that Slug upregulation in angiogenic endothelial cells (EC) regulates an EMT-like suite of target genes, and suppresses Dll4-Notch signaling thereby promoting VEGFR2 expression. Both EC-specific Slug re-expression and reduced Notch signaling, either by γ-secretase inhibition or loss of Dll4, rescue retinal angiogenesis in SlugKO mice. Conversely, inhibition of VEGF signaling prevents excessive angiogenic sprouting of Slug overexpressing EC. Finally, endothelial Slug (but not Snail) is activated by the pro-angiogenic factor SDF1α via its canonical receptor CXCR4 and the MAP kinase ERK5. Altogether, our data support a critical role for Slug in determining the angiogenic response during development and disease.
Abstract
Date Presented Accepted for AOTA INSPIRE 2021 but unable to be presented due to online event limitations.
Latinx cancer survivors experience worse physical and mental health during ...survivorship. This group's occupational participation during survivorship is a product of cultural values, environmental influences, and occupational gains and losses. To promote occupational justice, the OT profession is called to deliver culturally tailored care to capitalize on this group's strengths and prepare them for daily participation.
Primary Author and Speaker: Ricardo Daniel Ramirez
Additional Authors and Speakers: Susan Magasi
Due to the emergence of multidrug-resistant pathogens, it is necessary to develop options to fight infections caused by these agents. Lactoferrin (Lf) is a cationic nonheme multifunctional ...glycoprotein of the innate immune system of mammals that provides numerous benefits. Lf is bacteriostatic and/or bactericidal, can stimulate cell proliferation and differentiation, facilitate iron absorption, improve neural development and cognition, promote bone growth, prevent cancer and exert anti-inflammatory and immunoregulatory effects. Lactoferrin is present in colostrum and milk and is also produced by the secondary granules of polymorphonuclear leukocytes, which store this glycoprotein and release it at sites of infection. Lf is also present in many fluids and exocrine secretions, on the surfaces of the digestive, respiratory and reproductive systems that are commonly exposed to pathogens. Apo-Lf (an iron-free molecule) can be microbiostatic due to its ability to capture ferric iron, blocking the availability of host iron to pathogens. However, apo-Lf is mostly microbicidal via its interaction with the microbial surface, causing membrane damage and altering its permeability function. Lf can inhibit viral entry by binding to cell receptors or viral particles. Lf is also able to counter different important mechanisms evolved by microbial pathogens to infect and invade the host, such as adherence, colonization, invasion, production of biofilms and production of virulence factors such as proteases and toxins. Lf can also cause mitochondrial and caspase-dependent regulated cell death and apoptosis-like in pathogenic yeasts. All of these mechanisms are important targets for treatment with Lf. Holo-Lf (the iron-saturated molecule) can contain up to two ferric ions and can also be microbicidal against some pathogens. On the other hand, lactoferricins (Lfcins) are peptides derived from the N-terminus of Lf that are produced by proteolysis with pepsin under acidic conditions, and they cause similar effects on pathogens to those caused by the parental Lf. Synthetic analog peptides comprising the N-terminus Lf region similarly exhibit potent antimicrobial properties. Importantly, there are no reported pathogens that are resistant to Lf and Lfcins; in addition, Lf and Lfcins have shown a synergistic effect with antimicrobial and antiviral drugs. Due to the Lf properties being microbiostatic, microbicidal, anti-inflammatory and an immune modulator, it represents an excellent natural alternative either alone or as adjuvant in the combat to antibiotic multidrug-resistant bacteria and other pathogens. This review aimed to evaluate the data that appeared in the literature about the effects of Lf and its derived peptides on pathogenic bacteria, protozoa, fungi and viruses and how Lf and Lfcins inhibit the mechanisms developed by these pathogens to cause disease.
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