Nonphotochemical quenching kinetics GWAS in sorghum identifies genes that may play conserved roles in maize and Arabidopsis thaliana photoprotection.

Photosynthetic organisms must cope with rapid fluctuations in light intensity. Nonphotochemical quenching (NPQ) enables the dissipation of excess light energy as heat under high light conditions, whereas its relaxation under low light maximizes photosynthetic productivity. We quantified variation in NPQ kinetics across a large sorghum (Sorghum bicolor) association panel in four environments, uncovering significant genetic control for NPQ.

Population-level gene expression can repeatedly link genes to functions in maize.

Transcriptome-wide association studies (TWAS) can provide single gene resolution for candidate genes in plants, complementing genome-wide association studies (GWAS) but efforts in plants have been met with, at best, mixed success. We generated expression data from 693 maize genotypes, measured in a common field experiment, sampled over a 2-h period to minimize diurnal and environmental effects, using full-length RNA-seq to maximize the accurate estimation of transcript abundance. TWAS could identify roughly 10 times as many genes likely to play a role in flowering time regulation as GWAS conducted data from the same experiment.

Genotype-specific nonphotochemical quenching responses to nitrogen deficit are linked to chlorophyll a to b ratios.

Non-photochemical quenching (NPQ) protects plants from photodamage caused by excess light energy. Substantial variation in NPQ has been reported among different genotypes of the same species. However, comparatively little is known about how environmental perturbations, including nutrient deficits, impact natural variation in NPQ kinetics.

Novel orally bioavailable piperidine derivatives as extracellular arginase inhibitors developed by a ring expansion.

Arginase is a multifaced enzyme that plays an important role in health and disease being regarded as a therapeutic target for the treatment of various pathological states such as malignancies, asthma, and cardiovascular disease. The discovery of boronic acid-based arginase inhibitors in 1997 revolutionized attempts of medicinal chemistry focused on development of drugs targeting arginase. Unfortunately, these very polar compounds had limitations such as analysis and purification without chromophores, synthetically challenging space, and poor oral bioavailability.

Genetic control of photoprotection and photosystem II operating efficiency in plants.

Photoprotection against excess light via nonphotochemical quenching (NPQ) is indispensable for plant survival. However, slow NPQ relaxation under low light conditions can decrease yield of field-grown crops up to 40%. Using semi-high-throughput assay, we quantified the kinetics of NPQ and photosystem II operating efficiency (ΦPSII) in a replicated field trial of more than 700 maize (Zea mays) genotypes across 2 yr.

A role for heritable transcriptomic variation in maize adaptation to temperate environments.

Background: Transcription bridges genetic information and phenotypes. Here, we evaluated how changes in transcriptional regulation enable maize (Zea mays), a crop originally domesticated in the tropics, to adapt to temperate environments.

Result: We generated 572 unique RNA-seq datasets from the roots of 340 maize genotypes.

A common resequencing-based genetic marker data set for global maize diversity.

Maize (Zea mays ssp. mays) populations exhibit vast ranges of genetic and phenotypic diversity. As sequencing costs have declined, an increasing number of projects have sought to measure genetic differences between and within maize populations using whole-genome resequencing strategies, identifying millions of segregating single-nucleotide polymorphisms (SNPs) and insertions/deletions (InDels).

Variation in morpho-physiological and metabolic responses to low nitrogen stress across the sorghum association panel.

Background: Access to biologically available nitrogen is a key constraint on plant growth in both natural and agricultural settings. Variation in tolerance to nitrogen deficit stress and productivity in nitrogen limited conditions exists both within and between plant species. However, our understanding of changes in different phenotypes under long term low nitrogen stress and their impact on important agronomic traits, such as yield, is still limited.

OATD-02 Validates the Benefits of Pharmacological Inhibition of Arginase 1 and 2 in Cancer.

Background: Arginases play essential roles in metabolic pathways, determining the fitness of both immune and tumour cells. Along with the previously validated role of ARG1 in cancer, the particular significance of ARG2 as a therapeutic target has emerged as its levels correlate with malignant phenotype and poor prognosis. These observations unveil arginases, and specifically ARG2, as well-validated and promising therapeutic targets.

Association mapping across a multitude of traits collected in diverse environments in maize.

Classical genetic studies have identified many cases of pleiotropy where mutations in individual genes alter many different phenotypes. Quantitative genetic studies of natural genetic variants frequently examine one or a few traits, limiting their potential to identify pleiotropic effects of natural genetic variants. Widely adopted community association panels have been employed by plant genetics communities to study the genetic basis of naturally occurring phenotypic variation in a wide range of traits.

The Anti-Inflammatory Effect of Acidic Mammalian Chitinase Inhibitor OAT-177 in DSS-Induced Mouse Model of Colitis.

Inflammatory bowel diseases (IBD) are chronic and relapsing gastrointestinal disorders, where a significant proportion of patients are unresponsive or lose response to traditional and currently used therapies. In the current study, we propose a new concept for anti-inflammatory treatment based on a selective acidic mammalian chitinase (AMCase) inhibitor. The functions of chitinases remain unclear, but they have been shown to be implicated in the pathology of various inflammatory disorders regarding the lung (asthma, idiopathic pulmonary fibrosis) and gastrointestinal tract (IBD and colon cancer).

Potent but transient immunosuppression of T-cells is a general feature of CD71 erythroid cells.

CD71 erythroid cells (CECs) have been recently recognized in both neonates and cancer patients as potent immunoregulatory cells. Here, we show that in mice early-stage CECs expand in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). In the spleens of anemic mice, CECs expansion-induced -arginine depletion suppresses T-cell responses.

A Novel Oral Arginase 1/2 Inhibitor Enhances the Antitumor Effect of PD-1 Inhibition in Murine Experimental Gliomas by Altering the Immunosuppressive Environment.

Glioblastomas (GBM) are the common and aggressive primary brain tumors that are incurable by conventional therapies. Immunotherapy with immune checkpoint inhibitors is not effective in GBM patients due to the highly immunosuppressive tumor microenvironment (TME) restraining the infiltration and activation of cytotoxic T cells. Clinical and experimental studies showed the upregulation of expression of the arginase 1 and 2 (ARG1 and ARG2, respectively) in murine and human GBMs.

Inhibition of arginase modulates T-cell response in the tumor microenvironment of lung carcinoma.

Immunotherapy has demonstrated significant activity in a broad range of cancer types, but still the majority of patients receiving it do not maintain durable therapeutic responses. Amino acid metabolism has been proposed to be involved in the regulation of immune response. Here, we investigated in detail the role of arginase 1 (Arg1) in the modulation of antitumor immune response against poorly immunogenic Lewis lung carcinoma.

Hyperspectral reflectance-based phenotyping for quantitative genetics in crops: Progress and challenges.

Many biochemical and physiological properties of plants that are of interest to breeders and geneticists have extremely low throughput and/or can only be measured destructively. This has limited the use of information on natural variation in nutrient and metabolite abundance, as well as photosynthetic capacity in quantitative genetic contexts where it is necessary to collect data from hundreds or thousands of plants. A number of recent studies have demonstrated the potential to estimate many of these traits from hyperspectral reflectance data, primarily in ecophysiological contexts.

Chitinases and Chitinase-Like Proteins as Therapeutic Targets in Inflammatory Diseases, with a Special Focus on Inflammatory Bowel Diseases.

Chitinases belong to the evolutionarily conserved glycosyl hydrolase family 18 (GH18). They catalyze degradation of chitin to -acetylglucosamine by hydrolysis of the β-(1-4)-glycosidic bonds. Although mammals do not synthesize chitin, they possess two enzymatically active chitinases, i.

Meta-analysis identifies pleiotropic loci controlling phenotypic trade-offs in sorghum.

Community association populations are composed of phenotypically and genetically diverse accessions. Once these populations are genotyped, the resulting marker data can be reused by different groups investigating the genetic basis of different traits. Because the same genotypes are observed and scored for a wide range of traits in different environments, these populations represent a unique resource to investigate pleiotropy.

Maize Response to Low Temperatures at the Gene Expression Level: A Critical Survey of Transcriptomic Studies.

Maize is a cold-sensitive plant whose physiological reactions to sub-optimal temperatures are well understood, but their molecular foundations are only beginning to be deciphered. In an attempt to identify key genes involved in these reactions, we surveyed several independent transcriptomic studies addressing the response of juvenile maize to moderate or severe cold. Among the tens of thousands of genes found to change expression upon cold treatment less than 500 were reported in more than one study, indicating an astonishing variability of the expression changes, likely depending on the experimental design and plant material used.

Increased photosensitivity at early growth as a possible mechanism of maize adaptation to cold springs.

Maize is a cold-sensitive species, but selective breeding programs have recently succeeded in producing plants strikingly well adapted to the cold springs of a temperate climate, showing the potential for improved cold tolerance. The aim of the present study was to determine whether the adaptation of some inbred lines to spring chills is due to their increased true cold tolerance or whether it only represents an avoidance mechanism, which was the sole mode of adaptation during early stages of agricultural dispersal of maize towards higher latitudes. By characterizing numerous physiological features of several lines of different cold sensitivity, we show that a combination of both avoidance and tolerance is involved.

Molecular foundations of chilling-tolerance of modern maize.

Background: Recent progress in selective breeding of maize (Zea mays L.) towards adaptation to temperate climate has allowed the production of inbred lines withstanding cold springs with temperatures below 8 °C or even close to 0 °C, indicating that despite its tropical origins maize is not inherently cold-sensitive.

Results: Here we studied the acclimatory response of three maize inbred lines of contrasting cold-sensitivity selected basing on multi-year routine field data.

Mycobacterium tuberculosis AtsG (Rv0296c), GlmU (Rv1018c) and SahH (Rv3248c) Proteins Function as the Human IL-8-Binding Effectors and Contribute to Pathogen Entry into Human Neutrophils.

Mycobacterium tuberculosis is an extremely successful intracellular pathogen that has evolved a broad spectrum of pathogenic mechanisms that enable its manipulation of host defense elements and its survival in the hostile environment inside phagocytes. Cellular influx into the site of mycobacterial entry is mediated by a variety of chemokines, including interleukin-8 (IL-8), and the innate cytokine network is critical for the development of an adaptive immune response and infection control. Using affinity chromatography, liquid chromatography electrospray ionization tandem mass spectrometry and surface plasmon resonance techniques, we identified M.

Towards vaccine against toxoplasmosis: evaluation of the immunogenic and protective activity of recombinant ROP5 and ROP18 Toxoplasma gondii proteins.

Toxoplasmosis is one of the most common parasitic infections worldwide. An effective vaccine against human and animal toxoplasmosis is still needed to control this parasitosis. The polymorphic rhoptry proteins, ROP5 and ROP18, secreted by Toxoplasma gondii during the invasion of the host cell have been recently considered as promising vaccine antigens, as they appear to be the major determinants of T.

Phytoecdysteroids as modulators of the Toxoplasma gondii growth rate in human and mouse cells.

Background: Searching for new effective drugs against human and animal toxoplasmosis we decided to test the anti-Toxoplasma potential of phytoecdysteroids (α-ecdysone and 20-hydroxyecdysone) characterized by the pleiotropic activity on mammalian organisms including the enhancement of host's anti-parasitic defence. This objective was accomplished by the in vitro evaluation of T. gondii growth in phytoecdysteroid-treated immunocompetent cells of selected hosts: humans and two strains of inbred mice with genetically determined different susceptibility to toxoplasmosis.

Human toxoplasmosis: a comparative evaluation of the diagnostic potential of recombinant Toxoplasma gondii ROP5 and ROP18 antigens.

Toxoplasmosis is one of the most common parasitic diseases worldwide and it poses a serious challenge regarding prevention, diagnosis and therapy. The commonly used diagnostic methods are mostly based on the detection of specific antibodies in sera. Since they are not always accurate enough and do not allow precise definition of the phase of the Toxoplasma gondii infection, there is an urgent need to find specific molecular markers of acute or chronic infection stages.