Practical divergent synthesis of all possible regioisomers of myo-inositol trisphosphates

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The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana

Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific ‘‘avirulent’’ pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4) and RRS1 (resistance to Ralstonia solanacearum 1), function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NBLRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1) mutant encodes an RRS1 allele (RRS1SLH1) with a single amino acid (leucine) insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi) mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed new light on mechanisms by which NB-LRR protein pairs activate defense signaling, or are held inactive in the absence of a pathogen effector

Body Fat Is Related to Sedentary Behavior and Light Physical Activity but Not to Moderate-Vigorous Physical Activity in Type 2 Diabetes Mellitus

BACKGROUND: Sedentary behavior (SB) has emerged as a new risk factor for cardiovascular accidents. We investigated whether physical activity levels or SB were related to percent body fat (%BF) in type 2 diabetes mellitus (T2DM). METHODS: In this cross sectional study, we measured the duration of SB, light physical activity (LPA), moderate to vigorous physical activity (MVPA), total energy expenditure, and step counts using a wireless activity tracker (Fitbit HR; FB) for 7 days in free-living conditions, along with %BF using a bio impedance analyzer (Inbody; Biospace) in 120 smartphone users with T2DM. Subjects were divided into exercise (Exe, n=68) and non-exercise (nonExe, n=52) groups based on self-reports of whether the recommended exercises (30 min/day, 3 days/week for 3 months) were performed. SBt, LPAt, MVPAt were transformed from SB, LPA, MVPA for normally distributed variables. RESULTS: Participants were: female, 59.2%; age, 59.3+/-8.4 years; body mass index, 25.5+/-3.4 kg/m(2); glycosylated hemoglobin (HbA1c), 7.6%+/-1.2%; %BF, 30.4%+/-7.1%. They performed SB for 15.7+/-3.7 hr/day, LPA for 4.4+/-1.7 hr/day, and MVPA for 0.9+/-0.8 hr/day. The %BF was related to SBt and LPAt, but not to MVPA after adjustments for age, gender, and HbA1c. VPA was significantly higher in the Exe group than in the nonExe group, but SB, LPA, and moderate physical activity were not different. Predicted %BF was 89.494 to 0.105 (age), -13.047 (gender), -0.507 (HbA1c), -7.655 (LPAt) (F[4, 64]=62.929, P<0.001), with an R(2) of 0.785 in multiple linear regression analysis. CONCLUSION: Reduced body fat in elderly diabetic patients might be associated with reduced inactivity and increased LPA

Functionally Redundant RXLR Effectors from <em>Phytophthora infestans</em> Act at Different Steps to Suppress Early flg22-Triggered Immunity

Genome sequences of several economically important phytopathogenic oomycetes have revealed the presence of large families of so-called RXLR effectors. Functional screens have identified RXLR effector repertoires that either compromise or induce plant defense responses. However, limited information is available about the molecular mechanisms underlying the modes of action of these effectors in planta. The perception of highly conserved pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), such as flg22, triggers converging signaling pathways recruiting MAP kinase cascades and inducing transcriptional re-programming, yielding a generic anti-microbial response. We used a highly synchronizable, pathogen-free protoplast-based assay to identify a set of RXLR effectors from Phytophthora infestans (PiRXLRs), the causal agent of potato and tomato light blight that manipulate early stages of flg22-triggered signaling. Of thirty-three tested PiRXLR effector candidates, eight, called Suppressor of early Flg22-induced Immune response (SFI), significantly suppressed flg22-dependent activation of a reporter gene under control of a typical MAMP-inducible promoter (pFRK1-Luc) in tomato protoplasts. We extended our analysis to Arabidopsis thaliana, a non-host plant species of P. infestans. From the aforementioned eight SFI effectors, three appeared to share similar functions in both Arabidopsis and tomato by suppressing transcriptional activation of flg22-induced marker genes downstream of post-translational MAP kinase activation. A further three effectors interfere with MAMP signaling at, or upstream of, the MAP kinase cascade in tomato, but not in Arabidopsis. Transient expression of the SFI effectors in Nicotiana benthamiana enhances susceptibility to P. infestans and, for the most potent effector, SFI1, nuclear localization is required for both suppression of MAMP signaling and virulence function. The present study provides a framework to decipher the molecular mechanisms underlying the manipulation of host MAMP-triggered immunity (MTI) by P. infestans and to understand the basis of host versus non-host resistance in plants towards P. infestans

The Transcriptional Repressor TupA in Aspergillus niger Is Involved in Controlling Gene Expression Related to Cell Wall Biosynthesis, Development, and Nitrogen Source Availability.

The Tup1-Cyc8 (Ssn6) complex is a well characterized and conserved general transcriptional repressor complex in eukaryotic cells. Here, we report the identification of the Tup1 (TupA) homolog in the filamentous fungus Aspergillus niger in a genetic screen for mutants with a constitutive expression of the agsA gene. The agsA gene encodes a putative alpha-glucan synthase, which is induced in response to cell wall stress in A. niger. Apart from the constitutive expression of agsA, the selected mutant was also found to produce an unknown pigment at high temperatures. Complementation analysis with a genomic library showed that the tupA gene could complement the phenotypes of the mutant. Screening of a collection of 240 mutants with constitutive expression of agsA identified sixteen additional pigment-secreting mutants, which were all mutated in the tupA gene. The phenotypes of the tupA mutants were very similar to the phenotypes of a tupA deletion strain. Further analysis of the tupA-17 mutant and the DeltatupA mutant revealed that TupA is also required for normal growth and morphogenesis. The production of the pigment at 37 degrees C is nitrogen source-dependent and repressed by ammonium. Genome-wide expression analysis of the tupA mutant during exponential growth revealed derepression of a large group of diverse genes, including genes related to development and cell wall biosynthesis, and also protease-encoding genes that are normally repressed by ammonium. Comparison of the transcriptome of up-regulated genes in the tupA mutant showed limited overlap with the transcriptome of caspofungin-induced cell wall stress-related genes, suggesting that TupA is not a general suppressor of cell wall stress-induced genes. We propose that TupA is an important repressor of genes related to development and nitrogen metabolism

Bioavailable Trace Metals in Neurological Diseases

Medical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron

Association between Relative Handgrip Strength and Osteoporosis in Older Women: The Korea National Health and Nutrition Examination Survey 2014-2018

BACKGROUND: While handgrip strength is associated with osteoporosis (OS) in the older population and muscle weakness is related to a reduction in bone mineral density, no study has yet assessed the association between relative hand grip strength (RHGS) and OS in the older Korean population. This study assessed the associations between RHGS and OS in Korean older women aged over 60 years. METHODS: We used data of 4,179 older women from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2018. We applied binomial logistic regression to identify an association between RHGS and OS while controlling for other covariates such as age; socioeconomic status; smoking behavior; alcohol consumption, laboratory test results; and the prevalence of hypertension, diabetes mellitus, thyroid disease, and obesity. RESULTS: RHGS was significantly associated with OS of the left hand in older Korean women. RHGS levels 2 and 4 of the left hand showed an inverse association with the prevalence of OS in female participants aged 60-69 years (odds ratio [OR]=0.637; 95% confidence interval [CI], 0.452-0.898; p=0.010; and OR=0.496; 95% CI, 0.258-0.956; p=0.036, respectively) but not in those aged over 70 years and in the right hand. CONCLUSION: OS was significantly associated with left-hand RHGS in 60-69-year-old women, and the OS risks decreased by approximately 36.3% and 50.4% in women with RHGS levels 2 and 4, respectively. RHGS may be used to predict OS in pre-clinical settings such as public health care institutes

Cross-tolerance to abiotic stresses in halophytes: Application for phytoremediation of organic pollutants

International audienceHalopytes are plants able to tolerate high salt concentrations but no clear definition was retained for them. In literature, there are more studies that showed salt-enhanced tolerance to other abiotic stresses compared to investigations that found enhanced salt tolerance by other abiotic stresses in halophytes. The phenomenon by which a plant resistance to a stress induces resistance to another is referred to as cross-tolerance. In this work, we reviewed cross-tolerance in halophytes at the physiological, biochemical, and molecular levels. A special attention was accorded to the cross-tolerance between salinity and organic pollutants that could allow halophytes a higher potential of xenobiotic phytoremediation in comparison with glycophytes

Immunological characterizations of a cloned 13.1-kilodalton protein from pathogenic Naegleria fowleri.

We previously cloned an antigenic gene (named nfa1) from a cDNA library of Naegleria fowleri by immunoscreening. The nfa1 gene had a coding nucleotide sequence consisting of 357 bases and produced a recombinant 13.1-kDa protein (Nfa1). In this study, to get more information regarding the recombinant Nfa1 protein (rNfa1), we produced an anti-Nfa1 polyclonal antibody from mice immunized with rNfa1 and used a peroxidase staining method to carry out immunocytochemistry experiments. In addition, we observed the effect of the presence of an anti-Nfa1 antibody on the in vitro cytotoxicity of N. fowleri against Chinese hamster ovary (CHO) cells. Trophozoites of N. fowleri in cultivation reacted strongly with a peroxidase-labeled anti-Nfa1 antibody. In inflammatory and necrotic regions of brain tissue infected with N. fowleri, labeled trophozoites that were stained brown were also observed. When examined using a transmission electron microscope, the Nfa1 protein showed pseudopodium-specific immunolocalization on a trophozoite of N. fowleri. When examined using a light microscope, CHO cells grown in cocultures with N. fowleri trophozoites (group I) for 48 h showed morphologically severe destruction but CHO cells grown in cocultures with N. fowleri trophozoites and an anti-Nfa1 polyclonal antibody (group II) showed less destruction. The results of a lactate dehydrogenase release assay showed that group I CHO cells exhibited 81% cytotoxicity and group II CHO cells exhibited 13.8% cytotoxicity

Young off-axis volcanism along the ultraslow-spreading Southwest Indian Ridge

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 3 (2010): 286-292, doi:10.1038/ngeo824.Mid-ocean ridge crustal accretion occurs continuously at all spreading rates through a combination of magmatic and tectonic processes. Fast to slow spreading ridges are largely built by adding magma to narrowly focused neovolcanic zones. In contrast, ultraslow spreading ridge construction significantly relies on tectonic accretion, which is characterized by thin volcanic crust, emplacement of mantle peridotite directly to the seafloor, and unique seafloor fabrics with variable segmentation patterns. While advances in remote imaging have enhanced our observational understanding of crustal accretion at all spreading rates, temporal information is required in order to quantitatively understand mid-ocean ridge construction. However, temporal information does not exist for ultraslow spreading environments. Here, we utilize U-series eruption ages to investigate crustal accretion at an ultraslow spreading ridge for the first time. Unexpectedly young eruption ages throughout the Southwest Indian ridge rift valley indicate that neovolcanic activity is not confined to the spreading axis, and that magmatic crustal accretion occurs over a wider zone than at faster spreading ridges. These observations not only suggest that crustal accretion at ultraslow spreading ridges is distinct from faster spreading ridges, but also that the magma transport mechanisms may differ as a function of spreading rate.This work was supported by the following NSF grants: NSF-OCE 0137325; NSF-OCE 060383800; and NSF-OCE 062705300