Exposure to Oil and Hypoxia Results In Alterations of Immune Transcriptional Patterns In Developing Sheepshead Minnows (\u3ci\u3eCyprinodon variegatus\u3c/i\u3e)

The area and timing of the Deepwater Horizon oil spill highlight the need to study oil and hypoxia exposure in early life stage fishes. Though critical to health, little research has targeted the effect of oil and hypoxia exposure on developing immune systems. To this end, we exposed sheepshead minnows (Cyprinodon variegatus) at three early life stages: embryonic; post-hatch; and post-larval, to a high energy water accommodated fraction (HEWAF) of oil, hypoxia, or both for 48 hours. We performed RNAseq to understand how exposures alter expression of immune transcripts and pathways. Under control conditions, the embryonic to post-hatch comparison (first transition) had a greater number of significantly regulated immune pathways than the second transition (post-hatch to post-larval). The addition of oil had little effect in the first transition, however, hypoxia elicited changes in cellular and humoral immune responses. In the second transition, oil exposure significantly altered many immune pathways (43), and while hypoxia altered few pathways, it did induce a unique signature of generally suppressing immune pathways. These data suggest that timing of exposure to oil and/or hypoxia matters, and underscores the need to further investigate the impacts of multiple stressors on immune system development in early life stage fishes

Commercial production of Florida pompano (Trachinotus carolinus) larvae at low salinity induces variable changes in whole-larvae microbial diversity, gene expression, and gill histopathology

IntroductionSalinity presents economic and technical challenges in land-based recirculating aquaculture systems (RAS) in the U.S. warm water marine finfish aquaculture industry. Many studies have shown euryhaline fish reared at salinities closer to their iso-osmotic salinity can yield enhanced production performance as well as potential reduced costs to farms. However, there is potential for osmotic stress in fish larvae to negatively impact larvae microbiome and innate immune system. Florida pompano (Trachinotus carolinus) is a popular sportfish has been targeted for land-based RAS due to its impressive market value and euryhaline capacity. This study investigated the impacts of rearing Florida pompano larvae at salinities closer to their iso-osmotic salinity.Materials and methodsLarvae were cultured at 10, 20, and 30 ppt in triplicates, and larvae samples were collected for histopathology, microbiome, and whole transcriptomics analysis every three days from hatching until the time of weaning (24 days post hatch [DPH]). Water samples were also taken for microbiome analysis on every other larval sampling day. DiscussionThese changes were driven more by metamorphosis, causing an increase in expression of antioxidant genes (cat, gss, gsto1, and scara3) than by the presence of potentially pathogenic genera, which failed to induce an immune response (low or unchanged expression of downstream elements of the NOD1 or TLR5 pathways). These findings provide baseline information on Florida pompano low salinity tolerance in larviculture during early developmental stages. In addition, we have shown minimal effects on the immune system at salinities as low as 10 ppt. This work has important implications for larval health management and can be used to refine and direct future research regarding improving commercial production of warm water marine specie

Butane Dry Reforming Catalyzed by Cobalt Oxide Supported on Ti2AlC MAX Phase

MAX (M(n+1)AX(n)) phases are layered carbides or nitrides with a high thermal and mechanical bulk stability. Recently, it was shown that their surface structure can be modified to form a thin non-stoichiometric oxide layer, which can catalyze the oxidative dehydrogenation of butane. Here, the use of a Ti2AlC MAX phase as a support for cobalt oxide was explored for the dry reforming of butane with CO2, comparing this new catalyst to more traditional materials. The catalyst was active and selective to synthesis gas. Although the surface structure changed during the reaction, the activity remained stable. Under the same conditions, a titania-supported cobalt oxide catalyst gave low activity and stability due to the agglomeration of cobalt oxide particles. The Co3O4/Al(2)O(3)catalyst was active, but the acidic surface led to a faster deactivation. The less acidic surface of the Ti2AlC was better at inhibiting coke formation. Thanks to their thermal stability and acid-base properties, MAX phases are promising supports for CO(2)conversion reactions

Alternative polyadenylation and salicylic acid modulate root responses to low nitrogen availability

Nitrogen (N) is probably the most important macronutrient and its scarcity limits plant growth, development and fitness. N starvation response has been largely studied by transcriptomic analyses, but little is known about the role of alternative polyadenylation (APA) in such response. In this work, we show that N starvation modifies poly(A) usage in a large number of transcripts, some of them mediated by FIP1, a component of the polyadenylation machinery. Interestingly, the number of mRNAs isoforms with poly(A) tags located in protein-coding regions or 5 '-UTRs significantly increases in response to N starvation. The set of genes affected by APA in response to N deficiency is enriched in N-metabolism, oxidation-reduction processes, response to stresses, and hormone responses, among others. A hormone profile analysis shows that the levels of salicylic acid (SA), a phytohormone that reduces nitrate accumulation and root growth, increase significantly upon N starvation. Meta-analyses of APA-affected and fip1-2-deregulated genes indicate a connection between the nitrogen starvation response and salicylic acid (SA) signaling. Genetic analyses show that SA may be important for preventing the overgrowth of the root system in low N environments. This work provides new insights on how plants interconnect different pathways, such as defense-related hormonal signaling and the regulation of genomic information by APA, to fine-tune the response to low N availability

Incipient resistance to an effective pesticide results from genetic adaptation and the canalization of gene expression

The resistance of pest species to chemical controls has vast ecological, economic, and societal costs. In most cases, resistance is only detected after spreading throughout an entire population. Detecting resistance in its incipient stages, by comparison, provides time to implement preventative strategies. Incipient resistance can be detected by coupling standard toxicology assays with large-scale gene expression experiments. We apply this approach to a system where an invasive parasite, sea lamprey (Petromyzon marinus), has been treated with the highly effective pesticide 3-trifluoromethyl-4-nitrophenol (TFM) for 60 years. Toxicological experiments revealed that lamprey from treated populations did not have higher survival to TFM exposure than lamprey from untreated populations, demonstrating that full-fledged resistance has not yet evolved. In contrast, we find hundreds of genes differentially expressed in response to TFM in the population with the longest history of exposure, many of which relate to TFM's primary mode of action, the uncoupling of oxidative phosphorylation, and subsequent depletion of ATP. Three genes critical to oxidative phosphorylation, ATP5PB, PLCB1, and NDUFA9, were nearly fixed for alternative alleles in comparisons of SNPs between treated and untreated populations (FST > 5 SD from the mean). ATP5PB encodes subunit b of ATP synthase and an additional subunit, ATP5F1B, was canalized for high expression in treated populations, but remained plastic in response to TFM treatment in individuals from the untreated population. These combined genomic and transcriptomic results demonstrate that an adaptive, genetic response to TFM is likely driving incipient resistance in a damaging pest species

Emerging role of angiotensin type 2 receptor (AT2R)/Akt/NO pathway in vascular smooth muscle cell in the hyperthyroidism

Hyperthyroidism is characterized by increased vascular relaxation and decreased vascular contraction and is associated with augmented levels of triiodothyronine (T3) that contribute to the diminished systemic vascular resistance found in this condition. T3 leads to augmented NO production via PI3K/Akt signaling pathway, which in turn causes vascular smooth muscle cell (VSMC) relaxation; however, the underlying mechanisms involved remain largely unknown. Evidence from human and animal studies demonstrates that the renin-angiotensin system (RAS) plays a crucial role in vascular function and also mediates some of cardiovascular effects found during hyperthyroidism. Thus, in this study, we hypothesized that type 2 angiotensin II receptor (AT2R), a key component of RAS vasodilatory actions, mediates T3 induced-decreased vascular contraction. Marked induction of AT2R expression was observed in aortas from T3-induced hyperthyroid rats (Hyper). These vessels showed decreased protein levels of the contractile apparatus: α-actin, calponin and phosphorylated myosin light chain (p-MLC). Vascular reactivity studies showed that denuded aortic rings from Hyper rats exhibited decreased maximal contractile response to angiotensin II (AngII), which was attenuated in aortic rings pre-incubated with an AT2R blocker. Further study showed that cultured VSMC stimulated with T3 (0.1 µmol/L) for 24 hours had increased AT2R gene and protein expression. Augmented NO levels and decreased p-MLC levels were found in VSMC stimulated with T3, both of which were reversed by a PI3K/Akt inhibitor and AT2R blocker. These findings indicate for the first time that the AT2R/Akt/NO pathway contributes to decreased contractile responses in rat aorta, promoted by T3, and this mechanism is independent from the endothelium.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo; grants 06/61523-7 and 06/54064-6)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paul

Efecto del consumo de harina de maíz fortificada con ácido fólico sobre los niveles de folatos sanguíneos en mujeres de edad fértil

Fortification of foods is now widely used to prevent folate deficiency. Folic acid has been added to corn flour and its efficacy in the prevention of NTD has been proved. The aim of this study was to compare the effect of the intake of fortified corn-flour versus non fortified flour and to folic acid supplement, on blood folate levels in women of childbearing age. Forty-five women were randomized into three groups according to: (A) use of fortified flour (n=18), (B) non-fortified flour (n=17); (C) supplementation with 5 mg of oral folic acid (n=10). All females answer a dietary and anthropometric questionnaire applied once a month during three months. Blood red cell (IE) and plasmatic (P) folate were measured at the beginning and at the end of the study; also the DNA analysis for the 677T mutation was performed. The corn flour was provided to groups A and B during three months, to be consumed as eight tortillas daily. Group C received 5.0 mg tablet of folic acid (Valdecasas®), once per week, during three months. IE and P folate and hematocrito were significantly increased in women from group C (p<0.05) ). Only plasmatic folic acid levels were significantly increased in women from groups A and B. Genotype distribution was: 15.6% homozygous TT, 42.2% C/C and 42.2% CT. Weekly administration of 5.0 mg of folic acid is an effective way to increase blood folate levels and shows to be more efficient than fortified corn flour

Transforming Growth Factor Beta 2 and Heme Oxygenase 1 Genes Are Risk Factors for the Cerebral Malaria Syndrome in Angolan Children

BACKGROUND: Cerebral malaria (CM) represents a severe outcome of the Plasmodium falciparum infection. Recent genetic studies have correlated human genes with severe malaria susceptibility, but there is little data on genetic variants that increase the risk of developing specific malaria clinical complications. Nevertheless, susceptibility to experimental CM in the mouse has been linked to host genes including Transforming Growth Factor Beta 2 (TGFB2) and Heme oxygenase-1 (HMOX1). Here, we tested whether those genes were governing the risk of progressing to CM in patients with severe malaria syndromes. METHODOLOGY/PRINCIPAL FINDINGS: We report that the clinical outcome of P. falciparum infection in a cohort of Angolan children (n = 430) correlated with nine TGFB2 SNPs that modify the risk of progression to CM as compared to other severe forms of malaria. This genetic effect was explained by two haplotypes harboring the CM-associated SNPs (Pcorrec. = 0.035 and 0.036). In addition, one HMOX1 haplotype composed of five CM-associated SNPs increased the risk of developing the CM syndrome (Pcorrec. = 0.002) and was under-transmitted to children with uncomplicated malaria (P = 0.036). Notably, the HMOX1-associated haplotype conferred increased HMOX1 mRNA expression in peripheral blood cells of CM patients (P = 0.012). CONCLUSIONS/SIGNIFICANCE: These results represent the first report on CM genetic risk factors in Angolan children and suggest the novel hypothesis that genetic variants of the TGFB2 and HMOX1 genes may contribute to confer a specific risk of developing the CM syndrome in patients with severe P. falciparum malaria. This work may provide motivation for future studies aiming to replicate our findings in larger populations and to confirm a role for these genes in determining the clinical course of malaria

Thyroid Hormone T3 Counteracts STZ Induced Diabetes in Mouse

This study intended to demonstrate that the thyroid hormone T3 counteracts the onset of a Streptozotocin (STZ) induced diabetes in wild type mice. To test our hypothesis diabetes has been induced in Balb/c male mice by multiple low dose Streptozotocin injection; and a group of mice was contemporaneously injected with T3. After 48 h mice were tested for glucose tolerance test, insulin serum levels and then sacrified. Whole pancreata were utilized for morphological and biochemical analyses, while protein extracts and RNA were utilized for expression analyses of specific molecules. The results showed that islets from T3 treated mice were comparable to age- and sex-matched control, untreated mice in number, shape, dimension, consistency, ultrastructure, insulin and glucagon levels, Tunel positivity and caspases activation, while all the cited parameters and molecules were altered by STZ alone. The T3-induced pro survival effect was associated with a strong increase in phosphorylated Akt. Moreover, T3 administration prevented the STZ-dependent alterations in glucose blood level, both during fasting and after glucose challenge, as well as in insulin serum level. In conclusion we demonstrated that T3 could act as a protective factor against STZ induced diabetes

Non-β-Blocking Carvedilol Analog, VK-II-86, Prevents Ouabain-Induced Cardiotoxicity.

Background It has been shown that carvedilol and its non β-blocking analog, VK-II-86, inhibit spontaneous Ca2+ release from the sarcoplasmic reticulum (SR). The aim of this study is to determine whether carvedilol and VK-II-86 suppress ouabain-induced arrhythmogenic Ca2+ waves and apoptosis in cardiac myocytes. Methods and Results: Rat cardiac myocytes were exposed to toxic doses of ouabain (50 µmol/L). Cell length (contraction) was monitored in electrically stimulated and non-stimulated conditions. Ouabain treatment increased contractility, frequency of spontaneous contractions and apoptosis compared to control cells. Carvedilol (1 µmol/L) or VK-II-86 (1 µmol/L) did not affect ouabain-induced inotropy, but significantly reduced the frequency of Ca2+ waves, spontaneous contractions and cell death evoked by ouabain treatment. This antiarrhythmic effect was not associated with a reduction in Ca2+ calmodulin-dependent protein kinase II (CaMKII) activity, phospholamban and ryanodine receptor phosphorylation or SR Ca2+ load. Similar results could be replicated in human cardiomyocytes derived from stem cells and in a mathematical model of human myocytes. Conclusions Carvedilol and VK-II-86 are effective to prevent ouabain-induced apoptosis and spontaneous contractions indicative of arrhythmogenic activity without affecting inotropy and demonstrated to be effective in human models, thus emerging as a therapeutic tool for the prevention of digitalis-induced arrhythmias and cardiac toxicity.Centro de Investigaciones CardiovascularesConsejo Nacional de Investigaciones Científicas y Técnica