Cold stress is a significant environmental factor that negatively affects plant growth and development in particular when it occurs during the growth phase. Plants have evolved means to protect ...themselves from damage caused by chilling or freezing temperatures and some plant species, in particular those from temperate geographical zones, can increase their basal level of freezing tolerance in a process termed cold acclimation. Cold acclimation improves plant survival, but also represses growth, since it inhibits activity of the growth-promoting hormones gibberellins (GAs). In addition to GAs, the steroid hormones brassinosteroids (BRs) also take part in growth promotion and cold stress signaling; however, in contrast to Gas, BRs can improve cold stress tolerance with fewer trade-offs in terms of growth and yields. Here we summarize our current understanding of the roles of BRs in cold stress responses with a focus on freezing tolerance and cold acclimation pathways.
Circulating levels of fibroblast growth factor 23 (FGF23) are elevated in patients with chronic kidney disease (CKD), but the mechanisms are poorly understood. Here we tested whether inflammation and ...iron deficiency regulate FGF23. In wild-type mice, acute inflammation induced by single injections of heat-killed Brucella abortus or interleukin-1β (IL-1β) decreased serum iron within 6 h, and was accompanied by significant increases in osseous Fgf23 mRNA expression and serum levels of C-terminal FGF23, but no changes in intact FGF23. Chronic inflammation induced by repeated bacteria or IL-1β injections decreased serum iron, increased osseous Fgf23 mRNA, and serum C-terminal FGF23, but modestly increased biologically active, intact FGF23 serum levels. Chronic iron deficiency mimicked chronic inflammation. Increased osseous FGF23 cleavage rather than a prolonged half-life of C-terminal FGF23 fragments accounted for the elevated C-terminal FGF23 but near-normal intact FGF23 levels in inflammation. IL-1β injection increased Fgf23 mRNA and C-terminal FGF23 levels similarly in wildtype and Col4a3ko mice with CKD but markedly increased intact FGF23 levels only in the CKD mice. Inflammation increased Fgf23 transcription by activating Hif1α signaling. Thus, inflammation and iron deficiency stimulate FGF23 production. Simultaneous upregulation of FGF23 cleavage in osteocytes maintains near-normal levels of biologically active, intact circulating FGF23, whereas downregulated or impaired FGF23 cleavage may contribute to elevated intact serum FGF23 in CKD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A simple technique to produce spray-dried porous particles for inhalatory administration was developed. The particles were produced using water as solvent, Sodium Cromoglycate as model drug and ...ammonium bicarbonate as pore forming agent. A central composite design was employed to study the influence of the: pore-forming agent concentration (in the drug aqueous solution fed to the spray dryer) and air inlet temperature on: process yield and powder properties. The powder particle size distribution, moisture content, densities and estimated aerodynamic diameters were studied. Also, particles morphology, hygroscopicity, surface area, in vitro aerosolization properties, dissolution rate and stability were evaluated for some selected samples. In addition, a novel friability test was proposed for mechanical resistance evaluation of the porous materials.
A pore forming agent concentration of 1.25% (w/w) and an air inlet temperature of 170 °C were the optimal process parameters to produce porous particles suitable for inhalatory administration. The process yield was high and it was demonstrated that the particles were free of ammonium bicarbonate. The porous powder, obtained by a simple and scalable technique, exhibited low tap density, good stability even at long storage periods (12 months), appropriate mechanical resistance, high initial dissolution rate and excellent aerosolization performance.
Large porous inhalatory spray-dried particles obtained without using organic solvents and employing ammonium bicarbonate as pore forming agent. Display omitted
•Development of spray-dried inhalable porous particle without using organic solvents.•Cromoglycate porous particles with adequate in vitro aerosolization properties.•Appropriate long term stability of porous Cromoglycate inhalable particles.•Stable porous Cromoglycate inhalable particles even under mechanical stress.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Plants in temperate climates utilize cold acclimation modes to improve frost tolerance during phases of active growth. Two papers in this issue of Developmental Cell (Li et al., 2017; Zhao et al., ...2017) now highlight the important role MAP kinases play in this process in Arabidopsis thaliana.
Plants in temperate climates utilize cold acclimation modes to improve frost tolerance during phases of active growth. Two papers in this issue of Developmental Cell (Li et al., 2017; Zhao et al., 2017) now highlight the important role MAP kinases play in this process in Arabidopsis thaliana.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
RATIONALE:Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to various concerns. Recently, salutary effects of stem cells have been connected to exosome ...secretion. ESCs have the ability to produce exosomes, however, their effect in the context of the heart is unknown.
OBJECTIVE:Determine the effect of ESC-derived exosome for the repair of ischemic myocardium and whether c-kit cardiac progenitor cells (CPCs) function can be enhanced with ESC exosomes.
METHODS AND RESULTS:This study demonstrates that mouse ESC-derived exosomes (mES Ex) possess ability to augment function in infarcted hearts. mES Ex enhanced neovascularization, cardiomyocyte survival, and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex augmented CPC survival, proliferation, and cardiac commitment concurrent with increased c-kit CPCs in vivo 8 weeks after in vivo transfer along with formation of bonafide new cardiomyocytes in the ischemic heart. miRNA array revealed significant enrichment of miR290-295 cluster and particularly miR-294 in ESC exosomes. The underlying basis for the beneficial effect of mES Ex was tied to delivery of ESC specific miR-294 to CPCs promoting increased survival, cell cycle progression, and proliferation.
CONCLUSIONS:mES Ex provide a novel cell–free system that uses the immense regenerative power of ES cells while avoiding the risks associated with direct ES or ES-derived cell transplantation and risk of teratomas. ESC exosomes possess cardiac regeneration ability and modulate both cardiomyocyte and CPC-based repair programs in the heart.
Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that potently degrades angiotensin II to angiotensin 1-7. Previous studies showed that injection of the enzymatic ectodomain of ...recombinant ACE2 (rACE2) markedly increases circulatory levels of ACE2 activity, and effectively lowered blood pressure in angiotensin II-induced hypertension. However, due to the short plasma half-life of rACE2, its therapeutic potential for chronic use is limited. To circumvent this, we generated a chimeric fusion of rACE2 and the immunoglobulin fragment Fc segment to increase its plasma stability. This rACE2-Fc fusion protein retained full peptidase activity and exhibited greatly extended plasma half-life in mice, from less than two hours of the original rACE2, to over a week. A single 2.5 mg/kg injection of rACE2-Fc increased the overall angiotensin II-conversion activities in blood by up to 100-fold and enhanced blood pressure recovery from acute angiotensin II induced hypertension seven days after administration. To assess rACE2-Fc given weekly on cardiac protection, we performed studies in mice continuously infused with angiotensin II for 28 days and in a Renin transgenic mouse model of hypertension. The angiotensin II infused mice achieved sustained blood pressure control and reduced cardiac hypertrophy and fibrosis. In chronic hypertensive transgenic mice, weekly injections of rACE2-Fc effectively lowered plasma angiotensin II and blood pressure. Additionally, rACE2-Fc ameliorated albuminuria, and reduced kidney and cardiac fibrosis. Thus, our chimeric fusion strategy for rACE2-Fc is suitable for future development of new renin angiotensin system-based inhibition therapies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Epigenetic dysregulation plays a crucial role in cardiovascular diseases. Previously, we reported that acetyltransferase p300 (ATp300) inhibitor L002 prevents hypertension‐induced cardiac hypertrophy ...and fibrosis in a murine model. In this short communication, we show that treatment of hypertensive mice with ATp300‐specific small molecule inhibitor L002 or C646 reverses hypertension‐induced left ventricular hypertrophy, cardiac fibrosis and diastolic dysfunction, without reducing elevated blood pressures. Biochemically, treatment with L002 and C646 also reverse hypertension‐induced histone acetylation and myofibroblast differentiation in murine ventricles. Our results confirm and extend the role of ATp300, a major epigenetic regulator, in the pathobiology of cardiac hypertrophy and fibrosis. Most importantly, we identify the efficacies of ATp300 inhibitors C646 and L002 in reversing hypertension‐induced cardiac hypertrophy and fibrosis, and discover new anti‐hypertrophic and anti‐fibrotic candidates.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Language plays a crucial role in developing emotions. Diverse investigations studied the relationship between different components of emotional understanding and language skills. Specifically, we ...want to find out if this modulation is uniform or if there are variations in the different components of emotional understanding. The goals of this study were to compare the responses to tasks with different cognitive demands and different emotional information processing modalities and to demonstrate any variations in function to the language performance. For it, this paper analysed the responses to tasks with an emotional and neutral valence of preschool children grouped by different language performances. The children performed three tasks related to different emotional understanding components (video and images emotional appraisal, and an emotional memory task) and a language test that evaluated different language skills in a single sample of participants. Language skills are associated with different emotional appraisal task performances but only for dynamic visual stimuli and emotional valences (positive and negative). According to the type of stimulus used, the differences in emotional processing tasks’ performance align with the literature about using dynamic and ecological stimuli for studies with children. Language comprehension would play an essential role in assessing dynamic emotional stimuli, while other language skills would not affect the assessment of static or neutral dynamic stimuli during preschool.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
RATIONALE:Endothelial progenitor cell (EPC) survival and function in the injured myocardium is adversely influenced by hostile microenvironment such as ischemia, hypoxia, and inflammatory response, ...thereby compromising full benefits of EPC-mediated myocardial repair.
OBJECTIVE:We hypothesized that interleukin-10 (IL-10) modulates EPC biology leading to enhanced survival and function after transplantation in the ischemic myocardium.
METHODS AND RESULTS:Myocardial infarction (MI)-induced mobilization of bone marrow EPC (Sca-1+Flk1+cells) into the circulation was significantly impaired in IL-10 knockout (KO) mice. Bone marrow transplantation to replace IL-10 KO marrow with wild-type (WT) marrow attenuated these effects. Impaired mobilization was associated with lower stromal cell–derived factor (SDF)-1 expression levels in the myocardium of KO mice. Interestingly, SDF-1 administration reversed mobilization defect in KO mice. In vitro, hypoxia-mediated increases in CXCR4 expression and cell survival were lower in IL-10–deficient EPCs. Furthermore, SDF-1–induced migration of WT EPCs was inhibited by AMD3100, an inhibitor of CXCR4. To further study the effect of IL-10 on in vivo EPC survival and engraftment into vascular structures, GFP-labeled EPC were injected intramyocardially after induction of MI, and the mice were treated with either saline or recombinant IL-10. The IL-10–treated group showed increased retention of transplanted EPCs in the myocardium and was associated with significantly reduced EPC apoptosis after MI. Interestingly, increased EPC retention and their association with the vascular structures was observed in IL-10–treated mice. Increased EPC survival and angiogenesis in the myocardium of IL-10–treated mice corroborated with improved left ventricular function, reduced infarct size, and fibrosis in the myocardium. In vitro, IL-10–induced increase in VEGF expression in WT EPC was abrogated by STAT3 inhibitor, suggesting IL-10 signals through STAT3 activation.
CONCLUSIONS:Taken together, our studies demonstrate that MI-induced EPC mobilization was impaired in IL-10 KO mice and that IL-10 increases EPC survival and function possibly through activation of STAT3/VEGF signaling cascades, leading to attenuation of MI-induced left ventricular dysfunction and remodeling.
Despite the widely known mood enhancing and anxiolytic properties of alcohol, its link with affective state is not universal and rather nuanced. We examined whether dispositional traits of positive ...affect (PA) and negative affect (NA) influence the link between consumed alcohol and affective states (i.e. state PA and state NA), and state arousal. Self-report measures of state affect, state arousal, and objective measures of blood alcohol concentration (BAC), were obtained in naturalistic social drinking settings (i.e. bar and drinking venues) as individuals engaged in real-world social drinking activities. The sample consisted of 60 participants (55.9% females) whose age ranged from 20 to 27 years old (M = 21.85, SD = 1.24). Trait affect and demographic measures were obtained 48 hours later via an online survey. Results revealed a between-subject interaction of trait affect by BAC on state PA and state: at higher BAC levels, individuals with high levels of trait PA, but not low trait PA, experienced significantly higher state PA. Further analyses of state PA subscales showed that this interaction was present in state calmness but not state well-being or vigor. In the context of arousal, those with high trait NA, but not low trait NA, scored higher in state high-arousal levels. Main effects of trait PA/NA on state affect were detected, but not for BAC on state affect or arousal. This highlights the impactful role that dispositional affect can have in permeating or enhancing emotional states experienced in real-world social drinking contexts.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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