AA/12-Lipoxygenase Signaling Contributes to Inhibitory Learning in Hermissenda Type B Photoreceptors

Conditioned inhibition (CI) is a major category of associative learning that occurs when an organism learns that one stimulus predicts the absence of another. In addition to being important in its own right, CI is interesting because its occurrence implies that the organism has formed an association between stimuli that are non-coincident. In contrast to other categories of associative learning that are dependent upon temporal contiguity (pairings) of stimuli, the neurobiology of CI is virtually unexplored. We have previously described a simple form of CI learning in Hermissenda, whereby animals’ phototactic behavior is increased by repeated exposures to explicitly unpaired (EU) presentations of light and rotation. EU conditioning also produces characteristic reductions in the excitability and light response, and increases several somatic K+ currents in Type B photoreceptors. Type B photoreceptors are a major site of plasticity for classical conditioning in Hermissenda. Because arachidonic acid (AA) and/or its metabolites open diverse K+ channels in many cell types, we examined the potential contribution of AA to CI. Our results indicate that AA contributes to one of the major effects of EU-conditioning on Type B photoreceptors: decreases in light-evoked spike activity. We find that AA increases the transient (IA) somatic K+ current in Type B photoreceptors, further mimicking CI training. In addition, our results indicate that metabolism of AA by a 12-lipoxygenase enzyme is critical for these effects of AA, and further that 12-lipoxygenase metabolites are apparently generated during CI training

Update and new epidemiological aspects about grapevine yellows in Chile

none9siTo date, phytoplasmas belonging to six ribosomal subgroups have been detected to infect grapevines in Chile in 36 percent of the sampled plants. A new survey on the presence of grapevine yellows was carried out from 2016 to 2020, and 330 grapevine plants from the most important wine regions of the country were sampled and analyzed by nested PCR/RFLP analyses. Phytoplasmas enclosed in subgroups 16SrIII-J and 16SrVII-A were identified with infection rates of 17% and 2%, respectively. The vineyards in which the phytoplasma-infected plants were detected were further inspected to identify alternative host plants and insects of potential epidemiological relevance. Five previously unreported plant species resulted positive for 16SrIII-J phytoplasma (Rosa spp., Brassica rapa, Erodium spp., Malva spp. and Rubus ulmifolius) and five insect species were fully or partially identified (Amplicephalus ornatus, A. pallidus, A. curtulus, Bergallia sp., Exitianus obscurinervis) as potential vectors of 16SrIII-J phytoplasmas. The 16SrVII-A phytoplasmas were not detected in non-grape plant species nor in insects. This work establishes updated guidelines for the study, management, and prevention of grapevine yellows in Chile, and in other grapevine growing regions of South America.openQuiroga N., C. Gamboa, D. Soto, A.M. Pino, A. Zamorano, J. Campodonico, A. Alma, A. Bertaccini, N. FioreQuiroga N., C. Gamboa, D. Soto, A.M. Pino, A. Zamorano, J. Campodonico, A. Alma, A. Bertaccini, N. Fior

High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study

Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. Results. Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 \ub1 87 vs. 16 \ub1 41 mg/L; p < 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles (p for trend <0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23; p < 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 (p < 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. Conclusions. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome

Plasma exosome profile in st-elevation myocardial infarction patients with and without out-of-hospital cardiac arrest

The identification of new biomarkers allowing an early and more accurate characterization of patients with ST-segment elevation myocardial infarction (STEMI) is still needed, and exosomes represent an attractive diagnostic tool in this context. However, the characterization of their protein cargo in relation to cardiovascular clinical manifestation is still lacking. To this end, 35 STEMI patients (17 experiencing resuscitated out-of-hospital cardiac arrest (OHCA-STEMI) and 18 uncomplicated) and 32 patients with chronic coronary syndrome (CCS) were enrolled. Plasma exosomes were characterized by the nanoparticle tracking analysis and Western blotting. Exosomes from STEMI patients displayed a higher concentration and size and a greater expression of platelet (GPIIb) and vascular endothelial (VE-cadherin) markers, but a similar amount of cardiac troponin compared to CCS. In addition, a difference in exosome expression of acute-phase proteins (ceruloplasmin, transthyretin and fibronectin) between STEMI and CCS patients was found. GPIIb and brain-associated marker PLP1 accurately discriminated between OHCA and uncomplicated STEMI. In conclusion, the exosome profile of STEMI patients has peculiar features that differentiate it from that of CCS patients, reflecting the pathophysiological mechanisms involved in STEMI. Additionally, the exosome expression of brain-and platelet-specific markers might allow the identification of patients experiencing ischemic brain injury in STEMI

Vitamin d plasma levels and in-hospital and 1-year outcomes in acute coronary syndromes : a prospective study

Deficiency in 25-hydroxyvitamin D (25[OH]D), the main circulating form of vitamin D in blood, could be involved in the pathogenesis of acute coronary syndromes (ACS). To date, however, the possible prognostic relevance of 25 (OH)D deficiency in ACS patients remains poorly defined. The purpose of this prospective study was to assess the association between 25 (OH)D levels, at hospital admission, with in-hospital and 1-year morbidity and mortality in an unselected cohort of ACS patients.We measured 25 (OH)D in 814 ACS patients at hospital presentation. Vitamin D serum levels >30\u200ang/mL were considered as normal; levels between 29 and 21\u200ang/mL were classified as insufficiency, and levels\u200a<\u200a20\u200ang/mL as deficiency. In-hospital and 1-year outcomes were evaluated according to 25 (OH)D level quartiles, using the lowest quartile as a reference.Ninety-three (11%) patients had normal 25 (OH)D levels, whereas 155 (19%) and 566 (70%) had vitamin D insufficiency and deficiency, respectively. The median 25 (OH)D level was similar in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) patients (14.1 [IQR 9.0-21.9] ng/mL and 14.05 [IQR 9.1-22.05] ng/mL, respectively; P\u200a=\u200a.88). The lowest quartile of 25 (OH)D was associated with a higher risk for several in-hospital complications, including mortality. At a median follow-up of 366 (IQR 364-379) days, the lowest quartile of 25 (OH)D, after adjustment for the main confounding factors, remained significantly associated to 1-year mortality (P\u200a<\u200a.01). Similar results were obtained when STEMI and NSTEMI patients were considered separately.In ACS patients, severe vitamin D deficiency is independently associated with poor in-hospital and 1-year outcomes. Whether low vitamin D levels represent a risk marker or a risk factor in ACS remains to be elucidated

The Legionella effector WipB is a translocated Ser/Thr phosphatase that targets the host lysosomal nutrient sensing machinery

Legionella pneumophila infects human alveolar macrophages and is responsible for Legionnaire’s disease, a severe form of pneumonia. L. pneumophila encodes more than 300 putative effectors, which are translocated into the host cell via the Dot/Icm type IV secretion system. These effectors highjack the host’s cellular processes to allow bacterial intracellular growth and replication. Here we adopted a multidisciplinary approach to investigate WipB, a Dot/Icm effector of unknown function. The crystal structure of the N-terminal domain at 1.7 Å resolution comprising residues 25 to 344 revealed that WipB harbours a Ser/Thr phosphatase domain related to the eukaryotic phospho-protein phosphatase (PPP) family. The C-terminal domain (residues 365–524) is sufficient to pilot the effector to acidified LAMP1-positive lysosomal compartments, where WipB interacts with the v-ATPase and the associated LAMTOR1 phosphoprotein, key components of the lysosomal nutrient sensing (LYNUS) apparatus that controls the mammalian target of rapamycin (mTORC1) kinase complex at the lysosomal surface. We propose that WipB is a lysosome-targeted phosphatase that modulates cellular nutrient sensing and the control of energy metabolism during Legionella infection

Spatio-temporal variability in underwater light climate in a turbid river-floodplain system. Driving factors and estimation using Secchi disc

The underwater light climate has important effects on primary producers. The aim of this research was to evaluate its variability in a turbid river-floodplain system. Photosynthetically active radiation (PAR) was measured in the Middle Paraná River during different hydrological phases to (a) analyse the photosynthetically active radiation attenuation coefficient (k) and euphotic depth (Zeu) as well as their associations with optically active components and (b) develop and evaluate indices and regression models based on Secchi disc (SD) measurements to estimate k and Zeu. Values of k were higher in the fluvial system than in the floodplain and during low-water stage than high-water stage. Particulate components controlled the light climate variability. Chromophoric dissolved organic matter and chlorophyll-a had significant effects during floods. The estimation of k and Zeu was sensitive to temporal but not to spatial variations. The highest prediction accuracy was observed when using specific non-linear regressions for each hydrological phase, especially for Zeu estimation (low stage: k = 1.76 × SD−0.80, Zeu = 2.62 × 1/SD−0.80; high stage: k = 2.04 × SD−0.53, Zeu = 2.26 × 1/SD−0.53). The indices k × SD and Zeu/SD were significantly different from those proposed for clear water environments. It is concluded that temporal variations should be considered when estimating k and Zeu in turbid river-floodplain systems because of the temporal heterogeneity in optically active components. Considering that ecological implication of the light climate depends on Zeu:depth ratio, we propose to estimate Zeu instead of k. Finally, indices proposed for clear water environments are not recommended to be applied to turbid environments.Fil: Mayora, Gisela Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Devercelli, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentin

Flagellin-Induced Corneal Antimicrobial Peptide Production and Wound Repair Involve a Novel NF-κB–Independent and EGFR-Dependent Pathway

The bacterial protein flagellin plays a major role in stimulating mucosal surface innate immune response to bacterial infection and uniquely induces profound cytoprotection against pathogens, chemicals, and radiation. This study sought to determine signaling pathways responsible for the flagellin-induced inflammatory and cytoprotective effects on human corneal epithelial cells (HCECs).Flagellin purified from Pseudomonas aeruginosa (strain PAK) or live bacteria were used to challenge cultured HCECs. The activation of signaling pathways was assessed with Western blot, and the secretion of cytokine/chemokine and production of antimicrobial peptides (AMPs) were measured with ELISA and dot blot, respectively. Effects of flagellin on wound healing were assessed in cultured porcine corneas. L94A (a site mutation in TLR5 binding region) flagellin and PAK expressing L94A flagellin were unable to stimulate NF-kappaB activation, but were potent in eliciting EGFR signaling in a TGF-alpha-related pathway in HCECs. Concomitant with the lack of NF-kappaB activation, L94A flagellin was ineffective in inducing IL-6 and IL-8 production in HCECs. Surprisingly, the secretion of two inducible AMPs, LL-37 and hBD2, was not affected by L94A mutation. Similar to wild-type flagellin, L94A induced epithelial wound closure in cultured porcine cornea through maintaining EGFR-mediated signaling.Our data suggest that inflammatory response mediated by NF-kappaB can be uncoupled from epithelial innate defense machinery (i.e., AMP expression) and major epithelial proliferation/repair pathways mediated by EGFR, and that flagellin and its derivatives may have broad therapeutic applications in cytoprotection and in controlling infection in the cornea and other mucosal tissues

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban

Introduction: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. Materials and Methods: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. Results: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations’ survival appeared non-significantly different at the 2-year follow-up. Conclusions: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients

Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study

Intravesical gemcitabine (Gem) has shown promising activity against transitional cell carcinomas (TCC) of the bladder, with moderate urinary toxicity and low systemic absorption. The present phase II study evaluated the activity of biweekly intravesical treatment with Gem using a scheme directly derived from in vitro preclinical studies. Patients with Bacille Calmette-Guérin (BCG) -refractory Ta G3, T1 G1-3 TCC underwent transurethral bladder resection and then intravesical instillation with 2000 mg Gem diluted in 50 ml saline solution on days 1 and 3 for 6 consecutive weeks. Thirty-eight (95%) of the 40 patients showed persistent negative post-treatment cystoscopy and cytology 6 months after Gem treatment, while the remaining 2 patients relapsed at 5 and 6 months. At a median follow-up of 28 months, recurrences had occurred in 14 patients. Among these, four had downstaged (T) disease, three had a lower grade (G) lesion and three had a reduction in both T and G. Urinary and systemic toxicity was very low, with no alterations in biochemical profiles. In conclusion, biweekly instillation of Gem proved active in BCG-refractory Ta G3, T1 G1-3 TCC. Our results highlight the importance of preclinical studies using in vitro systems that adequately reproduce the conditions of intravesical clinical treatment to define the best therapeutic schedule