- Behaviour and cardiac response to stress in signal crayfish exposed to environmental concentrations of tramadol. [Journal Article]
- ATAquat Toxicol 2019 May 31; 213:105217
- Evidence of the ecological and biological impact of pharmaceuticals in surface waters on aquatic organisms is increasing. Tramadol is a synthetic opioid analgesic used to treat chronic and acute pain…
Evidence of the ecological and biological impact of pharmaceuticals in surface waters on aquatic organisms is increasing. Tramadol is a synthetic opioid analgesic used to treat chronic and acute pain. To investigate its long-term effects at environmentally relevant levels, we evaluated heart rate (HR) and locomotion of signal crayfish Pacifastacus leniusculus during a 21-day exposure to 1 μg L-1 tramadol followed by 14 days depuration. Locomotion and HR were recorded over a period 30 min before and 30 min after exposure to physiological fluids of an injured conspecific, a natural stressor, four times during the tramadol exposure and four times during depuration. A significant increase in HR following stress induction was found in the majority of tramadol-exposed and control crayfish, as well as significant group-specific HR changes between both groups. Locomotor activity during tramadol treatment differed from that during depuration, in general showing less time spent in locomotion and lower distance moved. The tramadol exposed crayfish exhibited higher velocity during depuration than during the exposure period. Results may suggest a potential shift in prey-predator relationships.
- Selective sampling and inductive inference: Drawing inferences based on observed and missing evidence. [Journal Article]
- CPCogn Psychol 2019 Jun 11; 113:101221
- We propose and test a Bayesian model of property induction with evidence that has been selectively sampled leading to "censoring" or exclusion of potentially relevant data. A core model prediction is…
We propose and test a Bayesian model of property induction with evidence that has been selectively sampled leading to "censoring" or exclusion of potentially relevant data. A core model prediction is that identical evidence samples can lead to different patterns of inductive inference depending on the censoring mechanisms that cause some instances to be excluded. This prediction was confirmed in four experiments examining property induction following exposure to identical samples that were subject to different sampling frames. Each experiment found narrower generalization of a novel property when the sample instances were selected because they shared a common property (property sampling) than when they were selected because they belonged to the same category (category sampling). In line with model predictions, sampling frame effects were moderated by the addition of explicit negative evidence (Experiment 1), sample size (Experiment 2) and category base rates (Experiments 3-4). These data show that reasoners are sensitive to constraints on the sampling process when making property inferences; they consider both the observed evidence and the reasons why certain types of evidence has not been observed.
- Promiscuous T cell epitopes boosts specific IgM immune response against a P0 peptide antigen from sea lice in different teleost species. [Journal Article]
- FSFish Shellfish Immunol 2019 Jun 11
- The development of vaccines employing conserved protein antigens, for instance ribosomal protein P0, has as disadvantage the high degree of identity between pathogen and host proteins due to possible…
The development of vaccines employing conserved protein antigens, for instance ribosomal protein P0, has as disadvantage the high degree of identity between pathogen and host proteins due to possible induction of tolerance or auto antibodies in the host organism. To overcome this drawback, peptide-based vaccines have been designed with a proved high efficacy. The use of defined peptides as antigens has the problem that they are generally poor immunogenic unless coupled to a carrier protein. Several studies have established the potential for promiscuous T cell epitopes incorporated into chimeric peptides to enhance the immunogenicity in mammals. On the contrary, studies about the role of these epitopes on teleost immune system are scarce. Therefore, the main objective of our present study was to evaluate the potential of promiscuous T cell epitopes to boost specific IgM immune response in teleost fish against a peptide antigen. With this aim, we used a peptide of 35 amino acids from the ribosomal P0 protein of Lepeophtheirus salmonis, an important parasite in salmon aquaculture. We fused this peptide to the C-terminal of T cell epitopes from tetanus toxin and measles virus and produced the chimeric protein in Escherichia coli. Following vaccination, IgM antibody production was monitored in different immunization schemes in Tilapia, African catfish and Atlantic salmon. The results demonstrated for first time that the addition of T cell epitopes at the N-terminal of a target peptide increased IgM specific response in different teleost species, revealing the potential of this approach to develop peptide-based vaccines for aquaculture. The results are also of great importance in the context of vaccine development against sea lice using ribosomal protein P0 as antigen taking into account the key role of P0 in protein synthesis and other essential physiological processes.
- Propofol relaxes isolated rat aorta through BKCa activation. [Journal Article]
- AVAnn Vasc Surg 2019 Jun 11
- CONCLUSIONS: The propofol induces relaxation in contracted RA and inhibits KCl, PE, 5-HT and CaCl2- induced contractions. The results demonstrate that the mechanism of action of propofol-induced vasodilation in the RA may be related to large conductance Ca2+ -activated K+ channel (BKCa) activation.
- Rationale and Design for the Remote Ischemic Preconditioning for Carotid Endarterectomy (RIP-CEA) Trial. [Journal Article]
- AVAnn Vasc Surg 2019 Jun 11
- CONCLUSIONS: RIPC, if shown to be effective in protecting patients from neurocognitive decline following CEA, represents a safe, inexpensive, and easily implementable method of neuroprotection.
- Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer. [Journal Article]
- CLCancer Lett 2019 Jun 11
- Macrophage-targeted therapy offers new options for intractable pancreatic ductal adenocarcinoma (PDAC), which has a low 5-year survival rate. However, the factors regulating the biological function a…
Macrophage-targeted therapy offers new options for intractable pancreatic ductal adenocarcinoma (PDAC), which has a low 5-year survival rate. However, the factors regulating the biological function and phenotype of macrophages in PDAC are incompletely understood. Here, we found that CD51 was positively associated with the poor prognosis of PDAC patients and was highly expressed on macrophages but not on pancreatic cancer cells. Subsequently, we found that CD51 was a marker of macrophages, which promoted the stemness of pancreatic cancer cells. Furthermore, knockdown of CD51 in macrophages drove macrophages toward an M1-like phenotype. Mechanistically, macrophage-expressed CD51 contributed to the acquisition of stemness traits of pancreatic cancer cells by regulating the TGF-β1/smad2/3 pathway. Our data demonstrate the central role played by macrophage-expressed CD51 in the acquisition of stemness traits of pancreatic cancer cells through the paracrine induction of TGF-β1. We first show the connection between the CD51/TGF-β1/smad2/3 axis and PDAC cancer stem cell properties and then indicate that CD51-targeted therapy is a new therapeutic modality for PDAC.
- Induction of endothelial dysfunction by oxidized low-density lipoproteins via downregulation of Erk-5/Mef2c/Klf2 signaling: Amelioration by fisetin. [Journal Article]
- BBiochimie 2019 Jun 11
- Extra-cellular signal regulated kinase-5 (Erk-5), a transcriptional activator and regulator of endothelial cells (ECs) homeostasis, has been implicated in shear stress-induced endothelial dysfunction…
Extra-cellular signal regulated kinase-5 (Erk-5), a transcriptional activator and regulator of endothelial cells (ECs) homeostasis, has been implicated in shear stress-induced endothelial dysfunction (ED), however its role in oxidized low-density lipoprotein (oxLDL)- induced ED during metabolic stress is not known. Herein, regulation and function of Erk-5 in oxLDL-induced EC death, inflammation and dysfunction has been investigated. Primary Human Umbilical Vein Endothelial Cells (pHUVECs) were stimulated with oxLDL. MTT and Trypan blue exclusion assays to assess cell viability, RT-qPCR and Western blotting assays to determine expression of endothelial and inflammatory markers and ED mediators at mRNA and protein levels, respectively were performed. Monocyte adhesion assay was performed to examine monocytes adherence to oxLDL-stimulated pHUVECs. The exposure of oxLDL induced a dose- and time-dependent decrease in pHUVECs viability, which concurred with decreased Erk-5 expression. Further, oxLDL (100 μg/ml) decreased the expression of endothelial markers eNOS and vWF, and increased the expression of ICAM-1, at both mRNA and protein levels. SiRNA-mediated silencing of Erk-5 or its inhibition showed that changes in eNOS, vWF and ICAM-1 expression could be mediated through Erk-5. Furthermore, oxLDL decreased the levels of Erk-5's upstream regulator MEK5 and downstream regulators Mef2c and KLF2, which were similar to their expressions in Erk-5 silenced cells. Fisetin, a phytochemical and bioflavonoid, could reduce the effect of oxLDL in ECs by upregulating the expression of endothelial markers including Erk-5, and downregulating the expression of inflammation markers. These results suggest that Erk-5 could be a critical regulator of oxLDL-induced EC death, inflammation and dysfunction via downregulation of Erk-5/Mef2c-KLF2 signaling pathway, which can be ameliorated by a bioflavonoid, fisetin.
- Insult-induced aberrant hippocampal neurogenesis: functional consequences and possible therapeutic strategies. [Review]
- BBBehav Brain Res 2019 Jun 11; :112032
- Adult hippocampal neurogenesis plays a critical role in a wide spectrum of hippocampus-dependent functions. Brain pathologies that involve the hippocampus like epilepsy, stroke, and traumatic brain i…
Adult hippocampal neurogenesis plays a critical role in a wide spectrum of hippocampus-dependent functions. Brain pathologies that involve the hippocampus like epilepsy, stroke, and traumatic brain injury, are commonly associated with cognitive impairments and mood disorders. These insults can affect the neural stem cells and the subsequent neurogenic cascade in the hippocampus, resulting in the induction of aberrant neurogenesis, which is thought to compromise hippocampal network function, thereby hampering hippocampus-dependent behavior. We here summarize recent preclinical literature on hippocampal insult-induced changes in neurogenesis and based on that, we propose that normalizing aberrant neurogenesis post-insult may help to prevent or rescue behavioral deficits which could help develop novel therapeutic strategies.
- Diverse Consequences in Liver Injury in Mice with Different Autophagy Functional Status Treated with Alcohol. [Journal Article]
- AJAm J Pathol 2019 Jun 11
- Alcoholic fatty liver disease is often complicated by other pathological insults, such as viral infection or high fat diet. Autophagy plays a homeostatic role in the liver but can be compromised by a…
Alcoholic fatty liver disease is often complicated by other pathological insults, such as viral infection or high fat diet. Autophagy plays a homeostatic role in the liver but can be compromised by alcohol, high fat diet, or viral infection, which in turn affect the disease process caused by these etiologies. To understand the full impact of autophagy modulation on alcohol-induced liver injury, several genetic models of autophagy deficiency, which have different levels of functional alterations, were examined following acute binge or chronic-plus-binge treatment. Alcohol given in either mode to the liver-specific inducible Atg7-deficient mice shortly after the induction of Atg7 deletion had an elevated liver injury, indicating the protective role of autophagy. Constitutive hepatic Atg7 deficient mice, in which Atg7 was deleted in embryos, were more susceptible to chronic-plus-binge but not to acute alcohol treatment. Constitutive hepatic Atg5 deficient mice, in which Atg5 was deleted in embryos, were more prone to acute alcohol treatment, but liver injury were surprisingly improved in the chronic-plus-binge regime. A prolonged autophagy deficiency may complicate the hepatic response to alcohol treatment, likely in part due to endogenous liver injury. The complexity of the relationship between autophagy deficiency and alcohol-induced liver injury can thus be affected by the timing of autophagy dysfunction, the exact autophagy gene being affected, and the alcohol treatment regime.
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- A time domain study of surfactin penetrating a phospholipid monolayer at the air-water Interface investigated using sum frequency generation spectroscopy, infrared reflection absorption spectroscopy, and AFM-nano infrared microscopy. [Journal Article]
- BBBiochim Biophys Acta Biomembr 2019 Jun 11
- We have investigated the interaction of surfactin with a monolayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at the air-water interface as a function of time, following its injection into…
We have investigated the interaction of surfactin with a monolayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at the air-water interface as a function of time, following its injection into the sub-phase, using non-linear Sum Frequency Generation (SFG) vibrational spectroscopy and Infrared Reflection Absorption Spectroscopy (IRRAS). SFG resonances from the phospholipid and from the surfactin were distinguished from each other by using selective deuteration. The surface pressure at the interface was measured concurrently for up to 8 h. After an induction period, the spectra from the lipid diminished and those of surfactin gradually appeared whilst at the same time the surface pressure increased. However, eventually the surfactin signals disappeared and those of the lipid reappeared. Although the SFG spectra of the lipid disappeared at intermediate times, the IRRAS spectra of the lipid were always present at the interface. Variation in the temporal SFG behaviour was investigated as the pH of the sub-phase, the initial surface pressure of the lipid, and the surfactin concentration were changed. Samples of the surface film were transferred onto mica substrates at selected times along the temporal profile and imaged by Atomic Force Microscopy - nano Infrared Spectroscopy (nano-IR). A model is proposed to account for the results from the four different experimental techniques used.