Does virulence assessment of Vibrio anguillarum using sea bass (Dicentrarchus labrax) larvae correspond with genotypic and phenotypic characterization?

Background: Vibriosis is one of the most ubiquitous fish diseases caused by bacteria belonging to the genus Vibrio such as Vibrio (Listonella) anguillarum. Despite a lot of research efforts, the virulence factors and mechanism of V. anguillarum are still insufficiently known, in part because of the lack of standardized virulence assays. Methodology/Principal Findings: We investigated and compared the virulence of 15 V. anguillarum strains obtained from different hosts or non-host niches using a standardized gnotobiotic bioassay with European sea bass (Dicentrarchus labrax L.) larvae as model hosts. In addition, to assess potential relationships between virulence and genotypic and phenotypic characteristics, the strains were characterized by random amplified polymorphic DNA (RAPD) and repetitive extragenic palindromic PCR (rep-PCR) analyses, as well as by phenotypic analyses using Biolog's Phenotype MicroArray (TM) technology and some virulence factor assays. Conclusions/Significance: Virulence testing revealed ten virulent and five avirulent strains. While some relation could be established between serotype, genotype and phenotype, no relation was found between virulence and genotypic or phenotypic characteristics, illustrating the complexity of V. anguillarum virulence. Moreover, the standardized gnotobiotic system used in this study has proven its strength as a model to assess and compare the virulence of different V. anguillarum strains in vivo. In this way, the bioassay contributes to the study of mechanisms underlying virulence in V. anguillarum

Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools

BACKGROUND: We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats (SHRs) and Sprague-Dawley rats (SDs) one week after tMCAo; (2) to present the practical use of the optical fractionator and 2D nucleator in stereological brain tissue analyses; and (3) to report our experiences with an intraluminal tMCAo model where the occluding filament is advanced 22 mm beyond the carotid bifurcation and the common carotid artery is clamped during tMCAo. METHODS: Twenty-three SDs and twenty SHRs were randomized into four groups subjected to 90 minutes tMCAo or sham. BrdU (50 mg/kg) was administered intraperitoneally twice daily on Day 4 to 7 after surgery. On Day 8 all animals were euthanized. NeuN-stained tissue sections were used for brain and infarct volume estimation with the 2D nucleator and Cavalieri principle. Brains were studied for the presence of activated microglia (ED-1) and hippocampal BrdU incorporation using the optical fractionator. RESULTS: We found no significant difference or increase in post-ischemic NPC proliferation between the two strains. However, the response to remote ischemia may differ between SDs and SHRs. In three animals increased post-stroke NPC proliferation was associated with hippocampal ischemic injury. The mean infarct volume was 89.2 ± 76.1 mm(3 )in SHRs and 16.9 ± 22.7 mm(3 )in SDs (p < 0.005). Eight out of eleven SHRs had ischemic neocortical damage in contrast to only one out of 12 SDs. We observed involvement of the anterior choroidal and hypothalamic arteries in several animals from both strains and the anterior cerebral artery in two SHRs. CONCLUSIONS: We found no evidence of an early hippocampal NPC proliferation one week after tMCAo in both strains. Infarction within the anterior choroidal artery could induce hippocampal ischemia and increase NPC proliferation profoundly. NPC proliferation was not aggravated by the presence of activated microglia. Intraluminal tMCAo in SHRs gave a more reliable infarct with neocortical involvement, but affected territories supplied by the anterior cerebral, anterior choroidal and hypothalamic arteries

Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

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A field study of auditory sensitivity of the Atlantic puffin, Fratercula Arctica

Author Posting. © Company of Biologists, 2020. This article is posted here by permission of Company of Biologists for personal use, not for redistribution. The definitive version was published in Journal of Experimental Biology (2020): jeb.228270, doi:10.1242/jeb.228270.Hearing is vital for birds as they rely on acoustic communication with parents, mates, chicks, and conspecifics. Amphibious seabirds face many ecological pressures, having to sense cues in air and underwater. Natural noise conditions have helped shape this sensory modality but anthropogenic noise is increasingly impacting seabirds. Surprisingly little is known about their hearing, despite their imperiled status. Understanding sound sensitivity is vital when we seek to manage manmade noise impacts. We measured the auditory sensitivity of nine wild Atlantic puffins, Fratercula arctica, in a capture-and-release setting in an effort to define their audiogram and compare these data to the hearing of other birds and natural rookery noise. Auditory sensitivity was tested using auditory evoked potential (AEP) methods. Responses were detected from 0.5 to 6 kHz. Mean thresholds were below 40 dB re 20 µPa from 0.75 to 3 kHz indicating that these were the most sensitive auditory frequencies, similar to other seabirds. Thresholds in the ‘middle’ frequency range 1-2.5 kHz were often down to 10-20 dB re 20 µPa. Lowest thresholds were typically at 2.5 kHz. These are the first in-air auditory sensitivity data from multiple wild-caught individuals of a deep-diving Alcid seabird. The audiogram was comparable to other birds of similar size, thereby indicating that puffins have fully functioning aerial hearing despite the constraints of their deep-diving, amphibious lifestyles. There was some variation in thresholds, yet animals generally had sensitive ears suggesting aerial hearing is an important sensory modality for this taxon.This work was supported by the U.S. Navy’s Living Marine Resources Program and the Woods Hole Oceanographic Institution.2021-06-1

YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration.

Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells. The fate change is orchestrated by remodeling the extracellular matrix (ECM), increased FAK/Src signaling, and ultimately YAP/TAZ activation. In a defined cell culture system recapitulating the extracellular matrix remodeling observed in vivo, we show that a collagen 3D matrix supplemented with Wnt ligands is sufficient to sustain endogenous YAP/TAZ and induce conversion of cell fate. This provides a simple model for tissue regeneration, implicating cellular reprogramming as an essential element.This work was supported by Worldwide Cancer Research (13-1216 to KBJ), Lundbeck Foundation (R105-A9755 to KBJ), the Danish Cancer Society (R56-A2907 and R124-A7724 to KBJ), the Carlsberg Foundation (to KBJ), EMBO Young Investigator programme (to KBJ), AIRC Special Program Molecular Clinical Oncology ‘‘5 per mille’’ (to SP), an AIRC PI-Grant (to SP), Epigenetics Flagship projects (CNR-Miur grants. to SP), the DFF mobilix programme (to SY), Marie Curie fellowship programme (SY and JG), Foundation of Aase and Ejnar Danielsen (OHN), Axel Muusfeldts Foundation (OHN), The Ragnar Söderberg Foundation (CDM). This project has received funding from the European Union’s Horizon 2020 research and innovation programme (grant agreements STEMHEALTH ERCCoG682665 and INTENS 668294 to KBJ and DENOVOSTEM No. 670126 to SP)

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

Emerging evidence indicates that certain behavioral traits, such as anxiety, are associated with the development of depression-like behaviors after exposure to chronic stress. However, single traits do not explain the wide variability in vulnerability to stress observed in outbred populations. We hypothesized that a combination of behavioral traits might provide a better characterization of an individual's vulnerability to prolonged stress. Here, we sought to determine whether the characterization of relevant behavioral traits in rats could aid in identifying individuals with different vulnerabilities to developing stress-induced depression-like behavioral alterations. We also investigated whether behavioral traits would be related to the development of alterations in the hypothalamic-pituitary-adrenal axis and in brain activity - as measured through phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) - in response to an acute stressor following either sub-chronic (2 weeks) or chronic (4 weeks) unpredictable stress (CUS). Sprague-Dawley rats were characterized using a battery of behavioral tasks, and three principal traits were identified: anxiety, exploration and activity. When combined, the first two traits were found to explain the variability in the stress responses. Our findings confirm the increased risk of animals with high anxiety developing certain depression-like behaviors (e.g., increased floating time in the forced swim test) when progressively exposed to stress. In contrast, the behavioral profile based on combined low anxiety and low exploration was resistant to alterations related to social behaviors, while the high anxiety and low exploration profile displayed a particularly vulnerable pattern of physiological and neurobiological responses after sub-chronic stress exposure. Our findings indicate important differences in animals' vulnerability and/or resilience to the effects of repeated stress, particularly during initial or intermediate levels of stress exposure, and they highlight that the behavioral inhibition profile of an animal provides a particular susceptibility to responding in a deleterious manner to stress

Effect of empagliflozin on plasma lipids and lipoproteins in type 2 diabetes and heart failure – Empire HF and SIMPLE

OBJECTIVE: Beyond glucose-lowering, sodium-glucose co-transporter 2 (SGLT2) inhibitors have cardioprotective effects with unclear mechanisms. We examined changes in an extensive panel of plasma lipids, lipoproteins, and apolipoproteins and whether these changes were independent of weight loss, hemoglobin A1c, and hematocrit in patients treated with empagliflozin vs placebo to better understand the observed cardioprotective effects. METHODS: Post-hoc analyses of 2 double-blind, placebo-controlled trials, the Empire HF trial including 190 patients with heart failure and reduced ejection fraction and the SIMPLE trial including 90 patients with type 2 diabetes randomized to, respectively, 10 mg and 25 mg empagliflozin daily or placebo for 12 weeks. RESULTS: In studies combined, empagliflozin reduced age and sex adjusted body weight by 1.40 kg (SEM: 0.10; P &lt; .001) and hemoglobin A1c by 2.71 mmol/mol (SEM: 0.24; P &lt; .001); and increased hematocrit by 1.9% (SEM: 0.12; P &lt; .001) compared to placebo. No mean changes were seen in concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, small dense LDL cholesterol, very low-density lipoprotein cholesterol, triglyceride rich lipoprotein cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, apolipoprotein B, lipoprotein(a), HDL cholesterol, and triglycerides adjusted for body weight, hemoglobin A1c, and hematocrit with empagliflozin compared to placebo. CONCLUSION: Empagliflozin treatment reduced body weight and hemoglobin A1c, and increased hematocrit. No changes were seen in concentrations of lipids and lipoproteins with empagliflozin compared to placebo. This suggests that the cardioprotective effects of SGLT2 inhibitors are independent of lipid and lipoprotein concentrations.</p

Abundance of whales in West and East Greenland in summer 2015

An aerial line transect survey of whales in West and East Greenland was conducted in August-September 2015. The survey covered the area between the coast of West Greenland and offshore (up to 100 km) to the shelf break. In East Greenland, the survey lines covered the area from the coast up to 50 km offshore crossing the shelf break. A total of 423 sightings of 12 cetacean species were obtained and abundance estimates were developed for common minke whale, (Balaenoptera acutorostrata) (32 sightings), fin whale (Balaenoptera physalus) (129 sightings), humpback whale (Megaptera novaeangliae) (84 sightings), harbour porpoise (Phocoena phocoena) (55 sightings), long-finned pilot whale, (Globicephala melas) (42 sightings) and white-beaked dolphin (Lagenorhynchus albirostri) (50 sightings). The developed at-surface abundance estimates were corrected for both perception bias and availability bias if possible. Data on surface corrections for minke whales and harbour porpoises were collected from whales instrumented with satellite-linked time-depth-recorders. Options for estimation methods are presented and the preferred estimates are: minke whales: 5,095 (95% CI: 2,171-11,961) in West Greenland and 2,762 (95% CI: 1,160-6,574) in East Greenland, fin whales: 2,215 (95% CI: 1,017-4,823) in West Greenland and 6,440 (95% CI: 3,901-10,632) in East Greenland, humpback whales: 993 (95% CI: 434-2,272) in West Greenland and 4,223 (95% CI: 1,845-9,666) in East Greenland, harbour porpoises: 83,321 (95% CI: 43,377-160,047) in West Greenland and 1,642 (95% CI: 319-8,464) in East Greenland, pilot whales: 9,190 (95% CI: 3,635-23,234) in West Greenland and 258 (95% CI: 50-1,354) in East Greenland, white-beaked dolphins 15,261 (95% CI: 7,048-33,046) in West Greenland and 11,889 (95% CI: 4,710-30,008) in East Greenland. The abundance of cetaceans in coastal areas of East Greenland has not been estimated before, but the limited historical information from the area indicates that the achieved abundance estimates were remarkably high. When comparing the abundance estimates from 2015 in West Greenland with a similar survey conducted in 2007, there is a clear trend towards lower densities in 2015 for the three baleen whale species and white-beaked dolphins. Harbour porpoises and pilot whales, however, did not show a similar decline. The decline in baleen whale and white-beaked dolphin abundance is likely due to emigration to the East Greenland shelf areas where recent climate driven changes in pelagic productivity may have accelerated favourable conditions for these species

Design and pre-trial dose planning quality assurance of the Nordic trial of inhomogeneous dose escalated radiotherapy for patients with limited disease small cell lung cancer:NIELS

Background and purpose: The NIELS trial will examine if inhomogeneous dose-escalated radiotherapy up to a mean dose of 80 Gy in 40 fractions (fx), twice-daily delivered (BID), for patients with limited disease small cell lung cancer can improve overall survival. Because of the inherent risks of dose-escalation, pre-trial QA is particularly important. This study aims to examine the feasibility of the NIELS trial planning approach in a multicenter setting. Materials and methods: The NIELS trial will randomize patients between standard dose radiotherapy (60 Gy/40fx BID) and inhomogeneous dose-escalated radiotherapy (up to 80 Gy/40fx BID). Five representative patient cases were distributed to seven Nordic centers for pre-trial QA planning of a standard and an escalated dose plan. Targets for escalation were primary tumor (GTVp) and involved lymph nodes (GTVn). We evaluated inter-center variation in achievable dose-escalation and doses to organs at risk (OAR). Results: All targets could be escalated beyond the standard dose, with a median mean dose of 79.6 Gy [76.9–81.0] and 75.8 Gy [68.3–81.1] for GTVp and GTVn. Some targets could not be fully escalated due to OAR proximity. Three separate breaches of mandatory OAR constraints were observed in 35 escalated dose plans. There was a statistical difference in mean lung dose between standard and escalated plans, though clinically small, with a median inter-patient difference of 0.3 Gy. There were no differences in mean doses to the heart and esophagus. Conclusion: Inhomogeneous dose-escalation as planned in the NIELS trial is feasible, and the dose-escalation can be performed respecting the OAR constraints in a multi-center setting.</p