Pharmacological effects of 3-iodothyronamine (T1AM) in mice include facilitation of memory acquisition and retention and reduction of pain threshold

BACKGROUND AND PURPOSE: 3-Iodothyronamine (T1AM), an endogenous derivative of thyroid hormones, is regarded as a rapid modulator of behaviour and metabolism. To determine whether brain thyroid hormone levels contribute to these effects, we investigated the effect of central administration of T1AM on learning and pain threshold of mice either untreated or pretreated with clorgyline (2.5 mg•kg-1, i.p.), an inhibitor of amine oxidative metabolism. EXPERIMENTAL APPROACH: T1AM (0.13, 0.4, 1.32 and 4 mg•kg-1) or vehicle was injected i.c.v. into male mice, and after 30 min their effects on memory acquisition capacity, pain threshold and curiosity were evaluated by the following tests: passive avoidance, licking latency on the hot plate and movements on the hole-board platform. Plasma glycaemia was measured using a glucorefractometer. Brain levels of triiodothyroxine (T3), thyroxine (T4) and T1AM were measured by HPLC coupled to tandem MS. ERK1/2 activation and c-fos expression in different brain regions were evaluated by Western blot analysis. RESULTS: T1AM improved learning capacity, decreased pain threshold to hot stimuli, enhanced curiosity and raised plasma glycaemia in a dose-dependent way, without modifying T3 and T4 brain concentrations. T1AM effects on learning and pain were abolished or significantly affected by clorgyline, suggesting a role for some metabolite(s), or that T1AM interacts at the rapid desensitizing target(s). T1AM activated ERK in different brain areas at lower doses than those effective on behaviour. CONCLUSIONS AND IMPLICATIONS: T1AM is a novel memory enhancer. This feature might have important implications for the treatment of endocrine and neurodegenerative-induced memory disorders

EUNIS Habitat Classification: Expert system, characteristic species combinations and distribution maps of European habitats

Aim: The EUNIS Habitat Classification is a widely used reference framework for European habitat types (habitats), but it lacks formal definitions of individual habitats that would enable their unequivocal identification. Our goal was to develop a tool for assigning vegetation‐plot records to the habitats of the EUNIS system, use it to classify a European vegetation‐plot database, and compile statistically‐derived characteristic species combinations and distribution maps for these habitats. Location: Europe. Methods: We developed the classification expert system EUNIS‐ESy, which contains definitions of individual EUNIS habitats based on their species composition and geographic location. Each habitat was formally defined as a formula in a computer language combining algebraic and set‐theoretic concepts with formal logical operators. We applied this expert system to classify 1,261,373 vegetation plots from the European Vegetation Archive (EVA) and other databases. Then we determined diagnostic, constant and dominant species for each habitat by calculating species‐to‐habitat fidelity and constancy (occurrence frequency) in the classified data set. Finally, we mapped the plot locations for each habitat. Results: Formal definitions were developed for 199 habitats at Level 3 of the EUNIS hierarchy, including 25 coastal, 18 wetland, 55 grassland, 43 shrubland, 46 forest and 12 man‐made habitats. The expert system classified 1,125,121 vegetation plots to these habitat groups and 73,188 to other habitats, while 63,064 plots remained unclassified or were classified to more than one habitat. Data on each habitat were summarized in factsheets containing habitat description, distribution map, corresponding syntaxa and characteristic species combination. Conclusions: EUNIS habitats were characterized for the first time in terms of their species composition and distribution, based on a classification of a European database of vegetation plots using the newly developed electronic expert system EUNIS‐ESy. The data provided and the expert system have considerable potential for future use in European nature conservation planning, monitoring and assessment

Distribution maps of vegetation alliances in Europe

Aim: The first comprehensive checklist of European phytosociological alliances, orders and classes (EuroVegChecklist) was published by Mucina et al. (2016, Applied Vegetation Science, 19 (Suppl. 1), 3–264). However, this checklist did not contain detailed information on the distribution of individual vegetation types. Here we provide the first maps of all alliances in Europe. Location: Europe, Greenland, Canary Islands, Madeira, Azores, Cyprus and the Caucasus countries. Methods: We collected data on the occurrence of phytosociological alliances in European countries and regions from literature and vegetation-plot databases. We interpreted and complemented these data using the expert knowledge of an international team of vegetation scientists and matched all the previously reported alliance names and concepts with those of the EuroVegChecklist. We then mapped the occurrence of the EuroVegChecklist alliances in 82 territorial units corresponding to countries, large islands, archipelagos and peninsulas. We subdivided the mainland parts of large or biogeographically heterogeneous countries based on the European biogeographical regions. Specialized alliances of coastal habitats were mapped only for the coastal section of each territorial unit. Results: Distribution maps were prepared for 1,105 alliances of vascular-plant dominated vegetation reported in the EuroVegChecklist. For each territorial unit, three levels of occurrence probability were plotted on the maps: (a) verified occurrence; (b) uncertain occurrence; and (c) absence. The maps of individual alliances were complemented by summary maps of the number of alliances and the alliance–area relationship. Distribution data are also provided in a spreadsheet. Conclusions: The new map series represents the first attempt to characterize the distribution of all vegetation types at the alliance level across Europe. There are still many knowledge gaps, partly due to a lack of data for some regions and partly due to uncertainties in the definition of some alliances. The maps presented here provide a basis for future research aimed at filling these gaps

Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses

Numerical study of pressure build-up in vertical tanks for cryogenic flammables storage

Large-scale installations for cryogenic fluid storages, such as liquefied natural gas (LNG) and ethylene are critical units in the framework of the chemical and petrochemical industries. Modelling the thermal performance of such installations is therefore a critical task to enhance the safety and effectiveness of operations. In the present work, Computational Fluid Dynamics (CFD) is used to investigate the pressurisation behaviour of cryogenic storage tanks by applying the Volume-Of-Fluid method and taking into account vaporization-condensation phenomena. The boundary conditions are estimated from a 1-dimensional model to solve the heat transfer through the tank insulation layers, eventually taking into account accidental damages. The tank CFD model is preliminary validated against small-scale experimental data obtained for cryogenic nitrogen and then extended to the simulation of an industrial cylindrical tank, whose volume is 100m3. The effect of fluid, i.e. ethylene and LNG (modelled as pure methane), filling level and possible insulation damage, on natural convection driving liquid stratification and ultimately tank pressurisation is analysed. Specific performance indexes are proposed to efficiently compare the different scenarios

CFD modelling of vertical LNG tanks adopted in heavy trucks refuelling stations

In the present study, a Computational Fluid Dynamics (CFD) model was set up to analyse the dynamic behaviour of LNG (Liquefied Natural Gas) tanks adopted in heavy trucks refuelling stations in normal operating conditions or during process upsets. The CFD model was based on the Volume-Of-Fluid (VOF) method to simulate the transient behaviour of a multi-phase flow in a 100 m3 vertical cylindrical tank. The model first considered a fully insulated vessel, and subsequently it was modified to take into account possible damages of the insulation layer, this being a critical upset scenario. The CFD model allowed predicting the dynamic pressure build up in the damaged tank, thus obtaining key indications for the evaluation of the vessel mechanical resistance and set up of safety measures. The model also provided the prediction of vapor temperature with respect to time and external heat source, that is a key issue to assess the effectiveness of the thermal insulation

The pro-healing effect of exendin-4 on wounds produced by abrasion in normoglycemic mice

Experimental evidence suggested that Exendin-4 (Exe4), an agonist at glucagon like receptor-1 (GLP-1R), promoted tissue regeneration. We aimed to verify the effect of Exe4, in the absence or in the presence of Exendin-4(9-39), an antagonist at GLP-1R, on the healing of abraded skin. Two wounds (approximately 1.1×1.1 cm; namely “upper” and “lower” in respect of the head) were produced by abrasion on the back of 12 mice, which were then randomly assigned to receive an intradermal injection (20 μl) of : Group 1: saline (NT) or Exe4 (62 ng) in the upper and lower wound respectively; Group 2: Exendin-4 (9-39)(70 ng) in the upper and Exendin-4 (9-39)(70 ng) and, after 15 min, Exe4 (62 ng) in the lower wound. Wounds were measured at the time of abrasion (T0) and 144 h (T3) afterward taking pictures with a ruler and by using a software. The inflammatory cell infiltrate, fibroblasts/myofibroblasts, endothelial cells and GLP-1R expression, were each labeled by immunofluorescence in each wound, pERK1/2 was evaluated by Western-blot in wound lysates. At T3, the percentage of healing surface was 53% and 92% for NT and Exe4 wounds respectively and 68% and 79% for those treated with Exendin-4 (9-39) and Exendin-4 (9-39) + Exe4 respectively. Exe4, but not Exendin-4(9-39) induced quantitative increase in fibroblasts/myofibroblasts and vessel density when compared to NT wounds. This increase was not evident in wounds treated with Exendin-4 (9-39) + Exe4. Exe4 promotes wound healing opening to the possible dermatological use of this incretin analogue

Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression

Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with clinical outcome. We evaluated 18 cytokines in breast cancer patients treated with eribulin before starting treatment (T0) and after four courses of therapy (T1). Longitudinal modifications were considered and cytokine clusters through PCA and HCPC correlated to patients’ outcomes were identified. Forty-one metastatic breast cancer patients and fifteen healthy volunteers were included. After clustering, we identified at T0 six patient clusters with different risk of relapse and death. At T1, only four clusters were identified, and three of them accounted for thirty-eight of forty-one patients, suggesting a possible role of treatment in reducing heterogeneity. The cluster with the best survival at T1 was characterized by low levels of IL-4, IL-6, IL-8, IL-10, CCL-2, CCL-4, and TGF-β. The cluster showing the worst survival encompassed high levels of IL-4, IL-6, IL-8, IL-10, CCL-2, and IFN-γ. A subgroup of patients with short progression-free survival (PFS) and long overall survival (OS) was comprised in the cluster characterized by low levels of CCL-2, IL-6, IL-8, IL-10, and IL-12 at T0. Our data support the prognostic significance of longitudinal serum cytokine analysis. This approach may help identify patients for whom early treatment stop avoids needless toxicity or might justify treatment beyond early progression. Further investigations are required to validate this hypothesis