Effects of deoxynivalenol (DON), zearalenone (ZEN), and related metabolites on equine peripheral blood mononuclear cells (PBMC) in vitro and background occurrence of these toxins in horses

Both deoxynivalenol (DON), zearalenone (ZEN), and their metabolites are known to modulate immune cells in various species whereby viability and proliferation are influenced. Such effects were rarely examined in horses. Therefore, one aim of the present study was to titrate the inhibitory concentrations of DON, 3-acetyl-DON (3AcDON), de-epoxy-DON (DOM-1), ZEN, and α- and β-zearalenol (ZEL) at which viability and proliferation of equine PBMC were reduced by 50 % (IC₅₀) and 10 % (IC₁₀) in vitro. For evaluation of practical relevance of the in vitro findings, a further aim was to screen horses for the background occurrence of DON, ZEN, and their metabolites in systemic circulation and to relate toxin residues both to the inhibitory toxin concentrations and to hematological and clinical-chemical characteristics.The IC₅₀ (μM) for DON, 3AcDON, β-ZEL, α-ZEL, and ZEN were determined at 3.09, 25.90, 75.44, 97.44, and 98.15 in unstimulated cells, respectively, while in proliferating cells, the corresponding IC₅₀ values were 0.73, 6.89, 45.16, 75.96, and 82.51. Neither viability nor proliferation was influenced by DOM-1 up to a concentration of 100 μM.The in vivo screening (N?=?49) revealed the occurrence of ZEN (N?=?24), α-ZEL (N?=?3), β-ZEL (N?=?37), DON, and DOM-1 (N?=?2). The detected concentrations were much lower than the corresponding IC₅₀ while the IC₁₀ of DON and β-ZEL for proliferating PBMC corresponded to approximately 26 and 35 ng/mL which might be relevant when contaminated diets are fed.Clinical-chemical and hematological traits were not related to mycotoxin residue levels excepting blood urea nitrogen which was positively correlated to the sum of β-ZEL, α-ZEL, and ZEN concentration. Whether this reflects simply the feeding history of the horses or renal failures giving rise to a prolonged half-life of the toxins needs to be clarified further.     

Gatekeeper role of brain antigen‐presenting CD11c+ cells in neuroinflammation

Multiple sclerosis is the most frequent chronic inflammatory disease of the CNS. The entry and survival of pathogenic T cells in the CNS are crucial for the initiation and persistence of autoimmune neuroinflammation. In this respect, contradictory evidence exists on the role of the most potent type of antigen‐presenting cells, dendritic cells. Applying intravital two‐photon microscopy, we demonstrate the gatekeeper function of CNS professional antigen‐presenting CD11c⁺ cells, which preferentially interact with Th17 cells. IL‐17 expression correlates with expression of GM‐CSF by T cells and with accumulation of CNS CD11c⁺ cells. These CD11c⁺ cells are organized in perivascular clusters, targeted by T cells, and strongly express the inflammatory chemokines Ccl5, Cxcl9, and Cxcl10. Our findings demonstrate a fundamental role of CNS CD11c⁺ cells in the attraction of pathogenic T cells into and their survival within the CNS. Depletion of CD11c⁺ cells markedly reduced disease severity due to impaired enrichment of pathogenic T cells within the CNS.     

Environmental conditions at arrival to the wintering grounds and during spring migration affect population dynamics of barn swallows Hirundo rustica breeding in Northern Italy

Several populations of long-distance migratory birds are currently suffering steep demographic declines. The identification of the causes of such declines is difficult because population changes may be driven by events occurring in distant geographical areas during different phases of the annual life-cycle of migrants. Furthermore, wintering areas and migration routes of populations of small-sized species are still largely unknown, with few exceptions. In this paper we identified the critical phases of the annual life-cycle that most influence the population dynamics of a small passerine, the Barn Swallow Hirundo rustica. We used information on temporal dynamics of a population breeding in Northern Italy, whose wintering range and timing of migration have been recently described by miniaturised tracking dataloggers. Our results indicated that primary productivity in the wintering grounds in the month when most individuals arrive from autumn migration and primary productivity in an area that is probably a stopover site during spring migration, influenced population dynamics more than habitat conditions at the breeding grounds. By using annual variation in primary productivity at the wintering grounds and stopover sites as predictors, we replicated the observed interannual population changes with great accuracy. However, the steep decline recently suffered by the population could be replicated only by including a constant annual decline in the model, suggesting that changes in primary productivity only predicted the interannual variation around the long-term trend. Our study therefore suggests the existence of critical periods during wintering and migration that may have large impact on population fluctuations of migrant birds.     

Proteomic analysis of Aspergillus fumigatus – clinical implications

Introduction: Aspergillus fumigatus is a ubiquitous saprophytic fungus capable of producing small airborne spores, which are frequently inhaled by humans. In healthy individuals, the fungus is rapidly cleared by innate mechanisms, including immune cells. However, in individuals with impaired lung function or immunosuppression the spores can germinate and prompt severe allergic responses, and disease with limited or extensive invasiveness.

Areas covered: The traits that make A. fumigatus a successful colonizer and pathogen of humans are multi-factorial. Thus, a global investigative approach is required to elucidate the mechanisms utilized by the fungus to cause disease.

Expert commentary: In doing so, a better understanding of disease pathology can be achieved with improved therapeutic/diagnostic solutions, thereby improving patient outcome. Proteomic analysis permits such investigations and recent work has yielded insight into these mechanisms.     

P2X7-mediated ATP secretion is accompanied by depletion of cytosolic ATP

Purinergic Signalling - ATP and its metabolites are important extracellular signal transmitters acting on purinergic P2 and P1 receptors. Most cells can actively secrete ATP in response to a...     

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from “nutrient supplements”, such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta‐analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta‐review of this top‐tier evidence, we identified, synthesized and appraised all meta‐analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta‐analyses of placebo‐controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention‐deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate‐based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high‐dose methylfolate in major depressive disorder. There was emergent evidence for N‐acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence‐based supplements, to further elucidate the underlying mechanisms.     

BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation

1. Download high-res image (141KB)
2. Download full-size image

     

1064 nm Nd:YAG laser light affects transmembrane mitochondria respiratory chain complexes

Photobiomodulation (PBM) is a non‐plant‐cell manipulation through a transfer of energy by means of light sources at the non‐ablative or thermal intensity. Authors showed that cytochrome‐c‐oxidase (complex IV) is the specific chromophore's target of PBM at the red (600‐700 nm) and NIR (760‐900 nm) wavelength regions. Recently, it was suggested that the infrared region of the spectrum could influence other chromospheres, despite the interaction by wavelengths higher than 900 nm with mitochondrial chromophores was not clearly demonstrated. We characterized the interaction between mitochondria respiratory chain, malate dehydrogenase, a key enzyme of Krebs cycle, and 3‐hydroxyacyl‐CoA dehydrogenase, an enzyme involved in the β‐oxidation (two mitochondrial matrix enzymes) with the 1064 nm Nd:YAG (100mps and 10 Hz frequency mode) irradiated at the average power density of 0.50, 0.75, 1.00, 1.25 and 1.50 W/cm² to generate the respective fluences of 30, 45, 60, 75 and 90 J/cm². Our results show the effect of laser light on the transmembrane mitochondrial complexes I, III, IV and V (adenosine triphosphate synthase) (window effects), but not on the extrinsic mitochondrial membrane complex II and mitochondria matrix enzymes. The effect is not due to macroscopical thermal change. An interaction of this wavelength with the Fe‐S proteins and Cu‐centers of respiratory complexes and with the water molecules could be supposed.      

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

1. Download high-res image (342KB)
2. Download full-size image

     

Dispersal patterns in a medium‐density Irish badger population: Implications for understanding the dynamics of tuberculosis transmission

European badgers (Meles meles) are group‐living mustelids implicated in the spread of bovine tuberculosis (TB) to cattle and act as a wildlife reservoir for the disease. In badgers, only a minority of individuals disperse from their natal social group. However, dispersal may be extremely important for the spread of TB, as dispersers could act as hubs for disease transmission. We monitored a population of 139 wild badgers over 7 years in a medium‐density population (1.8 individuals/km²). GPS tracking collars were applied to 80 different individuals. Of these, we identified 25 dispersers, 14 of which were wearing collars as they dispersed. This allowed us to record the process of dispersal in much greater detail than ever before. We show that dispersal is an extremely complex process, and measurements of straight‐line distance between old and new social groups can severely underestimate how far dispersers travel. Assumptions of straight‐line travel can also underestimate direct and indirect interactions and the potential for disease transmission. For example, one female disperser which eventually settled 1.5 km from her natal territory traveled 308 km and passed through 22 different territories during dispersal. Knowledge of badgers' ranging behavior during dispersal is crucial to understanding the dynamics of TB transmission, and for designing appropriate interventions, such as vaccination.