Widespread mitochondrial depletion via mitophagy does not compromise necroptosis

Programmed necrosis (or necroptosis) is a form of cell death triggered by the activation of receptor interacting protein kinase-3 (RIPK3). Several reports have implicated mitochondria and mitochondrial reactive oxygen species (ROS) generation as effectors of RIPK3-dependent cell death. Here, we directly test this idea by employing a method for the specific removal of mitochondria via mitophagy. Mitochondria-deficient cells were resistant to the mitochondrial pathway of apoptosis, but efficiently died via tumor necrosis factor (TNF)-induced, RIPK3-dependent programmed necrosis or as a result of direct oligomerization of RIPK3. Although the ROS scavenger butylated hydroxyanisole (BHA) delayed TNF-induced necroptosis, it had no effect on necroptosis induced by RIPK3 oligomerization. Furthermore, although TNF-induced ROS production was dependent on mitochondria, the inhibition of TNF-induced necroptosis by BHA was observed in mitochondria-depleted cells. Our data indicate that mitochondrial ROS production accompanies, but does not cause, RIPK3-dependent necroptotic cell death

Iohexol-based measurement of intestinal permeability in birds

Background: Iohexol has been successfully used as a marker to assess intestinal permeability in humans and various other mammals. The objective of this study was to evaluate the use of oral iohexol as an intestinal permeability marker in four anatomically and nutritionally diverse bird species. Methods: Three dosages (1 ml/kg, 2 ml/kg, 4 ml/kg) of iohexol (755 mg/ml) were administered orally to each six clinically healthy pigeons and chickens at two-week intervals. Iohexol plasma concentration was determined 45, 90 and 180 minutes after administration. A comparative study was performed by administering iohexol twice to each six clinically healthy cockatiels and falcons, and determining iohexol plasma concentration at 45 or 90 minutes after administration. Results: The recommended iohexol dosage for permeability testing in birds was determined to be 1 ml/kg. Median plasma iohexol concentrations were 27.77 mu g/ml in pigeons, 12.97 mu g/ml in chickens, 14.24 mu g/ml in cockatiels, and 47.81 mu g/ml in falcons, 45 minutes after this dosage was administered. At 90 minutes after administration, median plasma iohexol concentrations were 40.68 mu g/ml in pigeons, 21.59 mu g/ml in chickens, 32.03 mu g/ml in cockatiels, and 55.96 mu g/ml in falcons. Conclusions and clinical relevance: Oral iohexol was a safe and feasible marker for intestinal permeability assessment in birds. Further investigations are warranted to establish species-specific reference intervals in larger numbers of healthy birds, and to examine the use of iohexol as a permeability marker in birds with disorders associated with altered intestinal permeability.Peer reviewe

Indikatoren einer tiergerechten Mastputenhaltung unter den Bedingungen der ökologischen Geflügelmast

Ziel der Studie war eine Analyse der Häufigkeit und des Ausprägungsgrades tierschutzrelevanter Veränderungen bei Puten, die gemäß den Bedingungen der EU-Verordnung 889/2008 für den ökologischen Landbau gehalten wurden. In zwei Durchgängen wurden in neun Aufzucht- und 14 Mastbetrieben 32 Herden mit insgesamt 105.483 Tieren erfasst. Der Tiergesundheitsstatus der einzelnen Herden wurde stichprobenartig an fünf Zeitpunkten durch Beurteilung von 60 Einzeltieren dokumentiert. Bei jedem Bestandsbesuch wurden außerdem Einstreuproben entnommen und ihr Feuchtigkeitsgehalt thermogravimetrisch bestimmt. Die mittlere kumulierte Verlustrate in der Aufzuchtphase lag bei 3,3 % und in der 16. Lebenswoche bei 4,5%. Am Ende der Aufzuchtphase wiesen bis zu 44 % der untersuchten Tiere Epithelnekrosen an den Fußballen auf. Häufigkeit und Schweregrad von Ballenveränderungen nahmen im Verlauf der Mastphase weiter zu. So wurden in der 16. Lebenswoche bei über 80 % der untersuchten Puten Ballennekrosen festgestellt. Am Schlachthof erfolgte eine Aufnahme allgemeiner Daten zur Schlachtung und folgend die visuelle Beschau von 60 Puten je Herde. Der überwiegende Teil der Tiere (97,7%) wies zum Zeitpunkt der Schlachtung Veränderungen der Fußballen auf, während Brusthautveränderungen nur selten dokumentiert wurden. Vermehrt traten weiterhin Leberveränderungen, insbesondere Grünfärbungen auf, wobei deutliche Unterschiede zwischen verschiedenen Betrieben sowie zwischen den einzelnen Durchgängen festgestellt wurden. Auch Gelenksveränderungen waren häufige Befunde. Als ein maßgeblicher Faktor für die Gesunderhaltung eines Putenbestandes ist die Befähigung des bestandsbetreuenden Personenkreises anzusehen, gesundheitliche Probleme frühzeitig zu erkennen und zeitnah darauf zu reagieren. Neben der Qualität des Einstreusubstrates inklusive Beurteilung der Kotkonsistenz können Häufigkeit und Ausprägung von Ballenveränderungen wertvolle Hinweise für eine Einschätzung des Tierhaltungsstandards in einem Bestand liefern und sind als wichtige, einfach erfassbare Tierschutzindikatoren einzustufen . Auch Gelenks- und Leberveränderungen sind aufgrund hoher Prävalenzen als relevante Tiergesundheitsparameter zu betrachten, die im Rahmen eines Monitorings routinemäßig erfasst werden sollten

Towards a standardization of biomethane potential tests

8 PáginasProduction of biogas from different organic materials is a most interesting source of renewable energy. The biomethane potential (BMP) of these materials has to be determined to get insight in design parameters for anaerobic digesters. A workshop was held in June 2015 in Leysin Switzerland to agree on common solutions to the conundrum of inconsistent BMP test results. A discussion covers actions and criteria that are considered compulsory ito accept and validate a BMP test result; and recommendations concerning the inoculum substrate test setup and data analysis and reporting ito obtain test results that can be validated and reproduced.The workshop in Leysin, Switzerland, has been financed by the Swiss Federal Office for Energy, and co-sponsored by Bioprocess Control Sweden AB, Lund, Sweden. The authors thank Alexandra Maria Murray for editing the English

Induction of Neuronal Death by Microglial AGE-Albumin: Implications for Alzheimer’s Disease

Advanced glycation end products (AGEs) have long been considered as potent molecules promoting neuronal cell death and contributing to neurodegenerative disorders such as Alzheimer’s disease (AD). In this study, we demonstrate that AGE-albumin, the most abundant AGE product in human AD brains, is synthesized in activated microglial cells and secreted into the extracellular space. The rate of AGE-albumin synthesis in human microglial cells is markedly increased by amyloid-β exposure and oxidative stress. Exogenous AGE-albumin upregulates the receptor protein for AGE (RAGE) and augments calcium influx, leading to apoptosis of human primary neurons. In animal experiments, soluble RAGE (sRAGE), pyridoxamine or ALT-711 prevented Aβ-induced neuronal death in rat brains. Collectively, these results provide evidence for a new mechanism by which microglial cells promote death of neuronal cells through synthesis and secretion of AGE-albumin, thereby likely contributing to neurodegenerative diseases such as AD

Coccidian Infection Causes Oxidative Damage in Greenfinches

The main tenet of immunoecology is that individual variation in immune responsiveness is caused by the costs of immune responses to the hosts. Oxidative damage resulting from the excessive production of reactive oxygen species during immune response is hypothesized to form one of such costs. We tested this hypothesis in experimental coccidian infection model in greenfinches Carduelis chloris. Administration of isosporan coccidians to experimental birds did not affect indices of antioxidant protection (TAC and OXY), plasma triglyceride and carotenoid levels or body mass, indicating that pathological consequences of infection were generally mild. Infected birds had on average 8% higher levels of plasma malondialdehyde (MDA, a toxic end-product of lipid peroxidation) than un-infected birds. The birds that had highest MDA levels subsequent to experimental infection experienced the highest decrease in infection intensity. This observation is consistent with the idea that oxidative stress is a causative agent in the control of coccidiosis and supports the concept of oxidative costs of immune responses and parasite resistance. The finding that oxidative damage accompanies even the mild infection with a common parasite highlights the relevance of oxidative stress biology for the immunoecological research

Plus- and Minus-End Directed Microtubule Motors Bind Simultaneously to Herpes Simplex Virus Capsids Using Different Inner Tegument Structures

Many viruses depend on host microtubule motors to reach their destined intracellular location. Viral particles of neurotropic alphaherpesviruses such as herpes simplex virus 1 (HSV1) show bidirectional transport towards the cell center as well as the periphery, indicating that they utilize microtubule motors of opposing directionality. To understand the mechanisms of specific motor recruitment, it is necessary to characterize the molecular composition of such motile viral structures. We have generated HSV1 capsids with different surface features without impairing their overall architecture, and show that in a mammalian cell-free system the microtubule motors dynein and kinesin-1 and the dynein cofactor dynactin could interact directly with capsids independent of other host factors. The capsid composition and surface was analyzed with respect to 23 structural proteins that are potentially exposed to the cytosol during virus assembly or cell entry. Many of these proteins belong to the tegument, the hallmark of all herpesviruses located between the capsid and the viral envelope. Using immunoblots, quantitative mass spectrometry and quantitative immunoelectron microscopy, we show that capsids exposing inner tegument proteins such as pUS3, pUL36, pUL37, ICP0, pUL14, pUL16, and pUL21 recruited dynein, dynactin, kinesin-1 and kinesin-2. In contrast, neither untegumented capsids exposing VP5, VP26, pUL17 and pUL25 nor capsids covered by outer tegument proteins such as vhs, pUL11, ICP4, ICP34.5, VP11/12, VP13/14, VP16, VP22 or pUS11 bound microtubule motors. Our data suggest that HSV1 uses different structural features of the inner tegument to recruit dynein or kinesin-1. Individual capsids simultaneously accommodated motors of opposing directionality as well as several copies of the same motor. Thus, these associated motors either engage in a tug-of-war or their activities are coordinately regulated to achieve net transport either to the nucleus during cell entry or to cytoplasmic membranes for envelopment during assembly

»Ett av de bästa medlen i vår propaganda« : Cykeln i svensk och dansk politisk kultur under mellankrigstiden

Genom empiriska exempel från Danmark och Sverige diskuterar denna artikel hur den moderna, masstillverkade cykeln blev ett viktigt verktyg i händerna på en ny generation politiska ungdomar. Under mellankrigsåren (1918–1939) utgjorde de unga sig själva som en egen samhällsgrupp. För allra första gången i historien blev ungdomen nyckelaktörer på den politiska scenen och de tog med sig moderna former av propagandametoder inspirerade av internationella trender. Detta kom att forma den politiska kulturen även i de skandinaviska länderna under det tumultartade 1930-talet. Den politiska ungdomsmobiliseringen skedde framför allt i stadslandskapet på gator och torg. I detta sammanhang kom cykeln att spela en anmärkningsvärd roll för hur det offentliga stadsrummet utnyttjades politiskt. Cykeln gjorde det möjligt för unga att ta mer plats i dagens politiska liv genom att skapa tillgänglig rörlighet men också en ny typ av rumslighet. I detta sammanhang var cykeln inte bara ett transportmedel; det var ett redskap i kampen för det offentliga rummet som kom att forma 1930-talets politiska kultur. Cyklar användes för parader, för spridning av propaganda och till och med stora cykeldemonstrationer genom vilka ungdomsaktivister kunde skapa inte bara det symboliska, utan också det sociala utrymmet för sin politik. De använde cykeln som ett medel för rumslig anspråk och cykelpropaganda blev sedan en del av en pågående konflikt mellan vänster- och högerorienterade politiska ungdomar där de utmanade varandras anspråk på gatorna som ofta ledde till våldsam konfrontation. Därmed blev cykeln ett viktigt verktyg i en ny politisk kultur som växte fram i vågorna av det demokratiska genombrottet där kampen för tillgång till det offentliga rummet blev viktigare än någonsin