Background information about Avian Infl uenza and hints for ornithologists

Wildvögel, v.a. Wassergeflügel, sind Reservoir für alle Influenzaviren. Von wirtschaftlicher Bedeutung sind die Subtypen H5 und H7, während H1, H2 und H3 Erreger der Humangrippe sind. Diese niedrig pathogenen Vogelgrippeviren verursachen normalerweise bei infi zierten Vögeln keine klinischen Symptome. Nach Transfer niedrig pathogener Vogelgrippeviren in Geflügelhaltungen mit den daraus resultierenden, rasch aufeinander folgenden Virenzyklen durch rasche Vogelpassagen und sofortige Neuinfektion kann sich ein solches niedrig pathogenes Virus jedoch in ein hoch pathogenes Vogelgrippevirus (HPAI-Virus) umwandeln. Diese hoch pathogenen Viren können dann sowohl wieder über Wildvögel, als auch über Transport kontaminierter Vögel, Gefl ügelprodukte und Materialien sowie über Wasser weiterverbreitet werden. Der aktuelle, große Ausbruch der Gefl ügelgrippe geht auf den HPAI-Virus H5N1 zurück, der vermutlich in den späten 1990er Jahren in Hausenten in Südchina entstanden ist. Im Jahr 2005 begann diese Krankheit, sich von Südostasien aus westwärts zu verbreiten und trat damit als direkte Bedrohung für europäische Geflügelbestände in Erscheinung. Außerdem wurden einige wenige menschliche Fälle einer HPAI H5N1-Erkrankung aus Südostasien gemeldet. Alle diese menschlichen Erkrankungen standen mit sehr engen Kontakten zu oder Verspeisen von infizierten Tieren (vor allem Hühner, Enten und Schweine) in Verbindung und eine mögliche Mensch-zu-Mensch-Übertragung wird noch kontrovers diskutiert. Obwohl die Vogelgrippe nach wie vor eine Geflügelkrankheit ist, besteht die Möglichkeit, dass sich das Virus in seiner genetischen Struktur – z.B. durch Vermischung mit einem Humangrippevirus – so verändern kann, dass es leicht zwischen Menschen übertragen werden kann und bei diesen auf ein weitgehend unvorbereitetes Immunsystem trifft. Obwohl sich die Wahrscheinlichkeit einer solchen Veränderung nicht abschätzen lässt, liefern drei Pandemien im 20 Jahrhundert, die alle auf mutierte Vogelgrippeviren zurückzuführen sind, genug Anlass zur sorgfältigen Beobachtung der momentanen Lage.Waterfowl are known to be the major reservoir for all 16 H- and 9 N- Subtypes of low pathogenic avian infl uenza viruses (LPAIV), including the subtypes H5 and H7 being a serious economic threat to the poultry industry as well as H1, H2, H3 that are the main source for human infl uenza. LPAI neither cause any signs of disease in the infected wild birds nor in poultry. However, low pathogenic avian infl uenza virus of the subtypes H5 and H7 can be introduced into poultry holdings. Especially in industrial holdings with large numbers of highly susceptible animals, the previously stable viruses of low pathogenicity begin to evolve rapidly and may mutate into highly pathogenic avian infl uenza (HPAI) (known as fowl plague and also called „bird flu“) causing up to 100% mortatlity in infected birds. Aft erwards, infections of HPAI are usually spread by movement of stock, infectious feces, contaminated water or bird products. Free fl ying birds are usually also blamed to spread the disease, but this could be never proven to have happened. Since 1959 none of the outbreaks of HPAI has approached the size of the ongoing epizootic in Southeast Asia, which most probably originated in the late 1990 ies presumbly in captured ducks in Southern China and is caused by a new HPAI virus of the subtype H5N1. In 2005 the disease started to spread westwards and appears to be a threat for European poultry. Th e asian H5N1 cause serious public health concern for at least three reasons. Th ese AIV isolates can cause heavy economic losses in the poultry industry and through loss of poultry may exaggerate to human food protein defi cits in the developing world. In addition, they have the potential to cross the species barriers and cause human disease and death though only when connected to very close contacts with infected animals or raw consumption of infected birds (chicken, ducks). Last but not least there is the potential of the virus to change it‘s genetic structure – most probably by mixing with a human infl uenza virus (H1, H2, H3) that may achieve human-to-human spread by meeting the unprepared immune system of men resulting in a new human pandemia. Th ree pandemias during the 20 th century – all originating from HPAI viruses- emphasise the danger of the probability of H5N1 becoming the next pandemia virus

Filling the Void: Information Seeking and Processing in the Context of Violent Conflicts

This article explores the ways in which violent intergroup conflict affects how people acquire, use, and perceive information. Based on previous studies and empirical findings from field research in four fragile countries (Libya, Sudan, the Democratic Republic of Congo, and Iraq), including qualitative focus group discussions and standardized quantitative surveys, we show that the polarization and instrumentalization of media in these countries produce media skepticism, leading to increased fact-checking and cross-media use among the general public. Uncertainty leads to discussions in the community about what the media presents, indicating that media users try to establish agency through advanced information processing and validation strategies. We posit that this type of media environment facilitates critical media literacy among media-savvy individuals. Moreover, the present study develops a research agenda for analyzing communication and information processing in conflict contexts

Spatial Distribution of Macrophages During Callus Formation and Maturation Reveals Close Crosstalk Between Macrophages and Newly Forming Vessels

Macrophages are essential players in the process of fracture healing, acting by remodeling of the extracellular matrix and enabling vascularization. Whilst activated macrophages of M1-like phenotype are present in the initial pro-inflammatory phase of hours to days of fracture healing, an anti-inflammatory M2-like macrophage phenotype is supposed to be crucial for the induction of downstream cascades of healing, especially the initiation of vascularization. In a mouse-osteotomy model, we provide a comprehensive characterization of vessel (CD31+, Emcn+) and macrophage phenotypes (F4/80, CD206, CD80, Mac-2) during the process of fracture healing. To this end, we phenotype the phases of vascular regeneration-the expansion phase (d1-d7 after injury) and the remodeling phase of the endothelial network, until tissue integrity is restored (d14-d21 after injury). Vessels which appear during the bone formation process resemble type H endothelium (CD31hiEmcnhi), and are closely connected to osteoprogenitors (Runx2+, Osx+) and F4/80+ macrophages. M1-like macrophages are present in the initial phase of vascularization until day 3 post osteotomy, but they are rare during later regeneration phases. M2-like macrophages localize mainly extramedullary, and CD206+ macrophages are found to express Mac-2+ during the expansion phase. VEGFA expression is initiated by CD80+ cells, including F4/80+ macrophages, until day 3, while subsequently osteoblasts and chondrocytes are main contributors to VEGFA production at the fracture site. Using Longitudinal Intravital Microendoscopy of the Bone (LIMB) we observe changes in the motility and organization of CX3CR1+ cells, which infiltrate the injury site after an osteotomy. A transient accumulation, resulting in spatial polarization of both, endothelial cells and macrophages, in regions distal to the fracture site, is evident. Immunofluorescence histology followed by histocytometric analysis reveals that F4/80+CX3CR1+ myeloid cells precede vascularization

Polizei im Wandel: Abschlussbericht der standardisierten Befragung der Vollzugsbeamtinnen und -beamten der niedersächsischen Polizei 2001 sowie erste Ergebnisse der Gruppendiskussionen 2002

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NAD(P)H fluorescence lifetime imaging of live intestinal nematodes reveals metabolic crosstalk between parasite and host

Infections with intestinal nematodes have an equivocal impact: they represent a burden for human health and animal husbandry, but, at the same time, may ameliorate auto-immune diseases due to the immunomodulatory effect of the parasites. Thus, it is key to understand how intestinal nematodes arrive and persist in their luminal niche and interact with the host over long periods of time. One basic mechanism governing parasite and host cellular and tissue functions, metabolism, has largely been neglected in the study of intestinal nematode infections. Here we use NADH (nicotinamide adenine dinucleotide) and NADPH (nicotinamide adenine dinucleotide phosphate) fluorescence lifetime imaging of explanted murine duodenum infected with the natural nematode Heligmosomoides polygyrus and define the link between general metabolic activity and possible metabolic pathways in parasite and host tissue, during acute infection. In both healthy and infected host intestine, energy is effectively produced, mainly via metabolic pathways resembling oxidative phosphorylation/aerobic glycolysis features. In contrast, the nematodes shift their energy production from balanced fast anaerobic glycolysis-like and effective oxidative phosphorylation-like metabolic pathways, towards mainly anaerobic glycolysis-like pathways, back to oxidative phosphorylation/aerobic glycolysis-like pathways during their different life cycle phases in the submucosa versus the intestinal lumen. Additionally, we found an increased NADPH oxidase (NOX) enzymes-dependent oxidative burst in infected intestinal host tissue as compared to healthy tissue, which was mirrored by a similar defense reaction in the parasites. We expect that, the here presented application of NAD(P)H-FLIM in live tissues constitutes a unique tool to study possible shifts between metabolic pathways in host-parasite crosstalk, in various parasitic intestinal infections

Human fetal heart rate variability-characteristics of autonomic regulation in the third trimester of gestation

Aim: To describe developmental aspects of the sympathovagal heart rate regulation in the human fetus by applying numerics to visual descriptions of fetal heart rate patterns throughout the third trimester of pregnancy. The focus is to determine potential benefits of this alternative means of assessing the maturation of the fetal autonomic nervous system by analysis of fetal heart rate variability (fHRV). Subjects and methods: The magnetocardiograms of 103 normal fetuses between 24q1 and 41q6 weeks of gestation were studied. Fetal heart beat intervals were determined with a temporal precision of 1 ms. The levels of fetal activity were estimated according to characteristic heart rate patterns (I–III) prior to 32, between 32–35 and beyond 35 (groups 1–3) completed weeks. Mean heart rate (mHR), standard deviation of normal-to-normal beat intervals (SDNN) and root mean square of successive differences of normal beats (RMSSD) served as fHRV indices, mean permutation entropy (PE_Mean) as complexity measure. SDNN/RMSSD was introduced as a potential marker for sympatho-vagal balance. Results: Low activity fHRP (I) were characterized by significantly lower level fHRV indices and higher PE_Mean when compared to fHRP II. We found that SDNN/RMSSD decreases with gestation in fHRP I, which suggests increasing vagal influence. In fHRP III (assigned to active awake fetuses only after 32 weeks), highest level SDNN and mHR are associated with a dramatically reduced complexity. fHRV indices cluster characteristically with the activity levels. Conclusions: We conclude that a combined analysis of fHRV, based on SDNN/RMSSD and PE_Mean, and fHRP is advantageous in the assessment of maturation of the fetal autonomic nervous system

Limbostomy: Longitudinal Intravital Microendoscopy in Murine Osteotomies

Bone healing involves the interplay of immune cells, mesenchymal cells, and vasculature over the time course of regeneration. Approaches to quantify the spatiotemporal aspects of bone healing at cellular resolution during long bone healing do not yet exist. Here, a novel technique termed Limbostomy is presented, which combines intravital microendoscopy with an osteotomy. This design allows a modular combination of an internal fixator plate with a gradient refractive index (GRIN) lens at various depths in the bone marrow and can be combined with a surgical osteotomy procedure. The field of view (FOV) covers a significant area of the fracture gap and allows monitoring cellular processes in vivo. The GRIN lens causes intrinsic optical aberrations which have to be corrected. The optical system was characterized and a postprocessing algorithm was developed. It corrects for wave front aberration-induced image plane deformation and for background and noise signals, enabling us to observe subcellular processes. Exemplarily, we quantitatively and qualitatively analyze angiogenesis in bone regeneration. We make use of a transgenic reporter mouse strain with nucleargreen fluorescent protein and membrane-bound tdTomato under the Cadherin-5 promoter. We observe two phases of vascularization. First, rapid vessel sprouting pervades the FOV within 3-4 days after osteotomy. Second, the vessel network continues to be dynamically remodeled until the end of our observation time, 14 days after surgery. Limbostomy opens a unique set of opportunities and allows further insight on spatiotemporal aspects of bone marrow biology, for example, hematopoiesis, analysis of cellular niches, immunological memory, and vascularization in the bone marrow during health and disease

Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site