Ortstreue und Genflu? bei Inselvogelarten: Eleonorenfalke (Falco eleonorae) und Gelbschnabelsturmtaucher (Calonectris diomedea)

Summary Young birds of both species return almost exclusively to their natal colony for breeding and breeders are higly faithful to both partner and territory in subsequent years. There is no or very limited emigration to other colonies which are 2–5 km distant. The consequences of the genetic isolation are discussed: In both species the tendency to form subspecies can be detected. High mortality rates are interpreted as a mean to eliminate any degenerated bird which could result from the close interbreeding in these small and isolated populations.     

RIG‐I detects infection with live Listeria by sensing secreted bacterial nucleic acids

Immunity against infection with Listeria monocytogenes is not achieved from innate immune stimulation by contact with killed but requires viable Listeria gaining access to the cytosol of infected cells. It has remained ill‐defined how such immune sensing of live Listeria occurs. Here, we report that efficient cytosolic immune sensing requires access of nucleic acids derived from live Listeria to the cytoplasm of infected cells. We found that Listeria released nucleic acids and that such secreted bacterial RNA/DNA was recognized by the cytosolic sensors RIG‐I, MDA5 and STING thereby triggering interferon β production. Secreted Listeria nucleic acids also caused RIG‐I‐dependent IL‐1β‐production and inflammasome activation. The signalling molecule CARD9 contributed to IL‐1β production in response to secreted nucleic acids. In conclusion, cytosolic recognition of secreted bacterial nucleic acids by RIG‐I provides a mechanistic explanation for efficient induction of immunity by live bacteria.     

Psychosocial Stress Increases Salivary Alpha-Amylase Activity Independently from Plasma Noradrenaline Levels

Salivary alpha-amylase activity (sAA) and plasma noradrenaline (NA) concentrations are often considered to be surrogate markers of sympathetic activation in response to stress. However, despite accumulating evidence for a close association between sAA and noradrenaline and other indicators of sympathetic activity, reliability and generality of this relation remains unclear. We employed the Trier Social Stress Test (TSST) in order to directly compare the responses in sAA and NA to psychological stress in healthy volunteers (n = 23). The TSST significantly increased sAA and NA plasma levels with no significant differences in females and males. However, when subjects were divided according to their NA responses into low versus high responders, both groups did not significantly differ in their sAA before, during or after stress exposure. These data suggest that in response to acute psychological stress both plasma NA levels and sAA reflect sympathetic activity, however seemed to increase independently from each other.     

Structural basis for budding by the ESCRT-III factor CHMP3

The vacuolar protein sorting machinery regulates multivesicular body biogenesis and is selectively recruited by enveloped viruses to support budding. Here we report the crystal structure of the human ESCRT-III protein CHMP3 at 2.8 A resolution. The core structure of CHMP3 folds into a flat helical arrangement that assembles into a lattice, mainly via two different dimerization modes, and unilaterally exposes a highly basic surface. The C terminus, the target for Vps4-induced ESCRT disassembly, extends from the opposite side of the membrane targeting region. Mutations within the basic and dimerization regions hinder bilayer interaction in vivo and reverse the dominant-negative effect of a truncated CHMP3 fusion protein on HIV-1 budding. Thus, the final steps in the budding process may include CHMP protein polymerization and lattice formation on membranes by employing different bilayer-recognizing surfaces, a function shared by all CHMP family members.     

Virtual screening,selection and development of a benzindolone structural scaffold for inhibition of lumazine synthase

Virtual screening of a library of commercially available compounds versus the structure of Mycobacterium tuberculosis lumazine synthase identified 2-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)acetic acid (9) as a possible lead compound. Compound 9 proved to be an effective inhibitor of M. tuberculosis lumazine synthase with a K_i of 70 μM. Lead optimization through replacement of the carboxymethylsulfonamide sidechain with sulfonamides substituted with alkyl phosphates led to a four-carbon phosphate 38 that displayed a moderate increase in enzyme inhibitory activity (K_i 38 μM). Molecular modeling based on known lumazine synthase/inhibitor crystal structures suggests that the main forces stabilizing the present benzindolone/enzyme complexes involve π–π stacking interactions with Trp27 and hydrogen bonding of the phosphates with Arg128, the backbone nitrogens of Gly85 and Gln86, and the side chain hydroxyl of Thr87.     

Trade-offs in the vertical distribution of zooplankton: ideal free distribution with costs?

Zooplankton vertical migratory patterns are a classic example of optimal habitat choice. We hypothesize that zooplankton distribute themselves vertically in the water column according to an ideal free distribution (IFD) with costs such as to optimize their fitness. In lakes with a deep-water chlorophyll maximum, zooplankton are faced with a trade-off, either experiencing high food (high reproductive potential) but low temperature (slow development) in the hypolimnion or high temperature and low food in the epilimnion. Thus, in the absence of fish predation (e.g. at night) they should allocate the time spent in the different habitats according to fitness gain dependent on the temperature gradient and distribution of food. We tested this hypothesis with a Daphnia hyalina x galeata clone in large indoor columns (Plön Plankton Towers) and with a dynamic energy budget model. In the tower experiments, we simulated a deep-water algal maximum below the thermocline with epilimnetic/hypolimnetic temperature differences of 2, 5 and 10 degrees C. Experimental data supported the model. We found a significantly larger proportion of daphniids in the hypolimnion when the temperature difference was smaller. Our results are consistent with the concept of IFD with costs originally developed for stream fishes. This concept can be applied to predict the vertical distribution of zooplankton in habitats where fish predation is of minor importance.     

Treatment Satisfaction and Well-Being in Patients with Myopic Choroidal Neovascularization Treated with Ranibizumab in the REPAIR Study

The Ranibizumab for the Treatment of Choroidal Neovascularisation (CNV) Secondary to Pathological Myopia (PM): an Individualized Regimen (REPAIR) trial was a prospective study exploring the efficacy and safety of intravitreal ranibizumab 0.5 mg using an individualized treatment regimen over 12 months. The current study investigated the impact of treatment with ranibizumab as needed (pro re nata [PRN]) on individuals with myopic choroidal neovascularization (mCNV) in the REPAIR study, using patient-reported outcome measures (PROMs) for treatment satisfaction and well-being. This study included 65 adults with mCNV and a best-corrected visual acuity (BCVA) letter score of 24–78 in the study eye. Patients completed the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) at months 1, 6 and 12, and the 12-item Well-Being Questionnaire (W-BQ12) at baseline and months 1, 6 and 12. Subgroup analyses investigated the relationship between PROM scores and treatment in the better- or worse-seeing eye (BSE/WSE), number of injections received, baseline BCVA, BCVA improvement and age. Pearson correlations between change in BCVA, MacTSQ scores and W-BQ12 scores were calculated. The main outcome measures were treatment satisfaction measured with the MacTSQ (score 0–72) and well-being measured with the W-BQ12 (score 0–36). Treatment satisfaction significantly increased over the study period (p = 0.0001). Mean MacTSQ scores increased by 9.7 and 10.0 in patients treated in their WSE and BSE, respectively. Treatment satisfaction was highest in individuals receiving only one injection at month 1; however, by month 12, scores were similar across injection subgroups. Patients aged 68 years or older had the highest MacTSQ scores. Well-being scores also significantly increased over the study period (p = 0.03). Mean W-BQ12 scores increased by 1.7 in patients treated in their WSE and by 2.1 in patients treated in their BSE. Individuals aged 40 years or younger had the greatest increases in general well-being. Patients who experienced stable or improved BCVA at month 12 had greater increases in W-BQ12 scores than those who experienced a decrease. Correlations between BCVA, MacTSQ scores and W-BQ12 scores were largely non-significant. In conclusion, treatment satisfaction and well-being increased during treatment with ranibizumab PRN. Although directly comparable data are limited for the MacTSQ and W-BQ12 in mCNV, these results complement PROM outcomes reported in related studies.     

Circadian locomotor activity of Musca flies: Recording method and effects of 10 Hz square-wave electric fields

Musca domestica flies that were exposed to a uniform vertical 10 Hz electric square-wave field of 1 kVm⁻¹ changed the period length of their circadian locomotor activity rhythm. Under constant conditions, the clock of short-period flies was slowed down by the field, whereas the clock of long-period flies either was affected only scarcely (experiments at about 19°C) or ran faster (experiments at 25°C). If the field was applied for only 12 h daily, then 30–40% of the flies were synchronized. Thus, the field could function as a weak “Zeitgeber” (synchronizer). If the field was increased to 10 kVm⁻¹, then 50–70% of the flies were synchronized. Flies avoided becoming active around the onset of the 12 h period of exposure to a 10 Hz field. The results of these experiments are discussed with respect to similar experiments by Wever on the effects of exposure to a 10 Hz field on the circadian system of man. © 1996 Wiley-Liss, Inc.     

CD8+ T Cell Fate and Function Influenced by Antigen-Specific Virus-Like Nanoparticles Co-Expressing Membrane Tethered IL-2

A variety of adjuvants fostering humoral immunity are known as of today. However, there is a lack of adjuvants or adjuvant strategies, which directly target T cellular effector functions and memory. We here determined whether systemically toxic cytokines such as IL-2 can be restricted to the site of antigen presentation and used as ‘natural adjuvants’. Therefore, we devised antigen-presenting virus-like nanoparticles (VNP) co-expressing IL-2 attached to different membrane-anchors and assessed their potency to modulate CD8⁺ T cell responses in vitro and in vivo. Efficient targeting of IL-2 to lipid rafts and ultimately VNP was achieved by fusing IL-2 at its C-terminus to a minimal glycosylphosphatidylinositol (GPI)-anchor acceptor sequence. To identify optimal membrane-anchor dimensions we inserted one (1Ig), two (2Ig) or four (4Ig) immunoglobulin(Ig)-like domains of CD16b between IL-2 and the minimal GPI-anchor acceptor sequence of CD16b (GPI). We found that the 2IgGPI version was superior to all other evaluated IL-2 variants (IL-2v) in terms of its i) degree of targeting to lipid rafts and to the VNP surface, ii) biological activity, iii) co-stimulation of cognate T cells in the absence of bystander activation and iv) potency to induce differentiation and acquisition of CD8⁺ T cell effector functions in vitro and in vivo. In contrast, the GPI version rather favored memory precursor cell formation. These results exemplify novel beneficial features of membrane-bound IL-2, which in addition to its mere T cell stimulatory capacity include the induction of differential effector and memory functions in CD8⁺ T lymphocytes.     

Natural and artificial routes to pluripotency

Pluripotent cells of the blastocyst inner cell mass (ICM) and their in vitro derivatives, embryonic stem (ES) cells, contain genomes in an epigenetic state that are poised for subsequent differentiation. Their chromatin is hyperdynamic in nature and relatively uncondensed. In addition, a large number of genes are expressed at low levels in both ICM and ES cells. Also, the chromatin of naturally pluripotent cells contains specialized histone modification patterns such as bivalent domains, which mark genes destined for later developmentally-regulated expression states. Female pluripotent cells contain X chromosomes that have yet to undergo the process of X chromosome inactivation. Collectively, these features of very early embyronic chromatin are required for the successful specification and production of differentiated cell lineages. Artificial reprogramming methods such as somatic nuclear transfer (SCNT), ES cell fusion-mediated reprogramming (FMR), and induced pluripotency (iPS) yield pluripotent cells that recapitulate many features of naturally pluripotent cells, including many of their epigenetic features. However, the route to pluripotent epigenomic states in artificial pluripotent cells differs drastically from that of their natural counterparts. Here, we compare and contrast the differing routes to pluripotency under natural and artificial conditions. In addition, we discuss the intrinsically metastable nature of the pluripotent epigenome and consider epigenetic aspects of reprogramming that may lead to incomplete or inaccurate reprogrammed states. Artificial methods of reprogramming hold immense promise for the development of autologous cell graft sources and for the development of cell culture models for human genetic disorders. However, the utility of artificially reprogrammed cells is highly dependent on the fidelity of the reprogramming process and it is therefore critically important to assess the epigenetic similarities between embryonic and induced pluripotent stem cells.