The antibody response in experimental ocular toxoplasmosis

BACKGROUND: The dynamics of the humoral immune response in ocular toxoplasmosis (OT) are poorly understood. We therefore investigated this process in a rabbit model of the disease. MATERIALS AND METHODS: Of 24 infection-naïve adult rabbits, 12 were left untreated and 12 were systematically infected with 5,000 tachyzoites of the non-cyst-forming BK strain of Toxoplasma gondii. Three months later, all rabbits were inoculated transvitreally with 5,000 tachyzoites of Toxoplasma gondii. Paired samples of aqueous humor and serum were analyzed temporally for their total and specific IgG contents. RESULTS: In infection-naïve rabbits with primary OT, specific IgG reached detectable levels in the inoculated eyes between 5 and 15 days after inoculation. In infection-immunized rabbits with secondary OT, a significant increase in specific IgG was regularly detected after 5 days. The antibody ratio C was diagnostic (>/=3) from day 15 onward in primary OT and from day 21 onward in secondary OT. In the uninfected partner eyes, the antibody ratio C was found sporadically diagnostic from day 15 onward in primary OT, but at no time in secondary OT. Specific IgG persisted both locally and in the serum until the end of the monitoring period (100 days). CONCLUSION: Our findings relating to the rabbit model of OT reveal three features of clinical relevance: a diagnostic window precedes the establishment of a humoral immune response; specific antibodies persist long after the cessation of disease activity; and in primary OT, the antibody ratio C may also increase in the uninfected partner eye.

Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field

The aim of the current study was to examine the effect of theta burst repetitive transcranial magnetic stimulation (rTMS) on the blood oxygenation level-dependent (BOLD) activation during repeated functional magnetic resonance imaging (fMRI) measurements. Theta burst rTMS was applied over the right frontal eye field in seven healthy subjects. Subsequently, repeated fMRI measurements were performed during a saccade-fixation task (block design) 5, 20, 35, and 60 min after stimulation. We found that theta burst rTMS induced a strong and long-lasting decrease of the BOLD signal response of the stimulated frontal eye field at 20 and 35 min. Furthermore, less pronounced alterations of the BOLD signal response with different dynamics were found for remote oculomotor areas such as the left frontal eye field, the pre-supplementary eye field, the supplementary eye field, and both parietal eye fields. Recovery of the BOLD signal changes in the anterior remote areas started earlier than in the posterior remote areas. These results show that a) the major inhibitory impact of theta burst rTMS occurs directly in the stimulated area itself, and that b) a lower effect on remote, oculomotor areas can be induced.

Forcing of stratospheric chemistry and dynamics during the Dalton Minimum

The response of atmospheric chemistry and dynamics to volcanic eruptions and to a decrease in solar activity during the Dalton Minimum is investigated with the fully coupled atmosphere–ocean chemistry general circulation model SOCOL-MPIOM (modeling tools for studies of SOlar Climate Ozone Links-Max Planck Institute Ocean Model) covering the time period 1780 to 1840 AD. We carried out several sensitivity ensemble experiments to separate the effects of (i) reduced solar ultra-violet (UV) irradiance, (ii) reduced solar visible and near infrared irradiance, (iii) enhanced galactic cosmic ray intensity as well as less intensive solar energetic proton events and auroral electron precipitation, and (iv) volcanic aerosols. The introduced changes of UV irradiance and volcanic aerosols significantly influence stratospheric dynamics in the early 19th century, whereas changes in the visible part of the spectrum and energetic particles have smaller effects. A reduction of UV irradiance by 15%, which represents the presently discussed highest estimate of UV irradiance change caused by solar activity changes, causes global ozone decrease below the stratopause reaching as much as 8% in the midlatitudes at 5 hPa and a significant stratospheric cooling of up to 2 °C in the mid-stratosphere and to 6 °C in the lower mesosphere. Changes in energetic particle precipitation lead only to minor changes in the yearly averaged temperature fields in the stratosphere. Volcanic aerosols heat the tropical lower stratosphere, allowing more water vapour to enter the tropical stratosphere, which, via HOx reactions, decreases upper stratospheric and mesospheric ozone by roughly 4%. Conversely, heterogeneous chemistry on aerosols reduces stratospheric NOx, leading to a 12% ozone increase in the tropics, whereas a decrease in ozone of up to 5% is found over Antarctica in boreal winter. The linear superposition of the different contributions is not equivalent to the response obtained in a simulation when all forcing factors are applied during the Dalton Minimum (DM) – this effect is especially well visible for NOx/NOy. Thus, this study also shows the non-linear behaviour of the coupled chemistry-climate system. Finally, we conclude that especially UV and volcanic eruptions dominate the changes in the ozone, temperature and dynamics while the NOx field is dominated by the energetic particle precipitation. Visible radiation changes have only very minor effects on both stratospheric dynamics and chemistry.

The Individualized Genetic Barrier Predicts Treatment Response in a Large Cohort of HIV-1 Infected Patients

The success of combination antiretroviral therapy is limited by the evolutionary escape dynamics of HIV-1. We used Isotonic Conjunctive Bayesian Networks (I-CBNs), a class of probabilistic graphical models, to describe this process. We employed partial order constraints among viral resistance mutations, which give rise to a limited set of mutational pathways, and we modeled phenotypic drug resistance as monotonically increasing along any escape pathway. Using this model, the individualized genetic barrier (IGB) to each drug is derived as the probability of the virus not acquiring additional mutations that confer resistance. Drug-specific IGBs were combined to obtain the IGB to an entire regimen, which quantifies the virus' genetic potential for developing drug resistance under combination therapy. The IGB was tested as a predictor of therapeutic outcome using between 2,185 and 2,631 treatment change episodes of subtype B infected patients from the Swiss HIV Cohort Study Database, a large observational cohort. Using logistic regression, significant univariate predictors included most of the 18 drugs and single-drug IGBs, the IGB to the entire regimen, the expert rules-based genotypic susceptibility score (GSS), several individual mutations, and the peak viral load before treatment change. In the multivariate analysis, the only genotype-derived variables that remained significantly associated with virological success were GSS and, with 10-fold stronger association, IGB to regimen. When predicting suppression of viral load below 400 cps/ml, IGB outperformed GSS and also improved GSS-containing predictors significantly, but the difference was not significant for suppression below 50 cps/ml. Thus, the IGB to regimen is a novel data-derived predictor of treatment outcome that has potential to improve the interpretation of genotypic drug resistance tests.

Glacial–interglacial dynamics of Antarctic firn columns: comparison between simulations and ice core air-δ15N measurements

Correct estimation of the firn lock-in depth is essential for correctly linking gas and ice chronologies in ice core studies. Here, two approaches to constrain the firn depth evolution in Antarctica are presented over the last deglaciation: outputs of a firn densification model, and measurements of δ15N of N2 in air trapped in ice core, assuming that δ15N is only affected by gravitational fractionation in the firn column. Since the firn densification process is largely governed by surface temperature and accumulation rate, we have investigated four ice cores drilled in coastal (Berkner Island, BI, and James Ross Island, JRI) and semi-coastal (TALDICE and EPICA Dronning Maud Land, EDML) Antarctic regions. Combined with available ice core air-δ15N measurements from the EPICA Dome C (EDC) site, the studied regions encompass a large range of surface accumulation rates and temperature conditions. Our δ15N profiles reveal a heterogeneous response of the firn structure to glacial–interglacial climatic changes. While firn densification simulations correctly predict TALDICE δ15N variations, they systematically fail to capture the large millennial-scale δ15N variations measured at BI and the δ15N glacial levels measured at JRI and EDML – a mismatch previously reported for central East Antarctic ice cores. New constraints of the EDML gas–ice depth offset during the Laschamp event (~41 ka) and the last deglaciation do not favour the hypothesis of a large convective zone within the firn as the explanation of the glacial firn model–δ15N data mismatch for this site. While we could not conduct an in-depth study of the influence of impurities in snow for firnification from the existing datasets, our detailed comparison between the δ15N profiles and firn model simulations under different temperature and accumulation rate scenarios suggests that the role of accumulation rate may have been underestimated in the current description of firnification models.

Carbon dioxide and climate impulse response functions for the computation of greenhouse gas metrics: a multi-model analysis

The responses of carbon dioxide (CO2) and other climate variables to an emission pulse of CO2 into the atmosphere are often used to compute the Global Warming Potential (GWP) and Global Temperature change Potential (GTP), to characterize the response timescales of Earth System models, and to build reduced-form models. In this carbon cycle-climate model intercomparison project, which spans the full model hierarchy, we quantify responses to emission pulses of different magnitudes injected under different conditions. The CO2 response shows the known rapid decline in the first few decades followed by a millennium-scale tail. For a 100 Gt-C emission pulse added to a constant CO2 concentration of 389 ppm, 25 ± 9% is still found in the atmosphere after 1000 yr; the ocean has absorbed 59 ± 12% and the land the remainder (16 ± 14%). The response in global mean surface air temperature is an increase by 0.20 ± 0.12 °C within the first twenty years; thereafter and until year 1000, temperature decreases only slightly, whereas ocean heat content and sea level continue to rise. Our best estimate for the Absolute Global Warming Potential, given by the time-integrated response in CO2 at year 100 multiplied by its radiative efficiency, is 92.5 × 10−15 yr W m−2 per kg-CO2. This value very likely (5 to 95% confidence) lies within the range of (68 to 117) × 10−15 yr W m−2 per kg-CO2. Estimates for time-integrated response in CO2 published in the IPCC First, Second, and Fourth Assessment and our multi-model best estimate all agree within 15% during the first 100 yr. The integrated CO2 response, normalized by the pulse size, is lower for pre-industrial conditions, compared to present day, and lower for smaller pulses than larger pulses. In contrast, the response in temperature, sea level and ocean heat content is less sensitive to these choices. Although, choices in pulse size, background concentration, and model lead to uncertainties, the most important and subjective choice to determine AGWP of CO2 and GWP is the time horizon.

Inverse modelling of the 14C bomb pulse in stalagmites to constrain the dynamics of soil carbon cycling at selected European cave sites

The decomposition of soil organic matter (SOM) is temperature dependent, but its response to a future warmer climate remains equivocal. Enhanced rates of decomposition of SOM under increased global temperatures might cause higher CO2 emissions to the atmosphere, and could therefore constitute a strong positive feedback. The magnitude of this feedback however remains poorly understood, primarily because of the difficulty in quantifying the temperature sensitivity of stored, recalcitrant carbon that comprises the bulk (>90%) of SOM in most soils. In this study we investigated the effects of climatic conditions on soil carbon dynamics using the attenuation of the 14C ‘bomb’ pulse as recorded in selected modern European speleothems. These new data were combined with published results to further examine soil carbon dynamics, and to explore the sensitivity of labile and recalcitrant organic matter decomposition to different climatic conditions. Temporal changes in 14C activity inferred from each speleothem was modelled using a three pool soil carbon inverse model (applying a Monte Carlo method) to constrain soil carbon turnover rates at each site. Speleothems from sites that are characterised by semi-arid conditions, sparse vegetation, thin soil cover and high mean annual air temperatures (MAATs), exhibit weak attenuation of atmospheric 14C ‘bomb’ peak (a low damping effect, D in the range: 55–77%) and low modelled mean respired carbon ages (MRCA), indicating that decomposition is dominated by young, recently fixed soil carbon. By contrast, humid and high MAAT sites that are characterised by a thick soil cover and dense, well developed vegetation, display the highest damping effect (D = c. 90%), and the highest MRCA values (in the range from 350 ± 126 years to 571 ± 128 years). This suggests that carbon incorporated into these stalagmites originates predominantly from decomposition of old, recalcitrant organic matter. SOM turnover rates cannot be ascribed to a single climate variable, e.g. (MAAT) but instead reflect a complex interplay of climate (e.g. MAAT and moisture budget) and vegetation development.

Forest dynamics during the transition from the Oldest Dryas to the Bølling–Allerød at Gerzensee—a simulation study

The aim of this study was to explore potential causes and mechanisms for the sequence and temporal pattern of tree taxa, specifically for the shift from shrub-tundra to birch–juniper woodland during and after the transition from the Oldest Dryas to the Bølling–Allerød in the region surrounding the lake Gerzensee in southern Central Europe. We tested the influence of climate, forest dynamics, community dynamics compared to other causes for delays. For this aim temperature reconstructed from a δ18O-record was used as input driving the multi-species forest-landscape model TreeMig. In a stepwise scenario analysis, population dynamics along with pollen production and transport were simulated and compared with pollen-influx data, according to scenarios of different δ18O/temperature sensitivities, different precipitation levels, with/without inter-specific competition, and with/without prescribed arrival of species. In the best-fitting scenarios, the effects on competitive relationships, pollen production, spatial forest structure, albedo, and surface roughness were examined in more detail. The appearance of most taxa in the data could only be explained by the coldest temperature scenario with a sensitivity of 0.3‰/°C, corresponding to an anomaly of − 15 °C. Once the taxa were present, their temporal pattern was shaped by competition. The later arrival of Pinus could not be explained even by the coldest temperatures, and its timing had to be prescribed by first observations in the pollen record. After the arrival into the simulation area, the expansion of Pinus was further influenced by competitors and minor climate oscillations. The rapid change in the simulated species composition went along with a drastic change in forest structure, leaf area, albedo, and surface roughness. Pollen increased only shortly after biomass. Based on our simulations, two alternative potential scenarios for the pollen pattern can be given: either very cold climate suppressed most species in the Oldest Dryas, or they were delayed by soil formation or migration. One taxon, Pinus, was delayed by migration and then additionally hindered by competition. Community dynamics affected the pattern in two ways: potentially by facilitation, i.e. by nitrogen-fixing pioneer species at the onset, whereas the later pattern was clearly shaped by competition. The simulated structural changes illustrate how vegetation on a larger scale could feed back to the climate system. For a better understanding, a more integrated simulation approach covering also the immigration from refugia would be necessary, for this combines climate-driven population dynamics, migration, individual pollen production and transport, soil dynamics, and physiology of individual pollen production.

Grazing response patterns indicate isolation of semi-natural European grasslands

Identifying drivers of species diversity is a major challenge in understanding and predicting the dynamics of species-rich semi-natural grasslands. In particular in temperate grasslands changes in land use and its consequences, i.e. increasing fragmentation, the on-going loss of habitat and the declining importance of regional processes such as seed dispersal by livestock, are considered key drivers of the diversity loss witnessed within the last decades. It is a largely unresolved question to what degree current temperate grassland communities already reflect a decline of regional processes such as longer distance seed dispersal. Answering this question is challenging since it requires both a mechanistic approach to community dynamics and a sufficient data basis that allows identifying general patterns. Here, we present results of a local individual- and trait-based community model that was initialized with plant functional types (PFTs) derived from an extensive empirical data set of species-rich grasslands within the `Biodiversity Exploratories' in Germany. Driving model processes included above- and belowground competition, dynamic resource allocation to shoots and roots, clonal growth, grazing, and local seed dispersal. To test for the impact of regional processes we also simulated seed input from a regional species pool. Model output, with and without regional seed input, was compared with empirical community response patterns along a grazing gradient. Simulated response patterns of changes in PFT richness, Shannon diversity, and biomass production matched observed grazing response patterns surprisingly well if only local processes were considered. Already low levels of additional regional seed input led to stronger deviations from empirical community pattern. While these findings cannot rule out that regional processes other than those considered in the modeling study potentially play a role in shaping the local grassland communities, our comparison indicates that European grasslands are largely isolated, i.e. local mechanisms explain observed community patterns to a large extent.

Real-time observation of the charge-transfer-to-solvent dynamics

Intermolecular electron-transfer reactions have a crucial role in biology, solution chemistry and electrochemistry. The first step of such reactions is the expulsion of the electron to the solvent, whose mechanism is determined by the structure and dynamical response of the latter. Here we visualize the electron transfer to water using ultrafast fluorescence spectroscopy with polychromatic detection from the ultraviolet to the visible region, upon photo-excitation of the so-called charge transfer to solvent states of aqueous iodide. The initial emission is short lived (~60 fs) and it relaxes to a broad distribution of lower-energy charge transfer to solvent states upon rearrangement of the solvent cage. This distribution reflects the inhomogeneous character of the solvent cage around iodide. Electron ejection occurs from the relaxed charge transfer to solvent states with lifetimes of 100–400 fs that increase with decreasing emission energy.

A model-data comparison of Holocene timberline changes in the Swiss Alps reveals past and future drivers of mountain forest dynamics

Mountain vegetation is strongly affected by temperature and is expected to shift upwards with climate change. Dynamic vegetation models are often used to assess the impact of climate on vegetation and model output can be compared with paleobotanical data as a reality check. Recent paleoecological studies have revealed regional variation in the upward shift of timberlines in the Northern and Central European Alps in response to rapid warming at the Younger Dryas/Preboreal transition ca. 11700years ago, probably caused by a climatic gradient across the Alps. This contrasts with previous studies that successfully simulated the early Holocene afforestation in the (warmer) Central Alps with a chironomid-inferred temperature reconstruction from the (colder) Northern Alps. We use LandClim, a dynamic landscape vegetation model to simulate mountain forests under different temperature, soil and precipitation scenarios around Iffigsee (2065m a.s.l.) a lake in the Northwestern Swiss Alps, and compare the model output with the paleobotanical records. The model clearly overestimates the upward shift of timberline in a climate scenario that applies chironomid-inferred July-temperature anomalies to all months. However, forest establishment at 9800 cal. BP at Iffigsee is successfully simulated with lower moisture availability and monthly temperatures corrected for stronger seasonality during the early Holocene. The model-data comparison reveals a contraction in the realized niche of Abies alba due to the prominent role of anthropogenic disturbance after ca. 5000 cal. BP, which has important implications for species distribution models (SDMs) that rely on equilibrium with climate and niche stability. Under future climate projections, LandClim indicates a rapid upward shift of mountain vegetation belts by ca. 500m and treeline positions of ca. 2500m a.s.l. by the end of this century. Resulting biodiversity losses in the alpine vegetation belt might be mitigated with low-impact pastoralism to preserve species-rich alpine meadows.

Characterization of the Effect of the Mitochondrial Protein Hint2 on Intracellular Ca2+ dynamics

Hint2, one of the five members of the superfamily of the histidine triad AMP-lysine hydrolase proteins, is expressed in mitochondria of various cell types. In human adrenocarcinoma cells, Hint2 modulates Ca2+ handling by mitochondria. As Hint2 is highly expressed in hepatocytes, we investigated if this protein affects Ca2+ dynamics in this cell type. We found that in hepatocytes isolated from Hint2−/− mice, the frequency of Ca2+ oscillations induced by 1 μM noradrenaline was 150% higher than in the wild-type. Using spectrophotometry, we analyzed the rates of Ca2+ pumping in suspensions of mitochondria prepared from hepatocytes of either wild-type or Hint2−/− mice; we found that Hint2 accelerates Ca2+ pumping into mitochondria. We then resorted to computational modeling to elucidate the possible molecular target of Hint2 that could explain both observations. On the basis of a detailed model for mitochondrial metabolism proposed in another study, we identified the respiratory chain as the most probable target of Hint2. We then used the model to predict that the absence of Hint2 leads to a premature opening of the mitochondrial permeability transition pore in response to repetitive additions of Ca2+ in suspensions of mitochondria. This prediction was then confirmed experimentally.

Impact of geomagnetic excursions on atmospheric chemistry and dynamics

Geomagnetic excursions, i.e. short periods in time with much weaker geomagnetic fields and substantial changes in the position of the geomagnetic pole, occurred repeatedly in the Earth's history, e.g. the Laschamp event about 41 kyr ago. Although the next such excursion is certain to come, little is known about the timing and possible consequences for the state of the atmosphere and the ecosystems. Here we use the global chemistry climate model SOCOL-MPIOM to simulate the effects of geomagnetic excursions on atmospheric ionization, chemistry and dynamics. Our simulations show significantly increased concentrations of nitrogen oxides (NOx) in the entire stratosphere, especially over Antarctica (+15%), due to enhanced ionization by galactic cosmic rays. Hydrogen oxides (HOx) are also produced in greater amounts (up to +40%) in the tropical and subtropical lower stratosphere, while their destruction by reactions with enhanced NOx prevails over the poles and in high altitudes (by −5%). Stratospheric ozone concentrations decrease globally above 20 km by 1–2% and at the northern hemispheric tropopause by up to 5% owing to the accelerated NOx-induced destruction. A 5% increase is found in the southern lower stratosphere and troposphere. In response to these changes in ozone and the concomitant changes in atmospheric heating rates, the Arctic vortex intensifies in boreal winter, while the Antarctic vortex weakens in austral winter and spring. Surface wind anomalies show significant intensification of the southern westerlies at their poleward edge during austral winter and a pronounced northward shift in spring. Major impacts on the global climate seem unlikely.

Dispersal dynamics in food webs

Studies of food webs suggest that limited nonrandom dispersal can play an important role in structuring food webs. It is not clear, however, whether density-dependent dispersal fits empirical patterns of food webs better than density-independent dispersal. Here, we study a spatially distributed food web, using a series of population-dispersal models that contrast density-independent and density-dependent dispersal in landscapes where sampled sites are either homogeneously or heterogeneously distributed. These models are fitted to empirical data, allowing us to infer mechanisms that are consistent with the data. Our results show that models with density-dependent dispersal fit the α, β, and γ tritrophic richness observed in empirical data best. Our results also show that density-dependent dispersal leads to a critical distance threshold beyond which site similarity (i.e., β tritrophic richness) starts to decrease much faster. Such a threshold can also be detected in the empirical data. In contrast, models with density-independent dispersal do not predict such a threshold. Moreover, preferential dispersal from more centrally located sites to peripheral sites does not provide a better fit to empirical data when compared with symmetric dispersal between sites. Our results suggest that nonrandom dispersal in heterogeneous landscapes is an important driver that shapes local and regional richness (i.e., α and γ tritrophic richness, respectively) as well as the distance-decay relationship (i.e., β tritrophic richness) in food webs.

Dynamics of the nasal microbiota in infancy: A prospective cohort study.

BACKGROUND Understanding the composition and dynamics of the upper respiratory tract microbiota in healthy infants is a prerequisite to investigate the role of the microbiota in patients with respiratory diseases. This is especially true in early life, when the immune system is in development. OBJECTIVE We sought to describe the dynamics of the upper respiratory tract microbiota in healthy infants within the first year of life. METHODS After exclusion of low-quality samples, microbiota characterization was performed by using 16S rDNA pyrosequencing of 872 nasal swabs collected biweekly from 47 unselected infants. RESULTS Bacterial density increased and diversity decreased within the first year of life (R(2) = 0.95 and 0.73, respectively). A distinct profile for the first 3 months of life was found with increased relative abundances of Staphlyococcaceae and Corynebacteriaceae (exponential decay: R(2) = 0.94 and 0.96, respectively). In addition, relative bacterial abundance and composition differed significantly from summer to winter months. The individual composition of the microbiota changed with increasing time intervals between samples and was best modeled by an exponential function (R(2) = 0.97). Within-subject dissimilarity in a 2-week time interval was consistently lower than that between subjects, indicating a personalized microbiota. CONCLUSION This study reveals age and seasonality as major factors driving the composition of the nasal microbiota within the first year of life. A subject's microbiota is personalized but dynamic throughout the first year. These data are indispensable to interpretation of cross-sectional studies and investigation of the role of the microbiota in both healthy subjects and patients with respiratory diseases. They might also serve as a baseline for future intervention studies.