Paternal age at birth is an important determinant of offspring telomere length

Although evidence supports the function of telomere length (TL) as a marker for biological aging, no major determinants of TL are known besides inheritance, age and gender. Here we validate and, more importantly, assess the impact of paternal age at birth as a determinant for the offspring's peripheral blood leukocyte TL within the Asklepios study population. Telomere restriction fragment length and paternal age information were available for 2433 volunteers (1176 men and 1257 women) aged similar to 35-55 years old. Paternal age at birth was positively associated with offspring TL (offspring age and gender adjusted, P < 10 (-14)). The increase in TL was estimated at 17 base pairs for each supplemental year at birth and was not statistically different between male and female offspring. The effect size of paternal age outweighed the classical TL determinant gender by a factor of 2, demonstrating the large impact. Maternal age at birth was not independently associated with offspring TL. The peculiar interaction between paternal age at birth and inheritance might explain a large part of the genetic component of TL variance on a population level. This finding also provides further proof for the theory that TL is not completely reset in the zygote. Furthermore, as paternal age is subject to demographic evolution, its association with TL might have a substantial impact on the results and comparability of TL within and between epidemiological studies. In conclusion, paternal age is an important determinant for TL, with substantial consequences for future studies

Detection and attribution of aerosol-cloud interactions in large-domain large-eddy simulations with the ICOsahedral Non-hydrostatic model

Clouds and aerosols contribute the largest uncertainty to current estimates and interpretations of the Earth’s changing energy budget. Here we use a new-generation large-domain large-eddy model, ICON-LEM (ICOsahedral Non-hydrostatic Large Eddy Model), to simulate the response of clouds to realistic anthropogenic perturbations in aerosols serving as cloud condensation nuclei (CCN). The novelty compared to previous studies is that (i) the LEM is run in weather prediction mode and with fully interactive land surface over a large domain and (ii) a large range of data from various sources are used for the detection and attribution. The aerosol perturbation was chosen as peak-aerosol conditions over Europe in 1985, with more than fivefold more sulfate than in 2013. Observational data from various satellite and ground-based remote sensing instruments are used, aiming at the detection and attribution of this response. The simulation was run for a selected day (2 May 2013) in which a large variety of cloud regimes was present over the selected domain of central Europe. It is first demonstrated that the aerosol fields used in the model are consistent with corresponding satellite aerosol optical depth retrievals for both 1985 (perturbed) and 2013 (reference) conditions. In comparison to retrievals from ground-based lidar for 2013, CCN profiles for the reference conditions were consistent with the observations, while the ones for the 1985 conditions were not. Similarly, the detection and attribution process was successful for droplet number concentrations: the ones simulated for the 2013 conditions were consistent with satellite as well as new ground-based lidar retrievals, while the ones for the 1985 conditions were outside the observational range. For other cloud quantities, including cloud fraction, liquid water path, cloud base altitude and cloud lifetime, the aerosol response was small compared to their natural variability. Also, large uncertainties in satellite and ground-based observations make the detection and attribution difficult for these quantities. An exception to this is the fact that at a large liquid water path value (LWP > 200 g m−2), the control simulation matches the observations, while the perturbed one shows an LWP which is too large. The model simulations allowed for quantifying the radiative forcing due to aerosol–cloud interactions, as well as the adjustments to this forcing. The latter were small compared to the variability and showed overall a small positive radiative effect. The overall effective radiative forcing (ERF) due to aerosol–cloud interactions (ERFaci) in the simulation was dominated thus by the Twomey effect and yielded for this day, region and aerosol perturbation −2.6 W m$^{-2}$. Using general circulation models to scale this to a global-mean present-day vs. pre-industrial ERFaci yields a global ERFaci of −0.8 W m$^{-2}$

Plasma Membrane Domains Participate in pH Banding of Chara Internodal Cells

We investigated the identity and distribution of cortical domains, stained by the endocytic marker FM 1-43, in branchlet internodal cells of the characean green algae Chara corallina and Chara braunii. Co-labeling with NBD C6-sphingomyelin, a plasma membrane dye, which is not internalized, confirmed their location in the plasma membrane, and co-labelling with the fluorescent pH indicator Lysotracker red indicated an acidic environment. The plasma membrane domains co-localized with the distribution of an antibody against a proton-translocating ATPase, and electron microscopic data confirmed their identity with elaborate plasma membrane invaginations known as charasomes. The average size and the distribution pattern of charasomes correlated with the pH banding pattern of the cell. Charasomes were larger and more frequent at the acidic regions than at the alkaline bands, indicating that they are involved in outward-directed proton transport. Inhibition of photosynthesis by DCMU prevented charasome formation, and incubation in pH buffers resulted in smaller, homogenously distributed charasomes irrespective of whether the pH was clamped at 5.5 or 8.5. These data indicate that the differential size and distribution of charasomes is not due to differences in external pH but reflects active, photosynthesis-dependent pH banding. The fact that pH banding recovered within several minutes in unbuffered medium, however, confirms that pH banding is also possible in cells with evenly distributed charasomes or without charasomes. Cortical mitochondria were also larger and more abundant at the acid bands, and their intimate association with charasomes and chloroplasts suggests an involvement in carbon uptake and photorespiration

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Kognitiver Aufbau: Neuronale Plastizität macht’s möglich!

Entgegen mancher Aussagen führt ein konventionelles "Gehirntraining" nicht zu einer generellen und anhaltenden Verbesserung kognitiver Funktionen, sagt Prof. Dr. Patric Meyer, SRH Heidelberg, in seinem Vortrag. Neue Interventionen, welche an sensomotorischen, neuro-modulatorischen und spezifischen Hirnprozessen ansetzen, scheinen hingegen in der Lage, gesunde und pathologische Alterungsprozesse teilweise zu durchbrechen. Untersuchungen in Versuchspersonen mit leichter kognitiver Beeinträchtigung zeigen, dass diese Art von Interventionen in der Lage ist, Plastizitätsprozesse gerade in demenzkritischen Hirnstrukturen anzustoßen. Sensomotorisches Training verspricht also, die Fähigkeit, relevanten Input zu verarbeiten, sowie neuro-modulatorische Funktionen zu verbessern und sich darüber hinaus in einem Leistungsanstieg in anderen kognitiven Bereichen wie etwa dem Gedächtnis und einer Zunahme von Hirnmasse niederzuschlagen

Usefulness of a familiarity signal during recognition depends on test format

This study used a recognition memory paradigm in which participants studied black/white drawings. Two test conditions were compared by means of event-related potential (ERP) old/new effects: a forced-choice corresponding (FCC) test format, where targets and corresponding similar foils are presented next to each other, and a forced-choice non-corresponding (FCNC) test, where targets are presented together with foils that are similar to other studied pictures. After intentionally encoding pictures of objects, participants were tested in both conditions. To record ERPs for targets and foils separately, they were presented sequentially. For reasons of higher ecological validity, the whole sequence was repeated allowing participants to look at each picture twice. Additionally, as the manipulation takes effect not before both pictures have been presented, we only analyzed the second presentation of both pictures. Moreover, the target-foil amplitude difference was used to predict the accuracy of the recognition judgment in a given trial

State of the art concepts and verification strategies for passive de-orbiting systems using deployable booms and membranes

- Space Debris and Drag Augmentation Introduction - What can we learn from precursor projects? Applications for Deployable Membranes Membrane Stowing Membrane Design Aspects Materials and Space Environment Deployable Booms - Gossamer Structures Verification Strategie

Effects of response facilitation upon the N400 amplitude at two exemplary right fronto-lateral electrode sites (F2 and FC2) around 400 ms after target onset.

<p>The amplitude of the dashed waveform, reflecting the response to negative targets, is significantly lower than the solid waveform, reflecting the response to positive targets, when the word euthanasia acted as prime. In the upper right the scalp distribution of the difference between euthanasia-positive and euthanasia-negative between 380 to 420 ms is mapped.</p