Reversal of aging-induced increases in aortic stiffness by targeting cytoskeletal protein-protein interfaces

Background: The proximal aorta normally functions as a critical shock absorber that protects small downstream vessels from damage by pressure and flow pulsatility generated by the heart during systole. This shock absorber function is impaired with age because of aortic stiffening. Methods and Results: We examined the contribution of common genetic variation to aortic stiffness in humans by interrogating results from the AortaGen Consortium genome-wide association study of carotid-femoral pulse wave velocity. Common genetic variation in the N-WASP (WASL) locus is associated with carotid-femoral pulse wave velocity (rs600420, P=0.0051). Thus, we tested the hypothesis that decoy proteins designed to disrupt the interaction of cytoskeletal proteins such as N-WASP with its binding partners in the vascular smooth muscle cytoskeleton could decrease ex vivo stiffness of aortas from a mouse model of aging. A synthetic decoy peptide construct of N-WASP significantly reduced activated stiffness in ex vivo aortas of aged mice. Two other cytoskeletal constructs targeted to VASP and talin-vinculin interfaces similarly decreased aging-induced ex vivo active stiffness by on-target specific actions. Furthermore, packaging these decoy peptides into microbubbles enables the peptides to be ultrasound-targeted to the wall of the proximal aorta to attenuate ex vivo active stiffness. Conclusions: We conclude that decoy peptides targeted to vascular smooth muscle cytoskeletal protein-protein interfaces and microbubble packaged can decrease aortic stiffness ex vivo. Our results provide proof of concept at the ex vivo level that decoy peptides targeted to cytoskeletal protein-protein interfaces may lead to substantive dynamic modulation of aortic stiffness

Securing Your Relationship: Quality of Intimate Relationships During the COVID-19 Pandemic Can Be Predicted by Attachment Style

The COVID-19 pandemic along with the restrictions that were introduced within Europe starting in spring 2020 allows for the identification of predictors for relationship quality during unstable and stressful times. The present study began as strict measures were enforced in response to the rising spread of the COVID-19 virus within Austria, Poland, Spain and Czech Republic. Here, we investigated quality of romantic relationships among 313 participants as movement restrictions were implemented and subsequently phased out cross-nationally. Participants completed self-report questionnaires over a period of 7 weeks, where we predicted relationship quality and change in relationship quality using machine learning models that included a variety of potential predictors related to psychological, demographic and environmental variables. On average, our machine learning models predicted 29% (linear models) and 22% (non-linear models) of the variance with regard to relationship quality. Here, the most important predictors consisted of attachment style (anxious attachment being more influential than avoidant), age, and number of conflicts within the relationship. Interestingly, environmental factors such as the local severity of the pandemic did not exert a measurable influence with respect to predicting relationship quality. As opposed to overall relationship quality, the change in relationship quality during lockdown restrictions could not be predicted accurately by our machine learning models when utilizing our selected features. In conclusion, we demonstrate cross-culturally that attachment security is a major predictor of relationship quality during COVID-19 lockdown restrictions, whereas fear, pathogenic threat, sexual behavior, and the severity of governmental regulations did not significantly influence the accuracy of prediction

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease

Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system

Searching for periodic sources with LIGO

We investigate the computational requirements for all-sky, all-frequency searches for gravitational waves from spinning neutron stars, using archived data from interferometric gravitational wave detectors such as LIGO. These sources are expected to be weak, so the optimal strategy involves coherent accumulaton of signal-to-noise using Fourier transforms of long stretches of data (months to years). Earth-motion-induced Doppler shifts, and intrinsic pulsar spindown, will reduce the narrow-band signal-to-noise by spreading power across many frequency bins; therefore, it is necessary to correct for these effects before performing the Fourier transform. The corrections can be implemented by a parametrized model, in which one does a search over a discrete set of parameter values. We define a metric on this parameter space, which can be used to determine the optimal spacing between points in a search; the metric is used to compute the number of independent parameter-space points Np that must be searched, as a function of observation time T. The number Np(T) depends on the maximum gravitational wave frequency and the minimum spindown age tau=f/(df/dt) that the search can detect. The signal-to-noise ratio required, in order to have 99% confidence of a detection, also depends on Np(T). We find that for an all-sky, all-frequency search lasting T=10^7 s, this detection threshhold is at a level of 4 to 5 times h(3/yr), where h(3/yr) is the corresponding 99% confidence threshhold if one knows in advance the pulsar position and spin period.Comment: 18 pages, LaTeX, 12 PostScript figures included using psfig. Submitted to Phys. Rev.

Seasonally stable temperature gradients through supraglacial debris in the Everest region of Nepal, Central Himalaya

Rock debris covers about 30% of glacier ablation areas in the Central Himalaya and modifies the impact of atmospheric conditions on mass balance. The thermal properties of supraglacial debris are diurnally variable but remain poorly constrained for monsoon-influenced glaciers over the timescale of the ablation season. We measured vertical debris profile temperatures at 12 sites on four glaciers in the Everest region with debris thickness ranging from 0.08–2.8 m. Typically, the length of the ice ablation season beneath supraglacial debris was 160 days (15 May to 22 October)—a month longer than the monsoon season. Debris temperature gradients were approximately linear (r2 > 0.83), measured as –40°C m–1 where debris was up to 0.1 m thick, –20°C m–1 for debris 0.1–0.5 m thick, and –4°C m–1 for debris greater than 0.5 m thick. Our results demonstrate that the influence of supraglacial debris on the temperature of the underlying ice surface, and therefore melt, is stable at a seasonal timescale and can be estimated from near-surface temperature. These results have the potential to greatly improve the representation of ablation in calculations of debris-covered glacier mass balance and projections of their response to climate change.Peer reviewe

Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.

Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio