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.Published versio

Genome of Drosophila suzukii, the spotted wing drosophila.

Drosophila suzukii Matsumura (spotted wing drosophila) has recently become a serious pest of a wide variety of fruit crops in the United States as well as in Europe, leading to substantial yearly crop losses. To enable basic and applied research of this important pest, we sequenced the D. suzukii genome to obtain a high-quality reference sequence. Here, we discuss the basic properties of the genome and transcriptome and describe patterns of genome evolution in D. suzukii and its close relatives. Our analyses and genome annotations are presented in a web portal, SpottedWingFlyBase, to facilitate public access

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

A Spitzer c2d Legacy Survey to Identify and Characterize Disks with Inner Dust Holes

Understanding how disks dissipate is essential to studies of planet formation. However, identifying exactly how dust and gas dissipates is complicated due to difficulty in finding objects clearly in the transition of losing their surrounding material. We use Spitzer IRS spectra to examine 35 photometrically-selected candidate cold disks (disks with large inner dust holes). The infrared spectra are supplemented with optical spectra to determine stellar and accretion properties and 1.3mm photometry to measure disk masses. Based on detailed SED modeling, we identify 15 new cold disks. The remaining 20 objects have IRS spectra that are consistent with disks without holes, disks that are observed close to edge-on, or stars with background emission. Based on these results, we determine reliable criteria for identifying disks with inner holes from Spitzer photometry and examine criteria already in the literature. Applying these criteria to the c2d surveyed star-forming regions gives a frequency of such objects of at least 4% and most likely of order 12% of the YSO population identified by Spitzer. We also examine the properties of these new cold disks in combination with cold disks from the literature. Hole sizes in this sample are generally smaller than for previously discovered disks and reflect a distribution in better agreement with exoplanet orbit radii. We find correlations between hole size and both disk and stellar masses. Silicate features, including crystalline features, are present in the overwhelming majority of the sample although 10 micron feature strength above the continuum declines for holes with radii larger than ~7 AU. In contrast, PAHs are only detected in 2 out of 15 sources. Only a quarter of the cold disk sample shows no signs of accretion, making it unlikely that photoevaporation is the dominant hole forming process in most cases.Comment: 24 pages, 18 figures and 8 tables. Fixed a typo in Table

Sequencing of Tuta absoluta genome to develop SNP genotyping assays for species identification

Tuta absoluta is one of the most devastating pests of fresh market and processing tomatoes. Native to South America, its detection was confined to that continent until 2006 when it was identified in Spain. It has now spread to almost every continent, threatening countries whose economies rely heavily on tomatoes. This insect causes damage to all developmental stages of its host plant, leading to crop losses as high as 80–100%. Although T. absoluta has yet to be found in the USA and China, which makes up a large portion of the tomato production in the world, computer models project a high likelihood of invasion. To halt the continued spread of T. absoluta and limit economic loss associated with tomato supply chain, it is necessary to develop accurate and efficient methods to identify T. absoluta and strengthen surveillance programs. Current identification of T. absoluta relies on examination of morphology and assessment of host plant damage, which are difficult to differentiate from that of native tomato pests. To address this need, we sequenced the genomes of T. absoluta and two closely related Gelechiidae, Keiferia lycopersicella and Phthorimaea operculella, and developed a bioinformatic pipeline to design a panel of 21-SNP markers for species identification. The accuracy of the SNP panel was validated in a multiplex format using the iPLEX chemistry of Agena MassARRAY system. Finally, the new T. absoluta genomic resources we generated can be leveraged to study T. absoluta biology and develop species-specific management strategies.info:eu-repo/semantics/acceptedVersio

Photographed Rapid HIV Test Results Pilot Novel Quality Assessment and Training Schemes

HIV rapid diagnostic tests (RDTs) are now used widely in non-laboratory settings by non-laboratory-trained operators. Quality assurance programmes are essential in ensuring the quality of HIV RDT outcomes. However, there is no cost-effective means of supplying the many operators of RDTs with suitable quality assurance schemes. Therefore, it was examined whether photograph-based RDT results could be used and correctly interpreted in the non-laboratory setting. Further it was investigated if a single training session improved the interpretation skills of RDT operators. The photographs were interpreted, a 10-minute tutorial given and then a second interpretation session was held. It was established that the results could be read with accuracy. The participants (n = 75) with a range of skills interpreted results (>80% concordance with reference results) from a panel of 10 samples (three negative and seven positive) using four RDTs. Differences in accuracy of interpretation before and after the tutorial were marked in some cases. Training was more effective for improving the accurate interpretation of more complex results, e.g. results with faint test lines or for multiple test lines, and especially for improving interpretation skills of inexperienced participants. It was demonstrated that interpretation of RDTs was improved using photographed results allied to a 10-minute training session. It is anticipated that this method could be used for training but also for quality assessment of RDT operators without access to conventional quality assurance or training schemes requiring wet samples

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity

Biotic and abiotic factors impacting development, behavior, phenology, and reproductive biology of Drosophila suzukii

Spotted wing drosophila, Drosophila suzukii, is a devastating invasive pest of small and stone fruits in the Americas and Europe. To better understand the population dynamics of D. suzukii, we reviewed recent work on juvenile development, adult reproduction, and seasonal variation in life history parameters including the abiotic/biotic factors that influence these processes. Juvenile development is optimal at moderately warm temperatures, and larvae exhibit some immunity to parasitism. Adults use visual cues and substrate-borne vibrations for courtship and exhibit a bimodal locomotor activity pattern (except mated females). Under 20–27 °C and various conditions, development from egg to adult can take 10–17 days, females first lay eggs within 1–8 days and their lifetime fecundity varies from 400. Oviposition is consistently high in raspberry hosts and fruits with lower penetration force, and the presence of Wolbachia endosymbionts can lower fertility. Drosophila suzukii exhibit seasonal variation with a darker winter morph that is more cold tolerant. Also, D. suzukii likely undergo reproductive diapause in the fall, with colder temperatures and shorter day lengths influencing reproduction. To develop viable IPM programs for D. suzukii, knowledge of abiotic and biotic conditions that impact D. suzukii life history parameters and population dynamics is critical, and gaps in the current knowledge are discussed.Keywords: Development, Overwintering, Spotted wing drosophila, Chronobiology, Reproduction, Invasive specie

Integrating Temperature-Dependent Life Table Data into a Matrix Projection Model for Drosophila suzukii Population Estimation

Temperature-dependent fecundity and survival data was integrated into a matrix population model to describe relative Drosophila suzukii Matsumura (Diptera: Drosophilidae) population increase and age structure based on environmental conditions. This novel modification of the classic Leslie matrix population model is presented as a way to examine how insect populations interact with the environment, and has application as a predictor of population density. For D. suzukii, we examined model implications for pest pressure on crops. As case studies, we examined model predictions in three small fruit production regions in the United States (US) and one in Italy. These production regions have distinctly different climates. In general, patterns of adult D. suzukii trap activity broadly mimicked seasonal population levels predicted by the model using only temperature data. Age structure of estimated populations suggest that trap and fruit infestation data are of limited value and are insufficient for model validation. Thus, we suggest alternative experiments for validation. The model is advantageous in that it provides stage-specific population estimation, which can potentially guide management strategies and provide unique opportunities to simulate stage-specific management effects such as insecticide applications or the effect of biological control on a specific life-stage. The two factors that drive initiation of the model are suitable temperatures (biofix) and availability of a suitable host medium (fruit). Although there are many factors affecting population dynamics of D. suzukii in the field, temperature-dependent survival and reproduction are believed to be the main drivers for D. suzukii populations