102 research outputs found
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 genomeâwide association study of carotidâfemoral pulse wave velocity. Common genetic variation in the NâWASP (WASL) locus is associated with carotidâfemoral 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 NâWASP 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 NâWASP significantly reduced activated stiffness in ex vivo aortas of aged mice. Two other cytoskeletal constructs targeted to VASP and talinâvinculin interfaces similarly decreased agingâinduced ex vivo active stiffness by onâtarget specific actions. Furthermore, packaging these decoy peptides into microbubbles enables the peptides to be ultrasoundâtargeted 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 proteinâprotein 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 proteinâprotein 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 80â100%. 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 (nâ=â75) 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 1.78â
Ă
resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-Îą-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 Îą-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity
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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 20â27 °C and various conditions, development from egg to adult can take 10â17 days, females first lay eggs within 1â8 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
Recommended from our members
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 20â27 °C and various conditions, development from egg to adult can take 10â17 days, females first lay eggs within 1â8 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.To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work.
This is the publisherâs final pdf. The published article is copyrighted by Springer and can be found at: https://doi.org/10.1007/s10340-016-0756-
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