38 research outputs found
Angiotensin Converting Enzyme (ACE) and ACE2 Bind Integrins and ACE2 Regulates Integrin Signalling
The angiotensin converting enzymes (ACEs) are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated. Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates. We show that cellular expression of ACE2 enhanced cell adhesion. Furthermore, we present evidence that soluble ACE2 (sACE2) is capable of suppressing integrin signalling mediated by FAK. In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt. These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling. Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation. As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling
Demonstration of Protein-Based Human Identification Using the Hair Shaft Proteome
YesHuman identification from biological material is largely dependent on the ability to characterize genetic polymorphisms in DNA. Unfortunately, DNA can degrade in the environment, sometimes below the level at which it can be amplified by PCR. Protein however is chemically more robust than DNA and can persist for longer periods. Protein also contains genetic variation in the form of single amino acid polymorphisms. These can be used to infer the status of non-synonymous single nucleotide polymorphism alleles. To demonstrate this, we used mass spectrometry-based shotgun proteomics to characterize hair shaft proteins in 66 European-American subjects. A total of 596 single nucleotide polymorphism alleles were correctly imputed in 32 loci from 22 genes of subjectsâ DNA and directly validated using Sanger sequencing. Estimates of the probability of resulting individual non-synonymous single nucleotide polymorphism allelic profiles in the European population, using the product rule, resulted in a maximum power of discrimination of 1 in 12,500. Imputed non-synonymous single nucleotide polymorphism profiles from EuropeanâAmerican subjects were considerably less frequent in the African population (maximum likelihood ratio = 11,000). The converse was true for hair shafts collected from an additional 10 subjects with African ancestry, where some profiles were more frequent in the African population. Genetically variant peptides were also identified in hair shaft datasets from six archaeological skeletal remains (up to 260 years old). This study demonstrates that quantifiable measures of identity discrimination and biogeographic background can be obtained from detecting genetically variant peptides in hair shaft protein, including hair from bioarchaeological contexts.The Technology Commercialization Innovation Program (Contracts #121668, #132043) of the Utah Governors Office of Commercial Development, the Scholarship Activitie
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Limitations in timing precision due to single-pulse shape variability in millisecond pulsars
High-sensitivity radio-frequency observations of millisecond pulsars usually show stochastic, broad-band, pulse-shape variations intrinsic to the pulsar emission process. These variations induce jitter noise in pulsar timing observations; understanding the properties of this noise is of particular importance for the effort to detect gravitational waves with pulsar timing arrays. We assess the short-term profile and timing stability of 22 millisecond pulsars that are part of the Parkes Pulsar Timing Array sample by examining intraobservation arrival time variability and single-pulse phenomenology. In 7 of the 22 pulsars, in the band centred at approximately 1400 MHz, we find that the brightest observations are limited by intrinsic jitter. We find consistent results, either detections or upper limits, for jitter noise in other frequency bands. PSR J1909-3744 shows the lowest levels of jitter noise, which we estimate to contribute ~10 ns root mean square error to the arrival times for hour-duration observations. Larger levels of jitter noise are found in pulsars with wider pulses and distributions of pulse intensities. The jitter noise in PSR J0437-4715 decorrelates over a bandwidth of âŒ2 GHz. We show that the uncertainties associated with timing pulsar models can be improved by including physically motivated jitter uncertainties. Pulse-shape variations will limit the timing precision at future, more sensitive, telescopes; it is imperative to account for this noise when designing instrumentation and timing campaigns for these facilities. © 2014 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society