An electrospray ionization study of some novel alkylamine thiohydantoin amino acid derivatives

An electrospray ionization-mass spectrometric (ES-MS) study of some novel alkylamine thiohydantoin amino acid derivatives is presented. The alkylamine derivatives are being developed as part of an on-going effort to couple an Edmanlike protein sequencer to a bench-top electrospray ionization (ES) mass spectrometer. The ES-MS and capillary-skimmer collision-induced dissociation (CID) mass spectra of eight dimethylaminopropylthiohydantoin (DMAP-TH) amino acid derivatives as well as the trimethylaminopropylthiohydantoin (TMAP-TH), diethylaminopropylthiohydantoin, and dibutylaminopropylthiohydantoin (DBAP-TH) derivatives of Phe are presented. The spectra contain prominent [M + H]+ ions as well as fragment ions due to the loss of the respective neutral alkylamines. The CID spectrum of DMAP-TH-Phe also contains the dibutylaminoethyl cation. The relative responses of the alkylamine thiohydantoin derivatives obtained under identical solvent conditions are found to increase as the solvophobicity of the amino acid R group increases; the most solvophobic DBAP-TH-Phe gives rise to the highest overall response. DMAP-TH-Phe and the quaternary amine derivative TMAP-TH-Phe have comparable sensitivities when a sufficiently acidic solvent (pH = 3) is employed. Implications of these studies in the coupling of a protein sequencer to an ES mass spectrometer are discussed as are the requisite modifications of a single quadrupole mass spectrometer for ES analyses

Peripheral Blood and Salivary Biomarkers of Blood-Brain Barrier Permeability and Neuronal Damage:Clinical and Applied Concepts

International audienceWithin the neurovascular unit (NVU), the blood-brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from peripheral blood and compartments. Increased BBB permeability is clinically relevant for at least two reasons: it actively participates to the etiology of central nervous system (CNS) diseases, and it enables the diagnosis of neurological disorders based on the detection of CNS molecules in peripheral body fluids. In pathological conditions, a suite of glial, neuronal, and pericyte biomarkers can exit the brain reaching the peripheral blood and, after a process of filtration, may also appear in saliva or urine according to varying temporal trajectories. Here, we specifically examine the evidence in favor of or against the use of protein biomarkers of NVU damage and BBB permeability in traumatic head injury, including sport (sub)concussive impacts, seizure disorders, and neurodegenerative processes such as Alzheimer's disease. We further extend this analysis by focusing on the correlates of human extreme physiology applied to the NVU and its biomarkers. To this end, we report NVU changes after prolonged exercise, freediving, and gravitational stress, focusing on the presence of peripheral biomarkers in these conditions. The development of a biomarker toolkit will enable minimally invasive routines for the assessment of brain health in a broad spectrum of clinical, emergency, and sport settings

Atomic Resonance and Scattering

Contains research objectives, summary of research and reports on five research projects.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300National Science Foundation (Grant GP 28679)National Bureau of Standards (Grant 1-35857

Heterologous expression of the avirulence gene ACE1 from the fungal rice pathogen Magnaporthe oryzae

The ACE1 and RAP1 genes from the avirulence signalling gene cluster of the rice blast fungus Magnaporthe oryzae were expressed in Aspergillus oryzae and M. oryzae itself. Expression of ACE1 alone produced a polyenyl pyrone (magnaporthepyrone), which is regioselectively epoxidised and hydrolysed to give different diols, 6 and 7, in the two host organisms. Analysis of the three introns present in ACE1 determined that A. oryzae does not process intron 2 correctly, while M. oryzae processes all introns correctly in both appressoria and mycelia. Co-expression of ACE1 and RAP1 in A. oryzae produced an amide 8 which is similar to the PKS-NRPS derived backbone of the cytochalasans. Biological testing on rice leaves showed that neither the diols 6 and 7, nor amide 8 was responsible for the observed ACE1 mediated avirulence, however, gene cluster analysis suggests that the true avirulence signalling compound may be a tyrosine-derived cytochalasan compound.Government of Egypt ScholarshipThe School of Chemistry at the University of Bristol and the Mark Evans ScholarshipKano State Government NigeriaMacArthur FoundationBayero UniversityNigerian Petroleum Technology FundMalaysian Govenment ScholarshipEP/F066104/

Constraints on the architecture of the HD 95086 planetary system with the Gemini Planet Imager

We present astrometric monitoring of the young exoplanet HD 95086 b obtained with the Gemini Planet Imager between 2013 and 2016. A small but significant position angle change is detected at constant separation; the orbital motion is confirmed with literature measurements. Efficient Monte Carlo techniques place preliminary constraints on the orbital parameters of HD 95086 b. With 68% confidence, a semimajor axis of 61.7^{+20.7}_{-8.4} au and an inclination of 153.0^{+9.7}_{-13.5} deg are favored, with eccentricity less than 0.21. Under the assumption of a co-planar planet-disk system, the periastron of HD 95086 b is beyond 51 au with 68% confidence. Therefore HD 95086 b cannot carve the entire gap inferred from the measured infrared excess in the SED of HD 95086. We use our sensitivity to additional planets to discuss specific scenarios presented in the literature to explain the geometry of the debris belts. We suggest that either two planets on moderately eccentric orbits or three to four planets with inhomogeneous masses and orbital properties are possible. The sensitivity to additional planetary companions within the observations presented in this study can be used to help further constrain future dynamical simulations of the planet-disk system.Comment: Accepted for publication in ApJ

Dynamical Mass Measurement of the Young Spectroscopic Binary V343 Normae AaAb Resolved With the Gemini Planet Imager

We present new spatially resolved astrometry and photometry from the Gemini Planet Imager of the inner binary of the young multiple star system V343 Normae, which is a member of the beta Pictoris moving group. V343 Normae comprises a K0 and mid-M star in a ~4.5 year orbit (AaAb) and a wide 10" M5 companion (B). By combining these data with archival astrometry and radial velocities we fit the orbit and measure individual masses for both components of M_Aa = 1.10 +/- 0.10 M_sun and M_Ab = 0.290 +/- 0.018 M_sun. Comparing to theoretical isochrones, we find good agreement for the measured masses and JHK band magnitudes of the two components consistent with the age of the beta Pic moving group. We derive a model-dependent age for the beta Pic moving group of 26 +/- 3 Myr by combining our results for V343 Normae with literature measurements for GJ 3305, which is another group member with resolved binary components and dynamical masses.Comment: 12 pages, 7 figures. Accepted to A

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article