The Future of Proteomics is Up in the Air: Can Ion Mobility Replace Liquid Chromatography for High Throughput Proteomics?

The coevolution of liquid chromatography (LC) with mass spectrometry (MS) has shaped contemporary proteomics. LC hyphenated to MS now enables quantification of more than 10,000 proteins in a single injection, a number that likely represents most proteins in specific human cells or tissues. Separations by ion mobility spectrometry (IMS) have recently emerged to complement LC and further improve the depth of proteomics. Given the theoretical advantages in speed and robustness of IMS in comparison to LC, we envision that ongoing improvements to IMS paired with MS may eventually make LC obsolete, especially when combined with targeted or simplified analyses, such as rapid clinical proteomics analysis of defined biomarker panels. In this perspective, we describe the need for faster analysis that might drive this transition, the current state of direct infusion proteomics, and discuss some technical challenges that must be overcome to fully complete the transition to entirely gas phase proteomics.

Extensive field evidence for the release of HONO from the photolysis of nitrate aerosols.

Particulate nitrate ([Formula: see text]) has long been considered a permanent sink for NOx (NO and NO2), removing a gaseous pollutant that is central to air quality and that influences the global self-cleansing capacity of the atmosphere. Evidence is emerging that photolysis of [Formula: see text] can recycle HONO and NOx back to the gas phase with potentially important implications for tropospheric ozone and OH budgets; however, there are substantial discrepancies in "renoxification" photolysis rate constants. Using aircraft and ground-based HONO observations in the remote Atlantic troposphere, we show evidence for renoxification occurring on mixed marine aerosols with an efficiency that increases with relative humidity and decreases with the concentration of [Formula: see text], thus largely reconciling the very large discrepancies in renoxification photolysis rate constants found across multiple laboratory and field studies. Active release of HONO from aerosol has important implications for atmospheric oxidants such as OH and O3 in both polluted and clean environments.

Patched and Costal-2 mutations lead to differences in tissue overgrowth autonomy.

Genetic screens are used in Drosophila melanogaster to identify genes key in the regulation of organismal development and growth. These screens have defined signalling pathways necessary for tissue and organismal development, which are evolutionarily conserved across species, including Drosophila. Here, we have used an FLP/FRT mosaic system to screen for conditional regulators of cell growth and cell division in the Drosophila eye. The conditional nature of this screen utilizes a block in the apoptotic pathway to prohibit the mosaic mutant cells from dying via apoptosis. From this screen, we identified two different mutants that mapped to the Hedgehog signalling pathway. Previously, we described a novel Ptc mutation and here we add to the understanding of disrupting the Hh pathway with a novel allele of Cos2. Both of these Hh components are negative regulators of the pathway, yet they depict mutant differences in the type of overgrowth created. Ptc mutations lead to overgrowth consisting of almost entirely wild-type tissue (non-autonomous overgrowth), while the Cos2 mutation results in tissue that is overgrown in both the mutant and wild-type clones (both autonomous and non-autonomous). These differences in tissue overgrowth are consistent in the Drosophila eye and wing. The observed difference is correlated with different deregulation patterns of pMad, the downstream effector of DPP signalling. This finding provides insight into pathway-specific differences that help to better understand intricacies of developmental processes and human diseases that result from deregulated Hedgehog signalling, such as basal cell carcinoma.

Randomized Controlled Trial of Micronized Dehydrated Human Amnion/Chorion Membrane (dHACM) Injection Compared to Placebo for the Treatment of Plantar Fasciitis.

BACKGROUND: Failure of conservative management to reduce/eliminate symptoms of plantar fasciitis (PF) may indicate need for advanced treatments. This study reports Level 1 evidence supporting 3-month safety and efficacy of micronized dehydrated human amnion/chorion membrane (dHACM) injection as a treatment for PF. METHODS: A prospective, single-blind, randomized controlled trial was conducted at 14 sites in the United States. Subjects were randomized to receive 1 injection, in the affected area, of micronized dHACM (n=73) or 0.9% sodium chloride placebo (n=72). Safety/efficacy assessments were conducted at 4 weeks, 8 weeks, 3 months, 6 months, and 12 months postinjection, using visual analog scale (VAS) for pain, Foot Function Index-Revised (FFI-R) score, and presence/absence of adverse events. Primary outcome was mean change in VAS score between baseline and 3 months expressed as difference in means for treatment versus control subjects. Secondary outcome was mean change in FFI-R score between baseline and 3 months expressed as difference in means for treatment versus control subjects. RESULTS: Baseline VAS scores were similar between groups. At the 3-month follow-up, mean VAS scores in the treatment group were 76% lower compared with a 45% reduction for controls ( P < .0001), FFI-R scores for treatment subjects had mean reduction of 60% versus baseline, whereas control subjects had mean reduction of 40% versus baseline ( P = .0004). Of 4 serious adverse events, none were related to study procedures. CONCLUSION: Pain reduction and functional improvement outcomes were statistically significant and clinically relevant, supporting use of micronized dHACM injection as a safe and effective treatment for PF. LEVEL OF EVIDENCE: Level I, prospective randomized trial.