The mechanism whereby gaseous protein ions are released from charged solvent droplets during electrospray ionization (ESI) remains a matter of debate. Also, it is unclear to what extent electrosprayed proteins retain their solution structure. Molecular dynamics (MD) simulations offer insights into the temporal evolution of protein systems. Surprisingly, there have been no all-atom simulations of the protein ESI process to date. The current work closes this gap by investigating the behavior of protein-containing aqueous nanodroplets that carry excess positive charge. We focus on "native ESI", where proteins initially adopt their biologically active solution structures. ESI proceeds while the protein remains entrapped within the droplet. Protein release into the gas phase occurs upon solvent evaporation to dryness. Droplet shrinkage is accompanied by ejection of charge carriers (Na(+) for the conditions chosen here), keeping the droplet at ∼85% of the Rayleigh limit throughout its life cycle. Any remaining charge carriers bind to the protein as the final solvent molecules evaporate. The outcome of these events is largely independent of the initial protein charge and the mode of charge carrier binding. ESI charge states and collision cross sections of the MD structures agree with experimental data. Our results confirm the Rayleigh/charged residue model (CRM). Field emission of excess Na(+) plays an ancillary role by governing the net charge of the shrinking droplet. Models that envision protein ejection from the droplet are not supported. Most nascent CRM ions retain native-like conformations. For unfolded proteins ESI likely proceeds along routes that are different from the native state mechanism explored here.

Abstract. The question whether electrosprayed protein ions retain solution-like conformations continues to be a matter of debate. One way to address this issue involves comparisons of collision cross sections (Ω) measured by ion mobility spectrometry (IMS) with Ω values calculated for candidate structures. Many investigations in this area employ traveling wave IMS (TWIMS). It is often implied that nanoESI is more conducive for the retention of solution structure than regular ESI. Focusing on ubiquitin, cytochrome c, myoglobin, and hemoglobin, we demonstrate that Ω values and collisional unfolding profiles are virtually indistinguishable under both conditions. These findings suggest that gas-phase structures and ion internal energies are independent of the type of electrospray source. We also note that TWIMS calibration can be challenging because differences in the extent of collisional activation relative to drift tube reference data may lead to ambiguous peak assignments. It is demonstrated that this problem can be circumvented by employing collisionally heated calibrant ions. Overall, our data are consistent with the view that exposure of native proteins to electrospray conditions can generate kinetically trapped ions that retain solution-like structures on the millisecond time scale of TWIMS experiments.

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Nitrate contamination of water is a worldwide environmental problem. Recent studies have demonstrated that the nitrogen (N) and oxygen (O) isotopes of nitrate (NO3(-)) can be used to trace nitrogen dynamics including identifying nitrate sources and nitrogen transformation processes. This paper analyzes the current state of identifying nitrate sources and nitrogen transformation processes using N and O isotopes of nitrate. With regard to nitrate sources, δ(15)N-NO3(-) and δ(18)O-NO3(-) values typically vary between sources, allowing the sources to be isotopically fingerprinted. δ(15)N-NO3(-) is often effective at tracing NO(-)3 sources from areas with different land use. δ(18)O-NO3(-) is more useful to identify NO3(-) from atmospheric sources. Isotopic data can be combined with statistical mixing models to quantify the relative contributions of NO3(-) from multiple delineated sources. With regard to N transformation processes, N and O isotopes of nitrate can be used to decipher the degree of nitrogen transformation by such processes as nitrification, assimilation, and denitrification. In some cases, however, isotopic fractionation may alter the isotopic fingerprint associated with the delineated NO3(-) source(s). This problem may be addressed by combining the N and O isotopic data with other types of, including the concentration of selected conservative elements, e.g., chloride (Cl(-)), boron isotope (δ(11)B), and sulfur isotope (δ(35)S) data. Future studies should focus on improving stable isotope mixing models and furthering our understanding of isotopic fractionation by conducting laboratory and field experiments in different environments.

Recent research suggests that exposure to monetary cues strengthens an individual’s motivation to pursue monetary rewards by inducing the ‘market mode’ (i.e. thinking and behaving in accordance with market principles). Here, we examined the effect of market mode on social reward processes by means of event-related potentials (ERPs). Participants primed with monetary images or neutral images acted as advisors who selected one of two options for a putative advisee. Subsequently, all participants passively observed the advisee accepting or rejecting their advice and receiving a gain or loss outcome. After money priming, the feedback-related negativity (FRN) to the advisee’s gain/loss outcome was larger following incorrect as compared to correct advice irrespective of whether the advice had been accepted or rejected. A smaller P3 following incorrect advice showed only when the advice was rejected. After neutral priming, the FRN was larger for incorrect relative to correct advice only when the advice had been rejected. However, the P3 was larger for correct relative to incorrect advice irrespective of the advisee’s final choice. These findings suggest that the market mode facilitates early and automatic feedback processing but reduces later and controlled responding to outcomes that had been accepted.

Summary Background A new therapeutic device passes radiofrequency energy through microneedles to targeted tissue. Three‐dimensional photography may be useful for evaluating the clinical efficacy of microneedle fractional radiofrequency (MFR) used on the appearance of rhytids and to improve facial laxity. Aim To evaluate the efficacy and safety of MFR in the treatment of facial photoageing. Methods In total, participants with facial photoageing were enrolled in the study. All volunteers were randomized to receive split‐face treatments with MFR 2 months apart. The participants self‐evaluated at baseline, Days 1–7, and Months 1 and 3 after the final treatment. Objective evaluation was provided by a three‐dimensional in vivo imaging system. In addition, skin melanin index, erythema index, immediate reactions, healing times and other adverse effects were evaluated. Results Compared with the untreated side, the treated side of most participants improved, based on clinical assessments at the 1‐ and 3‐month follow‐up visits after treatment. Both objective and participative assessments were satisfactory. The participants demonstrated a decrease of roughness parameter (Sa) value at each follow‐up visit. Compared with pretreatment value, Sa decreased significantly at Months 1 and 3 on the treated side (P < 0.05). Minimal and reversible adverse effects and rapid healing were recorded. Conclusions MFR appears to be an excellent treatment for photodamaged facial skin in Chinese patients.

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