Site-specific identification and quantitation of endogenous SUMO modifications under native conditions.

Small ubiquitin-like modifier (SUMO) modification regulates numerous cellular processes. Unlike ubiquitin, detection of endogenous SUMOylated proteins is limited by the lack of naturally occurring protease sites in the C-terminal tail of SUMO proteins. Proteome-wide detection of SUMOylation sites on target proteins typically requires ectopic expression of mutant SUMOs with introduced tryptic sites. Here, we report a method for proteome-wide, site-level detection of endogenous SUMOylation that uses α-lytic protease, WaLP. WaLP digestion of SUMOylated proteins generates peptides containing SUMO-remnant diglycyl-lysine (KGG) at the site of SUMO modification. Using previously developed immuno-affinity isolation of KGG-containing peptides followed by mass spectrometry, we identified 1209 unique endogenous SUMO modification sites. We also demonstrate the impact of proteasome inhibition on ubiquitin and SUMO-modified proteomes using parallel quantitation of ubiquitylated and SUMOylated peptides. This methodological advancement enables determination of endogenous SUMOylated proteins under completely native conditions

RF Characterization of Self-Interference Cancellation Using Phase Modulation and Optical SideBand Filtering

Full-Duplex scheme transmitting and receiving signals simultaneously in the same frequency band can significantly improve the throughput and the spectrum efficiency, and is considered as a candidate technology for the fifth generation (5G) wireless communication. However, the high power transmitted signal will interfere with the in-band weak received signal, which is called as RF self-interference. It cannot be simply removed by a notch filter or a narrow bandpass filter because the same frequency band is used for both transmitter and receiver. An optical approach to implement RF self-interference cancellation is proposed. Based on the inherent out-of-phase property between the left and right sidebands of phase-modulated signal and optical sideband filtering, the RF self-interference cancellation is achieved by tuning the delay time and amplitude in the optical domain. The cancellation depth of the system was measured for different frequencies and bandwidths. The cancellation performance affected by the time delay deviation, the amplitude deviation and phase response is analyzed according to experimental results. It gives the direction for the improvement of system performance. Finally, the full-duplex communication by using the optical SIC approach was also investigated. Signal of interest is recovered and the constellation diagram was also shown

Optical Multipath RF Self-Interference Cancellation Based on Phase Modulation for Full-Duplex Communication

Optical multipath RF self-interference cancellation (SIC) based on phase modulation for full-duplex communication is proposed and demonstrated experimentally. Phase modulation is utilized to convert the RF signal into optical domain, in which the time delay tuning, amplitude tuning and phase inversion for multipath RF SIC are completed. The comprehensive theoretical model of the optical multipath RF SIC system is established, and the factors affecting SIC performance including the time delay, amplitude and phase deviations are analyzed. The experimental results verify the feasibility of the proposed scheme for full-duplex communication with the cancellation depth of 26 dB and 28 dB over 100 MHz at central frequency of 6 GHz and 10 GHz, respectively. A figure of merit of the maximum interference to signal of interest ratio is defined to characterize the SOI recovery capability of optical RF SIC system

Performance analysis of photonic RF self-interference cancellation for full-duplex communication

A photonic RF self-interference cancellation (SIC) scheme for full-duplex communication is proposed and demonstrated experimentally. It is based on phase modulation to convert the RF signal into optical domain. The interference cancellation performance of the photonic RF SIC system under different delay deviation (Δτ) and amplitude deviation (Δα) is analyzed. The cancellation depth of 34.5 dB is measured for 10 GHz signal with bandwidth of 50MHz. According to experimental results, the interference cancellation performance affected by the time delay deviation, the amplitude deviation and the phase response is investigated. The results give a direction for the improvement of system performance

Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in Mice

Blood–brain barrier (BBB) dysfunction, e.g., increase in BBB permeability, has been reported to contribute to cognitive impairment. However, the effects of anesthesia and surgery on BBB permeability, the underlying mechanisms, and associated cognitive function remain largely to be determined. Here, we assessed the effects of surgery (laparotomy) under 1.4% isoflurane anesthesia (anesthesia/surgery) for 2 h on BBB permeability, levels of junction proteins and cognitive function in both 9- and 18-month-old wild-type mice and 9-month-old interleukin (IL)-6 knockout mice. BBB permeability was determined by dextran tracer (immunohistochemistry imaging and spectrophotometric quantification), and protein levels were measured by Western blot and cognitive function was assessed by using both Morris water maze and Barnes maze. We found that the anesthesia/surgery increased mouse BBB permeability to 10-kDa dextran, but not to 70-kDa dextran, in an IL-6-dependent and age-associated manner. In addition, the anesthesia/surgery induced an age-associated increase in blood IL-6 level. Cognitive impairment was detected in 18-month-old, but not 9-month-old, mice after the anesthesia/surgery. Finally, the anesthesia/surgery decreased the levels of β-catenin and tight junction protein claudin, occludin and ZO-1, but not adherent junction protein VE-cadherin, E-cadherin, and p120-catenin. These data demonstrate that we have established a system to study the effects of perioperative factors, including anesthesia and surgery, on BBB and cognitive function. The results suggest that the anesthesia/surgery might induce an age-associated BBB dysfunction and cognitive impairment in mice. These findings would promote mechanistic studies of postoperative cognitive impairment, including postoperative delirium

A glycosylated Phr1 protein is induced by calcium stress and its expression is positively controlled by the calcium/calcineurin signaling transcription factor Crz1 in Candida albicans

Abstract As one of the most important human fungal pathogens, Candida albicans senses and adapts to host niches with different pH values through the pH-responsive Rim101 pathway. Its transcription factor Rim101 activates the expression of alkaline pH-induced genes including PHR1 that encodes a glycosylphosphatidylinsitol-anchored β(1,3)-glucanosyltransferase critical for hyphal wall formation. The calcium/calcineurin signaling pathway is mediated by the transcription factor Crz1 in yeasts and other lower eukaryotes. Here we report that deletion of PHR1 leads to calcium sensitivity of C. albicans cells. In addition, expression of Phr1 is induced by calcium stress and under the control of Crz1 in C. albicans. EMSA assay demonstrates that Crz1 binds to one CDRE element in the PHR1 promoter. Alkaline treatment induces two species of glycosylated Phr1 proteins with different degrees of glycosylation, which is independent of Crz1. In contrast, only one species of Phr1 protein with a low degree of glycosylation is induced by calcium stress in a Crz1-dependent fashion. Therefore, we have provided an evidence that regulation of cell wall remodeling is integrated through differential degrees of Phr1 glycosylation by both the pH-regulated Rim101 pathway and the calcium/calcineurin signaling pathway in C. albicans. Video Abstrac

The association between sarcopenia and incident chronic lung disease in the general population: A longitudinal study based on CHARLS data

Background: Data regarding the association of sarcopenia with chronic lung disease (CLD) has led to inconclusive results. The main goal of this research was to investigate the association between sarcopenia and CLD in middle-aged and elderly individuals in China. Methods: The study sample consisted of 11,077 individuals without CLD at baseline chosen from the China Health and Retirement Longitudinal Study (CHARLS) data from 2015, followed up until 2018. Sarcopenia was identified utilizing the criteria set by the Asian Working Group on Sarcopenia (AWGS 2019) in 2019. Individuals were categorized into no-sarcopenia, possible-sarcopenia, and sarcopenia groups. The outcome of the study was considered to be incident CLD, which included chronic bronchitis, emphysema, pulmonary heart disease, and asthma. The association between sarcopenia and the risk of CLD was also examined by employing weighted Cox proportional hazard regression models. Results: A total of 356 (3.20 %) participants developed CLD during the 3.6-year follow-up period. The cumulative incidence of CLD in the no-sarcopenia, possible-sarcopenia, and sarcopenia groups was 2.80 % (230/8222), 4.37 % (55/1260), and 4.45 % (71/1595), respectively. Individuals with possible sarcopenia {hazard ratio [HR] [95 % confidence interval (CI)]: 1.48 [1.04–2.09]} and sarcopenia [HR (95 % CI): 1.68 (1.12–2.51)] demonstrated a considerably high risk of developing CLD compared to individuals in the no-sarcopenia group. Moreover, individuals diagnosed with sarcopenia, as per the criteria established by the European Working Group on Sarcopenia in Older People (EWGSOP) 2018, were at considerably high risk for developing CLD compared to those in the no-sarcopenia group. Conclusion: This research involving adult Chinese individuals demonstrated a significant association between, possible sarcopenia and sarcopenia with an elevated risk of incident CLD, thereby emphasizing the importance of monitoring respiratory health in this population. Key points: Question: Whether muscle mass and sarcopenia are associated with the development of chronic lung disease (CLD) in Asian middle-aged and elderly individuals.Findings: This longitudinal study encompassing 11,077 adults aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS) data with 3.6 years of follow-up revealed a positive association between sarcopenia at baseline and incidence of CLD.Meaning: The findings suggest that possible sarcopenia and sarcopenia are linked to the development of CLD. Consequently, middle-aged and elderly individuals with possible sarcopenia and sarcopenia can be considered vulnerable regarding the primary prevention strategies for CLD