Defining protein-protein interactions (PPIs) in their native environment is crucial to understanding protein structure and function. Cross-linking-mass spectrometry (XL-MS) has proven effective in ...capturing PPIs in living cells; however, the proteome coverage remains limited. Here, we have developed a robust in vivo XL-MS platform to facilitate in-depth PPI mapping by integrating a multifunctional MS-cleavable cross-linker with sample preparation strategies and high-resolution MS. The advancement of click chemistry-based enrichment significantly enhanced the detection of cross-linked peptides for proteome-wide analyses. This platform enabled the identification of 13,904 unique lysine-lysine linkages from in vivo cross-linked HEK 293 cells, permitting construction of the largest in vivo PPI network to date, comprising 6,439 interactions among 2,484 proteins. These results allowed us to generate a highly detailed yet panoramic portrait of human interactomes associated with diverse cellular pathways. The strategy presented here signifies a technological advancement for in vivo PPI mapping at the systems level and can be generalized for charting protein interaction landscapes in any organisms.
Multifunctional platforms that can dynamically modulate their color and appearance have attracted attention for applications as varied as displays, signaling, camouflage, anti-counterfeiting, ...sensing, biomedical imaging, energy conservation, and robotics. Within this context, the development of camouflage systems with tunable spectroscopic and fluorescent properties that span the ultraviolet, visible, and near-infrared spectral regions has remained exceedingly challenging because of frequently competing materials and device design requirements. Herein, we draw inspiration from the unique blue rings of the Hapalochlaena lunulata octopus for the development of deception and signaling systems that resolve these critical challenges. As the active material, our actuator-type systems incorporate a readily-prepared and easily-processable nonacene-like molecule with an ambient-atmosphere stability that exceeds the state-of-the-art for comparable acenes by orders of magnitude. Devices from this active material feature a powerful and unique combination of advantages, including straightforward benchtop fabrication, competitive baseline performance metrics, robustness during cycling with the capacity for autonomous self-repair, and multiple dynamic multispectral operating modes. When considered together, the described exciting discoveries point to new scientific and technological opportunities in the areas of functional organic materials, reconfigurable soft actuators, and adaptive photonic systems.
In nature, cephalopods employ unique dynamic camouflage mechanisms. Herein, we draw inspiration from self‐assembled structures found in cephalopods to fabricate tunable biomimetic camouflage ...coatings. The reflectance of these coatings is dynamically modulated between the visible and infrared regions of the electromagnetic spectrum in situ. Our studies represent a crucial step towards reconfigurable and disposable infrared camouflage for stealth applications.
Historically, open biopsy (OB) was the gold standard for sarcoma diagnosis. Core needle biopsy (CNB) has become increasingly common. There are limited data evaluating how the type of biopsy impacts ...definitive surgical resection or postoperative outcomes. The aims of this study were to (1) characterize current international biopsy practice patterns, and (2) evaluate how the type of biopsy performed impacts the resection surgery, infection risk, oncological complications, and patient-reported functional outcome scores.
This study was a preplanned secondary analysis of the prospective, multicenter PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) study. Patients with a benign diagnosis, metastatic disease, or no biopsy prior to surgery were excluded. Prospectively collected demographic, biopsy, surgical, and outcome variables were analyzed, and differences between patients undergoing OB and CNB were assessed. Parametric and nonparametric tests were used to compare variables between groups, and the Cox proportional hazards method was used to compare infection-related and oncological outcomes at 1 year. Median functional outcome scores at 1 year were compared.
Four hundred and sixty-four patients met the inclusion criteria. Data were collected from 48 sarcoma centers in 12 countries. CNB was the more utilized biopsy modality overall (57.5%). OB was more common in the U.S. and Canada. The median operative time was significantly longer for patients who underwent OB (324 versus 260 minutes; p < 0.001). Significantly more skin (p < 0.001) and fascial tissue (p < 0.001) were excised in the OB group, which also had a lower rate of primary closure (86.3% versus 92.9%; p = 0.03). There were no differences in surgical site infection or oncological outcomes between the groups at 1-year follow-up.
CNB was the more common biopsy modality in the PARITY study in most countries. However, OB was more common in the U.S. and Canada. Patients undergoing OB had longer operative times, more excised tissue, and lower rates of primary closure, but this did not translate to differences in infection rates or oncological outcomes, including local recurrence.
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Geriatric patients have the highest rates of Traumatic Brain Injury (TBI)-related hospitalization and death. This contributes to an assumption of futility in aggressive management in this population.
...To evaluate the effect of surgical intervention on the morbidity and mortality of geriatric patients with TBI.
A retrospective analysis of patients ≥80 yr old with TBI from 2003 to 2016 was performed using the National Trauma Data Bank. Univariate and multivariate analyses were performed to compare outcomes between surgery and nonsurgery groups.
A total of 127 129 patient incidents were included: 121 185 (95.3%) without surgery and 5944 (4.7%) with surgery. The surgical group was slightly younger (84.0 vs 84.3, P < .001) and predominantly male (60.2% vs 44.4%, P < .001). Mean emergency department (ED) Glasgow Coma Scale (GCS) was lower in surgical patients (12.4 vs 13.7, P < .001). Complications (OR = 1.91, CI:1.80-2.02, P < .001) and hospital length of stay (LOS, ß = 5.25, CI:5.08-5.42, P < .001) were independently associated with surgery. Intensive care unit (ICU) LOS (ß = 3.19, CI:3.05-3.34, P < .001), ventilator days (ß = 1.57, CI:1.22-1.92, P < .001), and reduced discharge home (OR = 0.434, CI:0.400-0.470, P < .001) were also independently associated with surgery. However, surgery was not independently associated with mortality on multivariate analysis (OR = 1.03, CI:0.955-1.12, P = .423). Recursive partitioning analysis identified ED GCS and injury severity score (ISS) as prognosticators of mortality following surgical intervention.
Surgical treatment of geriatric patients with TBI is associated with increased complications, hospital LOS, ICU LOS, and ventilator days as well as reduced discharge to home. However, surgery is not associated with increased mortality. ISS and ED GCS are prognosticators of mortality following surgical intervention.
Diagnosis of spinal cord injury (SCI) severity at the ultra-acute stage is of great importance for emergency clinical care of patients as well as for potential enrollment into clinical trials. The ...lack of a diagnostic biomarker for SCI has played a major role in the poor results of clinical trials. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared with healthy and trauma controls and in direct relation to SCI severity. Unsupervised coexpression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Specifically, for complete SCIs (AIS A), ROC analysis showed impressive specificity and sensitivity (AUC: 0.865). Similar precision was also shown for AIS D SCIs (AUC: 0.938). Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.
As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune ...responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus-neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate that children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that can likely contribute to protection from reinfection.
True intrathoracic subclavian artery aneurysms (SCAAs) are rare and have various etiologies. Right intrathoracic SCAAs pose specific anatomic challenges to repair. We present three different ...operative approaches, open, endovascular, and hybrid repair, for the repair of a right intrathoracic SCAA in three patients with genetic arteriopathy: Marfan syndrome, vascular Ehlers-Danlos syndrome, and unspecified Ehlers-Danlos syndrome, respectively. These cases demonstrate an individualized operative approach based on the genetic diagnosis for each patient presenting with a right intrathoracic SCAA.
Radiation-associated sarcoma of the pelvis and/or sacrum (RASB) is a rare but challenging disease process associated with a poor prognosis. We hypothesized that patients with RASB would have worse ...surgical and oncologic outcomes than patients diagnosed with primary pelvic or sacral bone sarcomas. This was a retrospective, multi-institution, comparative analysis. We reviewed surgically treated patients from multiple tertiary care centers who were diagnosed with a localized RASB. We also identified a comparison group including all patients diagnosed with a primary localized pelvic or sacral osteosarcoma/spindle cell sarcoma of bone (POPS). There were 35 patients with localized RASB and 73 patients with POPS treated with surgical resection. Patients with RASB were older than those with POPS (57 years vs. 38 years, p < 0.001). Patients with RASB were less likely to receive chemotherapy (71% for RASB vs. 90% for POPS, p = 0.01). Seventeen percent of patients with RASB died in the perioperative period (within 90 days of surgery) as compared to 4% with POPS (p = 0.03). Five-year disease-specific survival (DSS) (31% vs. 54% p = 0.02) was worse for patients with RASB vs. POPS. There was no difference in 5-year local recurrence free survival (LRFS) or metastasis free survival (MFS). RASB and POPS present challenging disease processes with poor oncologic outcomes. Rates of perioperative mortality and 5-year DSS are worse for RASB when compared to POPS.
Methane (CH4) emissions from climate‐sensitive ecosystems within the northern permafrost region represent a potentially large but highly uncertain source, with current estimates spanning a factor of ...seven (11–75 Tg CH4 yr−1). Accelerating permafrost thaw threatens significant increases in pan‐Arctic CH4 emissions, amplifying the permafrost carbon feedback. We used airborne imaging spectroscopy with meter‐scale spatial resolution and broad coverage to identify a previously undiscovered CH4 emission hotspot adjacent to a thermokarst lake in interior Alaska. Hotspot emissions were confined to <1% of the 10 ha lake study area. Ground‐based chamber measurements confirmed average daily fluxes from the hotspot of 1,170 mg CH4 m−2 d−1, with extreme daily maxima up to 24,200 mg CH4 m−2 d−1. Ground‐based geophysical measurements revealed thawed permafrost directly beneath the CH4 hotspot, extending to a depth of ∼15 m, indicating that the intense CH4 emissions likely originated from recently thawed permafrost. Hotspot emissions accounted for ∼40% of total diffusive CH4 emissions from the lake study site. Combining study site findings with hotspot statistics from our 70,000 km2 airborne survey across Alaska and northwestern Canada, we estimate that pan‐Arctic terrestrial thermokarst hotspots currently emit 1.1 (0.1–5.2) Tg CH4 yr−1, or roughly 4% of the annual pan‐Arctic wetland budget from just 0.01% of the northern permafrost land area. Our results suggest that significant proportions of pan‐Arctic CH4 emissions originate from disproportionately small areas of previously undetermined thermokarst emissions hotspots, and that pan‐Arctic CH4 emissions may increase non‐linearly as thermokarst processes increase under a warming climate.
Plain Language Summary
We conducted high‐resolution airborne surveys of near‐surface methane (CH4, a powerful greenhouse gas) anomalies in permafrost ecosystems in Alaska and northwestern Canada as part of NASA's Arctic Boreal Vulnerability Experiment (ABoVE). These measurements provided fine‐scale resolution for the remote detection of CH4 emission hotspots from natural Arctic environments. Repeated flights over Big Trail Lake near Fairbanks, AK revealed a previously undiscovered CH4 hotspot at this intensive study site. Ground‐based measurements confirmed extremely high surface‐to‐atmosphere emissions at this location, on the shore of a permafrost‐thaw pond that formed after 1963. Geophysical surveys confirmed the presence of thawed permafrost underneath the hotspot, extending to a depth ∼15 m. We hypothesize that recent permafrost thaw and subsidence made soils with highly decomposable organic carbon available for microbial metabolism, conversion into CH4, and enhanced emission to the atmosphere. Extrapolating our observed hotspot fluxes across the pan‐Arctic, we estimate that thermokarst CH4 hotspots constitute less than 0.01% of the pan‐Arctic land area, but contribute roughly 4% of annual pan‐Arctic wetland emissions. We further hypothesize that Arctic CH4 emissions may grow significantly in the future with anticipated increases in thermokarst across the permafrost landscape.
Key Points
Repeat airborne spectral imaging geolocated a thermokarst methane (CH4) hotspot with ground‐validated emissions >10 g CH4 m−2 d−1
Hotspot CH4 emissions arose from <1% of our 10 ha thermokarst lake study area but comprised ∼40% of the total diffusive emissions
Ground‐based and airborne observations suggest thermokarst hotspots emit roughly 1.1 Tg CH4 yr−1 or 4% of pan‐Arctic wetland CH4 emissions
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