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The exfoliative toxins (ETs) cause staphylococcal scalded skin syndrome, a disease characterized by specific separation of layers of the skin. Research has shown that the toxins act as serin proteases, though the specific substrate and mode of action are not known for certain. The crystal structure of exfoliative toxin A (ETA) has been found previously to be similar to that of chymotrypsin-like serine proteases. The 2.4 angstrom resolution crystal structure of the other exfoliative toxin, ETB, which is 40% identical to ETA.

Abstract Background The engineering of many-component, synthetic biological systems is being made easier by the development of collections of reusable, standard biological parts. However, the complexity of biology makes it difficult to predict the extent to which such efforts will succeed. As a first practical example, the Registry of Standard Biological Parts started at MIT now maintains and distributes thousands of BioBrick™ standard biological parts. However, BioBrick parts are only standardized in terms of how individual parts are physically assembled into multi-component systems, and most parts remain uncharacterized. Standardized tools, techniques, and units of measurement are needed to facilitate the characterization and reuse of parts by independent researchers across many laboratories. Results We found that the absolute activity of BioBrick promoters varies across experimental conditions and measurement instruments. We choose one promoter (BBa_J23101) to serve as an in vivo reference standard for promoter activity. We demonstrated that, by measuring the activity of promoters relative to BBa_J23101, we could reduce variation in reported promoter activity due to differences in test conditions and measurement instruments by ~50%. We defined a Relative Promoter Unit (RPU) in order to report promoter characterization data in compatible units and developed a measurement kit so that researchers might more easily adopt RPU as a standard unit for reporting promoter activity. We distributed a set of test promoters to multiple labs and found good agreement in the reported relative activities of promoters so measured. We also characterized the relative activities of a reference collection of BioBrick promoters in order to further support adoption of RPU-based measurement standards. Conclusion Relative activity measurements based on an in vivoreference standard enables improved measurement of promoter activity given variation in measurement conditions and instruments. These improvements are sufficient to begin to support the measurement of promoter activities across many laboratories. Additional in vivo reference standards for other types of biological functions would seem likely to have similar utility, and could thus improve research on the design, production, and reuse of standard biological parts.

Cytotoxic CD8 + T cells (CTL) are a crucial component of the immune system notable for their ability to eliminate rapidly proliferating malignant cells. However, the T-cell intrinsic factors required for human CTLs to accomplish highly efficient antitumor cytotoxicity are not well defined. By evaluating human CD8 + T cells from responders versus nonresponders to treatment with immune checkpoint inhibitors, we sought to identify key factors associated with effective CTL function. Single-cell RNA-sequencing analysis of peripheral CD8 + T cells from patients treated with anti-PD-1 therapy showed that cells from nonresponders exhibited decreased expression of the cytolytic granule-associated molecule natural killer cell granule protein-7 ( NKG7 ). Functional assays revealed that reduced NKG7 expression altered cytolytic granule number, trafficking, and calcium release, resulting in decreased CD8 + T-cell-mediated killing of tumor cells. Transfection of T cells with NKG7 mRNA was sufficient to improve the tumor-cell killing ability of human T cells isolated from nonresponders and increase their response to anti-PD-1 or anti-PD-L1 therapy in vitro . NKG7 mRNA therapy also improved the antitumor activity of murine tumor antigen-specific CD8 + T cells in an in vivo model of adoptive cell therapy. Finally, we showed that the transcription factor ETS1 played a role in regulating NKG7 expression. Together, our results identify NKG7 as a necessary component for the cytotoxic function of CD8 + T cells and establish NKG7 as a T-cell-intrinsic therapeutic target for enhancing cancer immunotherapy. See related article by Li et al., p. 154., (©2021 The Authors; Published by the American Association for Cancer Research.)

Objective: The authors sought to investigate the incidence and predictors of venous thromboembolic events (VTEs) after craniotomy for tumor resection, which are not well established, and the efficacy of and risks associated with VTE chemoprophylaxis, which remains controversial., Methods: The authors investigated the incidence of VTEs in a consecutive series of patients presenting to the authors' institution for resection of an intracranial lesion between 2012 and 2017. Information on patient and tumor characteristics was collected and independent predictors of VTEs were determined using stepwise multivariate logistic regression analysis. Review of the literature was performed by searching MEDLINE using the keywords "venous thromboembolism," "deep venous thrombosis," "pulmonary embolism," "craniotomy," and "brain neoplasms.", Results: There were 1622 patients included for analysis. A small majority of patients were female (52.6%) and the mean age of the cohort was 52.9 years (SD 15.8 years). A majority of intracranial lesions were intraaxial (59.3%). The incidence of VTEs was 3.0% and the rates of deep venous thromboses and pulmonary emboli were 2.3% and 0.9%, respectively. On multivariate analysis, increasing patient age (unit OR 1.02, 95% CI 1.00-1.05; p = 0.018), history of VTE (OR 7.26, 95% CI 3.24-16.27; p < 0.001), presence of motor deficit (OR 2.64, 95% CI 1.43-4.88; p = 0.002), postoperative intracranial hemorrhage (OR 4.35, 95% CI 1.51-12.55; p < 0.001), and prolonged intubation or reintubation (OR 3.27, 95% CI 1.28-8.32; p < 0.001) were independently associated with increased odds of a VTE. There were 192 patients who received VTE chemoprophylaxis (11.8%); the mean postoperative day of chemoprophylaxis initiation was 4.6 (SD 3.8). The incidence of VTEs was higher in patients receiving chemoprophylaxis than in patients not receiving chemoprophylaxis (8.3% vs 2.2%; p < 0.001). There were 30 instances of clinically significant postoperative hemorrhage (1.9%), with only 1 hemorrhage occurring after initiation of VTE chemoprophylaxis (0.1%)., Conclusions: The study results show the incidence and predictors of VTEs after craniotomy for tumor resection in this patient population. The incidence of VTE within this cohort appears low and comparable to that observed in other institutional series, despite the lack of routine prophylactic anticoagulation in the postoperative setting.