Herein we describe the use of dynamic combinatorial chemistry to self-assemble complex coiled coil motifs. We amide-coupled a series of peptides designed to form homodimeric coiled coils with 3,5-dithiobenzoic acid (B) at the N-terminus and then allowed each B-peptide to undergo disulfide exchange. In the absence of peptide, monomer B forms cyclic trimers and tetramers, and thus we expected that addition of the peptide to monomer B would shift the equilibrium towards the tetramer to maximize coiled coil formation.
View Article and Find Full Text PDFAllogeneic hematopoietic stem cell transplantation (alloSCT) is curative for severe inborn errors of immunity (IEIs), with recent data suggesting alloSCT in adulthood is safe and effective in selected patients. However, questions remain regarding the indications for and optimal timing of transplant. We retrospectively compared outcomes of transplanted vs matched nontransplanted adults with severe IEIs.
View Article and Find Full Text PDFSensor arrays using synthetic receptors have found great utility in analyte detection, resulting from their ability to distinguish analytes based on differential signals via indicator displacement. However, synthesis and characterization of receptors for an array remain a bottleneck in the field. Receptor discovery has been streamlined using dynamic combinatorial libraries (DCLs), but the resulting receptors have primarily been utilized in isolation rather than as part of the entire library, with only a few examples that make use of the complexity of a library of receptors.
View Article and Find Full Text PDFBackground: Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).
Objectives: This study sought to characterize HCT outcomes in APDS.
Methods: Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.
The formation of mammalian dendritic cells (DCs) is controlled by multiple hematopoietic transcription factors, including IRF8. Loss of IRF8 exerts a differential effect on DC subsets, including plasmacytoid DCs (pDCs) and the classical DC lineages cDC1 and cDC2. In humans, cDC2-related subsets have been described including AXLSIGLEC6 pre-DC, DC2 and DC3.
View Article and Find Full Text PDFPLoS Pathog
March 2020
The primary immunodeficiencies (PIDs), rare inherited diseases characterized by severe dysfunction of immunity, have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in childhood. Controversy exists regarding optimal timing and use of Allo-HSCT in adults, due to lack of experience and previous poor outcomes. Twenty-nine consecutive adult patients, with a mean age at transplant of 24 years (range, 17-50 years), underwent Allo-HSCT.
View Article and Find Full Text PDFUnlabelled: Clavicular fractures are common injuries that traditionally are managed nonsurgically without clinically significant sequelae. However, they may develop hypertrophic callus formation that compresses the brachial plexus. These cases may present months to years after initial injury with varying degrees of pain, paresthesia, and weakness on the affected side and usually are treated by surgical resection of the hypertrophic callus.
View Article and Find Full Text PDFContext: Robotic surgery has been used with rapidly increasing frequency within urology and across many other surgical specialties. A standardized curriculum for the training and credentialing of robotic surgeons has unfortunately trailed far behind the adoption of this surgical technology.
Objective: To review the current available surgical skills training models, assessments, and curricula for the purpose of training resident, fellow, and practicing surgeons in an effort to promote surgical skill proficiency and mastery and to minimize the risk of patient harm.