Folding of VemP into translation-arresting secondary structure is driven by the ribosome exit tunnel.

The ribosome is a fundamental biomolecular complex that synthesizes proteins in cells. Nascent proteins emerge from the ribosome through a tunnel, where they may interact with the tunnel walls or small molecules such as antibiotics. These interactions can cause translational arrest with notable physiological consequences. Here, we studied the arrest caused by the regulatory peptide VemP, which is known to form α-helices inside the ribosome tunnel near the peptidyl transferase center under specific conditions. We used all-atom molecular dynamics simulations of the entire ribosome and circular dichroism spectroscopy to study the driving forces of helix formation and how VemP causes the translational arrest. To that aim, we compared VemP dynamics in the ribosome tunnel with its dynamics in solution. We show that the VemP peptide has a low helical propensity in water and that the propensity is higher in mixtures of water and trifluorethanol. We propose that helix formation within the ribosome is driven by the interactions of VemP with the tunnel and that a part of VemP acts as an anchor. This anchor might slow down VemP progression through the tunnel enabling α-helix formation, which causes the elongation arrest.

Superior Capsular Reconstruction Provides Sufficient Biomechanical Outcomes for Massive, Irreparable Rotator Cuff Tears: A Systematic Review.

PURPOSE: To critically review the literature reporting biomechanical outcomes of superior capsular reconstruction (SCR) for the treatment of massive and/or irreparable rotator cuff tears. METHODS: A systematic review was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines using the PubMed, MEDLINE, and Cochrane Library databases in August 2020. Cadaveric studies were assessed for glenohumeral translation, subacromial contact pressure, and superior humeral translation comparing SCR with an intact cuff with reference to a torn control state. RESULTS: A total of 15 studies (142 shoulders) were included in our data analysis. SCR showed improvements in superior humeral translation, subacromial contact force, and glenohumeral contact force when biomechanically compared with the massive and/or irreparably torn rotator cuff. No statistically significant differences were found between SCR and the intact rotator cuff regarding superior humeral translation (standard mean difference [SMD], 2.09 mm vs 2.50 mm; P = .54) or subacromial contact force (SMD, 2.85 mPa vs 2.83 mPa; P = .99). Significant differences were observed between SCR and the intact cuff for glenohumeral contact force only, in favor of the intact cuff (SMD, 1.73 N vs 5.45 N; P = .03). CONCLUSIONS: SCR may largely restore static restraints to superior humeral translation in irreparable rotator cuff tears, although active glenohumeral compression is diminished relative to the intact rotator cuff. CLINICAL RELEVANCE: Investigating the biomechanical outcomes of SCR will help surgeons better understand the effectiveness of this treatment option.

Transient Non-local Interactions Dominate the Dynamics of Measles Virus NTAIL.

The RNA genome of measles virus is encapsidated by the nucleoprotein within a helical nucleocapsid that serves as template for both transcription and replication. The intrinsically disordered domain of the nucleoprotein (NTAIL), partly protruding outward from the nucleocapsid, is essential for binding the polymerase complex responsible for viral transcription and replication. As for many IDPs, binding of NTAIL occurs through a short molecular recognition element (MoRE) that folds upon binding, with the majority of NTAIL remaining disordered. Though NTAIL regions far from the MoRE influence the binding affinity, interactions between them and the MoRE have not been investigated in depth. Using an integrated approach, relying on photo-induced electron transfer (PET) experiments between tryptophan and cysteine pairs placed at different positions in the protein under varying salt and pH conditions, combined with simulations and analytical models, we identified transient interactions between two disordered regions distant in sequence, which dominate NTAIL dynamics, and regulate the conformational preferences of both the MoRE and the entire NTAIL domain. Co-evolutionary analysis corroborates our findings, and suggests an important functional role for the same intramolecular interactions. We propose mechanisms by which these non-local interactions may regulate binding to the phosphoprotein, polymerase recruitment, and ultimately viral transcription and replication. Our findings may be extended to other IDPs, where non-local intra-protein interactions affect the conformational preferences of intermolecular binding sites.

Return to play rates after ulnar nerve transposition and decompression surgery: a retrospective analysis.

BACKGROUND: Medial elbow pain is a common complaint in overhead throwing athletes. The throwing motion places repetitive tensile and compressive forces on the elbow resulting in significant stress across the ulnohumeral joint. This stress can result in soft-tissue, ligamentous, and ulnar nerve injury. The purpose of this study was to retrospectively investigate the clinical findings and outcomes, including return to play rates, of patients who underwent ulnar nerve transposition surgery for isolated ulnar neuritis. METHODS: Throwing athletes who underwent isolated, primary ulnar nerve transposition surgery over an eight-year period, 2009 to 2017, were identified and included in our analysis. Nonthrowing athletes, those who underwent revision ulnar nerve transposition surgery, and those who underwent concomitant ulnar collateral ligament reconstruction or repair were excluded. Patients were contacted to complete the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score as well as a return to play rate questionnaire. The minimum follow-up was 2 years. RESULTS: Fifteen patients met the inclusion criteria: 13 (86.7%) men and 2 (13.3%) women. The average age at the time of surgery was 19.2 years old (range, 15.6-28.0). Preoperatively, 13 (86.7%) patients played baseball and 2 (13.3%) patients played softball. Two patients (13.3%) underwent a previous ulnar collateral ligament reconstruction. There were no complications. The average final follow-up was 65.26 (range, 24.44-113.29) months with an average Kerlan-Jobe Orthopaedic Clinic Score of 64.51 (range, 28.60-100.00). Thirteen (86.7%) patients were able to return to their preinjury sport, 2 to a higher level of competition, 8 to the same level, and 3 to a lower level. Seven of the 13 (53.8%) patients sustained a postoperative ipsilateral shoulder or elbow injury at an average of 19.57 (range, 7.00-36.00) months postoperatively. All patients reported sustaining the injury as a result of throwing. CONCLUSION: The results of our study indicate that ulnar nerve transposition surgery in throwing athletes allows athletes to return to throwing with low reoperation rates. However, more than half of the athletes in our analysis sustained a subsequent ipsilateral shoulder or elbow injury. Further investigation regarding outcomes in throwing athletes after ulnar nerve transposition surgery is warranted.

Clinical Outcomes of Superior Capsular Reconstruction for Massive, Irreparable Rotator Cuff Tears: A Systematic Review Comparing Acellular Dermal Allograft and Autograft Fascia Lata.

PURPOSE: To investigate clinical outcomes after superior capsular reconstruction (SCR) for the treatment of massive and/or irreparable rotator cuff tears treated with either allograft or autograft. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, in April 2020 a systematic review was performed using PubMed, MEDLINE, EMBASE, and Cochrane databases. Clinical studies were assessed for patient-reported outcomes and range of motion, comparing dermal allografts to fascia lata autografts, with a minimum follow-up of 12 months. RESULTS: A total of 16 clinical studies involving 598 patients (606 shoulders) were included for data analysis, with a weighted mean follow-up of 36.9 months (range 12 to 60). Visual analogue scale (VAS) pain scores decreased from 4.0 to 6.9 mm preoperatively to 0 to 2.5 mm postoperatively. American Shoulder & Elbow Surgeons score increased from 20.3 to 54.5 preoperatively to 73.7 to 97.0 postoperatively. Forward flexion increased from 27.0° to 142.7° preoperatively to 134.5° to 167.0° postoperatively. External rotation increased from 13.2° to 41.0° preoperatively to 30.0° to 59.0° postoperatively. Acromiohumeral distance increased from 3.4 to 7.1 mm preoperatively to 6.0 to 9.7 mm postoperatively. The total rates of complications, graft failure, and revision surgery were 5.6%, 13.9%, and 6.9%, respectively. CONCLUSIONS: Irrespective of tissue source, SCR serves as a reasonable joint-preserving option for massive, irreparable rotator cuff tears, with favorable short- to midterm improvements in patient-reported outcomes and range of motion. LEVEL OF EVIDENCE: IV, systematic review of level III and IV studies.