An ultra-conserved poison exon in the <em>Tra2b </em>gene encoding a splicing activator is essential for male fertility and meiotic cell division

\ua9 The Author(s) 2025.The cellular concentrations of splicing factors (SFs) are critical for controlling alternative splicing. Most serine and arginine-enriched (SR) protein SFs regulate their own concentration via a homeostatic feedback mechanism that involves regulation of inclusion of non-coding ‘poison exons’ (PEs) that target transcripts for nonsense-mediated decay. The importance of SR protein PE splicing during animal development is largely unknown despite PE ultra-conservation across animal genomes. To address this, we used mouse genetics to disrupt an ultra-conserved PE in the Tra2b gene encoding the SR protein Tra2β. Focussing on germ cell development, we found that Tra2b PE deletion causes azoospermia due to catastrophic cell death during meiotic prophase. Failure to proceed through meiosis was associated with increased Tra2b expression sufficient to drive aberrant Tra2β protein hyper-responsive splice patterns. Although critical for meiotic prophase, Tra2b PE deletion spared earlier mitotically active germ cells, even though these still required Tra2b gene function. Our data indicate that PE splicing control prevents the accumulation of toxic levels of Tra2β protein that are incompatible with meiotic prophase. This unexpected connection with male fertility helps explain Tra2b PE ultra-conservation and indicates the importance of evaluating PE function in animal models

A prospective, observational cohort study of patients presenting to an emergency department with acute shoulder trauma: the Manchester emergency shoulder (MESH) project

Background Fracture and dislocation of the shoulder are usually identifiable through the use of plain radiographs in an emergency department. However, other significant soft tissue injuries can be missed at initial presentation. This study used contrast enhanced magnetic resonance arthrography (MRA) to determine the pattern of underlying soft tissue injuries in patients with traumatic shoulder injury, loss of active range of motion, and normal plain radiography. Methods A prospective, observational cohort study. Twenty-six patients with acute shoulder trauma and no identifiable radiograph abnormality were screened for inclusion. Those unable to actively abduction their affected arm to 90° at initial presentation and at two week’s clinical review were consented for MRA. Results Twenty patients (Mean age 44 years, 4 females) proceeded to MRA. One patient had no abnormality, three patients showed minimal pathology. Four patients had an isolated bony/labral injury. Eight patients had injuries isolated to the rotator cuff. Four patients had a combination of bony and rotator cuff injury. Four patients were referred to a specialist shoulder surgeon following MRA and underwent surgery. Conclusions Significant soft tissue pathology was common in our cohort of patients with acute shoulder trauma, despite the reassurance of normal plain radiography. These patients were unable to actively abduct to 90° both at initial presentation and at two week’s post injury review. A more aggressive management and diagnostic strategy may identify those in need of early operative intervention and provide robust rehabilitation programmes

DOES THE CLINICAL ENVIRONMENT INFLUENCE THE PROPERTIES OF BONE CEMENT?

Cementation is an important part of arthroplasty operations. Recent publication of results of Charnley total hip replacement found a rate of early aseptic loosening of 2.3% at 5 years following surgery across a NHS region. There are possibly many reasons for early loosening but precise reasons are still not fully understood, however, it is felt that cementation technique is very important. There seems to be a number of factors involved such as cement mixing techniques and conditions, physical properties of the cement, cementation and surgical techniques, bone-cement interface as well as bone- prosthesis interface. The purpose of this study was to evaluate the effectiveness of the clinical environment in producing bone cement of predictable mechanical and physical properties, and how those properties compare with published data. The investigation compared samples of bone cement, taken from material prepared and used in surgery with cement samples prepared under controlled laboratory conditions and in accordance with ISO materials testing standards.During 2000–01, 10 total hip replacements were selected for study. All operations involved the use of CMW1 (DePuy) radio-opaque cement, which was mixed using the Vacumix system. In this cohort, all femoral cementations were performed using an 80g cement mix. After careful preparation of the femoral canal, the scrub nurse mixed the cement in accordance with the manufacturer’s instructions. The cement was introduced into the femoral canal, via a nozzle, using the cementation gun and a pressurizer. Following introduction of cement into the canal, the nozzle and cement contained within, was broken off the gun distal to the pressurizer. Once cured, the cement samples were removed from the nozzle, sectioned, and mechanically tested. Due to this novel sample preparation procedure, the tested cement was expected to exhibit mechanical and physical properties characteristic of the cement present in the femoral canal. Samples of CMW1 (Vacumixed) of similar mass and aspect ratio were produced within the laboratory, in accordance with the manufacturers mixing instructions. PMMA bone cement is a brittle, glassy polymer that is susceptible to stress raisers, such as pores, which can reduce the load carrying ability, which in vivo is predominantly compressive in nature. Published mechanical properties of PMMA bone cement vary somewhat, reflecting the dependence of properties on flaw distribution. The density, which provides a measure of porosity, hardness and ultimate compressive strength of the cement samples was measured and compared.The surgical samples were found to be very consistent in compressive strength (121 ± 6 MPa), density (1.20 ± 0.02 gcm−3) and hardness (23.2 ± 1.6 VHN) and closely matched the mechanical properties of the cement mixed in the laboratory.This study suggests that for the studied cement and mixing regime, the clinical environment is capable of producing a well-controlled cement product that has reproducible and predictable mechanical properties. Further, the novel sample preparation procedure used suggests that the cement within the femoral cavity should demonstrate equally predictable, mechanical and physical properties