APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks

Aprataxin and polynucleotide kinase (PNK) are DNA end processing factors that are recruited into the DNA single- and double-strand break repair machinery through phosphorylation-specific interactions with XRCC1 and XRCC4, respectively. These interactions are mediated through a divergent class of forkhead-associated (FHA) domain that binds to peptide sequences in XRCC1 and XRCC4 that are phosphorylated by casein kinase 2 (CK2). Here, we identify the product of the uncharacterized open reading frame C2orf13 as a novel member of this FHA domain family of proteins and we denote this protein APLF (aprataxin- and PNK-like factor). We show that APLF interacts with XRCC1 in vivo and in vitro in a manner that is stimulated by CK2. Yeast two-hybrid analyses suggest that APLF also interacts with the double-strand break repair proteins XRCC4 and XRCC5 (Ku86). We also show that endogenous and yellow fluorescent protein-tagged APLF accumulates at sites of H(2)O(2) or UVA laser-induced chromosomal DNA damage and that this is achieved through at least two mechanisms: one that requires the FHA domain-mediated interaction with XRCC1 and a second that is independent of XRCC1 but requires a novel type of zinc finger motif located at the C terminus of APLF. Finally, we demonstrate that APLF is phosphorylated in a DNA damage- and ATM-dependent manner and that the depletion of APLF from noncycling human SH-SY5Y neuroblastoma cells reduces rates of chromosomal DNA strand break repair following ionizing radiation. These data identify APLF as a novel component of the cellular response to DNA strand breaks in human cells

Investigating the role of ELN rs2071307 gene variant as a risk factor for Achilles Tendon Pathologies in a British Cohort

Injuries to the Achilles tendon (tendinopathies or ruptures) are considered as ones of the most severe musculoskeletal traumas in sports with an incidence rate of 50% in athletes and 10% in the general population. A number of gene variants coding for tendon structural proteins such as COL5A11 and FBN22 have previously been associated with Achilles tendon pathologies (ATP). These protein along with others maintain a harmonious interaction with elastin to allow tendons to respond to tensile load by stretching and returning to their original lengths. The ELN rs2071307 variant has been associated with soft tissue pathologies and is believed to be a good candidate gene as it results in the substitution of the hydrophobic amino acid glycine with the hydrophilic serine. However, in a previous study this variant was not associated with either Achilles tendinopathy or ACL rupture in populations from Australia and South Africa2. As recent evidence suggests that genetic risk factors for tendinopathy may depend, to some extent, on geographic location 3, the aim of this study was to determine whether the ELN rs2071307 variant was associated with the risk of ATP in a British cohort

Endoscopic Unroofing of a Choledochocele

A 42-year-old man with previous laparoscopic cholecystectomy was referred for further evaluation of recurrent acute pancreatitis. Secretin-enhanced magnetic resonance cholangiopancreatography showed a 16 mm × 11 mm T2 hyperintense cystic lesion at the major papilla (Figure 1). Upper endoscopic ultrasound (EUS) showed a 15 mm × 10 mm oval, intramural, subepithelial lesion at the major papilla (Figure 2). Endoscopic retrograde cholangiopancreatography (ERCP) showed an 18-mm bulging lesion at the major papilla with normal overlying mucosa (Figure 3); injected contrast collected into a 16-mm cystic cavity (Figure 4). Findings were suggestive of type A choledochocele. A 10–12-mm freehand precut papillotomy was made with a monofilament needle-knife (Huibregtse Single-Lumen Needle Knife, Cook Medical, Bloomington, IN) using an ERBE VIO electrocautery system (ERBE USA; Marietta, GA). The incision was made as long as safely possible in an attempt to open the choledochocele completely and thus expose its walls and contents. We used a standard pull sphincterotome and ERBE electrocautery to perform the pancreatic sphincterotomy, followed by placement of a pancreatic stent. Biliary sphincterotomy was performed using the same technique (settings for needle-knife and pull sphincterotomies: Endocut I, blend current, effect 2/duration 2/interval 3). Biopsies of the inverted choledochocele showed biliary mucosa and duodenal columnar epithelium with inflammation and fibrosis, and no dysplasia. Follow-up ERCP at 4 weeks showed adequate unroofing of the choledochocele (Figure 5); the pancreatic stent was subsequently removed. The patient reported no recurrence of acute pancreatitis at 6-, 12-, and 18-month follow-up intervals

SAfety and feasibility of EArly resistance training after median sternotomy : the SAFE-ARMS study

Objective: The purpose of this study was to determine the safety and feasibility of subacute upper limb resistance exercise on sternal micromotion and pain and the reliability of sternal ultrasound assessment following cardiac surgery via median sternotomy. Methods: This experimental study used a pretest-posttest design to investigate the effects of upper limb resistance exercise on the sternum in patients following their first cardiac surgery via median sternotomy. Six bilateral upper limb machine-based exercises were commenced at a base resistance of 20 lb (9 kg) and progressed for each participant. Sternal micromotion was assessed using ultrasound at the mid and lower sternum at 2, 8, and 14 weeks postsurgery. Intrarater and interrater reliability was calculated using intraclass correlation coefficients (ICCs). Participant-reported pain was recorded at rest and with each exercise using a visual analogue scale. Results: Sixteen adults (n = 15 males; 71.3 [SD = 6.2] years of age) consented to participate. Twelve participants completed the study, 2 withdrew prior to the 8-week assessment, and 2 assessments were not completed at 14 weeks due to assessor unavailability. The highest median micromotion at the sternal edges was observed during the bicep curl (median = 1.33 mm; range = -0.8 to 2.0 mm) in the lateral direction and the shoulder pulldown (median = 0.65 mm; range = -0.8 to 1.6 mm) in the anterior-posterior direction. Furthermore, participants reported no increase in pain when performing any of the 6 upper limb exercises. Interrater reliability was moderate to good for both lateral-posterior (ICC = 0.73; 95% CI = 0.58 to 0.83) and anterior-posterior micromotion (ICC = 0.83; 95% CI = 0.73 to 0.89) of the sternal edges. Conclusion: Bilateral upper limb resistance exercises performed on cam-based machines do not result in sternal micromotion exceeding 2.0 mm or an increase in participant-reported pain. Impact: Upper limb resistance training commenced as early as 2 weeks following cardiac surgery via median sternotomy and performed within the safe limits of pain and sternal micromotion appears to be safe and may accelerate postoperative recovery rather than muscular deconditioning. © 2022 The Author(s). Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved