Anterior glenoid rim erosion in the early stage after arthroscopic Bankart repair affects postoperative recurrence.

Background: Recent studies reported that anterior glenoid rim erosion can occur in the early period after arthroscopic Bankart repair (ABR) for traumatic anterior shoulder instability. However, it is unknown whether such erosion is a risk factor for postoperative recurrence. This study evaluated risk factors for postoperative recurrence after ABR, specifically aiming to elucidate whether reduction of postoperative glenoid width due to anterior glenoid rim erosion is one of such factors. Methods: A total of 220 shoulders that underwent ABR alone between 2013 and 2020 were retrospectively investigated. Patient age at surgery, whether the patient was a collision/contact athlete, anchor placement, preoperative glenoid bone defect (%), localization of the Hill-Sachs lesion, and change of glenoid width (%) in the 6 months after surgery were investigated for their statistical relation to recurrence by univariate and multiple logistic regression analysis. Results: Postoperative recurrence occurred in 32 of 220 shoulders (14.5%). In univariate analysis, being a collision/contact athlete was the only variable with a significant effect on recurrence (odds ratio [OR], 2.555; 95% confidence interval [CI], 1.123-5.814; P = .03). Change of glenoid width reduction was larger in those with recurrence than without recurrence, but the difference was not statistically significant (-7.0 ± 6.6% vs. -5.0 ± 9.3%; P = .14). However, in multivariate logistic analysis, preoperative glenoid bone defect (%) (adjusted unit OR, 1.076; 95% CI, 1.018-1.137; P = .010) and postoperative change of glenoid width (%) (adjusted unit OR, 0.946; 95% CI, 0.900-0.994; P = .028) had a significant influence on postoperative recurrence. Conclusion: Glenoid width reduction due to anterior glenoid rim erosion after ABR is a risk factor for recurrence.

Tolerability of the first infusion of once-yearly zoledronic acid within one to two weeks after hip fracture surgery.

OBJECTIVE: Once-yearly infusions of zoledronic acid (ZA) 5 mg may be optimal for secondary fracture prevention after hip fracture (HF), but there are crucial side effects of ZA. This study assessed the tolerability of the first infusion of once-yearly ZA within one to two weeks after HF surgery and to identify risk factors for acute-phase reactions (APRs) and the decrease in serum calcium (Ca) concentration. METHODS: We analyzed 84 patients (average age: 83 years, 18 men and 66 women) who met the inclusion criteria. The patients underwent the first infusion of ZA one to two weeks after HF surgery and received antipyretic analgesics and active vitamin D analog. RESULTS: APRs occurred in ten patients (11.9%) and all these patients had pyrexia (>37.5 °C) and/or other symptoms. The asymptomatic hypocalcemia (serum Ca < 8.3 mg/dL) incidence was 6.0% at 7 days after ZA infusion. Compared with female patients without APRs, female patients with APRs had significantly higher levels of serum 25-dihydroxyvitamin D at baseline and serum C-reactive protein on the day ZA was administered (day 0). Multiple linear regression analyses showed that serum level of tartrate-resistant acid phosphatase-5b were significantly associated with an absolute decrease in serum corrected Ca from day 0 to day 7. CONCLUSIONS: The first infusion of ZA within one to two weeks after HF surgery was well tolerated with the combined use of antipyretic analgesics and active vitamin D analog. Higher inflammatory condition after surgery which is more likely sensitized by ZA administration may increase the risk of APRs, and high bone turnover may increase hypocalcemia risk.

Bottom-up reconstitution of focal adhesion complexes.

Focal adhesions (FA) are large macromolecular assemblies relevant for various cellular and pathological events such as migration, polarization, and metastatic cancer formation. At FA sites at the migrating periphery of a cell, hundreds of players gather and form a network to respond to extra cellular stimuli transmitted by the integrin receptor, the most upstream component within a cell, initiating the FA signaling pathway. Numerous cellular experiments have been performed to understand the FA architecture and functions; however, their intricate network formation hampers unraveling the precise molecular actions of individual players. Here, in vitro bottom-up reconstitution presents an advantageous approach for elucidating the FA machinery and the hierarchical crosstalk of involved cellular players.

Mitochondrial dysfunction generates aggregates that resist lysosomal degradation in human breast cancer cells.

Disrupting functional protein homeostasis is an established therapeutic strategy for certain tumors. Ongoing studies are evaluating autophagy inhibition for overcoming chemotherapeutic resistance to such therapies by neutralizing lysosomal pH. New and sensitive methods to monitor autophagy in patients are needed to improve trial design and interpretation. We report that mitochondrial-damaged breast cancer cells and rat breast tumors accumulate p53-positive protein aggregates that resist lysosomal degradation. These aggregates were localized to enzymatically-active autolysosomes that were degrading autophagosomes and the autophagic receptor proteins TAX1BP1 and NDP52. NDP52 was identified to associate with aggregated proteins and knocking down NDP52 led to the accumulation of protein aggregates. TAX1BP1 was identified to partly localize with aggregates, and knocking down TAX1BP1 enhanced aggregate formation, suppressed autophagy, impaired NDP52 autophagic degradation and induced cell death. We propose that quantifying aggregates and autophagic receptors are two potential methods to evaluate autophagy and lysosomal degradation, as confirmed using primary human tumor samples. Collectively, this report establishes protein aggregates and autophagy receptors, TAX1BP1 and NDP52, as potential endpoints for monitoring autophagy during drug development and clinical studies.

Insufficient integrity of partial articular surface tendon avulsion lesions after arthroscopic trans-tendon repair: Comparison with integrity after arthroscopic repair after conversion to a full thickness tear.

BACKGROUND: For the surgical treatment of severe partial articular surface tendon avulsion (PASTA) lesions, 2 repair techniques, i.e., arthroscopic trans-tendon repair and arthroscopic repair after conversion to a full thickness tear, are widely used, and a satisfactory clinical outcome with both has been reported. The purpose of this study was to investigate integrity of the repaired rotator cuff based on second-look arthroscopy and to compare the above two repair techniques. METHODS: Thirty-seven shoulders underwent PASTA lesion repair arthroscopically, with 20 shoulders receiving second-look arthroscopy. According to the repair technique, the shoulders were divided into 2 groups, which were 10 shoulders with trans-tendon repair (group P) and 10 shoulders with repair after conversion to a full thickness tear (group C). Second-look arthroscopy was done at a minimum of 3 months after initial surgery, with the mean interval until second-look arthroscopy being 5.6 months (3-13) in group P and 5.1 months (3-9) in group C. The reasons for second-look arthroscopy were pain with contracture in 15 patients, as well as pain in 4 patients and muscle weakness at abduction in one patient. RESULTS: In group P, there was complete rotator cuff continuity in 3 shoulders, partial continuity in 4, and failure in 3, while group C had complete continuity in 8 shoulders, partial continuity in 1, and failure in 1. Adhesions of the subacromial bursa were seen in all shoulders, while contracture of the posterior capsule was noted in 5 shoulders from group P and 9 shoulders from group C, and contracture of the rotator interval was identified in 7 shoulders from group P and 9 shoulders from group C. CONCLUSIONS: Second-look arthroscopy revealed that the integrity of the rotator cuff after trans-tendon repair of severe PASTA lesions was often unsatisfactory in patients with symptomatic shoulder. On the other hand, complete continuity was seen in most shoulders underwent repair after conversion to a full thickness tear.

Benefits of bone graft augmentation to arthroscopic Bankart repair for recurrent anterior shoulder instability with glenoid bone loss.

PURPOSE: Glenoid bone loss contributes to recurrent instability after arthroscopic Bankart repair alone. With significant glenoid bone loss, better results have been reported after arthroscopic Bankart repair with glenoid arc reconstruction. However, no reports compare augmentation using bone graft with non-augmentation for glenoid bone loss. The purpose of this study was to assess clinical results of an arthroscopic Bankart repair with or without arthroscopic bone graft augmentation. It was hypothesized that such bone graft augmentation would restore shoulder stability, and lead to excellent outcomes. METHODS: Of 552 patients treated for anterior glenohumeral instability with arthroscopic Bankart repair, 68 met this study's inclusion criteria of glenoid bone loss over 20% and follow-up of at least 2 years. Patients were divided into 2 groups based on whether with bone graft augmentation for glenoid bone loss [Group A: n = 35, median age; 21 years (range 13-72 years)], or not (Group B: n = 33, median age; 21 years (range 13-50 years)]. For grafting, either autologous iliac bone or artificial bone made of hydroxyapatite was used. Rowe score, recurrence rate, and return to sport were used to assess the results. RESULTS: Mean Rowe score was 95.0 (SD 10.6) in Group A and 69.7 (SD 27.2) in Group B (p < 0.05). The recurrence rate was 2.9% (1/36) in Group A and 48.5% (16/33) in Group B (p < 0.05). Regarding contact/collision athletes, 24 were contained in Group A and 22 in Group B. Of the patients with recurrence in Group B, 13 (59.1%) were contact/collision athletes. Finally, 50% of the contact/collision sports athletes for both groups returned to their sports at the same as pre-injury level. Of the 11 patients who returned to the same level of contact/collision sports in Group B, seven returned with residual instability. Nine athletes in Group A and 3 in Group B quit their sports for personal or social reasons. CONCLUSIONS: Bone graft augmentation was beneficial when used with Arthroscopic Bankart repair for recurrent anterior shoulder instability with glenoid bone loss. Especially, for recurrent anterior shoulder instability with glenoid bone loss in contact/collision sports athletes, bone graft augmentation should be strongly considered as beneficial. LEVEL OF EVIDENCE: Level IV.

Clinical Outcome of Arthroscopic Bankart Repair Combined With Simultaneous Capsular Repair.

BACKGROUND: A capsular tear and humeral avulsion of the glenohumeral ligament lesion are not uncommon findings in association with a Bankart lesion. However, there have been few reports regarding the prevalence of such capsular lesions and the postoperative recurrence after capsular repair. Purpose/Hypothesis: This study investigated the prevalence of capsular lesions and clarified their influence on the postoperative recurrence of instability. In addition, factors were identified that were associated with the occurrence of capsular lesions and the postoperative recurrence of instability. We hypothesized that clinical outcomes would be improved by combining arthroscopic Bankart repair with simultaneous capsular repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Capsular lesions were retrospectively examined through operative records, still pictures, and videos in 172 shoulders with traumatic anterior instability. First, the prevalence of capsular lesions and their severity were investigated. Then, postoperative recurrence was determined in shoulders observed for a minimum of 2 years. Finally, factors were assessed that were associated with the occurrence of capsular lesions and the postoperative recurrence of instability. RESULTS: A capsular lesion was recognized in 37 shoulders (21.5%), being severe and mild in 20 and 17, respectively. All were repaired simultaneously with the arthroscopic Bankart procedure. After follow-up for at least 2 years, recurrence of instability was detected in 10 of 34 shoulders (29.4%), including 6 (31.6%) with severe capsular lesions and 4 (26.7%) with mild lesions. The recurrence rate was significantly higher in shoulders with a capsular lesion than in shoulders without a capsular lesion (18 of 120, 15%; P = .013), but there was no significant difference between severe and mild lesions. Regardless of the sport played, capsular lesions were significantly more frequent in patients ≥30 years old, patients with complete dislocation, and patients with a coexisting Hill-Sachs lesion. Postoperative recurrence of instability was significantly more frequent in patients <30 years and competitive athletes. CONCLUSION: In shoulders undergoing arthroscopic Bankart repair, capsular lesions were often present and were associated with higher postoperative recurrence of instability. While these lesions were more frequent in older patients, postoperative recurrence of instability was more likely in young competitive athletes.

The pathology of the anterior capsule in patients over forty years of age with recurrent shoulder dislocation.

PURPOSE: We evaluated the pathologies of anterior capsular mechanism in older patients with recurrent anterior shoulder dislocation in the absence of full-thickness rotator cuff tears. METHODS: Three hundred and ninety-five shoulders with recurrent anterior shoulder dislocation were assessed. The patients were divided into three groups by the age at the first dislocation and the surgical treatment: group A (onset and treatment were at an age over 40 years), group B (onset was at an age under 40 years and treatment was at an age over 40 years) and group C (onset and treatment were at an age under 40 years). Groups A, B and C involved nine, 31 and 355 shoulders, respectively. RESULTS: The prevalence of an isolated Bankart lesion was 81.7 % in group C, 33.3 % in group A and 64.5 % in group B, and each of A and B was significantly lower than group C. The prevalence of an isolated capsular tear was 3.1 % in group C, while it was 33.3 % in group A, which was significantly higher. CONCLUSIONS: The prevalence of an isolated Bankart lesion was low and the prevalence of a capsular tear was high in older patients. We should keep in mind the existence of a capsular tear in older patients and examine the whole anterior capsular mechanism meticulously.

Side-binding proteins modulate actin filament dynamics.

Actin filament dynamics govern many key physiological processes from cell motility to tissue morphogenesis. A central feature of actin dynamics is the capacity of filaments to polymerize and depolymerize at their ends in response to cellular conditions. It is currently thought that filament kinetics can be described by a single rate constant for each end. In this study, using direct visualization of single actin filament elongation, we show that actin polymerization kinetics at both filament ends are strongly influenced by the binding of proteins to the lateral filament surface. We also show that the pointed-end has a non-elongating state that dominates the observed filament kinetic asymmetry. Estimates of flexibility as well as effects on fragmentation and growth suggest that the observed kinetic diversity arises from structural alteration. Tuning elongation kinetics by exploiting the malleability of the filament structure may be a ubiquitous mechanism to generate a rich variety of cellular actin dynamics.

Hill-sachs lesions in shoulders with traumatic anterior instability: evaluation using computed tomography with 3-dimensional reconstruction.

BACKGROUND: In patients with traumatic anterior shoulder instability, a large Hill-Sachs lesion is a risk factor for postoperative recurrence. However, there is no consensus regarding the occurrence and enlargement of Hill-Sachs lesions. PURPOSE: To investigate the influence of the number of dislocations and subluxations on the prevalence and size of Hill-Sachs lesions evaluated by computed tomography (CT) with 3-dimensional reconstruction. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: The prevalence and size of Hill-Sachs lesions were evaluated preoperatively by CT in 142 shoulders (30 with primary instability and 112 with recurrent instability) before arthroscopic Bankart repair. First, the prevalence of Hill-Sachs lesions was compared with the arthroscopic findings. Then, the size of Hill-Sachs lesions confirmed by arthroscopy was remeasured using the previous CT data. In addition, the relationship of Hill-Sachs lesions with the number of dislocations and subluxations was investigated. RESULTS: Hill-Sachs lesions were detected in 90 shoulders by initial CT evaluation and were found in 118 shoulders at arthroscopy. The Hill-Sachs lesions missed by initial CT were 15 chondral lesions and 13 osseous lesions. However, all 103 osseous Hill-Sachs lesions were detected by reviewing the CT data. In patients with primary subluxation, the prevalence of Hill-Sachs lesions was 26.7%, and the mean length, width, and depth of the lesions (calculated as a percentage of the diameter of the humeral head) were 9.0%, 5.3%, and 2.1%, respectively, while the corresponding numbers for primary dislocation were 73.3%, 27.7%, 14.8%, and 7.0%, all showing statistically significant differences. Among all 142 shoulders, the corresponding numbers were, respectively, 56.3%, 20.7%, 11.2%, and 4.8% in patients who had subluxations but never a dislocation; 83.3%, 33.4%, 19.1%, and 7.6% in patients with 1 episode of dislocation; and 87.5%, 46.8%, 22.2%, and 10.2% in patients with ≥2 episodes, all showing statistically significant differences. There were no differences in lesion measurements in relation to the number of subluxations. CONCLUSION: Computed tomography is a useful imaging modality for evaluating Hill-Sachs lesions except for purely cartilaginous lesions. Hill-Sachs lesions were more frequent and larger when the primary episode was dislocation than when it was subluxation. Among patients with recurrent episodes of complete dislocation, the prevalence of Hill-Sachs lesions is increased, and the lesions are larger.

Cofilin recruits F-actin to SPCA1 and promotes Ca2+-mediated secretory cargo sorting.

The actin filament severing protein cofilin-1 (CFL-1) is required for actin and P-type ATPase secretory pathway calcium ATPase (SPCA)-dependent sorting of secretory proteins at the trans-Golgi network (TGN). How these proteins interact and activate the pump to facilitate cargo sorting, however, is not known. We used purified proteins to assess interaction of the cytoplasmic domains of SPCA1 with actin and CFL-1. A 132-amino acid portion of the SPCA1 phosphorylation domain (P-domain) interacted with actin in a CFL-1-dependent manner. This domain, coupled to nickel nitrilotriacetic acid (Ni-NTA) agarose beads, specifically recruited F-actin in the presence of CFL-1 and, when expressed in HeLa cells, inhibited Ca(2+) entry into the TGN and secretory cargo sorting. Mutagenesis of four amino acids in SPCA1 that represent the CFL-1 binding site also affected Ca(2+) import into the TGN and secretory cargo sorting. Altogether, our findings reveal the mechanism of CFL-1-dependent recruitment of actin to SPCA1 and the significance of this interaction for Ca(2+) influx and secretory cargo sorting.

Structural basis for the extended CAP-Gly domains of p150(glued) binding to microtubules and the implication for tubulin dynamics.

p150(glued) belongs to a group of proteins accumulating at microtubule plus ends (+TIPs). It plays a key role in initiating retrograde transport by recruiting and tethering endosomes and dynein to microtubules. p150(glued) contains an N-terminal microtubule-binding cytoskeleton-associated protein glycine-rich (CAP-Gly) domain that accelerates tubulin polymerization. Although this copolymerization is well-studied using light microscopic techniques, structural consequences of this interaction are elusive. Here, using electron-microscopic and spectroscopic approaches, we provide a detailed structural view of p150(glued) CAP-Gly binding to microtubules and tubulin. Cryo-EM 3D reconstructions of p150(glued)-CAP-Gly complexed with microtubules revealed the recognition of the microtubule surface, including tubulin C-terminal tails by CAP-Gly. These binding surfaces differ from other retrograde initiation proteins like EB1 or dynein, which could facilitate the simultaneous attachment of all accessory components. Furthermore, the CAP-Gly domain, with its basic extensions, facilitates lateral and longitudinal interactions of tubulin molecules by covering the tubulin acidic tails. This shielding effect of CAP-Gly and its basic extensions may provide a molecular basis of the roles of p150(glued) in microtubule dynamics.

Long-term results of the Latarjet procedure for anterior instability of the shoulder.

BACKGROUND: The Latarjet procedure is effective in managing anterior glenohumeral instability in the short term, but there is concern for postoperative arthritis. The purpose of this study was to evaluate the long-term functional outcome after the Latarjet procedure and to assess the prevalence of and risk factors for glenohumeral arthritis after this procedure. MATERIALS AND METHODS: A retrospective review was conducted of 68 Latarjet procedures at a mean of 20 years postoperatively. The mean age at surgery was 29.4 years. Functional outcome was determined by the Rowe score, subjective shoulder value, and recurrence of instability. Preoperative arthritis and postoperative radiographs were reviewed to evaluate the development or progression of arthritis. RESULTS: The mean Rowe score increased from 37.9 preoperatively to 89.6 at final follow-up (P < .001). The mean subjective shoulder value was 90.9% at final follow-up. The postoperative rate of recurrence was 5.9%. Of the 60 shoulders without arthritis preoperatively, 12 (20%) had developed arthritis at final follow-up. Among the 8 shoulders with preoperative arthritis (all stage 1), 4 (50%) demonstrated progression of arthritis at final follow-up. Overall, postoperative arthritis was stage 1 in 14.7%, stage 2 in 5.9%, and stage 3 in 8.8% of cases; no stage 4 arthritis was observed. Risk factors for postoperative arthritis were older age, high-demand sports activity, and lateral overhang of coracoid bone graft. CONCLUSION: The Latarjet procedure provides excellent long-term outcomes in the treatment of recurrent anterior glenohumeral instability. Twenty years after the Latarjet procedure, arthritis may develop or progress in 23.5% of cases, but the majority of arthritis is mild.

Conformational switching in PolyGln amyloid fibrils resulting from a single amino acid insertion.

The established correlation between neurodegenerative disorders and intracerebral deposition of polyglutamine aggregates motivates attempts to better understand their fibrillar structure. We designed polyglutamines with a few lysines inserted to overcome the hindrance of extreme insolubility and two D-lysines to limit the lengths of ß-strands. One is 33 amino acids long (PolyQKd-33) and the other has one fewer glutamine (PolyQKd-32). Both form well-dispersed fibrils suitable for analysis by electron microscopy. Electron diffraction confirmed cross-ß structures in both fibrils. Remarkably, the deletion of just one glutamine residue from the middle of the peptide leads to substantially different amyloid structures. PolyQKd-32 fibrils are consistently 10-20% wider than PolyQKd-33, as measured by negative staining, cryo-electron microscopy, and scanning transmission electron microscopy. Scanning transmission electron microscopy analysis revealed that the PolyQKd-32 fibrils have 50% higher mass-per-length than PolyQKd-33. This distinction can be explained by a superpleated ß-structure model for PolyQKd-33 and a model with two ß-solenoid protofibrils for PolyQKd-32. These data provide evidence for ß-arch-containing structures in polyglutamine fibrils and open future possibilities for structure-based drug design.

Molecular basis of tubulin transport within the cilium by IFT74 and IFT81.

Intraflagellar transport (IFT) of ciliary precursors such as tubulin from the cytoplasm to the ciliary tip is involved in the construction of the cilium, a hairlike organelle found on most eukaryotic cells. However, the molecular mechanisms of IFT are poorly understood. Here, we found that the two core IFT proteins IFT74 and IFT81 form a tubulin-binding module and mapped the interaction to a calponin homology domain of IFT81 and a highly basic domain in IFT74. Knockdown of IFT81 and rescue experiments with point mutants showed that tubulin binding by IFT81 was required for ciliogenesis in human cells.

Reverse total shoulder arthroplasty for primary glenohumeral osteoarthritis in patients with a biconcave glenoid.

BACKGROUND: The biconcave glenoid in patients with primary glenohumeral osteoarthritis represents a surgical challenge because of the associated static posterior instability of the humeral head and secondary posterior glenoid erosion. The purpose of the present study was to evaluate the clinical and radiographic results of reverse total shoulder arthroplasty for the treatment of primary osteoarthritis in patients with a biconcave glenoid without rotator cuff insufficiency. METHODS: We performed a retrospective review of twenty-seven reverse shoulder arthroplasties that were performed from 1998 to 2009 for the treatment of primary glenohumeral osteoarthritis and biconcave glenoid. Eighty-one percent of the patients were female, and the mean age of the patients at the time of surgery was 74.1 years (range, sixty-six to eighty-two years). All patients had a preoperative computed tomography arthrogram to allow for the measurement of glenoid retroversion and humeral head subluxation. The mean preoperative retroversion was 32°, and the mean subluxation of the humeral head with respect to the scapular axis was 87%. Seventeen patients had a reverse shoulder arthroplasty without bone graft, whereas ten had an associated bone graft to compensate for posterior glenoid erosion. Clinical outcomes were evaluated with the Constant score and shoulder range of motion. RESULTS: The mean duration of follow-up was fifty-four months (range, twenty-four to 139 months). The mean Constant score increased from 31 points preoperatively to 76 points at the time of the latest follow-up (p < 0.0001). Active forward flexion, external rotation, and internal rotation also significantly increased (p < 0.0001). Complications occurred in four patients (15%) and included early loosening of the glenoid component (one patient) and neurologic complications (three patients). No radiolucent lines were observed around the central peg or screws of the glenoid component. Grade-1 or 2 scapular notching was present in ten shoulders (37%). No recurrence of posterior instability was observed. CONCLUSIONS: Reverse shoulder arthroplasty for the treatment of primary glenohumeral osteoarthritis in patients with a biconcave glenoid without rotator cuff insufficiency can result in excellent clinical outcomes. Reverse shoulder arthroplasty is a viable surgical option to solve both the problem of severe static posterior glenohumeral instability and severe glenoid erosion.

MuB is an AAA+ ATPase that forms helical filaments to control target selection for DNA transposition.

MuB is an ATP-dependent nonspecific DNA-binding protein that regulates the activity of the MuA transposase and captures target DNA for transposition. Mechanistic understanding of MuB function has previously been hindered by MuB's poor solubility. Here we combine bioinformatic, mutagenic, biochemical, and electron microscopic analyses to unmask the structure and function of MuB. We demonstrate that MuB is an ATPase associated with diverse cellular activities (AAA+ ATPase) and forms ATP-dependent filaments with or without DNA. We also identify critical residues for MuB's ATPase, DNA binding, protein polymerization, and MuA interaction activities. Using single-particle electron microscopy, we show that MuB assembles into a helical filament, which binds the DNA in the axial channel. The helical parameters of the MuB filament do not match those of the coated DNA. Despite this protein-DNA symmetry mismatch, MuB does not deform the DNA duplex. These findings, together with the influence of MuB filament size on strand-transfer efficiency, lead to a model in which MuB-imposed symmetry transiently deforms the DNA at the boundary of the MuB filament and results in a bent DNA favored by MuA for transposition.

Influence of posterior capsular tightness on throwing shoulder injury.

PURPOSE: The role of posterior capsular tightness in throwing shoulder injury has not yet been clarified. Accordingly, the influence of posterior capsular tightness on the occurrence of throwing shoulder injury was investigated. METHODS: Sixty-one shoulders with throwing injury were retrospectively reviewed, including 50 tight shoulders and 11 non-tight shoulders. Occurrence of long head of biceps (LHB) lesions, superior glenohumeral ligament (SGHL) and middle glenohumeral ligament (MGHL) injuries, type 2 SLAP lesions, and supraspinatus and subscapularis tendon injuries was compared between the tight and non-tight groups. RESULTS: There were LHB lesions in 8 tight shoulders and 6 non-tight shoulders, SGHL injury in 14 and 8 shoulders, and subscapularis tendon injury in 6 and 5 shoulders, respectively, showing significant differences between tight and non-tight shoulders. In contrast, MGHL injury, type 2 SLAP lesions, and supraspinatus tendon injury showed no significant differences. The SLAP lesion was located anteriorly in 6 tight shoulders, posteriorly in 5, and combined in 4 versus 0, 3, and 0 for the non-tight shoulders, respectively, so anterior SLAP lesions only occurred in tight shoulders. Similarly, anterior supraspinatus tendon injuries had a higher incidence in tight shoulders than in non-tight shoulders (19 vs 3). CONCLUSIONS: Rotator interval lesions were frequent in non-tight shoulders, while anterior SLAP lesions and anterior supraspinatus tendon injuries were predominant in tight shoulders. The significance of posterior capsular tightness should be reconsidered. LEVEL OF EVIDENCE: Retrospective, Level IV.

Structural studies of ciliary components.

Cilia are organelles found on most eukaryotic cells, where they serve important functions in motility, sensory reception, and signaling. Recent advances in electron tomography have facilitated a number of ultrastructural studies of ciliary components that have significantly improved our knowledge of cilium architecture. These studies have produced nanometer-resolution structures of axonemal dynein complexes, microtubule doublets and triplets, basal bodies, radial spokes, and nexin complexes. In addition to these electron tomography studies, several recently published crystal structures provide insights into the architecture and mechanism of dynein as well as the centriolar protein SAS-6, important for establishing the 9-fold symmetry of centrioles. Ciliary assembly requires intraflagellar transport (IFT), a process that moves macromolecules between the tip of the cilium and the cell body. IFT relies on a large 20-subunit protein complex that is thought to mediate the contacts between ciliary motor and cargo proteins. Structural investigations of IFT complexes are starting to emerge, including the first three-dimensional models of IFT material in situ, revealing how IFT particles organize into larger train-like arrays, and the high-resolution structure of the IFT25/27 subcomplex. In this review, we cover recent advances in the structural and mechanistic understanding of ciliary components and IFT complexes.

Structural basis for iron piracy by pathogenic Neisseria.

Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small-angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process.