Structure-function analysis of pneumococcal DprA protein reveals that dimerization is crucial for loading RecA recombinase onto DNA during transformation

Transformation promotes genome plasticity in bacteria via RecA-driven homologous recombination. In the Gram-positive human pathogen Streptococcus pneumoniae, the transformasome a multiprotein complex, internalizes, protects, and processes transforming DNA to generate chromosomal recombinants. Double-stranded DNA is internalized as single strands, onto which the transformation-dedicated DNA processing protein A (DprA) ensures the loading of RecA to form presynaptic filaments. We report that the structure of DprA consists of the association of a sterile alpha motif domain and a Rossmann fold and that DprA forms tail-to-tail dimers. The isolation of DprA self-interaction mutants revealed that dimerization is crucial for the formation of nucleocomplexes in vitro and for genetic transformation. Residues important for DprA-RecA interaction also were identified and mutated, establishing this interaction as equally important for transformation. Positioning of key interaction residues on the DprA structure revealed an overlap of DprA-DprA and DprA-RecA interaction surfaces. We propose a model in which RecA interaction promotes rearrangement or disruption of the DprA dimer, enabling the subsequent nucleation of RecA and its polymerization onto ssDNA.     

Malignant Transformation of a Benign Enchondroma of the Hand to Secondary Chondrosarcoma with Isolated Pulmonary Metastasis

Malignant transformation of solitary enchondromas of the hand to secondary chondrosarcomas is extremely rare. We report a case of a recurrent chondromatous tumor of the hand that initially presented with the typical histology of a cellular enchondroma of the small tubular bones but with clinical and radiological signs of malignancy. After development of a single pulmonary metastasis of a chondromyxoid tumor a malignant transformation of the primary enchondroma of the hand must be assumed.     

Outcomes of oral squamous cell carcinoma arising from oral epithelial dysplasia: rationale for monitoring premalignant oral lesions in a multidisciplinary clinic

Surveillance of oral epithelial dysplasia results in a number of newly diagnosed cases of oral squamous cell carcinoma (SCC). The clinical stage of oral SCC at diagnosis influences the magnitude of treatment required and the prognosis. We aimed to document the stage, treatment, and outcome of oral SCC that arose in patients who were being monitored for oral epithelial dysplasia in a dedicated multidisciplinary clinic. Those with histologically diagnosed lesions were enrolled on an ethically approved protocol and molecular biomarker study. Details of clinical and pathological TNM, operation, radiotherapy, recurrence, second primary tumour, and prognosis, were recorded in patients whose lesions underwent malignant transformation. Of the 91 patients reviewed (median follow-up 48 months, IQR 18-96), 23 (25%) had malignant transformation. All were presented to the multidisciplinary team with stage 1 disease (cT1N0M0). Of these, 21 were initially treated by wide local excision, 2 required resection of tumour and reconstruction, and 2 required adjuvant radiotherapy. At follow-up 3 had local recurrence, one had regional recurrence, one had metachronous lung cancer, and 5 had second primary oral SCC. There were further diagnoses of oral dysplasia in 5 during follow-up, and it is estimated that 76% of patients will have one or other event in 5 years. Disease-specific survival was 100% and overall survival was 96% (22/23). Median follow-up after diagnosis of oral SCC was 24 months (IQR 11-58). Specialist monitoring of oral epithelial dysplasia by a multidisciplinary team allows oral SCC to be detected at an early stage, and enables largely curative treatment with simple and usually minor surgical intervention. The high incidence of second primary oral SCC in high-risk patients with oral epithelial dysplasia further supports intensive targeted surveillance in this group.     

Microstructure of veneered zirconia after surface treatments: A TEM study

Objective

Clinical studies reveal that veneer chipping is one major problem associated with zirconia based dental restorations, the underlying mechanisms being still investigated. We semi-quantitatively analyzed the effects of different surface treatments (thermal etching, 35/105 μm sandblasting and coarse bur drilling (150 μm)) on the microstructure of a zirconia veneered dental ceramic.

Methods

The relative monoclinic content on zirconia surfaces was determined using X-ray diffraction (XRD). The microstructure at the zirconia–veneer interface has thereafter been investigated using transmission electron microscopy (TEM). Selected area electron diffraction (SAED) was used to qualitatively assess the depth of the stress-induced phase transformation.

Results

Sandblasting or bur drilling significantly roughened the zirconia surface. A reverse transformation of already transformed monoclinic zirconia grains back into the tetragonal polymorph has been observed after thermal veneering treatment. In TEM, the mechanically treated samples revealed a highly damaged area of 1–3 μm from the interface. The presence of monoclinic phase in veneered zirconia samples has been observed in SAED up to depths of 4 μm (35 μm sandblasted), 11 μm (105 μm sandblasted) and 9 μm (150 μm diamond drilled) below the interface.

Significance

Regardless of the treatment protocol and produced roughness, the veneering ceramic perfectly sealed the zirconia surface. XRD showed an increased amount of monoclinic phase on the surface treated zirconia. However after thermal treatment, the monoclinic phase was re-transformed into the tetragonal polymorph. TEM/SAED analysis has found indication for a greater extend of the monoclinic transformation into the bulk zirconia compared to the treatment related defective zone depth.     

腹腔镜胆囊切除术中合并门静脉海绵样变性的处理体会(附10例报告)

目的:探讨腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)术中合并门静脉海绵样变性(cavernous transfor-mation of the portal vein,CTPV)的处理方法。方法:回顾分析2009年7月至2012年6月为10例胆囊良性疾病合并CTPV患者行LC的临床资料。9例患者于术前经彩色多谱勒超声、CT及DSA检查明确合并CTPV;1例患者术中发生大量出血,中转开腹证实合并CTPV并门静脉右支纵行劈裂损伤。结果:7例患者顺利完成手术,3例中转开腹。手术时间45～130 min,平均(60±15)min;术中出血量5～100 ml,平均(65±25)ml。术后1例发生毛细胆管漏,余者均无胆漏、出血等并发症发生。患者均顺利出院,术后平均住院(3.2±1.0)d。结论:术前明确诊断,术中仔细辨别变性迂曲血管,必要时行预防性缝扎止血,解剖困难时及时中转开腹,为合并门静脉海绵样变性的患者行LC是可行的。     

Clinical outcome of surgically treated low-grade gliomas: A retrospective analysis of a single institute

Objective

Low grade gliomas (LGGs) are slow-growing primary brain tumors with heterogeneous clinical behaviors. The aim of our study is to review the treatment outcome of 63 patients with LGGs focusing on surgical outcome and the current therapeutic strategy.

Methods

We retrospectively enrolled 63 patients surgically treated for LGGs. The gross total resection (GTR) was performed in 35 patients (60.3%), subtotal resection (STR) was performed in 19 patients (31.7%) and partial resection (PR) or biopsy was performed in 9 patients (14.3%). We analyzed their progression-free survival (PFS), overall survival (OS), and malignant transformation with regard to age, gender, Karnofsky performance score (KPS), clinical presentation, tumor location, radiologic pattern, contrast enhancement, extent of removal, pathologic subtype, chemotherapy (CT) and radiotherapy (RT) treatment.

Results

Among all LGGs, the 3-year OS rate was 80% and the 5-year OS was 76%. The 3-year PFS rate was 83.6% and the 5-year PFS was 25%. The non-eloquent area location showed a longer PFS than the eloquent area location (p = 0.05). Oligodendroglial pathology showed a longer PFS compared to oligoastrocytomas and astrocytomas (p = 0.02). Patients older than 60 years had poorer OS than younger patients (p < 0.05). Female gender had a shorter OS than male gender (p < 0.05), and a KPS of 90 or 100 had a longer OS than a KPS of 80 (p < 0.05). Oligodendroglial pathology statistically correlated with a longer OS (p < 0.05).

Conclusion

The findings from our study, which were confirmed by uni- and multivariate analyses, demonstrated that radical tumor resection was associated with better long-term outcomes and tumor progression for patients with LGG.