Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii

Toxoplasma gondii contains an expanded number of calmodulin (CaM)-like proteins whose functions are poorly understood. Using a combination of CRISPR/Cas9-mediated gene editing and a plant-like auxin-induced degron (AID) system, we examined the roles of three apically localized CaMs. CaM1 and CaM2 were individually dispensable, but loss of both resulted in a synthetic lethal phenotype. CaM3 was refractory to deletion, suggesting it is essential. Consistent with this prediction auxin-induced degradation of CaM3 blocked growth. Phenotypic analysis revealed that all three CaMs contribute to parasite motility, invasion, and egress from host cells, and that they act downstream of microneme and rhoptry secretion. Super-resolution microscopy localized all three CaMs to the conoid where they overlap with myosin H (MyoH), a motor protein that is required for invasion. Biotinylation using BirA fusions with the CaMs labeled a number of apical proteins including MyoH and its light chain MLC7, suggesting they may interact. Consistent with this hypothesis, disruption of MyoH led to degradation of CaM3, or redistribution of CaM1 and CaM2. Collectively, our findings suggest these CaMs may interact with MyoH to control motility and cell invasion

Relationship between period of survival and clinicopathological characteristics in patients with colorectal liver metastasis

AIM: Cancer death in the early period after hepatectomy still occurs in patients with colorectal liver metastasis (CLM). We examined the relationship between clinicopathological parameters and survival periods in 130 CLM patients who underwent hepatectomy. PATIENTS/METHODS: Patients were divided into four groups: Group 1 (5-year survivors without tumor relapse), Group 2 (survivors at 2-5years), Group 3 (cancer death at 2-5years), and Group 4 (cancer death within 2years). RESULTS: A short surgical margin was frequent in Group 4 compared to Group 1 (31 vs. 78%, P<0.05). Primary node-positive status, absence of fibrous pseudo-capsular formation, higher Clinical Risk Score, and tumor recurrence within 12months were frequent in Group 4 (P<0.05). Multivariate analysis revealed a short surgical margin (HR; 3.5) and early tumor relapse (HR; 5.9) as independently significant related parameters (P<0.05). CONCLUSIONS: Sufficient surgical margins and careful follow-up for early tumor relapse may be important for improving postoperative outcomes for CLM patients

Video-assisted thoracoscopic resection for intralobar pulmonary sequestration.

Video-assisted thoracoscopic treatment of intralobar pulmonary sequestration in an obese (120 kg, body mass index 42) young man is described. Two aberrant arteries originating from the descending thoracic aorta were transected with a vascular stapler, and a left lower lobectomy was successfully performed thoracoscopically. Three-dimensional chest computed tomography was used to identify the aberrant vessels. Video-assisted thoracoscopic lobectomy is useful and minimally invasive for treating pulmonary sequestration, especially in obese patients.The original publication is available at www.springerlink.co

Anterior chest wall reconstruction with titanium plate sandwiched between two polypropylene sheets

Extensive sternal resection carries the risk of difficult reconstruction and surgical complications. A 79-year-old woman underwent sternal resection and reconstruction for sternal chondrosarcoma. However, 18 months after the first operation, she developed six metastatic tumors on the anterior chest wall. She underwent subtotal sternectomy and rib resection, leaving a defect measuring 17 × 14 cm. Reconstruction of the anterior chest wall using a titanium plate sandwiched between two polypropylene mesh sheets is described. This method is potentially applicable to extensive anterior chest resection, and its advantages compared with conventional prostheses are rigidity, flexibility, and usability

The IASLC/ITMIG thymic epithelial tumors staging project: Proposals for the T component for the forthcoming (8th) edition of the TNM classification of malignant tumors

Despite longstanding recognition of thymic epithelial neoplasms, there is no official American Joint Committee on Cancer/ Union for International Cancer Control stage classification. This article summarizes proposals for classification of the T component of stage classification for use in the 8th edition of the tumor, node, metastasis classification for malignant tumors. This represents the output of the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group Staging and Prognostics Factor Committee, which assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. The committee proposes division of the T component into four categories, representing levels of invasion. T1 includes tumors localized to the thymus and anterior mediastinal fat, regardless of capsular invasion, up to and including infiltration through the mediastinal pleura. Invasion of the pericardium is designated as T2. T3 includes tumors with direct involvement of a group of mediastinal structures either singly or in combination: lung, brachiocephalic vein, superior vena cava, chest wall, and phrenic nerve. Invasion of more central structures constitutes T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium, trachea, and esophagus. Size did not emerge as a useful descriptor for stage classification. This classification of T categories, combined with a classification of N and M categories, provides a basis for a robust tumor, node, metastasis classification system for the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control stage classification

Development of the rhopalial nervous system in Aurelia sp.1 (Cnidaria, Scyphozoa)

We examined the development of the nervous system in the rhopalium, a medusa-specific sensory structure, in Aurelia sp.1 (Cnidaria, Scyphozoa) using confocal microscopy. The rhopalial nervous system appears primarily ectodermal and contains neurons immunoreactive to antibodies against tyrosinated tubulin, taurine, GLWamide, and FMRFamide. The rhopalial nervous system develops in an ordered manner: the presumptive gravity-sensing organ, consisting of the lithocyst and the touch plate, differentiates first; the “marginal center,” which controls swimming activity, second; and finally, the ocelli, the presumptive photoreceptors. At least seven bilaterally arranged neuronal clusters consisting of sensory and ganglion cells and their neuronal processes became evident in the rhopalium during metamorphosis to the medusa stage. Our analysis provides an anatomical framework for future gene expression and experimental studies of development and functions of scyphozoan rhopalia