Septin-associated protein kinase Gin4 affects localization and phosphorylation of Chs4, the regulatory subunit of the Baker's yeast chitin synthase III complex.

Chitin is mainly formed by the chitin synthase III complex (CSIII) in yeast cells. This complex is considered to be composed of the catalytic subunit Chs3 and the regulatory subunit Chs4, both of which are phosphoproteins and transported to the plasma membrane by different trafficking routes. During cytokinesis, Chs3 associates with Chs4 and other proteins at the septin ring, which results in an active CSIII complex. In this study, we focused on the role of Chs4 as a regulatory subunit of the CSIII complex. We analyzed the dynamic localization and interaction of Chs3 and Chs4 during cell division, and found that both proteins transiently co-localize and physically interact only during bud formation and later in a period during septum formation and cytokinesis. To identify unknown binding partners of Chs4, we conducted different screening approaches, which yielded several novel candidates of Chs4-binding proteins including the septin-associated kinase Gin4. Our further studies confirmed this interaction and provided first evidence that Chs4 phosphorylation is partially dependent on Gin4, which is required for proper localization of Chs4 at the bud neck.

The tetraspanin TSP3 of Neurospora crassa is a vacuolar membrane protein and shares characteristics with IDI proteins.

The fungal vacuole is an organelle, which adopts pleiotropic morphologies and functions. In aging and starving hyphae it is the compartment of degradation and recycling of cellular constituents. Here we identified TSP3, one of three tetraspanins present in the filamentous ascomycete fungus Neurospora crassa, as a vacuolar membrane protein. The protein is detected only in aging and starving cultures and under other conditions, which induce autophagy, such as vegetative incompatibility or the presence of the macrolide antibiotic rapamycin. Mutant analysis revealed that TSP3 is dispensable for growth and development of the fungus under laboratory conditions. Together these findings indicate that tsp3 shares characteristics with idi (induced during incompatibility) genes and might promote vacuolar functions related to autophagy.

Two case reports of synchronous unilateral pleomorphic adenoma and cystadenolymphoma of the parotid gland with literature review.

Background: Synchronous unilateral tumors in the parotid glands account for less than 5-10% of all salivary gland neoplasms. Mostly these are cystadenolymphomas, but tumors of different histological types can be found as well. In these cases it is often pleomorphic adenoma in combination with cystadenolymphoma. Ultrasound is the first choice imaging modality. Case report: We present two patients with two simultaneous tumors in a unilateral parotid gland. In each case, B-mode ultrasound showed two hypoechoic masses, one of which was predominantly cystic. The subsequent use of Virtual Touch Imaging Quantification (VTIQ) showed tumors of elastic tissue. After a parotidectomy, both cases were diagnosed with pleomorphic adenoma combined with cystadenolymphoma. Conclusion: The combination of B-mode ultrasound and VTIQ is an important diagnostic modality and may improve diagnostic accuracy to differentiate between benign and malignant lesions. Every clinician should be aware of the co-existence of different histological types of tumors in unilateral salivary glands.Background: Synchronous unilateral tumors in the parotid glands account for less than 5­10% of all salivary gland neoplasms. Mostly these are cystadenolymphomas, but tumors of different histological types can be found as well. In these cases it is often pleomorphic adenoma in combination with cystadenolymphoma. Ultrasound is the first choice imaging modality. Case report: We present two patients with two simultaneous tumors in a unilateral parotid gland. In each case, B-mode ultrasound showed two hypoechoic masses, one of which was predominantly cystic. The subsequent use of Virtual Touch Imaging Quantification (VTIQ) showed tumors of elastic tissue. After a parotidectomy, both cases were diagnosed with pleomorphic adenoma combined with cystadenolymphoma. Conclusion: The combination of B-mode ultrasound and VTIQ is an important diagnostic modality and may improve diagnostic accuracy to differentiate between benign and malignant lesions. Every clinician should be aware of the co-existence of different histological types of tumors in unilateral salivary glands.

Expression and clinical significance of MAGE and NY-ESO-1 cancer-testis antigens in adenoid cystic carcinoma of the head and neck.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the head and neck is a rare but highly malignant tumor. Cancer-testis antigens (CTAs) represent an immunogenic family of cancer-specific proteins and thus represent an attractive target for immunotherapy. METHODS: Eighty-four cases of ACC were identified, the CTAs pan-Melanoma antigen (pan-MAGE; M3H67) and New York esophageal squamous cell carcinoma (NY-ESO-1; E978) were detected immunohistochemically (IHC) and correlated with clinical data. RESULTS: Expression of NY-ESO-1 was found in 48 of 84 patients (57.1%) and of pan-MAGE in 28 of 84 patients (31.2%). Median overall survival (OS) in NY-ESO-1 positive versus negative patients was 130.8 and 282.0 months (p = .223), respectively. OS in pan-MAGE positive versus negative patients was 105.3 and 190.5 months, respectively (p = .096). Patients expressing both NY-ESO-1 and pan-MAGE simultaneously had significantly reduced OS with a median of 90.5 months compared with 282.0 months in negative patients (p = .047). CONCLUSION: A significant fraction of patients with ACC show expression of the CTAs NY-ESO-1 and/or pan-MAGE with promising immunotherapeutic implications. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1008-1016, 2016.

Dual melanocortin-4 receptor and GLP-1 receptor agonism amplifies metabolic benefits in diet-induced obese mice.

We assessed the efficacy of simultaneous agonism at the glucagon-like peptide-1 receptor (GLP-1R) and the melanocortin-4 receptor (MC4R) for the treatment of obesity and diabetes in rodents. Diet-induced obese (DIO) mice were chronically treated with either the long-acting GLP-1R agonist liraglutide, the MC4R agonist RM-493 or a combination of RM-493 and liraglutide. Co-treatment of DIO mice with RM-493 and liraglutide improves body weight loss and enhances glycemic control and cholesterol metabolism beyond what can be achieved with either mono-therapy. The superior metabolic efficacy of this combination therapy is attributed to the anorectic and glycemic actions of both drugs, along with the ability of RM-493 to increase energy expenditure. Interestingly, compared to mice treated with liraglutide alone, hypothalamic Glp-1r expression was higher in mice treated with the combination therapy after both acute and chronic treatment. Further, RM-493 enhanced hypothalamic Mc4r expression. Hence, co-dosing with MC4R and GLP-1R agonists increases expression of each receptor, indicative of minimized receptor desensitization. Together, these findings suggest potential opportunities for employing combination treatments that comprise parallel MC4R and GLP-1R agonism for the treatment of obesity and diabetes.