Calculations of binding affinity between C8-substituted GTP analogs and the bacterial cell-division protein FtsZ

The FtsZ protein is a self-polymerizing GTPase that plays a central role in bacterial cell division. Several C8-substituted GTP analogs are known to inhibit the polymerization of FtsZ by competing for the same binding site as its endogenous activating ligand GTP. Free energy calculations of the relative binding affinities to FtsZ for a set of five C8-substituted GTP analogs were performed. The calculated values agree well with the available experimental data, and the main contribution to the free energy differences is determined to be the conformational restriction of the ligands. The dihedral angle distributions around the glycosidic bond of these compounds in water are known to vary considerably depending on the physicochemical properties of the substituent at C8. However, within the FtsZ protein, this substitution has a negligible influence on the dihedral angle distributions, which fall within the narrow range of −140° to −90° for all investigated compounds. The corresponding ensemble average of the coupling constants 3J(C4,H1′) is calculated to be 2.95 ± 0.1 Hz. The contribution of the conformational selection of the GTP analogs upon binding was quantified from the corresponding populations. The obtained restraining free energy values follow the same trend as the relative binding affinities to FtsZ, indicating their dominant contribution

Palliative surgery for advanced tumours of the oral cavity

This journal suppl. contain abstracts of the 3rd IAOO 2011INTRODUCTION: With better education and improved self-awareness, a greater proportion of patients present themselves earlier in the course of disease. However, there remains a group of patients who present with advanced tumour when the role of surgery is not well defined. This study reports our experience with surgery as palliation for advanced tumours in the oral cavity. METHODS: Over the last 2 decades, we have performed palliative surgeries on 34 patients with advanced tumours of the oral cavity. The tumour pathology, mode of resection and reconstruction, symptom palliation and hospital stay were retrieved and data were analyzed retrospectively. RESULTS: Among our patients, 14 (41.2%) had squamous cell carcinoma (SCC) of the tongue, 8 (23.5%) had radiation induced sarcoma, 6 (17.6%) had SCC of the maxillary sinus, 4 (11.8%) had SCC of the inferior alveolus and 2 (5.9%) had SCC of the buccal mucosa. Six patients have systemic metastasis found during pre-operative workup. The major symptoms for palliation included bleeding (n = 14), pain (n = 12), airway obstruction (n = 4), swallowing problem (n = 2) and fungating tumour (n = 2). Majority of the patients (88.2%) required various methods of reconstruction to maximize post-operative functional outcome, among which, the pectoralis major myocutaneous flap was the most popular option. The mean hospital stay was 18.2 days and there was no hospital mortality. Postoperative chemo-irradiation was given in 26 patients. Mean duration of survival was 18.8 months. All patients achieved satisfactory palliation of symptoms, including haemostasis and avoidance of analgesia, tracheostomy and nasogastric feeding tubes. DISCUSSION: In selected patients presenting with advanced stage malignancies of the oral cavity, carefully planned surgical treatment achieves satisfactory palliation of symptoms, thereby improving their quality of life during the subsequent time to come.The 3rd World Congress of the International Academy of Oral Oncology (IAOO 2011), Singapore, 14-17 July 2011. In Oral Oncology, 2011, v. 47 suppl. 1, p. S68, abstract O11

Yucatán carnivorans shed light on the Great American Biotic Interchange

The Great American Biotic Interchange is considered to be a punctuated process, primarily occurring during four major pulses that began approximately 2.5 Ma. Central America and southeastern Mexico have a poor fossil record of this dynamic faunal history due to tropical climates. Exploration of submerged caves in the Yucatán, particularly the natural trap Hoyo Negro, is exposing a rich and remarkably well-preserved late Pleistocene fauna. Radiometric dates on megafauna range from approximately 38 400–12 850 cal BP, and extinct species include the ursid Arctotherium wingei and canid Protocyon troglodytes. Both genera were previously thought to be indigenous to and confined to South America and appear to represent an instance of large placental mammals, descended from North American progenitors, migrating back north across the Panama Isthmus. This discovery expands the distribution of these carnivorans greater than 2000 km outside South America. Their presence along with a diverse sloth assemblage suggests a more complex history of these organisms in Middle America. We suggest that landscape and ecological changes caused by latest Pleistocene glaciation supported an interchange pulse that included A. wingei, P. troglodytes and Homo sapiens