Cyclobutane derivatives as potent NK1 selective antagonists

A series of novel cyclobutane derivatives as potent and selective NK1 receptor antagonists is described. Several compounds in this series exhibited high in vitro binding affinity (Ki 相似文献   

Protein evolution of ANTP and PRD homeobox genes

Background  

Although homeobox genes have been the subject of many studies, little is known about the main amino acid changes that occurred early in the evolution of genes belonging to different classes.     

The cystic fibrosis transmembrane conductance regulator gene and ion channel function in patients with idiopathic pancreatitis

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are associated with cystic fibrosis (CF)-related monosymptomatic conditions, including idiopathic pancreatitis. We evaluated prospectively enrolled patients who had idiopathic recurrent acute pancreatitis or idiopathic chronic pancreatitis, healthy controls, CF heterozygotes, and CF patients (pancreatic insufficient or sufficient) for evidence of CFTR gene mutations and abnormalities of ion transport by sweat chloride and nasal potential difference testing. DNA samples from anonymous blood donors were controls for genotyping. At least one CFTR mutation or variant was carried in 18 of 40 patients (45%) with idiopathic chronic pancreatitis and in 6 of 16 patients (38%) with idiopathic recurrent acute pancreatitis but in only 11 of the 50 controls (22%, P=0.005). Most identified mutations were rare and would not be identified in routine genetic screening. CFTR mutations were identified on both alleles in six patient (11%). Ion transport measurements in patients with pancreatitis showed a wide range of results, from the values in patients with classically diagnosed CF to those in the obligate heterozygotes and healthy controls. In general, ion channel measurements correlated with the number and severity of CFTR mutations. Twelve of 56 patients with pancreatitis (21%) fulfilled current clinical criteria for the diagnosis of CF, but CFTR genotyping alone confirmed the diagnosis in only two of these patients. We concluded that extensive genotyping and ion channel testing are useful to confirm or exclude the diagnosis of CF in the majority of patients with idiopathic pancreatitis.     

Induction of apoptosis by penta-acetyl geniposide in rat C6 glioma cells

Penta-acetyl geniposide, (Ac)(5)-GP, was produced by acetylation of a glycoside, isolated from an extract of Gardenia fructus. Previously, we have reported that C6 glioma cells could be inhibited in culturing as well as in bearing rats by treating with (Ac)(5)-GP. In this study, the effect and action of (Ac)(5)-GP on inducing cell death was examined in rat C6 glioma cells. Treatment of C6 glioma cells with (Ac)(5)-GP caused cell death, chromatin condensation, and internucleosomal DNA ladder. Also, cell cycle arrest at G(0)/G(1) phase revealed that (Ac)(5)-GP-induced cell death appears to be mediated by apoptosis. In addition, the results also showed that p53 and c-Myc increased due to treatment of (Ac)(5)-GP in a dose-response and time-dependent manner. Concomitant with the expression of p53 and c-Myc, decreased level of Bcl-2 and increased level of Bax protein were observed. These results suggest that cell death caused by (Ac)(5)-GP through apoptosis and cell cycle arrest at G(0)/G(1) may be associated with the induction of p53, c-Myc and may be mediated with apoptosis-related Bcl-2 family proteins.     

Comparison of protein solution structures refined by molecular dynamics simulation in vacuum,with a generalized Born model,and with explicit water

The inclusion of explicit solvent water in molecular dynamics refinement of NMR structures ought to provide the most physically meaningful accounting for the effects of solvent on structure, but is computationally expensive. In order to evaluate the validity of commonly used vacuum refinements and of recently developed continuum solvent model methods, we have used three different methods to refine a set of NMR solution structures of a medium sized protein, Escherichia coliglutaredoxin 2, from starting structures calculated using the program DYANA. The three different refinement protocols used molecular dynamics simulated annealing with the program AMBER in vacuum (VAC), including a generalized Born (GB) solvent model, and a full calculation including explicit solvent water (WAT). The structures obtained using the three methods of refinements were very similar, a reflection of their generally well-determined nature. However, the structures refined with the generalized Born model were more similar to those from explicit water refinement than those refined in vacuum. Significant improvement was seen in the percentage of backbone dihedral angles in the most favored regions of , space and in hydrogen bond pattern for structures refined with the GB and WAT models, compared with the structures refined in vacuum. The explicit water calculation took an average of 200 h of CPU time per structure on an SGI cluster, compared to 15–90 h for the GB calculation (depending on the parameters used) and 2 h for the vacuum calculation. The generalized Born solvent model proved to be an excellent compromise between the vacuum and explicit water refinements, giving results comparable to those of the explicit water calculation. Some improvement for and angle distribution and hydrogen bond pattern can also be achieved by energy minimizing the vacuum structures with the GB model, which takes a much shorter time than MD simulations with the GB model.     

Cognitive status and behavioral problems in older hospitalized patients

OBJECTIVES: (a) To determine the quantity and quality of behavioral problems in older hospitalized patients on acute care units; (b) to determine the burden of these behaviors on staff; and (c) to identify predictors of behavioral problems. METHODS: Upon admission, patients performed the Mini-Mental State Exam (MMSE), the Geriatric Depression Scale (GDS), and information was obtained on age, ethnicity, level of education, living arrangement, and psychiatric history. Two days post-admission, a clinical staff member caring for each patient, performed the Neuropsychiatric Inventory-Questionnaire (NPI-Q) to assess patients' behavioral problems and staff distress. PARTICIPANTS AND SETTING : Forty-two patients, over 60 years of age, admitted to medical and surgical units of the Veterans Affairs Hospitals in Palo Alto and San Francisco, participated. RESULTS: Twenty-three of 42 (55%) patients exhibited behavioral problems. Anxiety, depression, irritability, and agitation/aggression were the most frequently observed behaviors. The severity of the behavioral problems was significantly correlated with staff distress. Lower performance on the MMSE at admission was significantly associated with higher NPI-Q ratings. Specifically, of those cases with scores less than or equal to 27 on the MMSE, 66% had behavioral problems during hospitalization, compared to only 31% of those with scores greater than 27. CONCLUSION: Behavioral problems in older hospitalized patients appear to occur frequently, are a significant source of distress to staff, and can result in the need for psychiatric consultation. Assessment of the mental status of older adults at admission to hospital may be valuable in identifying individuals at increased risk for behavioral problems during hospitalization.     

Reflections on the genus Vanakripa, and a description of V. ellipsoidea sp. nov

The genus Vanakripa (hyphomycetes) is reviewed based on the examination of type specimens, and V. ellipsoidea sp. nov. is described on submerged wood from Hong Kong. Vanakripa is characterized by punctiform sporodochial colonies, micronematous conidiogenous cells and pigmented conidia with vermiform separating cells. Vanakripa is compared with similar genera, and a synopsis of its morphological characters is provided.     

Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence

Background  

Previous studies have suggested that recent segmental duplications, which are often involved in chromosome rearrangements underlying genomic disease, account for some 5% of the human genome. We have developed rapid computational heuristics based on BLAST analysis to detect segmental duplications, as well as regions containing potential sequence misassignments in the human genome assemblies.