Design and experimental validation of the oxazole and thiazole derivatives as potential antivirals against of human cytomegalovirus.

QSAR studies of a set of previously synthesized azole derivatives tested against human cytomegalovirus (HCMV) were performed using the OCHEM web platform. The predictive ability of the classification models has a balanced accuracy (BA) of 73-79%. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds with a reasonable accuracy within the applicability domain (BA = 76-83%). The models were applied to screen a virtual chemical library with expected activity of compounds against HCMV. The five most promising new compounds were identified, synthesized and their antiviral activities against HCMV were evaluated in vitro. Two of them showed some activity against the HCMV strain AD169. According to the results of docking analysis, the most promising biotarget associated with HCMV is DNA polymerase. The docking of the most active compounds 1 and 5 in the DNA polymerase active site shows calculated binding energies of -8.6 and -7.8 kcal/mol, respectively. The ligand's complexation was stabilized by the formation of hydrogen bonds and hydrophobic interactions with amino acids Lys60, Leu43, Ile49, Pro77, Asp134, Ile135, Val136, Thr62 and Arg137.

Carrying on the legacy of Lillian Wald. Partnership with the Henry Street Settlement and the Lienhard School of Nursing at Pace University.

The Lienhard School of Nursing (LSN) at Pace University and the Henry Street Settlement (HSS) developed a partnership to bring nursing back to the HSS founded by nursing leader, Lillian Wald. Through this partnership HSS and LSN faculty and students explored how they could accomplish the goal of providing nursing care to a diverse urban population. Struggles to understand the community and the role of nursing in this kind of setting provided students with unique and complex community and leadership experiences. Students learned not only from the nursing care they provided but also from the behaviors of the stakeholders in the partnership. The partnership has provided an ongoing opportunity for continuing the legacy of Lillian Wald.

Evaluation of anti-AIDS drugs in conventional mice implanted with a permeable membrane device containing human T cells infected with HIV.

We now report the confirmation of the work of Hollingshead et al. (1995) on development of a cell based hollow fiber (HF) system for evaluating potential anti-AIDS drugs in vivo using conventional mice rather than SCID mice. CD4 +, CEM-SS cells infected with HIV/1, strain RF, at a multiplicity of infection of 0.1 were placed into HFs. The fibers were implanted into the peritoneal cavity of outbred Swiss mice. Using this model, the antiviral activity of azidothymidine (AZT) at doses of approximately 150, 75 and 37.5 mg/kg/day was evaluated by administering AZT to the mice in drinking water. Upon fiber removal on day 6, AZT treatment was shown to significantly increase CEM cell viability over the untreated, virus control group and significantly reduced the levels of HIV p24 and HIV RT activity.

Infant feeding choice among first-time mothers.

The choice of an infant feeding method is a poorly understood phenomenon. In all societies women are the infant feeders, regardless of the method of infant feeding. How women decide on an infant feeding method is not known; the decision making is complex and frequently unconscious. A qualitative study using the methods of grounded theory was undertaken to understand how women make an infant feeding decision. Eight women were interviewed; 14 themes were identified through the analysis of interview transcripts, field notes, researcher memos, and related literature. The themes were distilled into six conceptual categories which were used as a basis for a model: Conceptualization of the Decision-Making Process in Infant Feeding.

A rational approach in the search for potent inhibitors against HIV proteinase.

Synthetic peptides described as dog renin inhibitors were found to effectively inhibit the aspartyl protease of human immunodeficiency virus (HIV). The selection of oligopeptides for the HIV protease inhibition study was based on 1) the current strategy of inhibiting aspartyl proteases with transition state analogs, and 2) our previous observations regarding optimal structural differentiation at the P2 position among human, dog, and rat renin inhibitors. In an in vitro assay system consisting of recombinant HIV protease and a synthetic decapeptide substrate (at pH 5.5), results show that HIV protease was unaffected by statine-containing analogs carrying histidine at the P2 position whereas analogs containing valine at the same position yielded anti-protease IC50 values ranging from 50 to 500 nM. As anticipated, some analogs were also shown to inhibit processing of recombinant polyprotein substrate by HIV protease in vitro. The anti-viral activity of three inhibitors was studied in HIV-infected CEM and MT-2 cells. Results showed that one compound, Ac-Naphthylalanyl-Pro-Phe-Val-Statine-Leu-Phe-NH2 (antiprotease IC50 value = 0.4 microM), protected the infected cells effectively with IC50 values (0.73 microM for CEM cells and 0.88 microM for MT-2 cells). This antiviral effect is comparable to those obtained with AZT and ddC in parallel studies of MT-2 cells.

Stage-specific cuticular proteins of Ostertagia circumcincta and Ostertagia ostertagi.

In this study we have shown that NHS-biotin and I125-streptavidin can detect cuticular polypeptides of Ostertagia spp. The labelled polypeptide profile of intact nematodes is simple compared to the profile obtained by labelling homogenates. None of the major internal polypeptides are labelled and the subset of proteins labelled in intact nematodes appears to be mainly surface associated. The results presented here demonstrate that NHS-biotin may be used as a reagent for the analysis of surface polypeptides. The surface polypeptide profiles of the five major developmental stages (L1, L2, L3, L4 and adult) of Ostertagia circumcincta show a series of stage-specific molecules with no polypeptides common to all stages, indicating that the cuticle is a dynamic structure which changes throughout the life cycle. Similarily comparison of Ostertagia ostertagi L3 and L4 stage surface profiles showed that each stage is clearly distinct; comparison of these stages between the two species shows an overall similarity.

A comparison of the submergence response of deepwater and non-deepwater rice.

Twelve cultivars of rice (Oryza sativa L.), representing deepwater, short-statured, and semidwarf types, were tested for their response to submergence. The magnitude of the response varied between cultivars; however, all cultivars responded to submergence by rapid growth once internodal elongation had started. Three of these cultivars were tested for elongation capacity at four ages. The deepwater rice was capable of rapid internodal elongation in response to submergence at 4 weeks of age. Growth of the short-statured and semidwarf cultivars was not stimulated by submergence until about 10 weeks of age. In air, the internodes of deepwater rice grew slower than did those of the short-statured and semidwarf cultivars. We also investigated the elongation response of stem sections of all 12 cultivars to an atmosphere containing 3% O(2), 6% CO(2), 91% N(2) (all by volume), and 1 microliter per liter ethylene. We found that the response of each of the non-deepwater cultivars was qualitatively and quantitatively similar to that of the deepwater rice.