Papillomaviruses and potential copathogens

An in vitro multistage genital epithelial cell model for cervical cancer that parallels the in vivo neoplastic process has been developed using recombinant human papillomavirus (HPV) DNA and genital cells. HPV-16-immortalized genital cells are responsive to the genotoxic action of known chemical carcinogens (polycyclic hydrocarbons, alkylating agents or cigarette smoke condensate), but are not converted to malignancy. Ras oncogene and human herpes virus-2 did convert HPV immortalized cells to malignancy, whereas human herpes virus-6 infection only increased HPV expression. Human immunodeficiency virus did not infect genital cells.     

Landscape and the cultural politics of China’s anticipatory urbanism

China has seen a proliferation of monumental urban projects in recent years extending to lower tier cities. This paper examines the production of new urban landscapes in the Kangbashi New District of Ordos Municipality to assess the political economy and cultural logics of China’s current-day city-making programmes. The concept of ‘anticipatory urbanism’ is developed to interpret how monumentality in the built environment is aimed at foretelling new developmental futures promising to deliver power to the local state and prosperity to residents. The analysis assesses public responses to landscape transformations and discusses how speculation in the production of new city spaces generates conflict and crisis for the local state. Anticipatory urbanism is found to feed off government ambition and undermines sustainable urban growth.     

Visualization of cytoskeletal elements by the atomic force microscope

We describe a novel application of atomic force microscopy (AFM) to directly visualize cytoskeletal fibers in human foreskin epithelial cells. The nonionic detergent Triton X-100 in a low concentration was used to remove the membrane, soluble proteins, and organelles from the cell. The remaining cytoskeleton can then be directly visualized in either liquid or air-dried ambient conditions. These two types of scanning provide complimentary information. Scanning in liquid visualizes the surface filaments of the cytoskeleton, whereas scanning in air shows both the surface filaments and the total "volume" of the cytoskeletal fibers. The smallest fibers observed were ca. 50 nm in diameter. The lateral resolution of this technique was ca.20 nm, which can be increased to a single nanometer level by choosing sharper AFM tips. Because the AFM is a true 3D technique, we are able to quantify the observed cytoskeleton by its density and volume. The types of fibers can be identified by their size, similar to electron microscopy.     

Sensitive absorption spectroscopy by use of an asymmetric multiple-quantum-well diode laser in an external cavity

We have developed a broadly tunable diode laser system by employing custom-designed asymmetric multiple-quantum-well (AMQW) InGaAsP lasers in an external cavity configuration. Feedback is provided by a diffractive optical element with high coupling efficiency and wavelength selectivity, allowing for single-mode tuning of the output wavelength by varying the external cavity length. This tunable laser system was used experimentally to perform absorption spectroscopy on weak CO(2) lines over a broad wavelength region in the near infrared. An experimental tuning range of 80 nm has been observed for a laser cavity length of 600 mum, which is double the tuning range found with conventional, uncoated quantum-well lasers. We achieved a detection sensitivity of 5 x 10(-6) at 95% confidence over the wavelength range of 1.54-1.62 mum by employing a second-harmonic detection technique. The theoretical predictions of a broad gain profile from an ambipolar rate equation model are found to correspond to the experimentally observed increased tunability of the uncoated AMQW lasers.     

Comparative pharmacokinetics and glucodynamics of two human insulin mixtures. 70/30 and 50/50 insulin mixtures

OBJECTIVE: To compare and contrast the pharmacokinetics and glucodynamics of two insulin mixtures, one of 50% NPH human insulin and 50% Regular human insulin (50/50) and one of 70% NPH human insulin and 30% Regular human insulin (70/30), in healthy male volunteers after subcutaneous administrations of 0.3 U/kg. RESEARCH DESIGN AND METHODS: We administered single doses of 50/50 and 70/30 insulins to 18 volunteers in a randomized crossover fashion. All subjects received 0.3 U/kg of each mixture separated by at least 7 days. Each dose was given after an overnight fast and during a glucose clamp to maintain a euglycemic state. We measured serum insulin and C-peptide concentrations through frequent blood sampling after each treatment. Pharmacokinetic measurements were calculated from insulin data corrected for C-peptide, including maximum insulin concentration (Cmax), time to maximum insulin concentration (tmax), terminal rate constant (beta), area under the curve from 0 to infinity (AUCinfinity0), and mean residence time (MRT). Pharmacodynamic measurements were summarized from C-peptide concentrations (minimum C-peptide concentration [Cmin], time to minimum C-peptide concentration [tmin], area between the C-peptide baseline and the C-peptide suppression curve [AOCc], absolute maximal difference from baseline [Sdiff] and glucose clamp measurements. The glucose clamp measurements included maximum infusion rates (Rmax) and time to Rmax (TRmax) from glucose infusion rate (GIR) documentation, as well as cumulative glucose infused during the first 4 h ((0)4Gtot) and total glucose infused (Gtot) during the study. RESULTS: For the pharmacokinetic assessment, statistically greater values of insulin Cmax and beta were found for the 50/50 mixture, whereas the 70/30 mixture had a greater MRT. Statistical differences were also detected in glucodynamics, with greater values of Rmax and (0)4Gtot found with the 50/50 mixture. Notably, differences were not detected for insulin AUCinfinity0 and Gtot values. CONCLUSIONS: Higher insulin concentrations and a greater initial response were present with the 50/50 mixture, but the two mixtures had equivalent bioavailability and cumulative effects. These results support use of the 50/50 mixture in situations where greater initial glucose control is required.     

Mutations at nonliganding residues Tyr-85 and Glu-83 in the N-lobe of human serum transferrin. Functional second shell effects

The x-ray crystal structure of the N-lobe of human serum transferrin has shown that there is a hydrogen bond network, the so-called "second shell," around the transferrin iron binding site. Tyrosine at position 85 and glutamic acid at position 83 are two nonliganding residues in this network in the human serum transferrin N-lobe (hTF/2N). Mutation of each of these two amino acids has a profound effect on the metal binding properties of hTF/2N. When Tyr-85 is mutated to phenylalanine, iron release from the resulting mutant Y85F is much more facile than from the parent protein. Elimination of the hydrogen bond between Tyr-85 and Lys-296 appears to interfere with the "di-lysine (Lys-206-Lys-296) trigger," which affects the iron binding stability of the protein. Surprisingly, mutation of Glu-83 to alanine leads to the absence of one of the normal iron binding ligands; introduction of a monovalent anion is able to restore the normal first coordination sphere. The missing ligand appears to be His-249, as revealed by comparison of the metal binding behaviors of mutants H249Q and E83A and structural analysis. Glu-83 has a strong H bond linkage with His-249 in apo-hTF/2N, which helps to hold the His-249 in the proper position for iron binding. Disabling Glu-83 by mutation to an alanine seriously disturbs the H bond network, allowing His-249 to move away. A monovalent anion can help reestablish the normal network by providing a negative charge near the position of Glu-83 to reach charge balance, so that ligand His-249 is available again for iron binding.     

Two high-resolution crystal structures of the recombinant N-lobe of human transferrin reveal a structural change implicated in iron release

The N-lobe of human serum transferrin (hTF/2N) has been expressed in baby hamster kidney cells and crystallized in both orthorhombic (P212121) and tetragonal (P41212) space groups. Both crystal forms diffract to high resolution (1.6 and 1.8 A, respectively) and have been solved by molecular replacement. Subsequent refinement resulted in final models for the structure of hTF/2N that had crystallographic R-factors of 18.1 and 19.7% for the two crystal forms, respectively; these models represent the highest-resolution transferrin structures determined to date. The hTF/2N polypeptide has a folding pattern similar to those of other transferrins, including the presence of a deep cleft that contains the metal-binding site. In contrast to other transferrins, both crystal forms of hTF/2N display disorder at the iron-binding site; model building suggests that this disorder consists of alternative conformations of the synergistically bound carbonate anion, the side chain for Arg-124, and several solvent molecules. Subsequent refinement revealed that conformation A has an occupancy of 0.63-0. 65 and corresponds to the structure of the iron-binding site found in other transferrins. The alternative conformation B has an occupancy of 0.35-0.37; in this structure, the carbonate has rotated 30 degrees relative to the iron and the side chain for Arg-124 has moved to accommodate the new carbonate position. Several water molecules appear to stabilize the carbonate anion in the two conformations. These structures are consistent with the protonation of the carbonate and resulting partial removal of the anion from the metal; these events would occur prior to cleft opening and metal release.     

We Said, She Said: A Response to Loftus (2003).

Responds to the comments by E. F. Loftus (see record 2003-07215-003) on the target articles by A. D. Yarmey (see record 2003-07215-001) and S. Porter et al (see record 2003-07215-002) which both examined the influence of memory (false memory and repressed memory) on adjudication. In Loftus' commentary on the Porter et al article, Loftus agreed with many of their conclusions concerning allegations in "he said, she said" legal cases. However, Loftus focused some criticism on their coverage of recovered memory evidence. It appears that the main difference in their perspectives was not related to the science of memory but rather was one of scientific education versus advocacy in the legal system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)