The genetic code-function and evolution

The genetic code is reviewed from the standpoints of its function and evolution. The code has probably always consisted of 64 units (codons), each containing three bases. Each codon pairs with a three-base anticodon that is part of an adaptor molecule. The adaptors are transfer RNA molecules that are each joined to a specific amino acid. Many departures from the universal code have recently been discovered. These are discussed.     

A new,flexible and widely applicable software package for the simulation of one-dimensional moisture flow: SoWaM

Most one-dimensional soil moisture flow simulation models have restricted applicability due to (amongst other things): i) insufficient user flexibility; ii) a lack of user friendliness; iii) dependency on scale, temporal and/or spatial, and iv) fixed boundary conditions. Therefore, we developed a simple and highly flexible software package to simulate, visualize and analyze 1-D moisture flow in soils: SoWaM (Soil Water Model). The package has a modular setup and consists of a range of tools to visualize, analyze and compare input data and results. Soil hydraulic properties for each specified soil layer can be defined by either Van Genuchten parameters or cubical splines. Since the model does not impose limits on element size or time interval, it is possible to perform simulations in very high detail, both spatially and temporally. Furthermore, four different criteria for irrigation scheduling have been implemented. The SoWaM package provides an accurate, simple and highly flexible tool to simulate soil moisture flow and to evaluate the effects of various factors on soil water movement, such as timing and amount of irrigation, soil hydraulic properties and soil layering. Results of a case study are presented to illustrate model performance.     

Parallel Flow Asymmetries in Heat Exchangers

The effect of flow asymmetry was observed experimentally in vertical parallel channels of a continuous direct ohmic heater. While downward-oriented flow is evenly distributed at isothermal conditions, the flow rate in parallel channels differs in the case of heating due to buoyancy effects. Three different configurations of parallel flow (with and without internal heating in channels) are analyzed, giving critical values of Gr/Re or Ri = Gr/Re² and ensuring stable and even distribution of flow into parallel channels of vertically oriented heat exchangers or heaters. Experimental verification was based upon flow visualization (injection of a colored tracer and monitoring the tracer by a camera), measurement of temperature profiles, and stimulus response experiments using KCl as a tracer for conductivity methods (2 Pt conductivity probes) and Tc99 as a radioisotope tracer (collimated scintillation detectors).     

The membrane protein alkaline phosphatase is delivered to the vacuole by a route that is distinct from the VPS-dependent pathway

Membrane trafficking intermediates involved in the transport of proteins between the TGN and the lysosome-like vacuole in the yeast Saccharomyces cerevisiae can be accumulated in various vps mutants. Loss of function of Vps45p, an Sec1p-like protein required for the fusion of Golgi-derived transport vesicles with the prevacuolar/endosomal compartment (PVC), results in an accumulation of post-Golgi transport vesicles. Similarly, loss of VPS27 function results in an accumulation of the PVC since this gene is required for traffic out of this compartment. The vacuolar ATPase subunit Vph1p transits to the vacuole in the Golgi-derived transport vesicles, as defined by mutations in VPS45, and through the PVC, as defined by mutations in VPS27. In this study we demonstrate that, whereas VPS45 and VPS27 are required for the vacuolar delivery of several membrane proteins, the vacuolar membrane protein alkaline phosphatase (ALP) reaches its final destination without the function of these two genes. Using a series of ALP derivatives, we find that the information to specify the entry of ALP into this alternative pathway to the vacuole is contained within its cytosolic tail, in the 13 residues adjacent to the transmembrane domain, and loss of this sorting determinant results in a protein that follows the VPS-dependent pathway to the vacuole. Using a combination of immunofluorescence localization and pulse/chase immunoprecipitation analysis, we demonstrate that, in addition to ALP, the vacuolar syntaxin Vam3p also follows this VPS45/27-independent pathway to the vacuole. In addition, the function of Vam3p is required for membrane traffic along the VPS-independent pathway.     

A molecular mechanism for electrical tuning of cochlear hair cells

Cochlear frequency selectivity in lower vertebrates arises in part from electrical tuning intrinsic to the sensory hair cells. The resonant frequency is determined largely by the gating kinetics of calcium-activated potassium (BK) channels encoded by the slo gene. Alternative splicing of slo from chick cochlea generated kinetically distinct BK channels. Combination with accessory beta subunits slowed the gating kinetics of alpha splice variants but preserved relative differences between them. In situ hybridization showed that the beta subunit is preferentially expressed by low-frequency (apical) hair cells in the avian cochlea. Interaction of beta with alpha splice variants could provide the kinetic range needed for electrical tuning of cochlear hair cells.     

Incremental value of rubidium-82 positron emission tomography for prognostic assessment of known or suspected coronary artery disease

Myocardial perfusion imaging using positron emission tomography (PET) may be more accurate for the diagnosis of coronary artery disease (CAD) than conventional imaging. The purpose of this study was to evaluate the prognostic implications of perfusion abnormalities in 685 patients (age 62 +/- 11 years, 199 women) studied by PET, and to assess the incremental value of these data in relation to prognostic implications of clinical and angiographic findings. Rubidium (Rb)-82 PET was performed before and after dipyridamole stress. Transient defects were detected in 227 patients (33%), and were moderate or greater in severity (> 15% of the left ventricle) in 84 (12%). Resting defects were present in 435 (64%) and were moderate or greater in severity in 216 (32%). The total extent of abnormally perfused myocardium was small (< 15% of the left ventricle) in 198 (29%), moderate in 216 (32%), and extensive in 105 (15%). Clinic review or standardized phone interview in 657 patients (96%) identified 151 cardiac events, including 81 cardiac deaths, 16 patients with myocardial infarction, 7 with unstable angina, and 47 with late revascularization (> 3 months after PET). Normal scans had a 90% event-free survival, compared with 87% in patients with small, 75% with moderate, and 76% with extensive defects (log rank chi-square 30, p <0.0001). Functional class, extent of CAD, and the presence and extent of perfusion defects (both at rest and during stress) were independent predictors of cardiac death and total cardiac events. In sequential Cox proportional-hazards models, the results of PET were incremental to those of clinical and angiographic evaluation. Thus, the presence and extent of damaged and jeopardized myocardium are independent and incremental predictors of outcome in patients undergoing Rb-82 PET.     

Vasoactive intestinal peptide stimulation of human trabecular meshwork cell growth

PURPOSE: To demonstrate that vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide, is a growth factor of human trabecular meshwork (TM) cells in culture and in a corneoscleral explant organ culture treated with laser trabeculoplasty (LTP). METHODS: Proliferating human TM cells in cell cultures were incubated with VIP for 20 hours, followed by total cell number determination, using a Coulter counter. The percentage of proliferating TM cells was assessed, using an antibody against the proliferating cell nuclear antigen (PCNA). To test the growth effect of VIP on TM cells in situ, corneoscleral explants in organ cultures were first treated with argon LTP to initiate TM-cell proliferation and then were exposed to VIP for 48 hours. The mitotic TM cells were demonstrated immunocytochemically, using anti-PCNA in paraffin sections of the explants; and the total number of TM cells was determined after paraffin sections were counterstained by hematoxylin. RESULTS: Vasoactive intestinal peptide dose-dependently stimulated the proliferation of TM cells in cell culture. Treatment with 5 x 10(-10) M VIP resulted in a maximal increase of 40% in cell number. The effect of VIP was blocked by a VIP antagonist. The number of PCNA-stained TM cells and the total cell number in the TM in LTP-treated corneoscleral explants were increased by VIP. CONCLUSIONS: Exogenously applied VIP stimulated the proliferation of human TM cells in subconfluent cultures and in LTP-treated corneoscleral explants. In that LTP has been shown to increase the number of TM cells in situ, the growth stimulatory effect of VIP may help enhance this therapy.     

Successful cytologic diagnosis of cholangiocarcinoma from within a recently placed biliary Wallstent

A six year old boy with an epicardial pacing lead since infancy presented with thoracic pain triggered by movement. The pain was thought to be musculoskeletal, but two weeks later he collapsed and died in ventricular fibrillation. Necropsy showed strangulation of the ventricular apex by the epicardial lead.