Amylose conformational transitions in binary DMSO/water mixtures

The effects on amylose conformation of percentage water in dimethyl sulfoxide (DMSO)/water mixtures were measured by following changes in specific optical rotation, limiting viscosity number, and ¹³C-NMR chemical shifts. The temperature dependence of specific optical rotation showed differences in amylose conformation at four chosen ratios of dimethyl sulfoxide/water. An amylose conformational change was also deduced from ¹³C-NMR chemical shift data. Changes in limiting viscosity of amylose in different proportions of DMSO/water, and the effect of tetramethylurea on the specific rotation of amylose, indicate that intramolecular hydrogen bonding decreases with increased water content. 66.6% DMSO appears to be a crossover concentration, below which the helical conformation is progressively lost as water is added. When water content is over 60%, transition to a conformation which allows iodine complexation to take place is complete. A transition of amylose conformation from helix to loose helix to random coil with increasing water content was deduced from the experimental results.     

The Effect of the G 1 - S transition Checkpoint on an Age Structured Cell Cycle Model

Knowledge of how a population of cancerous cells progress through the cell cycle is vital if the population is to be treated effectively, as treatment outcome is dependent on the phase distributions of the population. Estimates on the phase distribution may be obtained experimentally however the errors present in these estimates may effect treatment efficacy and planning. If mathematical models are to be used to make accurate, quantitative predictions concerning treatments, whose efficacy is phase dependent, knowledge of the phase distribution is crucial. In this paper it is shown that two different transition rates at the - checkpoint provide a good fit to a growth curve obtained experimentally. However, the different transition functions predict a different phase distribution for the population, but both lying within the bounds of experimental error. Since treatment outcome is effected by the phase distribution of the population this difference may be critical in treatment planning. Using an age-structured population balance approach the cell cycle is modelled with particular emphasis on the - checkpoint. By considering the probability of cells transitioning at the - checkpoint, different transition functions are obtained. A suitable finite difference scheme for the numerical simulation of the model is derived and shown to be stable. The model is then fitted using the different probability transition functions to experimental data and the effects of the different probability transition functions on the model''s results are discussed.     

Nearest-neighbor thermodynamics of deoxyinosine pairs in DNA duplexes

Nearest-neighbor thermodynamic parameters of the ‘universal pairing base’ deoxyinosine were determined for the pairs I·C, I·A, I·T, I·G and I·I adjacent to G·C and A·T pairs. Ultraviolet absorbance melting curves were measured and non-linear regression performed on 84 oligonucleotide duplexes with 9 or 12 bp lengths. These data were combined with data for 13 inosine containing duplexes from the literature. Multiple linear regression was used to solve for the 32 nearest-neighbor unknowns. The parameters predict the T_m for all sequences within 1.2°C on average. The general trend in decreasing stability is I·C > I·A > I·T ≈ I· G > I·I. The stability trend for the base pair 5′ of the I·X pair is G·C > C·G > A·T > T·A. The stability trend for the base pair 3′ of I·X is the same. These trends indicate a complex interplay between H-bonding, nearest-neighbor stacking, and mismatch geometry. A survey of 14 tandem inosine pairs and 8 tandem self-complementary inosine pairs is also provided. These results may be used in the design of degenerate PCR primers and for degenerate microarray probes.     

Effectiveness of Septisol Antiseptic Foam as a Surgical Scrub Agent

Septisol antiseptic foam (0.23% hexachlorophene in a 46% ethyl alcohol base) is a new surgical scrub agent for both primary and re-entry use that is designed to minimize the harsh effects to the skin of the conventional scrub while retaining effective antibacterial properties. A preliminary surgical scrub study of 1-week duration yielded an immediate reduction in resident flora of 92% from an average single scrub coupled with a residual bacteriostatic effect from repeated use that gave a plateau at 57% of the pretest resident population level. A separate study demonstrated complete elimination of both gram-positive and gram-negative transients from the skin with a single application of the product. In an 8-week surgical scrub study, equal effectiveness was shown between Septisol antiseptic foam and a standard 3% hexachlorophene detergent. However, Septisol antiseptic foam offers considerable advantage in minimizing the harsh effects to the skin of the conventional surgical scrub and results in a substantially lower hemic level of hexachlorophene in the user than that obtained with 3% hexachlorophene detergent. Sampling was conducted by the fingerprint impression plate technique of Gale.     

SEQUENTIAL ELECTROCARDIOGRAPHIC ANALYSIS OF STONE HEART SYNDROME IN A PATIENT SUPPORTED SIX DAYS WITH AN ABDOMINAL LEFT VENTRICULAR ASSIST DEVICE (ALVAD)

A 21-year-old male patient underwent aortic and mitral valve replacement for progressive cardiac failure due to acute bacterial endocarditis. Ischemic myocardial contracture developed during attempts to restore cardiac activity following hypothermic, ischemic, cardioplegic arrest. An abdominal left ventricular assist device (ALVAD) was implanted and supported the circulation for nearly six days prior to cardiac transplantation. The preoperative EKG showed sinus tachycardia with left anterior hemiblock. Postoperatively, there was complete electromechanical dissociation. The postoperative EKG showed a superior and leftward shift of the axis. There was a marked loss of QRS voltage and variable degrees of atrioventricular block. At times, only P waves were present. On the fourth postoperative day, there was an axis shift to the extreme right. Prior to transplantation, sinus rhythm returned, and the axis shifted leftward once again. The common denominator of all the abnormal postoperative electrocardiograms was the conspicuous low voltage that probably signified early and extensive myocardial damage. To our knowledge, this is the first instance wherein a sequential electrocardiographic analysis of stone heart syndrome has been undertaken.     

Effects of aging on capillary geometry and hemodynamics in rat spinotrapezius muscle

The effects of aging on muscle microvascular structure and function may play a key role in performance deficits and impairment of O2 exchange within skeletal muscle of senescent individuals. To determine the effects of aging on capillary geometry, red blood cell (RBC) hemodynamics, and hematocrit in a muscle of mixed fiber type, spinotrapezius muscles from Fischer 344 x Brown Norway hybrid rats aged 6-8 mo [young (Y); body mass 421 +/- 10 g, n = 6] and 26-28 mo [old (O); 561 +/- 12 g, n = 6] were observed by high-resolution transmission light microscopy under resting conditions. The percentage of RBC-perfused capillaries (Y: 78 +/- 3%; O: 75 +/- 2%) and degree of tortuosity and branching (Y: 13 +/- 2%; O: 13 +/- 2%, additional capillary length) were not different in O vs. Y muscles. Lineal density of RBC-perfused capillaries in O was significantly reduced (Y: 30.7 +/- 1.8, O: 22.8 +/- 3.1 capillaries/mm; P < 0.05). However, RBC-perfused capillaries from O rats (n = 78) exhibited increased RBC velocity (VRBC) (Y: 219 +/- 12, O: 310 +/- 14 microm/s; P < 0.05) and RBC flux (FRBC) (Y: 27 +/- 2, O: 41 +/- 2 RBC/s; P < 0.05) vs. Y rats (n = 66). Thus O2 delivery per unit of muscle was not different between groups (Y: 894 +/- 111, O: 887 +/- 118 RBC. s-1. mm muscle-1). Capillary hematocrit was not different in Y vs. O rats (Y: 26 +/- 1%, O: 28 +/- 1%: P > 0.05). These data indicate that in resting spinotrapezius muscle, aging decreases the lineal density of RBC-perfused capillaries while increasing mean VRBC and FRBC within those capillaries. Whereas muscle conductive O2 delivery and capillary hematocrit were unchanged, elevated VRBC reduces capillary RBC transit time and may impair the diffusive transport of O2 from blood to myocyte particularly under exercise conditions.     

The Highly Conserved Codon following the Slippery Sequence Supports ?1 Frameshift Efficiency at the HIV-1 Frameshift Site

HIV-1 utilises −1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating −1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the ‘intercodon’) contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules—eRF1 protein or a cognate suppressor tRNA—were able to access and decode the intercodon prior to −1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted) ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.     

Integrin trafficking and the control of cell migration

In the late 1980s and early 1990s, the observation that certain integrin heterodimers are continually internalized from the plasma membrane into endosomal compartments and subsequently recycled back to the cell surface indicated that the endocytic and recycling pathways have the potential to exert minute-to-minute control over integrin function. This insight has prompted others to study the regulation of integrin trafficking in more detail. This review aims to summarize the findings of studies revealing the molecular mechanisms controlling integrin traffic, particularly those providing indications as to how these processes contribute to cell migration and tumour cell invasiveness.