Aetiology of pressure sores in patients with spinal cord injury.

One hundred consecutive patients admitted to the National Spinal Injuries Centre, Stoke Mandeville Hospital, with pressure sores were studied to assess the relative importance of factors known to predispose to the development of scores. Loss of feeling was critical, because patients were unable to appreciate pain when the sore was developing. Risk of developing a sore increased with age, but duration of the paralysis was of equal importance. After discharge from hospital the presence of a caring relative or friend was essential for survival. Many patients developed sores because of poor facilities at home or inappropriate advice from those who looked after them. An even more distressing factor was the number of patients who developed sores in hospital owing to inadequate nursing care. There are relatively few paralysed patients in the community, but the lessons learnt in this study may be applied to all patients with orthopaedic injuries and to geriatric patients with limited mobility. Nursing and medical staff must turn patients regularly and ensure that there is proper equipment to relieve pressure on the skin. Patients should not be allowed to sit in a chair if they develop a sacral or trochanteric sore. More effort should be directed towards the appropriate education of patients, their relatives, and all those who are concerned with their welfare.     

The role of sediment organic matter composition in larval habitat selection by the polychaete Capitella sp. I

The role of sediment organic matter composition in larval habitat selection by the polychaete Capitella sp. I was investigated using a still water multiple-choice experiment. Specifically, the following question was addressed: what are the roles of sediment labile organic compounds in larval habitat selection? A replicated Latin-square design was used to test larval preferences among sediments collected from five sites (TLC—Tung Lung Chau; VHE—Victoria Harbor east; VH—Victoria Harbor; VHW—Victoria Harbor west; PC—Peng Chau) in the vicinity of Victoria Harbor, Hong Kong. Although mean grain size was not different among sites, water content and the total organic matter were higher in VH Mud but were similar among other sites. Carbohydrate, lipid, and biopolymeric fractions followed the same trend. According to protein content, sites were ranked as: VH > VHW > TLC = VHE > PC. PC Mud had the highest carbohydrate/protein ratio, due to low concentration of protein. According to larval preference, sites were ranked as: TLC = VH = VHW = VHE > PC. Our study shows a precise relationship between sediment biochemical properties and larval habitat selection. Larvae tend to choose sediments with low carbohydrate/protein ratio. Results suggest that types of sediment organic matter may play more important role in the larval habitat selection process of Capitella sp. I than concentration of organic matter alone.     

The possible chain bendings in polydeoxynucleotides.

Energy minimization studies were carried out on the trimeric subunit of DNA, dApdApdA by treating the thirteen relevant dihedral angles as simultaneous variables in the total energy function. The four important sugar pucker states ³E-³E-³E, ²E-²E-²E, ³E-²E-³E and ²E-³E-²E were investigated. From the characteristic chain diverting properties of the low energy conformations four possible types of bend families were identified and their probable sites of occurrence in the polydeoxynucleotides predicted.     

Response of larval barnacle proteome to CO(2)-driven seawater acidification

The majority of benthic marine invertebrates have a complex life cycle, during which the pelagic larvae select a suitable substrate, attach to it, and then metamorphose into benthic adults. Anthropogenic ocean acidification (OA) is postulated to affect larval metamorphic success through an altered protein expression pattern (proteome structure) and post-translational modifications. To test this hypothesis, larvae of an economically and ecologically important barnacle species Balanus amphitrite, were cultured from nauplius to the cyprid stage in the present (control) and in the projected elevated concentrations of CO₂ for the year 2100 (the OA treatment). Cyprid response to OA was analyzed at the total proteome level as well as two protein post-translational modification (phosphorylation and glycosylation) levels using a 2-DE based proteomic approach. The cyprid proteome showed OA-driven changes. Proteins that were differentially up or down regulated by OA come from three major groups, namely those related to energy-metabolism, respiration, and molecular chaperones, illustrating a potential strategy that the barnacle larvae may employ to tolerate OA stress. The differentially expressed proteins were tentatively identified as OA-responsive, effectively creating unique protein expression signatures for OA scenario of 2100. This study showed the promise of using a sentinel and non-model species to examine the impact of OA at the proteome level.     

Structure based medicinal chemistry approach to develop 4-methyl-7-deazaadenine carbocyclic nucleosides as anti-HCV agent

The structure-based approaches were implemented to design and rationally select the molecules for synthesis and anti-HCV activity evaluation. The systematic structure–activity relationships of previously discovered molecules (types I, II, III) were analyzed to design new molecules (type IV) by bioisosteric replacement of the amino group. The ligand conformation, binding mode studies and drug like properties were major determinant for selection of molecules for final synthesis. The replacement of amino group with methyl restored the interactions with RNA-template (Tem 799) through bifurcated weak H-bond (C–H…O). This is an interesting finding observed from molecular modeling studies. It was found that 6c–e has anti-HCV activity (EC₅₀ in 37–46 μM) while 6a, 6b and 6g were inactive. The compound 6f (EC₅₀ 28 μM) was the most active among the series however it also showed some cytotoxicity (CC₅₀ 52.8 μM). Except 6f, none of the compounds were found to be cytotoxic (CC₅₀ > 100 μM). The present study discloses structure–based approach for novel anti-HCV lead discovery and opens a future scope of lead optimization.     

Saturation-transfer electron paramagnetic resonance detection of anisotropic motion by sickle hemoglobin molecules in the polymer state

The motional behavior of spin-labeled deoxygenated sickle hemoglobin has been studied by using both 9- and 35-GHz saturation-transfer electron paramagnetic resonance (EPR). Using spectral subtraction techniques and saturation-transfer EPR parameter correlation plots, we find that the saturation-transfer EPR spectra for the sickle hemoglobin gel state at high temperature and high hemoglobin concentration cannot be described as a simple superposition of spectra from immobilized hemoglobin plus solution-state hemoglobin but instead suggest that the individual sickle hemoglobin molecules exhibit limited, anisotropic, rotational oscillation within the polymer fiber. The spectra also imply that the symmetry axis for sickle hemoglobin rotational oscillation is approximately coincident with the nitroxide z axis of the covalently attached spin-label. We suggest that this anisotropic rotational motion may be produced by one or two of the known intermolecular contact sites within the sickle hemoglobin fiber acting as strong intermolecular binding sites, and producing "motional alignment" within the fiber; determining the location of the strong binding site should be important in focusing the future development of antisickling agents.     

Saturation transfer electron paramagnetic resonance detection of sickle hemoglobin aggregation during deoxygenation.

In Myxicola axons, substitution of tetramethylammonium (TMA+) for Cs+ alters intramembrane charge movements (gating currents). Although the total charge moved during and following a depolarizing step remains constant, with TMA+ the ON response has additional slower component(s), and the OFF response is retarded. Concommitantly, TMA+ produces the same voltage-dependent block of Na+ inactivation in Myxicola as has been observed in other preparations. At large positive potentials as many as 70% of the Na+ channels fail to inactivate in the steady state. In addition, TMA+ slows Na+ activation, retards the inactivation of those Na+ channels that remain able to inactivate, and decreases the maximum Na+ conductance. The steady-state Na+ conductance induced by internal TMA+ or Na+ is consistent with a scheme in which these internal cations simply modify Na+ channels in an all-or-none fashion so that a fraction become incapable of inactivating.     

Conformational characteristics of the trinucleoside diphosphate d(ApApA) from energy-minimization studies

Energy-minimization studies were carried out on the trinucleoside diphosphate d(ApApA). The potential energy contributions from nonbonded, electrostatic, hydrogen-bonding, and torsional interactions were minimized by treating the 13 relevant dihedral angles as simultaneous variables. For the C(3′)-endo trimer, 14 low-energy conformations are within 10 kcal/mol above the lowest energy found, compared to only 3 in the case of the C(2′)-endo trimer. This result shows the flexible character of the C(3′)-endo unit. The hairpin-type, loop-promoting conformer with (ω′,ω) = (101°, 59°) was found to be the most favored structure at the 3′-terminus of d(ApApA). The predicted U- and L-type bend conformers were found to lie within 5 kcal/mol, compared to the lowest energy B-DNA structure. The A-DNA and Watson-Crick DNA types of helical conformers also lie within very small energy barriers. The phosphate group at the 5′-end of the nucleotide residue has a definite influence on the base of the corresponding nucleotide, keeping it in the normal anti-region, and hence on the base-stacking property. The results are compared with the presently available experimental data, mainly with the tRNA^Phe crystal.     

Conformational characteristics of dApdA,dApdT, dTpdA,and dTpdT from energy minimization studies

The conformational characteristics of the deoxydinucleoside monophosphates with adenine and thymine bases in all possible sequences, namely, dApdA, dApdT, dTpdA, and dTpdT have been studied using an improved set of energy parameters to calculate the total potential energy and an improved set of energy parameters to calculate the total potential energy and an improved version of the minimization technique to minimize the total energy by allowing all seven dihedral angles of the molecular fragment to vary simultaneously. The results reveal that the most preferred conformation in all these units usually corresponds to one of the four helical conformations, namely, the A-DNA, B-DNA, C-DNA, and Watson-Crick DNA models. These helical conformations differ in energies by about 3 kcal/mol with respect to one another. The conformations which could promote a loop or bend in the backbone are, in general, less stable by about 3.5 kcal/mol with respect to the respective lowest-energy helical conformation. The results indicate that there is a definite influence of bases and their actual sequences on the preferred conformations of the deoxydinucleoside monophosphates. The lowest-energy structure, although corresponding to one of the four helical conformations, differ with the type of the deoxydinucleoside monophosphate. Good or reasonable base stacking is noted in dApdA and dTpdA with both C(3′)-endo and C(2′)-endo sugars and in dApdT and dTpdT with only C(3′)-endo sugar. The inversion of the base sequence in deoxydinucleoside monophosphates alters the order of preference of low-energy conformations as well as the base-stacking property of the unit. The paths linking the starting and final states in the (ω′, ω) plane show interesting features with regard to the energy spread, thus providing insight into the path of conformational movement ofthe molecule under slight perturbation. The stabilities of the A and B forms, including the internal energies of the C(3′)-endo ans C(2′)-endo sugar systems, indicate that for dTpdT the B → A transition is less probable. For dApdA, dApdT, and dTpdA this transition is probable in the same order of preference. We propose that the T-A sequence in the polynucleotide chain might serve as the site accessible for B ? A transitions. The theoretical predictions are in good agreement with the experimental observations.