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D H Williams

Publications and source records attributed to D H Williams.

At least 109 records · Page 6Linked to original sources
PubMed1991

Is the hydrophobic effect stabilizing or destabilizing in proteins? The contribution of disulphide bonds to protein stability.

It has been recently concluded that the hydrophobic effect, hitherto regarded as a major driving force in the folding of proteins, destabilizes the folded state relative to the unfolded state. We summarize the properties of the hydrophobic effect obtained from solvent transfer experiments and show that the recent conclusion is an artifact of crosslinking in the unfolded state, caused by disulphide bonds, metals or cofactors. We show that, for the proteins in the data set, crosslinks surprisingly destabilize folded structures entropically, but stabilize them enthalpically to a greater extent. We also calculate non-polar surface areas of these unfolded proteins. These surface areas are decreased by crosslinks. The unfolded state of proteins lacking constraints, such as myoglobin, is well approximated by a mixture of residues containing alpha-helical and beta-sheet dihedral angles. Surface areas of unfolded proteins cannot be obtained by summing the surface areas of individual residues, since this ignores any unavoidable side-chain-side-chain interactions.

Disulfides↗
PubMed1991

The natural design of vancomycin family antibiotics to bind their target peptides.

The vancomycin family of antibiotics provide a rare opportunity among natural systems to study a molecular recognition process in which both the 'receptor' and the 'ligand' are relatively small molecules. Unlike the vast majority of antibiotics, in the vancomycin family the antibiotic performs the role of the receptor. All members of the family are covalently cross-linked heptapeptides that contain a variety of glycosidic modifications. Their site of action in bacterial cell walls is modelled by simple dipeptides and tripeptides. NMR experiments have been used to characterize the binding of these species through the study of both the complex and the free components. In unbound antibiotics conformational freedom is observed in regions of the molecule not severely restricted by covalent linkages. On binding of the ligand much of this conformational freedom is lost and the hydrophobic side chains of the antibiotics reside close to the intermolecular hydrogen-bonding interactions, thus shielding these interactions from the solvent. The charged amino groups of the N-terminus and disaccharide region of vancomycin are orientated not to optimize intermolecular electrostatic interactions but rather to retain solvation. This causes further hydrophobic faces to be presented to the ligand. Removal of saccharide units from the antibiotics leads to small losses in binding energy but may have considerable influence on the selectivity of the antibiotics. Specific dimerization through the non-ligand-binding faces of ristocetin is observed at millimolar concentrations. The geometry of the dimeric complex enables a close approach of the ligand carboxylate anion and the charged amino group of the novel sugar, ristosamine.

Amino Acid Sequence↗
PubMed1991

Anatomic variation of the corpus callosum in persons with gender dysphoria.

Previous postmortem anatomical studies have demonstrated differences between male and female in the size and shape of the splenium of the corpus callosum. The current study using the magnetic resonance imager compares the corpus callosum in 20 transsexuals and 40 controls to determine if the anatomic variance is related to anatomic sex or gender identity. No statistical differences were found in the cross-sectional areas of the entire corpus callosum, regardless of genetic sex or gender. However, the genetic males did have a larger whole-brain cross-sectional area. Also, even though there was a wide range of differences in shape and size in the splenium, the study found no significant differences between the sexes or between transsexual patients of either sex and the controls.

Adult↗
PubMed1991

The extent and timing of prenatal loss in gilts.

The potential litter size of gilts that is based on the ovulation rate is much higher than the actual litter size, which depends on the fertilization rate and subsequent prenatal mortality. Prenatal mortality is divided into embryonic mortality (before Day 30) and fetal mortality (after Day 30). Prenatal loss includes both fertilization failure and prenatal mortality. Crossbred gilts (n = 149) were bred at the first observed estrus after being exposed to the boar at 200 days of age. Time of the first insemination after estrus detection was determined by measurement of vaginal conductivity using a Walsmeta meter. A second insemination was administered either 8 or 16 hours later. Artificial insemination with fresh semen (0 to 3 days old) was used throughout the experiment. Gilts were slaughtered on Day 3 (n = 26), Day 10 (n = 42), Day 30 of gestation (n = 45) or they were allowed to farrow (n = 36). Gilts slaughtered on Day 3 were used to estimate the fertilization rate. Gilts slaughtered on Day 10 and Day 30 were used to calculate embryonic mortality, while fetal mortality was calculated from the gilts that farrowed. The mean (+/-SEM) number of corpora lutea (CL) was 13.15+/-0.46, 13.36+/-0.37 and 12.97+/-0.39 for gilts slaughtered at Days 3, 10 and 30, respectively (P>0.05), and the mean (+/-SEM) number of normal embryos recovered was 11.12+/-0.69, 9.46+/-0.55 and 9.33+/-0.58, respectively. Litter size at parturition was 9.10+/-0.54. There was a significant difference between the number of normal embryos on Day 3 and Day 30 (P=0.05) and also between the number of normal embryos at Day 3 and the number of piglets at term. Ninety percent of the ova were recovered at Day 3. The fertilization rate was calculated either 1) assuming that unrecovered ova had a similar fertilization rate as the recovered ova (FRER=94.5+/-2.0%) or 2) assuming that unrecovered ova were unfertilized (FROR=84.5+/-2.5%). It was concluded that FRER was a more accurate estimation of the fertilization rate. Based on this fertilization rate, embryonic mortality between Day 3 and Day 10 was 20.8+/-8.3%, with an additional 12.5+/-7.1% loss between Day 10 and Day 30, when all gilts were included (P = 0.308). Thus the total prenatal loss, including fertilization failure, up to Day 10 was 26.3% and to Day 30 it was 38.8%. Fetal mortality was 2.2%, giving a total prenatal mortality (excluding fertilization failure) of 35.5% and a prenatal loss of 41%. Most of the prenatal loss was due to embryonic mortality. In those gilts that remained pregnant most of the embryonic loss occurred before Day 10 (19.0+/-6.3%; P=0.003). There was no further loss between Day 10 and 30 of pregnancy. There was a significant difference between the loss from Day 3 to Day 10 compared with the loss from Day 10 to Day 30 (P=0.05); therefore, most of the embryonic loss in pregnant gilts occurred before Day 10. Since fetal mortality was 3.2+/-6.3%, most of the prenatal loss was due to embryonic mortality.

Journal Article↗
PubMed1991

The effects of administration of gonadotrophins and estrogens on prenatal survival in gilts.

In gilts ovulation occurs over a 4 to 8-hour period, with 70% of the ova being shed over a relatively short span of time. These oocytes supposedly give rise to more developed embryos at Days 10 to 12 which advance the uterine environment and reduce survival rates of less developed embryos because of an asynchronous environment. The aim of this experiment was to reduce embryo mortality by influencing the duration and pattern of ovulation. Crossbred gilts (n=98) were bred at their first observed estrus after being exposed to boars at 200 days of age. Estrus detection was carried out daily at 0000, 0800 and 1600 hours. All gilts were artificially inseminated with fresh semen, with a minimum of 2.7 billion spermatozoa, at both 16 and 32 hours after detection of estrus. Gilts were randomly assigned to one of the following treatments at detection of estrus: 1) 500 IU (2 ml) chorionic gonadotrophin (hCG) injected intravenously at the onset of estrus (n=22); 2) 16 microg (4 ml) gonadotrophin releasing hormone (GnRH) injected intravenously at the onset of estrus (n=25); 3) 11.5 microg estrogen added to the semen at the time of AI (n=25); 4) control, untreated gilts (n=26). All gilts were slaughtered at Day 30 of gestation (Day 0=day of detected estrus). The mean (+/-SEM) number of ovulations in pregnant gilts per treatment was 13.0+/-0.52, 12.6+/-0.51, 13.6+/-0.54 and 13.3+/-0.52, while the mean (+/-SEM) number of normal embryos per treatment was 10.3+/-0.67, 10.5+/-0.66, 10.3+/-0.69 and 10.5+/-0.67 for hCG, GnRH, estrogen and control groups, respectively, for an embryonic survival rate of 80+/-4.2%, 83+/-4.1%, 74+/-4.3% and 79+/-4.2% in pregnant gilts. If nonpregnant gilts are included, the embryonic survival rate for treatments 1 to 4 was 76+/-7.0%, 73+/-6.5%, 60+/-6.5%, and 64+/-6.4%, respectively. There was no significant difference between treatments for any of these variables. There was no evidence that administration of hCG, or GnRH at the onset of estrus, or the addition of estrogen to semen improved embryonic survival in gilts by Day 30 in this experiment.

Journal Article↗
PubMed1990

The influence of proline residues on alpha-helical structure.

Proline lacks an amide proton when found within proteins. This precludes hydrogen bonding between it and hydrogen bond acceptors, and thus often restricts the residue to the first four positions of an alpha-helix. Helices with proline after position four have a pronounced kink [(1988) J. Mol. Biol. 203, 601-619]. In these cases, we find that the proline residue almost almost always occurs on the solvent exposed face of each helix. This positioning facilitates the compensatory hydrogen bonding between solvent and residues P-3 and P-4 (relative to proline, P), through the formation of the kink. Further, it aids in the packing of long helical structures around globular protein structures.

Citrate (si)-Synthase↗
PubMed1990

Molecular recognition by secondary metabolites.

Aspects of molecular recognition based on the interaction between the vancomycin group of antibiotics and bacterial cell wall precursor analogues are discussed. The energetically unfavourable folding-in of the residue 1 sidechain in vancomycin and ristocetin A is discussed in terms of the favourable entropy associated with simultaneous release of solvent molecules. The effect of the sugar amino substituent on the strength of an adjacent hydrophobic interaction in the vancomycin/acetyl-D-Ala-D-Ala complex is rationalised as an intramolecular "salting-out" of hydrocarbon entities. The slow on-rate for dimerisation of the ristocetin A/N,N-diacetyl-L-Lys-D-Ala-D-Ala complex is attributed to the need for the relatively rigid peptide backbone of the antibiotic to be extensively desolvated before dimerisation can occur. Some of these concepts are then applied to understanding the interactions between antibiotics and the minor groove of double-helical DNA, the receptor site with which they have probably evolved to interact. Two structural motifs (pi-polarised aromatic rings and deoxy sugars) are postulated to be important in this recognition process. The possible roles of these structural features are discussed.

Aminoglycosides↗
PubMed1990

Superovulation in heifers given FSH initiated either at day 2 or day 10 of the estrous cycle.

The aim of this study was to determine if initiation of superovulation in heifers during the time of development of the first dominant follicle (Days 2 to 6) would give equivalent ovulation and embryo production rates as treatment initiated at mid-cycle. Estrus was synchronized in 60 beef heifers using luprostiol (PG) and they were randomly allocated to treatment with 4.5, 3.5, 2.5 and 1.5 mg of porcine follicle stimulating hormone (FSH) administered twice daily, either on Days 2, 4, 5 and 6 (Day-2 group), respectively, or with similar doses at four consecutive days during mid-cycle (Day-10 group, initiation on Day 9 to 11). All heifers received 500 mug cloprostenol at the fifth FSH injection and 250 mug at the sixth injection. Blood samples for progesterone determination were collected at the time of FSH injections. Heifers were slaughtered 7 d post estrus, and the number of ovulations and large follicles (>/=10mm) were determined on visual inspection of the ovary. Following flushing of the uterine horns the quality of embryos and the fertilization rate were determined. Significant differences between treatments were determined using a two-sided t-test, and frequency distributions were compared using Chi-square tests. The mean number (+/-SEM) of ovulations for heifers in the Day-10 group was 12.9+/-1.0, and 8.5+/-0.9 embryos were recovered. Both the number of ovulations (6.7+/-0.8) and embryos recovered (4.1+/-0.6) were lower (P=0.0001) in heifers in the Day-2 group. Following grading based on a morphological basis, a higher number (P=0.002) of embryos was categorized as Grades 1 and 2 (4.1+/-0.6) and Grade 3 (2.1+/-0.4) in Day-10 heifers than in the Day-2 group (Grade 1 and 2, 1.9+/-0.3; Grade 3, 0.7+/-0.2). The number of Grade 4 and 5 embryos (Day 10, 1.6+/-0.2; Day 2, 1.4+/-0.2) and the number of unfertilized ova (Day 10, 0.7+/-0.4; Day 2, 0.2+/-0.1) did not differ between treatments. Progesterone concentrations were lower (P=0.0001) in Day-2 heifers at FSH treatment prior to prostaglandin, and the decline was more rapid following prostaglandin injection at Day 5 (P=0.02). Results of this study indicate that the number of ovulations and embryos recovered was lower in heifers when FSH treatment was initiated on Day 2 compared with Day 10 of the estrous cycle.

Journal Article↗
PubMed1990

Mild head injury classification.

Inconsistencies across studies concerning outcome after mild head injury may reflect differences in the diagnostic criteria used for selection of patients. Consequently, we compared the neurobehavioral outcome in three groups of consecutively hospitalized patients (aged 16 to 50 years) who sustained a closed head injury (CHI) and had a Glasgow Coma Scale (GCS) score in the 9 to 15 range. These groups included patients with uncomplicated CHI with mild impairment of consciousness as reflected by a GCS score in the 13 to 15 range (n = 78), patients with initially mild impairment of consciousness complicated by brain lesion or depressed skull fracture (n = 77), and patients with moderate CHI (n = 60). Tests of memory, information processing, and verbal fluency were administered within 1 to 3 months after injury, and the Glasgow Outcome Scale was completed at 6 months. Neurobehavioral functioning was impaired in the groups with complicated mild CHI and moderate CHI as compared to the group with uncomplicated mild CHI. Although moderate CHI produced longer durations of impaired consciousness and posttraumatic amnesia than complicated mild head injury, patients in these groups did not differ in neurobehavioral performance. Global outcome at 6 months was better in the patients with mild CHI than in patients with complicated mild and moderate injuries. Analysis of the various complications of mild CHI revealed that the presence of an intracranial lesion was related to more severe neurobehavioral sequelae than injuries complicated by a depressed fracture.

Adolescent↗
PubMed1990

Characterization of Hb Aalborg, a new unstable hemoglobin variant, by fast atom bombardment mass spectrometry.

Hb Aalborg is a new unstable hemoglobin variant found in association with mild anemia. Heinz bodies were readily inducible in red cells but there was no specific evidence of hemolysis and the variant therefore appears to be without significant clinical effect. The amino acid replacement was identified by fast atom bombardment mass spectrometry and is that of Gly----Arg at position beta 74 (E18). Hb Aalborg is moderately unstable.

Anemia↗
PubMed1990

Corpus callosal atrophy following closed head injury: detection with magnetic resonance imaging.

To investigate evidence for diffuse white matter injury and hemispheric disconnection sequelae after severe closed head injury (CHI), this study evaluates the degree of posttraumatic atrophy of the corpus callosum. Corpus callosal atrophy was quantitatively determined using a digitizer to measure sagittal magnetic resonance images of 32 patients with moderate-to-severe CHI and those of 31 control subjects of similar age. In the CHI patients, measurements were significantly reduced for the areas of the anterior four-fifths, the posterior one-fifth, and the total corpus callosum. Moreover, the minimum width of the callosal body was reduced in the CHI patients as compared to that of control individuals. Indices of corpus callosal atrophy were significantly correlated with the chronicity of injury and the degree of lateral ventricular enlargement. There was no difference in callosal measurements between men and women. Magnetic resonance imaging provides an in vivo determination of corpus callosal atrophy which may reflect the severity of diffuse axonal injury and predict the type and severity of hemispheric disconnection effects.

Adolescent↗
PubMed1990

Magnetic resonance imaging and neuropsychological findings in human immunodeficiency virus infection.

Neurobehavioral functioning and magnetic resonance imaging (MRI) were investigated in 25 patients with various Centers for Disease Control (CDC) stages of human immunodeficiency virus (HIV) infection and in a control group of seven normal subjects. Unequivocal slowing of information processing speed and cerebral atrophy were related to the stage of HIV infection, with patients in CDC group IV exhibiting the most abnormal findings. Slowing of response speed was directly related to the severity of cerebral atrophy.

Adult↗
PubMed1989

Identification of highly acidic peptides from processing of the skin prepropeptides of Xenopus laevis.

The skin secretion of the frog Xenopus laevis has been fractionated by reverse-phase HPLC and the most polar components studied by fast-atom-bombardment mass spectrometry (FAB/MS). Esterification of the hydrophilic peptides with methanol and ethanol was employed to improve the sensitivity of the technique. A number of small, highly acidic peptides have been identified, and alcoholysis of the peptide bonds within a number of these permitted their sequencing by FAB/MS. The sequences confirmed that they originate from acidic spacer regions found in the precursors to peptide hormones, such as caerulein, which have already been found in the secretion. In addition, acidic peptides derived from the spaces of the precursor to the antimicrobial peptides, PGS (or the magainins) have been isolated. The release of these from the preprotein cannot be fully accounted for by documented processing mechanisms, suggesting that a novel type of cleavage site has been identified.

Amino Acid Sequence↗
PubMed1989

Rapid determination of sequence variations in actinidin isolated from Actinidia chinensis (var. Hayward) using fast atom bombardment mapping mass spectrometry and gas phase microsequencing.

A current limitation in the use of fast atom bombardment (FAB) mass spectrometric mapping of peptide mixtures, derived from enzymic digestion of proteins, is that most of the hydrophilic peptides are not observed. However, it has been demonstrated from previous work that esterification of the peptide mixture results in the detection of almost all peptides in FAB mass spectrometry. This strategy of FAB mapping was applied to the protein actinidin, isolated from an Italian variety of Actinidia chinensis. Two of the 12 tryptic peptides in FAB mass spectrometry did not exhibit molecular ions predicted from the known sequence of actinidin isolated from the New Zealand variety of A. chinensis. The two peptides were isolated by high-performance liquid chromatography, subjected to Staphylococcus aureus V8 protease digestion and sequenced by gas-phase microsequencing. Nine changes in amino acid composition were detected using the rapid and powerful combination of FAB mass spectrometric mapping and gas-phase microsequencing.

Amino Acid Sequence↗
PubMed1989

Dichotic listening and manual performance in relation to magnetic resonance imaging after closed head injury.

In order to investigate post-traumatic hemispheric disconnection effects, dichotic listening and intermanual tasks were administered to 69 patients who had sustained a closed head injury of varying severity. The manual tasks consisted of naming objects palpated in either hand, transfer of postures from one hand to the other and writing. Consistent with predictions, the degree of ear asymmetry in dichotic listening performance was directly related to the severity of the head injury as reflected by the degree of impaired consciousness. Depth and localisation of parenchymal lesion characterised by magnetic resonance imaging were also related to the degree of ear asymmetry. Parenchymal lesions situated in sites which could potentially interfere with callosal auditory or geniculocortical pathways produced a greater disparity in response to left versus right ear inputs as compared with parenchymal lesions in areas such as the frontal lobes which are purportedly unrelated to asymmetries in dichotic listening performance. The results provide further evidence for the effects of multifocal brain lesions involving the white matter on tasks which require intra and/or interhemispheric integration.

Adolescent↗