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S Roberts

Publications and source records attributed to S Roberts.

At least 91 records · Page 5Linked to original sources
PubMed2000

The zinc ribbon domains of the general transcription factors TFIIB and Brf: conserved functional surfaces but different roles in transcription initiation.

The function of the conserved zinc-binding domains in the related Pol II- and Pol III-specific factors TFIIB and Brf was investigated. Three-dimensional structure modeling and mutagenesis studies indicated that for both factors, the functional surface of the zinc ribbon fold consists of a small conserved patch of residues located on one face of the domain comprised mainly of the second and third antiparallel beta strands. Previous studies have shown that the TFIIB zinc ribbon is essential for recruitment of Pol II into the preinitiation complex. In contrast, Pol III recruitment assays and in vitro transcription demonstrate that the disruption of the Brf zinc ribbon does not lead to a defect in Pol III recruitment but, rather, a defect in open complex formation. Therefore, the same conserved surface of the zinc ribbon domain has been adapted to serve distinct roles in the Pol II and Pol III transcription machinery.

Amino Acid Sequence↗
PubMed2000

X-Ray Absorption Spectroscopy of Strontium(II) Coordination.

Sorption of dissolved strontium on kaolinite, amorphous silica, and goethite was studied as a function of pH, aqueous strontium concentration, the presence or absence of atmospheric CO(2) or dissolved phosphate, and aging over a 57-day period. Selected sorption samples ([Sr(aq)](i) approximately 0.5-1x10(-3) m) were examined with synchrotron X-ray absorption spectroscopy (XAS) at low (13-23 K) and room temperatures to determine the local molecular coordination around strontium. Quantitative analyses of the extended X-ray absorption fine structure (EXAFS) of kaolinite, amorphous silica, and most goethite sorption samples showed a single first shell of 9-10 (+/-1) oxygen atoms around strontium at an average Sr-O bond-distance of 2.61 (+/-0.02) Å, indicating hydrated surface complexes. The EXAFS spectra were unchanged after reaction for up to 57 days. Likewise, in kaolinite sorption samples prepared in 100% nitrogen atmosphere, the presence of dissolved phosphate (0.5x10(-3) m) in addition to strontium did not change the local coordination around strontium. In two goethite sorption samples reacted in air at pH approximately 8.5, the EXAFS spectra (collected at low and room temperature) clearly showed that the local structure around strontium is that of strontianite (SrCO(3)(s)). We also noted an increase in strontium uptake on goethite in the presence of atmospheric CO(2) in batch experiments, relative to CO(2)-free experiments. These observations suggest that sorption of carbonate may nucleate the precipitation of SrCO(3) in the pH range in which carbonate sorption on goethite is near a maximum. At higher pH, carbonate surface sorption decreases as dissolved CO(2) decreases. For goethite sorption samples above pH 8.6, hydrated surface complexes, rather than a precipitate, were observed in the EXAFS spectra. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Nine independent F9 mutations in the Mexican hemophilia B population: nonrandom recurrences of point mutation events in the human germline.

The factor IX gene (F9) is a valuable model for studying germ-line mutations. Nine mutations were detected in nine Mexican patients with hemophilia B by direct sequencing using genomic amplification with transcript sequencing (GAWTS): six single base changes, one micro-deletion, and two large deletions. Germline origins of mutations were found in three of six families with sporadic cases. Curiously, the four independent single base substitutions which were not at CpG dinucleotides occurred at only two different nucleotide positions (17,678 and 17,747) one transition and one transversion at each. The two remaining substitutions were identical changes at a CpG dinucleotide, but were determined to be independent by germline origin analysis. A statistical analysis suggests that the independent recurrence of mutations at these locations may reflect an unusual aspect of F9 mutagenesis in the Mexican population. These data raise the possibility of population-specific differences in human germline mutations.

Factor IX↗
PubMed2000

The human factor IX gene as germline mutagen test: samples from Mainland China have the putatively endogenous pattern of mutation.

Germline mutations are the major source of genetic variation that allows a species to evolve over time but at the cost of Mendelian disease and genetic predisposition to multifactorial diseases. Previous analyses have revealed that the pattern of germline mutations in the factor IX gene (F9) is similar among a variety of ethnically and geographically diverse populations and compatible with the ancient pattern that has shaped the mammalian genome. Here, we compare the pattern of germline mutation in a population of hemophilia B patients from Mainland China (n=66) to that in U.S. Caucasians, Blacks, and Mexican Hispanics and stratify by disease severity and ethnicity. The similar pattern of germline mutation in all ethnic groups studied to date provides additional data compatible with the inference that endogenous processes predominate in germline mutations.

China↗
PubMed2000

Factor IX mutations in South Africans and African Americans are compatible with primarily endogenous influences upon recent germline mutations.

Similar patterns of germline mutations in the factor IX gene (F9) have been observed in certain geographically and racially diverse populations. Germline mutation data have not been available from any region of Africa or from the Black race. Analysis of mutation data for Blacks is of interest, since this race has a high frequency of polymorphism compared to other races. This high frequency has been interpreted as evidence for the "out of Africa" hypothesis for the origin of humans, but it is possible that Blacks have a higher mutation rate due to genetic differences or environmental exposures. We report 26 independent mutations that were detected in patients of mixed races with hemophilia B from South Africa. The pattern of mutation in patients from this African country was similar to that of U.S. Caucasians. In addition, 22 independent mutation were detected in African American patients. The patterns of independent germline mutation in 22 African Americans (and in a combination 34 North American and African Blacks) is similar to that of U.S. Caucasians. Neither genetic differences between the Black and Caucasian races nor environmental and cultural differences between South Africa and the U.S. alter the germline pattern of mutation observed in F9. Hum Mutat 16:372, 2000.

Black People↗
PubMed2000

Intentions to quit smoking in substance-abusing teens exposed to a tobacco program.

In 1993-94, fifty-five clients at an adolescent residential drug treatment facility with an innovative tobacco prevention, education and cessation program reported their tobacco attitudes, intentions, and behavior at admission and discharge. Of entering clients, 93% were current smokers and 93% felt the facility should help clients quit smoking. Clients interested in quitting increased from 61% at admission to 87% at discharge, as measured by the precontemplation/contemplation ladder of Rustin and Tate (1993). Clients who wanted to immediately quit smoking increased from 15% to 29%. Sixty-five percent of the teens studied said the tobacco-free activities were extremely helpful. At discharge, 16% of the smokers reported having quit tobacco and all four nonsmokers remained smoke-free. During the preceding year there was a naturally occurring quit rate of 1%. As a result of this work, the facility required residential clients to be nicotine-free as of July 1996.

Adolescent↗
PubMed2000

How persuasive is a good fit? A comment on theory testing.

Quantitative theories with free parameters often gain credence when they closely fit data. This is a mistake. A good fit reveals nothing about the flexibility of the theory (how much it cannot fit), the variability of the data (how firmly the data rule out what the theory cannot fit), or the likelihood of other outcomes (perhaps the theory could have fit any plausible result), and a reader needs all 3 pieces of information to decide how much the fit should increase belief in the theory. The use of good fits as evidence is not supported by philosophers of science nor by the history of psychology; there seem to be no examples of a theory supported mainly by good fits that has led to demonstrable progress. A better way to test a theory with free parameters is to determine how the theory constrains possible outcomes (i.e., what it predicts), assess how firmly actual outcomes agree with those constraints, and determine if plausible alternative outcomes would have been inconsistent with the theory, allowing for the variability of the data.

Humans↗
PubMed2000

The procedural validity of retrospective case note diagnosis.

OBJECTIVE: Deriving diagnoses from retrospective case note examination is a common practice in psychiatric research. The Operational Criteria (OPCRIT) diagnostic checklist is essentially a checklist built up of operational criteria defined by a comprehensive glossary and is designed to assign reliable diagnoses from case notes. However, the validity of such a procedure compared with procedures involving prospective assessment has never been tested. We examined the procedural validity of the OPCRIT diagnostic system in relation to four other diagnostic procedures mostly employing prospectively gathered information. METHOD: Three experienced psychopathology raters rated the case notes and clinical abstracts, using the OPCRIT method of diagnostic assignment, of 50 subjects who had participated in an early procedural validity study as an adjunct to the DSM-IV Field Trial for psychotic disorders. The setting was the Early Psychosis Prevention and Intervention Centre (EPPIC), which focuses on first episode psychosis. RESULTS: The pairwise concordance with the other procedures for DSM-III-R diagnoses assigned by OPCRIT using ratings derived from either the clinical abstracts or the case notes was found to be only poor to moderate when compared with the pairwise concordance of the four other procedures. The per cent agreement between OPCRIT clinical abstracts diagnoses and the other procedures ranged from 49% to 60% with kappa values between 0.30 and 0.45, and for OPCRIT case note diagnoses and the other procedures the per cent agreement range was between 44% and 57% and the kappa values were between 0.35 and 0.49. CONCLUSIONS: The procedural validity of diagnoses assigned via the application of checklists of operational criteria to case notes and clinical abstracts alone is unacceptably poor. Such sources need to be buttressed by other data, particularly direct patient interview and informant material.

Adolescent↗
PubMed2000

Assessment of long-term outcomes of community-acquired hepatitis C infection in a cohort with sera stored from 1971 to 1975.

The aim of this study was to examine the long-term effects of hepatitis C virus (HCV) infection on a cohort of patients admitted with acute viral hepatitis from 1971 through 1975. The availability of stored sera from this time enabled testing to identify those who were anti-HCV-positive on admission. Sixteen percent (n = 238) of the cohort tested anti-HCV-positive. The unexposed group was selected from those who were anti-HCV-negative. Systematic approaches were used to locate the cohort and health outcomes assessed by a study-specific questionnaire and clinical, serological, virological, and biochemical assessment. Complete follow-up was achieved on 98 anti-HCV-positive individuals and 201 negatives. Injecting drug use (IDU) was the presumed route of infection. At a mean of 25 years' follow-up, 54% of the anti-HCV-positive group had evidence of chronic HCV infection (both anti-HCV- and HCV-RNA-positive); the remainder were HCV-RNA-negative. Sixty-nine percent of those chronically infected had elevated serum alanine transaminase (ALT) levels, but only 8% had progressed to overt cirrhosis, and no cases of hepatocellular carcinoma (HCC) were identified. In summary, anti-HCV-positive subjects were 8 times more likely to have died from suicide or drug overdose than from HCV-related disease. Anti-HCV-positive study subjects were at increased risk of liver-related pathology after 25 years' follow-up, but few had progressed to overt cirrhotic liver disease. Excess mortality in this group was not the result of liver disease. This suggests that the natural history of community-acquired HCV may be more benign than previously thought.

Adult↗
PubMed2000

Transactional conflict between psychobiology and culture in the etiology of postpartum depression.

In vulnerable individuals, postpartum depression may be triggered by the disruption of neuropsychological processes during pregnancy and parturition. It is proposed that in Western societies pre- and postnatal psychological and instrumental needs are poorly met and this crisis may interact with neurophysiological factors in compromising maternal psychological functioning. The influence of developmental factors and psychological and physical stressors are discussed in relation to women's neuropsychological health during the peripartal transition. It is hypothesized that the environmental milieu may support, neglect or derail the mother's psychobiological transition from pregnancy to effective postnatal parenting and resumption of family and work roles.

Conflict, Psychological↗
PubMed2000

Transactional conflict between psychobiology and culture in the etiology of postpartum depression.

In vulnerable individuals, postpartum depression may be triggered by the disruption of neuropsychological processes during pregnancy and parturition. It is proposed that in Western societies pre- and postnatal psychological and instrumental needs are poorly met and this crisis may interact with neurophysiological factors in compromising maternal psychological functioning. The influence of developmental factors and psychological and physical stressors are discussed in relation to women's neuropsychological health during the peripartal transition. It is hypothesized that the environmental milieu may support, neglect or derail the mother's psychobiological transition from pregnancy to effective postnatal parenting and resumption of family and work roles.

Conflict, Psychological↗
PubMed2000

Granulocyte-macrophage colony-stimulating factor augments phagocytosis of Mycobacterium avium complex by human immunodeficiency virus type 1-infected monocytes/macrophages in vitro and in vivo.

The role of human immunodeficiency virus type 1 (HIV-1) infection on the ability of human monocytes/macrophages to phagocytose Mycobacterium avium complex (MAC) in vivo and in vitro and the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on this function were investigated. By use of a flow cytometric assay to quantify phagocytosis, HIV-1 infection was found to impair the ability of monocyte-derived macrophages to phagocytose MAC in vitro, whereas GM-CSF significantly improved this defect. Phagocytosis was not altered by exposure to a mutant form of GM-CSF (E21R) binding only to the alpha chain of the GM-CSF receptor, suggesting that signaling by GM-CSF that leads to augmentation of phagocytosis is via the beta chain of the receptor. In a patient with AIDS and disseminated multidrug-resistant MAC infection, GM-CSF treatment improved phagocytosis of MAC by peripheral blood monocytes and reduced bacteremia. These results imply that GM-CSF therapy may be useful in restoring antimycobacterial function by human monocytes/macrophages.

Adult↗
PubMed2000

The effect of gender and body composition method on the apparent decline in lean mass-adjusted resting metabolic rate with age.

BACKGROUND: Declining resting energy expenditure (REE) is a hallmark of normal aging, but the cause of this decline remains controversial. Some, but not all, studies have shown that the decline in REE with age is eliminated after adjustment for fat-free mass (FFM). METHODS: We examined the effect of four body composition methods used to assess FFM (underwater weighing [UWW], bioimpedance analysis [BIA], tritium dilution, and total body potassium [TBK]) on the relationship between REE and age in 30 healthy men and 101 healthy women aged 18 to 87 years. RESULTS: The decline in REE with age was significant in women (-80.3 kJ/d/y, p < .004) but not in men (-46.9 kJ/d/y, p = .328). After adjustment for FFM, the decline in REE with age persisted when FFM was measured by BIA, UWW, or tritium dilution, but no decline was seen when TBK was used to adjust for FFM. In both women and men, fat mass was significantly associated with REE after adjusting for age and FFM. CONCLUSION: It is the decline in cell mass with age, detectable by TBK but not by other methods, rather than any metabolic alteration, that explains the decline in FFM-adjusted REE with age.

Adult↗
PubMed2000

Analysis of correlations and search for evidence of deterministic chaos in rhythmic motor control by the human brain.

We investigate rhythmic finger tapping in both the presence and the absence of a metronome. We examine both the time intervals between taps and the time lags between the stimulus tones from the metronome and the response taps by the subject. We analyze the correlations in these data sets, and we search for evidence of deterministic chaos, as opposed to randomness, in the fluctuations.

Arm↗
PubMed2000

Pigeons flexibly time or count on cue.

In Experiment 1, pigeons were presented with a sequence of light flashes and cued to peck a key for reward either after a fixed time or after a fixed number of flashes. Curves that showed the rate of key pecking over time within trials indicated that peak rates of response were reached near the fixed time on timing-cued trials and near the fixed number of flashes on counting-cued trials. In Experiment 2, the key cue was shifted from timing to counting or from counting to timing midway through a trial. The peak times reached after the cue change indicated that pigeons kept track of time while cued to count but did not count while cued to time. These findings suggest a basic asymmetry in the dual-mode model of timing and counting.

Animals↗
PubMed2000

Do women have equitable access to quality breast prosthesis services?

Although up to 90% of women who have had a mastectomy use breast prostheses, significant gaps exist around current breast prosthesis services for Australian women. These gaps include the timeliness and quality of information provision, the disparity in financial assistance, and the lack of knowledge regarding the determinants of what constitutes a "quality" breast prosthesis. Revised policy initiatives are central to addressing these gaps to ensure equitable access to quality breast prosthesis services.

Australia↗
PubMed2000

gammadelta cells and the regulation of mucosal immune responses.

We are only now uncovering the potentially important contributions made to immune responses by gammadelta cells. These contributions are likely to be particularly important at mucosal sites, where gammadelta cells are disproportionately enriched. Indeed, gammadelta cells have proven biological activity in the lung. In addition, gammadelta cells are also enriched in young rather than adult animals. Studies of mutant mice have demonstrated that alphabeta T cells are seemingly essential for high-affinity, cognate immunological memory, whereas gammadelta cells contribute to the early stages of an immune response and to the regulation of alphabeta T cell- and B cell-mediated immunity. To explore further the role of gammadelta cells in immune responses, we have investigated whether their contribution is greater during the early period of life, when the cells are more abundant. In a natural system of coccidial infection of gut epithelial cells, we find that alphabeta T cell responses are less essential for immunoprotection during primary challenge of young mice than is true for adult animals. This "ineffectiveness" creates a "window of importance" for the immunoprotective capacity of gammadelta cells, which seem thereby to be more crucial in young compared with older animals. The relative ineffectiveness of alphabeta T cells in young mice may be attributable to a bias toward Th2 activity. We therefore hypothesize that gammadelta cell activity, elicited by infection early in life, may compensate for defects in Th1 activity and may actually accelerate the bias in alphabeta T cells away from Th2. This has obvious implications for susceptibility to Th2-type allergic responses.

Adult↗