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M McNeil

Publications and source records attributed to M McNeil.

At least 19 recordsLinked to original sources
PubMed2025

Optimising parent selection in plant breeding: comparing metaheuristic algorithms for genotype building.

Stacking desirable haplotypes across the genome to develop superior genotypes has been implemented in several crop species. A major challenge in Optimal Haplotype Selection is identifying a set of parents that collectively contain all desirable haplotypes, a complex combinatorial problem with countless possibilities. In this study, we evaluated the performance of metaheuristic search algorithms (MSAs)-genetic algorithm (GA), differential evolution (DE), particle swarm optimisation (PSO), and simulated annealing (SA) for optimising parent selection under two genotype building (GB) objectives: Optimal Haplotype Selection (OHS) and Optimal Population Value (OPV). Using a diverse wheat population of 583 lines genotyped for 29,972 SNPs, forming 7645 haplotype blocks and phenotyped for stripe rust scores, we assessed each algorithm's performance across fitness optimisation, convergence speed, and computational efficiency. GA consistently achieved high fitness and rapid convergence, while DE showed robustness but required longer runtime and careful tuning. PSO performed well under the OHS criterion but was less effective for OPV. SA, although computationally lighter, was less consistent in finding optimal solutions. Simulation over 100 breeding cycles showed that OHS outperformed both OPV and GEBV-based selection in long-term genetic gain and diversity retention. OHS maintained heterozygosity and additive variance, which are key for sustainable improvement, while GEBV selection led to early allele fixation. Our findings underscore the potential of GB strategies that prioritise the collective performance of parent sets rather than individual ranking to enhance selection outcomes in genomic-assisted breeding programmes.

Plant Breeding↗
PubMed2001

The relationship between eligibility criteria for participation in alcohol brief intervention trials and other alcohol and health-related variables.

In clinical trials of brief interventions for alcohol use, individuals typically are defined as eligible for the research through meeting quantity-frequency (QF) of alcohol consumption criteria, alcohol-related problems criteria, or both. The purpose of this study was to evaluate preintervention and posttreatment differences among three groups of research participants eligible for participation in a brief intervention clinical trial by meeting the AUDIT total score criterion only, the QF criterion only, or both. The participants were 301 men and women 21 years of age or older who presented for medical treatment at one of twelve primary care clinics and were screened for participation in the clinical trial. Participants completed an assessment protocol at preintervention and 1, 3, 6, 9, and 12 months postintervention. The analyses showed statistical differences among the three subgroups on three outcome dimensions of alcohol consumption, related consequences and behaviors, and medical complications; for both consumption and complications, the AUDIT + QF participants showed greater severity than participants in either of the other two groups. For consequences, AUDIT + QF participants scored higher than the QF participants on one variable constituting this dimension. The overall subgroup differences were maintained at six months in the consumption and consequences data. The implications of these findings for sensitivity of brief intervention trial design, the discovery of patient moderators of intervention effectiveness, and clinical practice are discussed.

Adult↗
PubMed2001

Cell wall core galactofuran synthesis is essential for growth of mycobacteria.

The mycobacterial cell wall core consists of an outer lipid (mycolic acid) layer attached to peptidoglycan via a galactofuranosyl-containing polysaccharide, arabinogalactan. This structural arrangement strongly suggests that galactofuranosyl residues are essential for the growth and viability of mycobacteria. Galactofuranosyl residues are formed in nature by a ring contraction of UDP-galactopyranose to UDP-galactofuranose catalyzed by the enzyme UDP-galactopyranose mutase (Glf). In Mycobacterium tuberculosis the glf gene overlaps, by 1 nucleotide, a gene, Rv3808c, that has been shown to encode a galactofuranosyl transferase. We demonstrate here that glf can be knocked out in Mycobacterium smegmatis by allelic replacement only in the presence of two rescue plasmids carrying functional copies of glf and Rv3808c. The glf rescue plasmid was designed with a temperature-sensitive origin of replication and the M. smegmatis glf knockout mutant is unable to grow at the higher temperature at which the glf-containing rescue plasmid is lost. In a separate experiment, the Rv3808c rescue plasmid was designed with a temperature-sensitive origin of replication and the glf-bearing plasmid was designed with a normal original of replication; this strain was also unable to grow at the nonpermissive temperature. Thus, both glf and Rv3808c are essential for growth. These findings and the fact that galactofuranosyl residues are not found in humans supports the development of UDP-galactopyranose mutase and galactofuranosyl transferase as important targets for the development of new antituberculosis drugs.

Bacterial Proteins↗
PubMed2001

Effects of two types of brief intervention and readiness to change on alcohol use in hazardous drinkers.

OBJECTIVE: Brief interventions for hazardous and low-dependent drinkers in the primary care setting have considerable empirical support. The purpose of this study was to (1) evaluate the effects of brief advice (BA) and motivational enhancement (ME) interventions on alcohol consumption. In addition, a hindsight matching design was used to (2) study the moderator effects of patient readiness to change (alcohol use) on alcohol consumption. METHOD: The subjects (N = 301, 70% men) were patients 21 years of age or older who presented for treatment at one of 12 primary care clinics. After screening for eligibility and providing consent to participate in the study, the patients completed a baseline assessment and were randomly assigned to the BA, ME or standard care (SC) interventions condition. Follow-up assessments were completed at 1-, 3-, 6-, 9- and 12-months postbaseline assessment. RESULTS: Evaluation of the first hypothesis (n = 232 for these analyses) showed that all participants tended to reduce their alcohol use considerably between the baseline and 12-month assessments. In addition, evaluation of the second hypothesis showed a moderator effect of readiness to change in predicting the number of drinks at 12 months, such that the BA intervention seemed more effective for patients relatively low in readiness to change compared to those higher in readiness. Readiness to change did not seem to be related to changes in drinking of participants in the SC or ME conditions. CONCLUSIONS: The results confirm that, among primary care patients, substantial changes in alcohol consumption are possible. They further suggest that matching studies of patient readiness to change their alcohol use, as well as other variables, are warranted.

Adult↗
PubMed2001

Three questions can detect hazardous drinkers.

OBJECTIVE: The researchers evaluated the Alcohol Use Disorders Identification Test (AUDIT), the first 3 questions of the AUDIT (AUDIT-C), the third AUDIT question (AUDIT-3), and quantity-frequency questions for identifying hazardous drinkers in a large primary care sample. STUDY DESIGN: Cross-sectional survey. POPULATION: Patients waiting for care at 12 primary care sites in western Pennsylvania from October 1995 to December 1997. OUTCOMES MEASURED: Sensitivity, specificity, likelihood ratios, and predictive values for the AUDIT, AUDIT-C, and AUDIT-3. RESULTS: A total of 13,438 patients were surveyed. Compared with a quantity-frequency definition of hazardous drinking (> or =16 drinks/week for men and > or =12 drinks/week for women), the AUDIT, AUDIT-C, and AUDIT-3 had areas under the receiver-operating characteristic curves (AUROC) of 0.940, 0.949, and 0.871, respectively. The AUROCs of the AUDIT and AUDIT-C were significantly different (P=.004). The AUROCs of the AUDIT-C (P<.001) and AUDIT (P <.001) were significantly larger than the AUDIT-3. When compared with a positive AUDIT score of 8 or higher, the AUDIT-C (score > or =3) and the AUDIT-3 (score > or =1) were 94.9% and 99.6% sensitive and 68.8% and 51.1% specific in detecting individuals as hazardous drinkers. CONCLUSIONS: In a large primary care sample, a 3-question version of the AUDIT identified hazardous drinkers as well as the full AUDIT when such drinkers were defined by quantity-frequency criterion. This version of the AUDIT may be useful as an initial screen for assessing hazardous drinking behavior.

Adult↗
PubMed2000

An empirical investigation of the factor structure of the AUDIT.

This study investigated the Alcohol Use Disorders Identification Test's (AUDIT) factor structure and psychometric properties. The factor structure was derived from a sample of 7,035 men and women primary care patients. A principal components analysis identified 2 factors in the AUDIT data and was supported in a confirmatory factor analysis (CFA). The 2 factors were Dependence/Consequences and Alcohol Consumption. The CFA also provided support for a 3-factor model whose factors (Alcohol Consumption, Alcohol Dependence, and Related Consequences) matched those proposed by the AUDIT's developers. Psychometric indexes were determined by use of the baseline and 12-month follow-up data of 301 men and women who entered a clinical trial. The results showed that the 2 factors had good reliability. Validity tests supported the interpretation of what the 2 factors measure, its implications for relationships to other variables, and the comparability of the 2- and 3-factor models.

Adult↗
PubMed2000

Does race make a difference among primary care patients with alcohol problems who agree to enroll in a study of brief interventions?

This study describes the severity, alcohol consumption, consequences, readiness to change, and coping behaviors of African-American and white primary care patients enrolled in a trial of brief interventions for problem drinking. In multivariate analysis, unemployment but not race was associated with clinical indicators of alcohol problems. African-Americans reported no difference in alcohol consumption and similar quality of life scores. African-American race and unemployment were both associated with increased identification and resolution of alcohol problems. There was no difference in readiness to change, but African-Americans reported more problems related to alcohol and greater use of coping behaviors to avoid drinking. African-Americans may be better equipped to manage drinking problems when they do occur due to increased familiarity with coping mechanisms.

Adaptation, Psychological↗
PubMed2000

Screening and identification of older adults with alcohol problems in primary care.

Primary care physicians can anticipate encountering more elderly patients with alcohol problems since this population is increasing and the prevalence of alcohol problems has been stable. Brief screening tools, originally developed and validated among younger adults, may not be appropriate in the elderly. Therefore, specific validation studies and the development of elderly specific instruments have been reported. The specific goals of this report are to (1) review available screening tools for alcohol problems, (2) summarize elderly focused studies, and (3) provide recommendations for use in primary care. Using a variety of standards, the CAGE (Cut down, Annoyed, Guilty, and Eye opener) is the most consistent brief screen, but its threshold may need to be adjusted in the elderly. The Michigan Alcoholism Screening Test-Geriatric Version includes elderly-specific consequences, but its length may hinder routine use even in shortened form. Finally, the Alcohol Use Disorders Identification Test, although less sensitive than the CAGE, can also capture problem drinkers. Efforts are needed to include elderly-specific consequences and meaningful consumption thresholds in a brief, easily applied screen.

Aged↗
PubMed1999

Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice.

Tuberculosis is the leading cause of death in the world resulting from a single bacterial infection. Despite its enormous burden on world health, little is known about the molecular mechanisms of pathogenesis of Mycobacterium tuberculosis. Bacterial multiplication and concomitant tissue damage within an infected host, including experimentally infected mice, occurs primarily in the lungs-the favoured niche of M. tuberculosis. Although it has been proposed that the distinctive cell wall of M. tuberculosis is important for virulence, rigorous genetic proof has been lacking. Here, using signature-tagged mutagenesis, we isolated three attenuated M. tuberculosis mutants that cannot synthesize or transport a complex, cell wall-associated lipid called phthiocerol dimycocerosate (PDIM) which is found only in pathogenic mycobacteria. Two mutants have transposon insertions affecting genes implicated in PDIM synthesis; the third has a disruption in a gene encoding a large transmembrane protein required for proper subcellular localization of PDIM. Synthesis and transport of this complex lipid is only required for growth in the lung; all three mutants are unaffected for growth in the liver and spleen. This clearly shows that a lipid is required for M. tuberculosis virulence.

Animals↗
PubMed1999

Alopecia areata and universalis in the Smyth chicken model for spontaneous autoimmune vitiligo.

The Smyth line (SL) chicken model for spontaneous, postnatal expression of vitiligo may also show varying incidences and degrees of severity ranging from alopecia areata-like to universalis-like integumental changes. Although human vitiligo patients are known to have a four times greater chance of having alopecia areata than do people without vitiligo, in the SL model, feather loss is limited to birds that show some degree of amelanosis of feather and skin tissue. Both the vitiligo and the alopecia have an autoimmune component, as shown by histologic and immunologic studies, including the correctional influences of corticosterone and cyclosporine-A. The major histocompatibility haplotype (MHC) has a major effect on the incidence and expression of the vitiligo, as well as the alopecia that occurs within vitiliginous birds. Three different MHC haplotypes were identified in the original line that was selected for vitiligo, and from these, three sublines were developed, each homozygous for a different haplotype. Of the three sublines (SL101, SL102, and SL103) the vitiligo has a significantly earlier onset and severity in the SL101 than in the other two lines. The incidence of alopecia, however, is significantly lower in the SL101 subline than in the other two. Inheritance of the vitiligo is polygenic with an additional genetic component for the alopecia trait. It is hypothesized, but as yet unproven, that a feather development defect interacts with the SL melanization and immunologic defects to initiate the partial (areata) and complete (universalis) alopecias. The alopecia universalis is rarely seen until adulthood and is characterized by short (<0.5 cm), undeveloped feathers. If feather growth resumes in these birds, the feathers dry up, cease to grow, and often break off.

Alopecia Areata↗
PubMed1997

Characterization of the in vitro synthesized arabinan of mycobacterial cell walls.

Previous studies have shown that polymerized [14C]arabinan can be synthesized from polyprenylphosphate-[14C]arabinose by the particulate enzymes of Mycobacterium smegmatis [R.E. Lee, K. Mikusová, P.J. Brennan and G.S Besra (1995) J. Am. Chem. Soc. 117, 11829-11832]. In the present investigation, the [14C]arabinan product was biochemically characterized. Sizing chromatography revealed a molecular weight consistent with that expected from mature arabinan. Digestion of the [14C]arabinan with a mixture of arabinases produced oligo[14C]arabinoside fragments including hexa[14C]arabinoside and tetra[14C]arabinoside which originated from the non-reducing terminal regions of the polymer, and di[14C]arabinoside from the internal regions of the polymer. These arabinoside fragments represent the major known structural motifs that comprise the arabinan segment of arabinogalactan and lipoarabinomannan. The presence of [14C]arabinose in both the internal and external regions of the [14C]arabinan suggests that polyprenylphosphate-arabinose is the major, and perhaps the only, donor of arabinosyl residues in mycobacteria.

Cell Wall↗
PubMed1997

Outbreak of sporotrichosis among tree nursery workers.

In spring 1994, an outbreak of sporotrichosis occurred at a tree nursery in Florida; 9 (14%) of 65 workers involved in production of sphagnum moss topiaries developed lymphocutaneous sporotrichosis. A cohort study of all 65 employees was conducted to identify risk factors for sporotrichosis, and an environmental investigation was done. The risk of sporotrichosis increased significantly with the duration of working with sphagnum moss (P < .05), in particular with filling topiaries (P < .05), and with having less gardening experience (P < .05). Wearing gloves was protective (P < .005). Sporothrix schenckii was cultured from patients and sphagnum moss used in topiary production. Use of restriction fragment length polymorphism revealed an identical pattern for patient isolates that was different from the patterns of environmental isolates. Physicians should be aware of sporotrichosis in patients with ulcerative skin lesions who have a history of occupational or recreational exposure to sphagnum moss.

Adult↗
PubMed1996

Polyprenylphosphate-pentoses in mycobacteria are synthesized from 5-phosphoribose pyrophosphate.

Polyprenylphosphate-arabinose (in which the polyprenyl unit is found both as decaprenyl and octahydroheptaprenyl) is a donor of mycobacterial cell wall arabinosyl residues. Because of this important role, its biosynthetic pathway, and that of the related lipid, polyprenylphosphate-D-ribose, was investigated. Surprisingly, phosphoribose pyrophosphate was shown to be a key intermediate on the pathway to both polyprenylphosphate-D-pentoses. Thus, incubation of 5-phospho-D-[14C]ribose pyrophosphate with membranes prepared from Mycobacterium smegmatis resulted in the presence of organic-soluble radioactivity that was shown to be, in part, polyprenylphosphate-[14C]arabinose and polyprenylphosphate-[14C]ribose. Two additional intermediates, polyprenylphosphate-5-phospho[14C]ribose and polyprenylphosphate-5-phospho[14C]arabinose, were identified. Further experiments showed that the mature polyprenylphosphate-ribose is formed from phosphoribose pyrophosphate via a two-step pathway involving a transferase to form polyprenylphosphate-5-phosphoribose and then a phosphatase to form the final polyprenylphosphateribose. Polyprenylphosphate-arabinose is formed by a similar pathway with an additional step being the epimerization at C-2 of the ribosyl residue. This epimerization occurs at either the level of phosphoribose pyrophosphate or at the level of polyprenylphosphate-5-phosphoribose.

Carbon Radioisotopes↗
PubMed1996

Enzymatic synthesis of UDP-galactofuranose and an assay for UDP-galactopyranose mutase based on high-performance liquid chromatography.

A method to prepare UDP-galactofuranose (UDP-Galf) free of UDP-galactopyranose (UDP-Galp) is described. The UDP-Galf is synthesized enzymatically from UDP-Galp using the enzyme UDP-galactopyranose mutase. Treatment of UDP-Galp with the enzyme yields an equilibrium mixture of UDP-Galp and UDP-Galf in which UDP-Galf is approximately 7%. In spite of its low yield, the UDP-Galf is readily purified from starting UDP-Galp using a Dionex PA-100 ion exchange HPLC column. The purified UDP-Galf was characterized by chemical degradations, by electrospray mass spectrometry, and by several nuclear magnetic resonance techniques. In addition, an HPLC assay for the enzyme UDP-galactopyranose mutase is presented that requires 0.5 microgram of UDP-Galf per assay and can be used for both qualitative and quantitative measurements of the enzyme activity. These procedures should thus aid in the characterization of the enzymes involved in galactofuranosyl biosynthesis for the cell walls of Mycobacteria, for the lipophosphoglycan of Leishmania, and for other microorganisms where galactofuranosyl residues are found.

Bacterial Proteins↗
PubMed1995

Physico-chemical fate of chromium compounds in the sheep lung model.

Transmission electron microscopy (TEM) equipped with energy-dispersive x-ray analysis (EDX), electron spectroscopy for chemical analysis (ESCA), secondary ion mass spectrometry (SIMS), and laser microprobe for mass analysis (LAMMA) were used to follow the fate of chromium compounds deposited in the sheep tracheal lobe. Four chromium compounds were used: two chromium(VI) compounds (lead chromate and chromium trioxide) and two chromium(III) compounds (chronic oxide and chromium sulfate). Chromium trioxide is very soluble and the other three are slightly soluble. The compositions, concentrations, and sizes of particles were determined in the bronchoalveolar lavages (BAL) at d 2, 3, 5, and 30 after instillation and on the lung samples collected at d 31. The concentrations of particles in the BAL samples separated the chromium compounds in two groups where Cr2O3 and PbCrO4 (as Pb) were higher than Cr2(SO4)3, PbCrO4 (as Cr), and CrO3. The half-life for alveolar clearance of Cr2O3 and Cr2(SO4)3 has been calculated respectively at 11 and 80 d. Prismatic PbCrO4 particles break up in the lung and sustain a high concentration of isometric particles of lead chromate and another lead-containing compound in the BAL. The CrO3 instilled particles react with endogenous compounds or are transformed to insoluble hydroxyl complexes instead of diffusing very rapidly through the alveolar-capillary barrier. The alveolar clearance as measured in the BAL is not different from the control.

Animals↗
PubMed1995

Biosynthetic origin of mycobacterial cell wall arabinosyl residues.

Designing new drugs that inhibit the biosynthesis of the D-arabinan moiety of the mycobacterial cell wall arabinogalactan is one important basic approach for treatment of mycobacterial diseases. However, the biosynthetic origin of the D-arabinosyl monosaccharide residues themselves is not known. To obtain information on this issue, mycobacteria growing in culture were fed glucose labeled with 14C or 3H in specific positions. The resulting radiolabeled cell walls were isolated and hydrolyzed, the arabinose and galactose were separated by high-pressure liquid chromatography, and the radioactivity in each sugar was determined. [U-14C]glucose, [6-3H]glucose, [6-14C]glucose, and [1-14C]glucose were all converted to cell wall arabinosyl residues with equal retention of radioactivity. The positions of the labeled atoms in the arabinose made from [1-14C]glucose and [6-3H]glucose were shown to be C-1 and H-5, respectively. These results demonstrated that the arabinose carbon skeleton is formed via the nonoxidative pentose shunt and not via hexose decarboxylation or via triose condensations. Since the pentose shunt product, ribulose-5-phosphate, is converted to arabinose-5-phosphate as the first step in 3-keto-D-manno-octulosonic acid biosynthesis by gram-negative bacteria, such a conversion was then searched for in mycobacteria. However, cell-free enzymatic analysis using both phosphorous nuclear magnetic resonance spectrometry and colorimetric methods failed to detect the conversion. Thus, the conversion of the pentose shunt intermediates to the D-arabino stereochemistry is not via the expected isomerase but rather must occur via novel metabolic transformations.

Arabinose↗