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PubMed1999

Error-tolerant RF litz coils for NMR/MRI.

A new class of NMR RF volume coils is being developed that permits improved tuning range, B(1) homogeneity, tuning stability, and sensitivity compared to birdcages over a wide range of practical conditions, especially for microscopy and wraparound flexible applications. They are denoted litz coils, as their flux transparency and current distribution is obtained from woven foil patterns with insulated crossovers. Contrary to the design criteria of phased arrays, the parallel routes in litz coils use high coupling coefficients to achieve optimal current distribution, which is highly independent of tuning, balancing, and matching adjustments and is compatible with multiple capacitive segmentation. Magnetic filling factors, loaded Q, and inhomogeneity measurements and calculations are presented for a variety of litz coils with frequency-diameter products from 7 to 20 MHz-m and are compared to similar birdcages.

Equipment Design↗
PubMed2000

Insulin lispro versus regular insulin in children with type 1 diabetes on twice daily insulin.

OBJECTIVE: The aim of this study was to compare the clinical efficacy and safety of insulin lispro with regular insulin in 5- to 10-yr-old prepubertal children on twice daily insulin. RESEARCH DESIGN AND METHODS: Thirty-five children (16 M, 19 F) completed an open-label randomised crossover study, with each child receiving insulin lispro for 3 months and regular insulin for 3 months in addition to their intermediate-acting insulin. Families were instructed to give regular insulin 30 min before meals and insulin lispro immediately before meals. Glycaemic control was monitored by eight-point blood glucose profiles and six weekly hemoglobin A1cs (HbA1cs) and the frequency and severity of hypoglycaemia was documented. RESULTS: The endpoint HbA1c after 3 months on insulin lispro (8.33%, SD+/-0.89) was not significantly different to that on regular insulin (8.14%, SD+/-0.77). No significant differences were found in blood glucose levels before or after meals, 2-h postprandial glucose excursions or in blood glucose levels before bed between the treatments. However, blood glucose levels at 3 am were significantly lower on regular insulin than on insulin lispro (mean difference -2.35 mmol/L (95%CI: -3.98, -0.72, p=0.01). There was no significant difference in the frequency of hypoglycaemic episodes between the groups. CONCLUSIONS: The main advantage of insulin lispro in children on twice daily insulin was found to be its greater convenience, this being achieved without a deterioration in glycaemic control. The higher 3 am blood glucose levels in those on insulin lispro could translate to reduced nocturnal hypoglycaemia in some individuals.

Clinical Trial↗
PubMed2002

The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview.

The new orally active angiotensin II (A II) type-1 receptor antagonist olmesartan medoxomil is a prodrug, which is rapidly converted in vivo to the active metabolite, olmesartan. The pharmacology, antihypertensive efficacy and safety of olmesartan medoxomil and/or the pharmacologically active metabolite, olmesartan, have been evaluated in both non-clinical and clinical models. Orally administered olmesartan medoxomil is rapidly absorbed from the gastrointestinal tract and converted during absorption to olmesartan, which is subsequently excreted without further metabolism. Peak plasma concentrations of olmesartan occur 1-3 h after administration, after which concentrations decrease with an elimination half-life of 10-15 h. The absolute bioavailability of olmesartan from olmesartan medoxomil tablets is 28.6%. In a single-dose crossover study in 16 patients with mild-to-moderate hypertension receiving a sodium-restricted diet, statistically significant lowering of mean 24-h blood pressure was seen at doses of 10-80 mg. Evaluation of 14 phase II/III studies has confirmed the antihypertensive efficacy of olmesartan medoxomil in over 3500 patients who received the drug for up to 2 years. Frequencies of adverse events during treatment with olmesartan medoxomil and placebo are similar, with no evidence of a dose response. There are no clinically significant effects on laboratory parameters, and the drug-interaction potential of olmesartan medoxomil is low. Current indications are that olmesartan medoxomil is a true once-daily, orally active A II antagonist with good antihypertensive efficacy and a favourable adverse-event profile. Clinical pharmaco- dynamic and efficacy studies support a usual dose of 20 mg once daily, increasing to 40 mg if needed.

Administration, Oral↗
PubMed1990

Sn, a light-dependent and tissue-specific gene of maize: the genetic basis of its instability.

The genetic system under investigation is defined by three major components: a gene, Sn, conferring tissue specific anthocyanin accumulation in different plant regions, light, required for color development in competent tissues, and another gene, Pl, substituting for light in its capacity to elicit pigment production. Attention is given in this paper to an Sn allele, symbolized Sn:bol3, capable of some constitutive pigmentation in seedlings and seed integuments. Sn:bol3 confers a higher pigment potential than the other alleles and is unstable. Its instability relates to its frequent changes from an original condition, indicated as Sn-s, to Sn-w, where -s and -w stand for strong and weak and refer to the two levels of seedling pigmentation. Weak derivatives arise spontaneously at a high frequency in homo- and heterozygous Sn:bol3 genotypes. In the latter, weak derivatives are also recovered on the chromosome originally devoid of Sn as if the heterozygous association had promoted "contamination" of one chromosome (recipient) with Sn coming from the other (donor). If the two chromosomes in the heterozygote are marked with contrasting alleles of R, a gene lying about two crossover units proximal to Sn, it appears that the R constitution of the recipient chromosome affects their constitution. Presence of R-r in fact leads to changes of both chromosomes in terms of Sn constitution, resulting in a majority of nonparental chromosomes, R-r Sn and r Sn-w or r sn, while replacement of R-r with R-g, a mutant derivative of R-r, leads to a drastic reduction in the yield of nonparental chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMedDate not supplied

Intrauterine insemination: a systematic review on determinants of success.

Intrauterine insemination (IUI) is a frequently indicated therapeutic modality in infertility. Here, a systematic review of the literature was performed to examine the current status of clinical and laboratory methodologies used in IUI and the impact of female and male factors on pregnancy success. Emphasis was centred in questioning the following: (i) the value of IUI against timed intercourse; (ii) IUI application with or without controlled ovarian hyperstimulation; (iii) timing and frequency of IUI; and (iv) impact of various parameters (male/female) on the prediction of pregnancy outcome. The odds of multiple pregnancy occurrence and its risk factors, as well as the cost-effectiveness of IUI treatment compared with more complex assisted reproductive technologies are discussed. A computerized literature search was performed including Medline and the Cochrane library, as well as a crossover search from retrieved papers. It is concluded that although IUI is a successful contemporary treatment for appropriately selected cases of female and/or male infertility, further research is needed through well-designed studies to improve the methodologies currently utilized. Importantly, the clinical management of the infertile couple should be performed in an expedited manner taking into consideration the age of the woman, the presence of multifactorial infertility and cost-effectiveness of the available treatment alternatives.

Female↗
PubMed2004

Effect of contrast on the active control of a moving line.

In many passive visual tasks, human perceptual judgments are contrast dependent. To explore whether these contrast dependencies of visual perception also affect closed-loop manual control tasks, we examined visuomotor performance as humans actively controlled a moving luminance-defined line over a range of contrasts. Four subjects were asked to use a joystick to keep a horizontal line centered on a display as its vertical position was perturbed by a sum of sinusoids under two control regimes. The total root mean square (RMS) position error decreased quasi-linearly with increasing log contrast across the tested range (mean slope across subjects: -8.0 and -7.7% per log2 contrast, for the two control regimes, respectively). Frequency-response (Bode) plots showed a systematic increase in open-loop gain (mean slope: 1.44 and 1.30 dB per log2 contrast, respectively), and decrease in phase lag with increasing contrast, which can be accounted for by a decrease in response time delay (mean slope: 32 and 40 ms per log2 contrast, respectively). The performance data are well fit by a Crossover Model proposed by McRuer and Krendel, which allowed us to identify both visual position and motion cues driving performance. This analysis revealed that the position and motion cues used to support manual control under both control regimes appear equally sensitive to changes in stimulus contrast. In conclusion, our data show that active control of a moving visual stimulus is as dependent on contrast as passive perception and suggest that this effect is attributed to a shared contrast sensitivity early in the visual pathway, before any specialization for motion processing.

Adult↗
PubMed1977

A double-blind comparative study of the inhibitory effect of intraduodenally administered hyoscine-N-butylbromide on human duodenal motility.

In a double-blind crossover study hyoscine-N-butylbromide (HBB) was compared with placebo in its inhibitory effect on duodenal motility stimulated by metoclopramide. Measurements were made both by the balloon technique and the open-tipped tube method with pressure transducer. 20 mg or 50 mg HBB or placebo were instilled in random sequence into the intestinal tract of 12 healthy volunteers. The frequency of Type II waves was determined in each experiment after administration of the test substance following prior metoclopramide stimulation. This frequency was used as the inhibitory index for each drug. The test substance was administered 15 minutes before a second stimulation. A four-way analysis of variance (mixed model) was applied to the calculated number of waves per period. Subjects were required to respond equally to stimulation with increased motility on both trial days as evidenced by a minimal difference in the averages following the first stimulation on each trial day and before application of the test substance. The frequency of Type II waves after 20 mg and 50 mg HBB was reduced in a statistically significant manner in each case when compared with placebo. The probabilities of error were p less than 0-05 and p less than 0-025.

Adolescent↗
PubMed1993

Regulation of dominant follicle turnover during the oestrous cycle in cows.

The effect of progestin and luteinizing hormone (LH) pulse frequency on dynamics of dominant follicle growth during the first follicular wave after oestrus was examined in non-lactating Holstein cows by ultrasonography. On day 8 of the cycle, cows (n = 8) received a luteolytic dose of prostaglandin F2 alpha (PGF2 alpha; 25 mg) and an ear implant of Norgestomet (6 mg). On day 18, cows were assigned to a crossover design in which the implants were retained (T1) or replaced with a new implant (T2). All implants were removed on day 23. After oestrus, cows underwent a normal intervening oestrus cycle. On day 8 of the third cycle, T1 and T2 were reversed among cows. Ultrasonography and blood sampling were performed on alternate days throughout the experiment. On days 10 and 19 of the third cycle, blood was sampled every 15 min for 8 h in concert with an additional control group (n = 3) sampled on day 10 of the cycle. Progesterone concentration on day 8 before PGF2 alpha was 6.5 +/- 0.5 ng ml-1. Dominance of the first wave dominant follicle was extended beyond day 18 in 15 of 16 cows for T1 and T2 periods. The original dominant follicle ovulated in five of eight T1 and none of eight T2 periods (P < 0.01). New dominant follicles were detected on day 24 +/- 1 in T1 (n = 3) and on day 20.6 +/- 1 in T2 (n = 8; P < 0.01) cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Morbidity among African immigrant population attended at a health center].

OBJECTIVE: To deepen the demographic study of the immigrant population from West Africa who regularly sought health-care at our Health Centre and to analyse their morbidity. DESIGN: A retrospective observation study of a crossover type. SETTING: Salt Basic Health Area, in the Girona Health Region. PATIENTS: The black population originating in West Africa and resident in Salt, whose clinical notes were in the Centre's records. RESULTS: The 57 people registered attended 436 times, of which 289 were for the Paediatric Clinics. Of these 289, 40% were handled by the paediatric nurses. The average frequency of visit by age ranged from 2 attendances a year (20-29 years old) to 14 per year (under 14 years old). In 25.95% of the consultations involving paediatric teams and in 19.05% of those involving adults, no medical diagnosis was made. The most common paediatric diagnoses were, following the CIPSAP-2-WONCA classification: Supplementary Classification (25.95%) and Pathology of the Respiratory System (20.07%). Among adults, Pathologies of the Digestive System (21.77%) and Infectious and Parasite Diseases (12.93%) were the two most common illnesses. Additional tests to assist diagnosis or a simple preventive screening were rarely requested. CONCLUSIONS: Tackling the problems of the black-african population at the Primary Care level is limited by lack of knowledge of tropical diseases, the scant specific bibliography available, linguistic and cultural barriers and the lack of institutional delivery of health-care to the clandestine population. Alternatives are proposed, such as: an operating procedure, and interdisciplinary socio-sanitary programme.

Adolescent↗
PubMed1999

Effects of inhaled nitric oxide and high-frequency ventilation in rabbits with meconium aspiration.

AIM: To evaluate effects of inhaled nitric oxide (iNO) in experimental meconium aspiration treated with high-frequency (HFV) or conventional mechanical ventilation (CMV). Ventilated adult rabbits had meconium instilled intratracheally resulting in respiratory failure as evidenced by more than 50% reduction of dynamic lung compliance (Cdyn) and increase in mean oxygenation index (OI) from 1 to 16. The animals were then allocated to 2 groups treated without (control) or with iNO at 20 ppm (NO). In each group the animals were initially ventilated with CMV or HFV mode for 3 h and then in a crossover fashion with HFV or CMV for another 3 h (CMV-->HFV, HFV-->CMV), respectively. In the first 3 h of treatment, the animals subjected to HFV-CMV in the control, and those with both HFV-CMV and CMV-HFV in the NO group had significantly reduced OI. In the subsequent 3 h, the animals in the control group with CMV-HFV did not improve in OI and those with HFV-CMV had deteriorated. In the NO group with both CMV-HFV and HFV-CMV moderate improvement of OI was observed. Platelet aggregation capability and counts were significantly decreased and bleeding time prolonged in animals receiving iNO treatment. These results suggest that both HFV alone and a combined treatment of iNO with either CMV or HFV are more effective in improving blood oxygenation than that of CMV in this animal model. The influence of iNO on platelet aggregation should be considered.

Administration, Inhalation↗
PubMed1996

[RO 48-6791--a short acting benzodiazepine. Pharmacokinetics and pharmacodynamics in young and old subjects in comparison to midazolam].

The objectives of the present study were to compare in a randomized double-blind crossover study design the concentration-effect relationships of Ro 48-6791, a new benzodiazepine agonist, and midazolam, following infusion in young and elderly male volunteers. Therefore, linearly increasing plasma concentrations were generated by computer controlled infusion pumps to achieve a deep hypnotic effect. The endpoint of the infusion was defined by loss of response to loud verbal commands and a median frequency of the recorded EEG power spectrum below 4 Hz. Arterial blood samples were collected in regular intervals up to 6 hours after cessation of the infusion. The method of pharmacokinetic-pharmacodynamic modeling was used to quantify the concentration-effect relationship, including age related differences, already in this early phase I study. The total clearance of Ro 48-6791 was found to be 1410 +/- 380 vs. 399 +/- 91 ml min-1 for midazolam (mean +/- SD; P < 0.005) and the central volume of distribution to be 20.5 +/- 7.1 vs. 7.9 +/- 3.0 l, respectively (P < 0.005). The comparison between young and elderly volunteers yielded for Ro 48-6791 a statistically not significant reduction of 16% for clearance with age and a slowed distribution of 47% for midazolam (P < 0.05). The recovery period for Ro 48-6791 was reduced by 66% (P < 0.005) in the young and 45% (P < 0.01) in the elderly, respectively, in comparison with midazolam. With respect to the total doses administered, Ro 48-6791 appeared to be 2.5 times as potent as midazolam in all volunteers (P < 0.001). Comparing both age groups, the doses necessary to cause similar effects were reduced by one half for both compounds in the elderly (P < 0.001). The major advantages of Ro 48-6791 compared to midazolam were its shorter duration of action as well as the faster recovery and thus the better controllability. Further investigations would have to confirm these results in a greater number of patients. The applied method of pharmacokinetic-pharmacodynamic modeling not only allowed to quantify the efficacy of Ro 48-6791 but also provided data to augment the safety for further investigations.

Adjuvants, Anesthesia↗
PubMed1999

High-fat dairy product consumption increases delta 9c,11t-18:2 (rumenic acid) and total lipid concentrations of human milk.

Conjugated octadecadienoic acids (18:2, conjugated linoleic acids) have been shown to be anticarcinogenic and may influence growth and nutrient partitioning. The delta 9c,11t-18:2 isomer (rumenic acid, RA) is most common in both food sources and human tissues. To determine if maternal diet can influence milk RA concentration, breastfeeding women (n = 16) were enrolled in a 3-wk crossover study. Women initially consumed minimal amounts of food containing RA during week 1, then were assigned randomly to consume diets rich in high-fat dairy foods (and thus RA) during week 2 or 3. Milk was collected by complete breast expression twice during each experimental week. Current and chronic RA intakes were estimated by 3-d dietary records and food frequency questionnaires, respectively. Estimated chronic RA intakes ranged from 49 to 659 mg/d. Dietary RA intake was greater during the high compared to the low dairy period (291 +/- 75 vs. 15 +/- 24 mg/d, respectively; P < 0.0001). Milk contained more RA during the high than the low dairy period (13.5 +/- 0.1 vs. 8.2 +/- 0.4 mumol/g lipid, respectively; P < 0.0001). Milk lipid concentration was influenced by diet, such that lipid concentration was greater during the high than the low dairy period (46.6 +/- 5.0 vs. 38.3 +/- 1.6 mg/g milk, respectively; P < 0.05). Additionally, multiple regression analyses suggested that body mass index was the primary predictor of milk RA and lipid concentrations. In summary, these data indicate that both lipid and RA concentrations of human milk can be influenced by diet.

Adult↗
PubMed1985

Effect of naloxone on menopausal flushes, skin temperature, and luteinizing hormone secretion.

The effect of naloxone (1.4 mg/hr for 3 hours) on subjectively experienced menopausal flushes, skin temperature, and luteinizing hormone secretion was investigated in seven women in a double-blind, saline-controlled, crossover study. Naloxone had no effect on the number of subjective flushes, episodic skin temperature elevation, luteinizing hormone pulses, variability of luteinizing hormone secretion, or total luteinizing hormone secretion. This study suggests that a naloxone-sensitive opioid mechanism is not active in modulating luteinizing hormone secretion in the postmenopausal woman and that opioid receptor blockade is not effective in altering the frequency of menopausal flushes.

Climacteric↗
PubMed2004

Study of lubricant-induced changes in chronic snorers (SLICCS).

OBJECTIVE: The efficacy of many of the noninvasive treatments for snoring has not been evaluated in controlled trials. This paper seeks to evaluate the efficacy of an oil-based spray in the treatment of snoring, in a double-blinded, placebo-controlled, crossover trial using objective acoustic analysis and subjective questionnaires. STUDY DESIGN AND SETTING: Participants were randomized to use both oil-based oral spray (treatment) and water-based oral spray (placebo) during a two-night in-home study period. Questionnaires were completed by participant and bed-partner in addition to audio-tape recordings which were analyzed for frequency, duration, and mean energy of snoring. RESULTS: Greatest snoring rate demonstrated 30% = benefit; 40% = no change; 30% = adverse effect (n = 20). Percent time snoring yielded: 30% benefit; 15% no change; 55% adverse effect (n = 20). Study data results for mean energy were (n = 12): benefit = 17%, no change = 33%, adverse effect = 50%. Bed-partner observations (n = 17) demonstrated 37% = benefit; 38% = no change; 25% = adverse effect. CONCLUSION/SIGNIFICANCE: Objective and subjective evaluation of the performance of the oil-based Snoreless spray in comparison to placebo demonstrated a lack of efficacy in snoring reduction.

Acoustics↗
PubMed1996

Effect of dietary fat content on oral bioavailability of menatetrenone in humans.

The purpose of this investigation was to determine the effects of fat content and frequency of meals on the oral bioavailability of menatetrenone (2-methyl-3-all-trans-tetraprenyl-1,4-naphthoquinone), a vitamin K2 with four isoprene units. In the first series of studies, menatetrenone (15 mg) was administered at breakfast time to 18 healthy male volunteers after meals with three different fat contents (meals A, B, and C) on three occasions in a crossover design. The three types of meals had almost the same calorie content (721-746 kcal) with varied fat contents (A, 8.8 g; B, 20.0 g; C, 34.9 g). The area under the plasma menatetrenone concentration-time curve within the first 24 h (AUC0-24) increased with increase of fat content: 371 +/- 194, 485 +/- 150, and 1024 +/- 341 ng.h/mL (mean +/- SD, n = 18) after meals A, B, and C, respectively. On the fourth occasion, the same dose of menatetrenone was administered to all volunteers after taking meal B, but in this case the lunch 5 h after drug administration was omitted from the protocol. The time profile of plasma menatetrenone showed a single peak when lunch was not taken, whereas it showed two peaks with lunch. On the fifth occasion, 12 out of 18 volunteers took the same dose of menatetrenone after a meal with the highest fat content (53.8 g of fat and 789 kcal; meal D), showing that AUC0-24 was almost the same as that for meal C, 1027 +/- 389 and 991 +/- 392 ng.h/mL (n = 12) for meals C and D, respectively. The oral bioavailability of lipid-soluble vitamin K was influenced by the fat content of a meal, although the increase in bioavailability seemed to reach a peak when the lipid content of the meal was > 35 g.

Administration, Oral↗
PubMed2003

Effects of procyclidine on eye movements in schizophrenia.

Smooth pursuit eye movement (SPEM) and antisaccade deficits are observed in the schizophrenia spectrum and have been used to study the pathophysiology as well as the genetic basis of this condition. The neurotransmitter acetylcholine has been implicated in a number of cognitive processes thought to underlie SPEM and antisaccade performance. This study investigates effects on eye movements of procyclidine, an anticholinergic drug often administered to schizophrenic patients. A total of 13 patients completed a double-blind placebo-controlled crossover design, receiving 15 mg procyclidine and placebo. Seven participants received procyclidine first and placebo second, six participants were tested in the reverse order. SPEM and antisaccade (as well as fixation and prosaccade) eye movements were recorded using infrared oculography. Results showed that procyclidine overall, relative to placebo, mildly worsened SPEM performance, as indicated by nonsignificantly reduced gain (p=0.08) and increased frequency of intrusive anticipatory saccades during pursuit (p=0.06). A significant interaction of group and order of administration indicated that procyclidine increased the rate of antisaccade reflexive errors only when administered first; the opposite pattern was observed when placebo was administered first, likely due to the operation of practice effects at second assessment. These findings indicate that acute administration of a clinically relevant dose of procyclidine leads to mild impairments in eye movement performance in schizophrenic patients, suggesting the need to consider this compound in oculomotor studies in schizophrenia. The action of this anticholinergic drug on oculomotor performance is consistent with the hypothesized role of the cholinergic system in the cognitive mechanisms of attention and working memory, processes thought to underlie SPEM and antisaccade performance. Effects of order of administration and practice on the antisaccade task suggest that these factors need to be taken into consideration in future pharmacological studies.

Adult↗
PubMed1985

Activity-sensing, rate-responsive pacing: improvement in myocardial performance with exercise.

A sensor that detects body activity by low frequency sonic impulses has been incorporated in a pacemaker so that body activity may be translated to an increased pacing rate in response to exercise. The pacemaker is designed for patients who may benefit from an increased cardiac output mediated by an increased heart rate during exercise. Following permanent pacemaker implantation, six patients (mean age 69 years) entered a single blind, randomized, crossover trial for comparison of activity-sensing, rate-responsive pacing (A) to fixed rate demand pacing (D). Ventricular function was assessed by gated radionuclide ventriculography at rest and at exercise, while exercise capacity was assessed by treadmill performance, along with measurements of oxygen consumption and carbon dioxide production. Total treadmill duration and maximum oxygen consumption were similar in the two pacing modes (A = 284 +/- 244 s, 13.4 +/- 3.4 ml O2/min/kg; D = 256 +/- 250 s, 11.7 +/- 3.7 ml O2/min/kg). Anaerobic threshold, however, was significantly improved (A = 266 +/- 199 s, (p less than .05), 13.0 +/- 2.2 ml O2/min/kg (p less than .01); D = 231 +/- 208 s, 10.8 +/- 2.3 ml O2/min/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Recombination hotspots flank the Cryptococcus mating-type locus: implications for the evolution of a fungal sex chromosome.

Recombination increases dramatically during meiosis to promote genetic exchange and generate recombinant progeny. Interestingly, meiotic recombination is unevenly distributed throughout genomes, and, as a consequence, genetic and physical map distances do not have a simple linear relationship. Recombination hotspots and coldspots have been described in many organisms and often reflect global features of chromosome structure. In particular, recombination frequencies are often distorted within or outside sex-determining regions of the genome. Here, we report that recombination is elevated adjacent to the mating-type locus (MAT) in the pathogenic basidiomycete Cryptococcus neoformans. Among fungi, C. neoformans has an unusually large MAT locus, and recombination is suppressed between the two >100-kilobase mating-type specific alleles. When genetic markers were introduced at defined physical distances from MAT, we found the meiotic recombination frequency to be approximately 20% between MAT and a flanking marker at 5, 10, 50, or 100 kilobases from the right border. As a result, the physical/genetic map ratio in the regions adjacent to MAT is distorted approximately 10- to 50-fold compared to the genome-wide average. Moreover, recombination frequently occurred on both sides of MAT and negative interference between crossovers was observed. MAT heterozygosity was not required for enhanced recombination, implying that this process is not due to a physical distortion from the two non-paired alleles and could also occur during same-sex mating. Sequence analysis revealed a correlation between high G + C content and these hotspot regions. We hypothesize that the presence of recombinational activators may have driven several key events during the assembly and reshaping of the MAT locus and may have played similar roles in the origins of both metabolic and biosynthetic gene clusters. Our findings suggest that during meiosis the MAT locus may be exchanged onto different genetic backgrounds and therefore have broad evolutionary implications with respect to mating-type switching in both model and pathogenic yeasts.

Base Composition↗