Fission yeast rad17: a homologue of budding yeast RAD24 that shares regions of sequence similarity with DNA polymerase accessory proteins.

Following DNA damage or a block to DNA synthesis, checkpoint pathways act to arrest mitosis and prevent the attempted segregation of damaged or unreplicated DNA. The rad17 locus of Schizosaccharomyces pombe is one of seven known radiation-sensitive (rad) loci which are absolutely required to prevent mitosis following DNA damage in fission yeast. Six of these (rad1, rad3, rad9, rad17, rad26 and hus1) are also required for the checkpoint which prevents mitosis from occurring before DNA replication is complete. We report here that the predicted rad17 gene product is a basic hydrophilic protein of 606 amino acids which contains five domains with sequence homology to replication factor C (RF-C)/activator 1 subunits. Western analysis and fusion with Green Fluorescent Protein indicate that the abundance and electrophoretic mobility of Rad17 is not significantly modified following a block to DNA synthesis or following DNA damage, and that Rad17 is localized in the nucleus. Rad17 function is not essential for growth, but is required for the function of the DNA structure-dependent checkpoints. Site-directed mutagenesis has been used to demonstrate the biological significance of the RF-C/activator 1-related domains. These studies have also defined an element of the radiation sensitivity caused by loss of Rad17 function which is not associated with the radiation-induced G2 arrest defect seen in the rad17.d null mutant cells.     

Seasonal variation in growth, mortality and fat stores of roach and perch in Lough Neagh, Northern Ireland

The annual cycle for roach ( Rutilus rutilus ) and perch ( Perca fluviatilis ) in Lough Neagh, Northern Ireland can be divided into warm 'growing' and cold 'non-growing' seasons. Summer water temperatures declined between 1991–1993, as did the sizes of 0+ fish of both species. Small overwinter increases in length occurred after poor summers due, in roach, to size-selective mortality. Fat content was size-dependent and increased over the summer in both species. All sizes of roach but only small perch lost fat overwinter. Dead roach collected towards the end of the 1992/3 winter had significantly less fat than live individuals. The allocation of energy to growth (and ultimately reproduction) and to fat (and overwinter survival) was modelled as a tradeoff, assuming that fat has twice the energy density of protein and using observed summer and winter changes in body composition. The predicted allocation optima were close to observed values but, for roach, this entailed a substantial survivorship cost.     

Impact of surgery for stress incontinence on morbidity: cohort study.

OBJECTIVES: To describe the impact of surgery for stress incontinence on the severity of symptoms, other mental and physical symptoms, and overall health. To describe the incidence of postoperative complications. DESIGN: Prospective cohort study; questionnaires completed by patients before and 3, 6, and 12 months after surgery. Questionnaires completed by surgeons both before and after surgery. SETTING: 18 hospitals in the North Thames region. SUBJECTS: 442 women treated surgically for stress incontinence between January 1993 and June 1994. 367 women returned the 3 month questionnaire; 364 returned the 6 month questionnaire; and 359 returned the 12 month questionnaire. 49 surgeons provided perioperative information on 285 of the 442 women and postoperative information on 278. MAIN OUTCOME MEASURES: Stress incontinence symptom severity index, other urinary symptoms, bowel function, mental health, complications, global measures. RESULTS: Most women (288; 87%) reported an improvement in the severity of their stress incontinence, though only 92 (28%) were cured (continent). These improvements persisted for at least 12 months. The likelihood of improvement was similar regardless of whether urodynamic pressure studies had been conducted before surgery. Following surgery, women were less likely to suffer from urinary frequency, nocturia, postvoid fullness, dysuria, and urgency. While mental health improved for 194 (71%), a quarter of women reported deterioration. Only 37 (10%) were satisfied with postoperative pain control. A third experienced one or more complications while in hospital, most commonly difficulty urinating. This problem affected 1 in 11 women after discharge. A year after surgery two thirds of women reported feeling better (251; 72%), that the outcome met or exceeded their expectations (230; 66%), and that they would recommend the operation to a friend in a similar situation (239; 68%), and that they would recommend the operation to a friend in a similar situation (239; 68%). Surgeons tended to be more optimistic about the effects of surgery; they were satisfied with the outcome in 176 (85%) cases and would again treat 245 (94%) of the women as they had done previously. CONCLUSIONS: Although surgery reduces the severity of stress incontinence it is not as effective as current textbooks suggest. Women considering surgery should be provided with more accurate information on the likelihood of an improvement in symptoms and the occurrence of complications, including postoperative pain. Urgency and urge incontinence should not be considered contraindications to surgery. The need for urodynamic assessment before surgery should be reappraised.     

Inferring Coalescence Times from DNA Sequence Data

The paper is concerned with methods for the estimation of the coalescence time (time since the most recent common ancestor) of a sample of intraspecies DNA sequences. The methods take advantage of prior knowledge of population demography, in addition to the molecular data. While some theoretical results are presented, a central focus is on computational methods. These methods are easy to implement, and, since explicit formulae tend to be either unavailable or unilluminating, they are also more useful and more informative in most applications. Extensions are presented that allow for the effects of uncertainty in our knowledge of population size and mutation rates, for variability in population sizes, for regions of different mutation rate, and for inference concerning the coalescence time of the entire population. The methods are illustrated using recent data from the human Y chromosome.     

Sulphur-Containing Amino Acids Modulate Noradrenaline Release from Hippocampal Slices

Abstract: The l - and d -enantiomers of the sulphur-containing amino acids (SAAs)—homocysteate, homocysteine sulphinate, cysteate, cysteine sulphinate, and S-sulphocysteine—stimulated [³H]noradrenaline release from rat hippocampal slices in a concentration-dependent manner. The relative potencies of the l -isomers (EC₅₀ values of 1.05–1.96 mM) were of similar order to that of glutamate (1.56 mM), which was 10-fold lower than that of NMDA (0.15 mM), whereas the d -isomers exhibited a wider range of potencies (0.75 to >5 mM). All stimulatory effects of the SAAs were significantly inhibited by the voltage-sensitive Na⁺ channel blocker tetrodotoxin (55–71%) and completely blocked by addition of Mg²⁺ or Co²⁺ to the incubation medium. All SAA-evoked responses were concentration-dependently antagonized by the selective NMDA receptor antagonist d -(?)-2-amino-5-phosphonopentanoic acid (IC₅₀ values of 3.2–49.5 µM). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, at 100 µM inhibited the [³H]noradrenaline release induced by glutamate and NMDA (65 and 76%, respectively) and by all SAAs studied (65–85%), whereas 10 µM CNQX only inhibited the effects of S-sulpho-l -cysteine and l - and d -homocysteate (33, 32, and 44%, respectively). However, the more selective AMPA/kainic acid receptor antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (100 µM), which did not antagonize the [³H]noradrenaline release induced by glutamate and NMDA, reduced only the S-sulpho-l -cysteine-evoked response (25%). Thus, the stimulation of Ca²⁺-dependent[³H]noradrenaline release from hippocampal slices elicited by the majority of the SAAs appears to be mediated by the NMDA receptor.     

Estimation of sample zooplankton abundance from Folsom splitter sub-samples

Procedures are described for estimating the abundance of eachzooplanklon species in a sample after counting at least twosub-samples from a Folsom splitter. A multinomiai model is assumedfor the splitting process. The method may be summarized as follows:two sub-samples, balanced with respect to the left — rightsplits, are counted. The counts for each species are testedfor homogeneity using a x² test. If the counts are homogeneous,an estimator is given which permits the estimation of the numberof animals in the sample, and the variance of this estimate.If the subsample counts are heterogeneous, it is assumed thatclumping has occurred. A procedure is described in which additionalsub-samples are counted to locate the clump, and estimatorsof abundance (and variance estimators) are derived. If the splitterbias is <5%, bias of the abundance estimator is negligiblecompared to the binomial sampling error. Comparisons of speciesabundance between plankton samples is made more rigorous usingthe estimates of mean abundance, and the variance of this mean,provided by the methods described here. ^*Present address: Dunoon Road, Dorroughby, NSW 2480, Australia.