A comparison of dynamic-state-dependent models of the trade-off between growth, damage, and reproduction

Fast growth can be costly, so trade-offs between growth and fitness are to be predicted when organisms adjust their growth to compensate for earlier environmental conditions. We developed four generic models of increasing complexity with different processes to predict the indeterminate growth of vertebrate ectotherms, which is sensitive to ambient temperature even when food is not limiting. We contrast the predictions of the models with observed experimental data on growth trajectories, feeding activity, and reproductive investment of three-spined sticklebacks and inferred patterns of accumulation of biomolecular damage arising from activity and growth. All models predicted observed patterns of compensatory growth (both accelerating and decelerating) in response to earlier temperature perturbations, but the more complex models provided the best fit to experimental data. Growth trajectories influenced future reproductive investment regardless of final body size at breeding. Our findings suggest that while models with fewer parameters can predict basic patterns of growth in stable conditions, they cannot capture the costly long-term effects of deviations from steady growth trajectories. In contrast, models in which foraging activity is assumed to carry costs are capable of predicting the complex patterns of feeding, growth, and reproductive investment seen in animals, with the cost of a heightened mortality risk (e.g., through predation) being more important than the cost of increased physiological damage.     

Molecular genetic advances in tuberous sclerosis

Over the past decade, there has been considerable progress in understanding the molecular genetics of tuberous sclerosis, a disorder characterised by hamartomatous growths in numerous organs. We review this progress, from cloning and characterising TSC1 and TSC2, the genes responsible for the disorder, through to gaining insights into the functions of their protein products hamartin and tuberin, and the identification and engineering of animal models. We also present the first comprehensive compilation and analysis of all reported TSC1 and TSC2 mutations, consider their diagnostic implications and review genotype/phenotype relationships.     

Differentially Expressed miRNAs Influence Metabolic Processes in Pituitary Oncocytoma

Neurochemical Research - Spindle cell oncocytomas (SCO) of the pituitary are rare tumors accounting for 0.1–0.4% of all sellar tumors. Due to their rarity, little information is available...     

Perinatal mortality and morbidity among babies delivered in water: surveillance study and postal survey

AimTo compare perinatal morbidity and mortality for babies delivered in water with rates for babies delivered conventionally (not in water).DesignSurveillance study (of all consultant paediatricians) and postal survey (of all NHS maternity units).SettingBritish Isles (surveillance study); England and Wales (postal survey).SubjectsBabies born in the British Isles between April 1994 and March 1996 who died perinatally or were admitted for special care within 48 hours of birth after delivery in water or after labour in water followed by conventional delivery (surveillance study); babies delivered in water in England and Wales in the same period (postal survey).Results4032 deliveries (0.6% of all deliveries) in England and Wales occurred in water. Perinatal mortality was 1.2/1000 (95% confidence interval 0.4 to 2.9) live births; 8.4/1000 (5.8 to 11.8) live births were admitted for special care. No deaths were directly attributable to delivery in water, but 2 admissions were for water aspiration. UK reports of mortality and special care admission rates for babies of women considered to be at low risk of complications during delivery who delivered conventionally ranged from 0.8/1000 (0.2 to 4.2) to 4.6/1000 (0.1 to 25) live births and from 9.2 (1.1 to 33) to 64/1000 (58 to 70) live births respectively. Compared with regional data for low risk, spontaneous, normal vaginal deliveries at term, the relative risk for perinatal mortality associated with delivery in water was 0.9 (99% confidence interval 0.2 to 3.6).ConclusionsPerinatal mortality is not substantially higher among babies delivered in water than among those born to low risk women who delivered conventionally. The data are compatible with a small increase or decrease in perinatal mortality for babies delivered in water.

Key messages

• Data on adverse effects of delivery in water have been limited
• Perinatal mortality and risk of admission for special care is similar for babies delivered in water and for low risk deliveries that do not take place in water
• The risk of perinatal mortality for babies delivered in water is similar to the risk for babies born by normal vaginal delivery to women at low risk of adverse outcome
• Delivery in water may have caused water aspiration in two babies and contributed to snapped umbilical cord in five

     

Method for Assessing the Frequency of Transfer of an R Factor on Solid Media and for Isolating Cells of the Donor Type from a Predominantly Repressed Culture

A method for assessing the incidence of R factor transfer on solid media is described. The method gives values similar to those obtained with conventional techniques but allows the derepressed cells from a predominantly repressed population to be isolated.     

A common and recurrent 13-bp deletion in the autoimmune regulator gene in British kindreds with autoimmune polyendocrinopathy type 1.

Autoimmune polyendocrinopathy type 1 (APS1) is an autosomal recessive disorder characterized by autoimmune hypoparathyroidism, autoimmune adrenocortical failure, and mucocutaneous candidiasis. Recently, an autoimmune regulator gene (AIRE-1), which is located on chromosome 21q22.3, has been identified, and mutations in European kindreds with APS1 have been described. We used SSCP analysis and direct DNA sequencing to screen the entire 1,635-bp coding region of AIRE-1 in 12 British families with APS1. A 13-bp deletion (964del13) was found to account for 17 of the 24 possible mutant AIRE-1 alleles, in our kindreds. This mutation was found to occur de novo in one affected subject. A common haplotype spanning the AIRE-1 locus was found in chromosomes that carried the 964del13 mutation, suggesting a founder effect in our population. One of 576 normal subjects was also a heterozygous carrier of the 964del13 mutation. Six other point mutations were found in AIRE-1, including two 1-bp deletions, three missense mutations (R15L, L28P, and Y90C), and a nonsense mutation (R257*). The high frequency of the 964del13 allele and the clustering of the other AIRE-1 mutations may allow rapid molecular screening for APS1 in British kindreds. Furthermore, the prevalence of the 964del13 AIRE-1 mutation may have implications in the pathogenesis of the more common autoimmune endocrinopathies in our population.     

Murine Toxicity of Agrobacterium tumefaciens

Eleven strains of the crown gall organism, Agrobacterium tumefaciens, tested by intraperitoneal injection into mice, were lethal within 48 hr. Five other species had some lethal strains. The lethal effect of A. tumefaciens appeared to be the result of a toxic rather than an infectious process, since histopathological anomalies were not found in mice injected with live cultures and since heat-killed cultures were lethal. The murine toxin disappeared when A. tumefaciens was grown at 36 C and reappeared when the organism was subsequently incubated below 30 C. The murine toxin itself was not inactivated by exposure to 100 C for 30 min. The toxin was associated with the cells and was not excreted into the medium. Centrifugal fractionation revealed that the toxin was associated with the smaller cells in 3-day stationary-phase cultures. These data suggested a possible relationship between toxin production and the production of the agents responsible for the initiation of plant tumors.     

Analysis of the genusZea (Poaceae) using polymorphic chloroplast simple sequence repeats

We have used polymorphic chloroplast simple sequence repeats (cpSSRs) to analyse levels of diversity and relationships within the genusZea. Between two and nine alleles were found at 15 polymorphic loci and combining the data from these loci gave 32 haplotypes in the 37 accessions studied. Genetic differentiation between the two sections within the genus was calculated using theST statistic which showed that 70% of the total variation was found to exist between the sections. A phylogenetic analysis based on the ² distance metric showed a large split between the two sections and suggested multiple origins of modern cultivated maizeZea mays subsp.mays. The agreement of the phylogenetic tree with other molecular, morphological and karyological studies suggests that cpSSRs may have value in phylogenetic studies in plants.     

Measurements of tumor tissue oxygen tension using a time-resolved luminescence-based optical oxylite probe: comparison with a paired survival assay

Recently, a system that measures tissue oxygen tension using time-resolved luminescence-based optical sensors has become available commercially (Oxford Optronix, Oxford, England). Two experiments were conducted using this system. First, the oxygen tension distribution was measured in two tumor lines: a spontaneous mouse fibrosarcoma, FSa-II, and a human squamous cell carcinoma xenograft, FaDu. The area in which the pO(2) was equal to or lower than 2.5 mmHg was defined as the hypoxic lesion, and the hypoxic cell fraction was taken as the fraction of these measurements in a tumor. The measured hypoxic cell fractions were compared with those determined by the paired cell survival assay for tumors of various sizes. Second, the tumor tissue pO(2) was measured continuously after administration of two different anesthetics to evaluate the effect of these drugs on tissue pO(2). Results indicated a good agreement between the hypoxic cell fractions measured by this system and those determined by the paired cell survival curve assay for tumors smaller than approximately 500 mm(3). For tumors larger than approximately 500 mm(3), the hypoxic cell fractions measured by the oxygen probe system were higher than those measured by the paired cell survival assay. This may suggest that the hypoxic cell fraction measured by the oxygen probes included both hypoxic and necrotic areas in large tumors where necrotic lesions occupied a significant portion of the tumor. Continuous measurements of pO(2) after anesthesia (Nembutal, or ketamine plus xylazine) showed a consistent rise in the pO(2) during the first 20-30 min of measurement. Subsequently, the pO(2) values became constant or continued to rise slowly. For comparison, the tumor cell survivals were assayed after a dose of 20 Gy given in air at 5, 20 and 60 min after anesthesia. The result showed a decrease in cell survival only in tumors irradiated 20 min after an injection of Nembutal.     

Genomics of steroid hormones: in silico analysis of nucleotide sequence variants (polymorphisms) of the enzymes involved in the biosynthesis and metabolism of steroid hormones

Alterations of steroid hormone biosynthesis and metabolism are suspected to be involved in the pathogenesis of several diseases. Several polymorphisms of the enzymes involved in these processes have already been described and some could be associated with certain diseases. We attempted to examine the sequence variants of these genes in order to find novel variants by an in silico analysis. We analyzed the known human nucleotide sequences of the enzymes p450 side-chain cleavage enzyme, steroid 17-alpha-hydroxylase/17,20-lyase, 3-beta-hydroxysteroid dehydrogenase types 1 and 2, 21-hydroxylase, 11-beta-hydroxylase, aldosterone synthase, aromatase, 11-beta-hydroxysteroid dehydrogenase types 1 and 2, steroid 5-alpha-reductase types 1 and 2, steroid 5-beta-reductase, dehydroepiandrosterone sulfotransferase, 17-beta-hydroxysteroid dehydrogenase types 1–3. The analysis was performed using the National Center for Biotechnology Information Database by the search tool blastn. We found numerous sequence variants in both coding and non-coding sequences. The majority of these sequence variants have already been described, nevertheless, some appear as novel variants. Some of these may also have functional significance. We hypothesize over the possible significance of these findings and briefly review the available literature.