The frequency of lysosomal storage diseases in The Netherlands

We have calculated the relative frequency and the birth prevalence of lysosomal storage diseases (LSDs) in The Netherlands based on all 963 enzymatically confirmed cases diagnosed during the period 1970–1996. The combined birth prevalence for all LSDs is 14 per 100,000 live births. Glycogenosis type II is the most frequent LSD with a birth prevalence of 2.0 per 100,000 live births, representing 17% of all diagnosed cases. Within the group of lipidoses, metachromatic leukodystrophy (MLD) is the most frequent LSD. MLD was diagnosed in 24% of lipidoses and the calculated birth prevalence was 1.42 per 100,000 for all types combined. Krabbe disease, diagnosed in 17% of cases, also belongs to the more frequent lipid storage diseases in The Netherlands with a birth prevalence of 1.35 per 100,000. The birth prevalence of Gaucher disease, commonly regarded as the most frequent lipid storage disease is 1.16 per 100,000 for all types combined. The combined birth prevalence for all lipid storage diseases is 6.2 per 100,000 live births. Within the group of mucopolysaccharidoses (MPSs), MPS I has the highest calculated birth prevalence of 1.19 per 100,000 (25% of all cases of MPS diagnosed), which is slightly more frequent than MPS IIIA with an estimated birth prevalence of 1.16 per 100,000. As a group, MPS III comprises 47% of all MPS cases diagnosed and the combined birth prevalence is 1.89 per 100,000 live births. The birth prevalence of MPS II is 0.67 per 100,000 (1.30 per 100,000 male live births). All other MPSs are rare. The combined birth prevalence for all MPSs is 4.5 per 100,000 live births. Mucolipidoses and oligosaccharidoses are very rare with birth prevalences between 0.04 and 0.20 for individual diseases. Only 49 cases were diagnosed between 1970 and 1996. Their combined birth prevalence is 1.0 per 100,000 live births.     

Cell death (apoptosis) in hair follicles and consequent changes in the width of hairs after irradiation of growing follicles

Irradiation of anagen (growing) hair follicles results in a dose-dependent increase in the number of histologically identifiable fragments of dead cells (apoptotic fragments). The incidence of apoptotic fragments is linearly related to dose, increasing at a rate of 2.92 fragments per follicle section per Gy. The effects of doses of 0.2 Gy can be easily detected. Subjective attempts to associate clusters of fragments with dead or dying cells suggests that the number of fragments per cell increases with dose (about 1.7 fragments per cell after 1 Gy to about 2.7 fragments per cell after 5 Gy). There is a natural incidence of cell death in controls (0.13 +/- 0.06 fragments per follicle section with about 1.4 fragments per dead or dying cell). Damage to the follicle cells is expressed in the differentiated product of the follicle, the hair, by a reduction in width. This is probably the cellular basis for the production of dysplastic hairs. The hair width has been measured and is reduced by about 7 per cent for every gray of radiation. The value of the hair and hair follicles as potential biological dosimeters is discussed.     

Circadian rhythms in Drosophila melanogaster: analysis of period as a function of gene dosage at the per (period) locus

Mutations at the per (period) locus of Drosophila melanogaster affect the period of its circadian rhythms. An analysis of published data on strains having duplications and deletions of the per locus indicates that the period is a logarithmic function of the level of the per gene product. The analysis also indicates that period is relatively insensitive to the level of that gene product; a presumed 300% increase in the gene product level produces only a 4.6% decrease in the period. The period of a strain transformed with per+ DNA conforms to the same logarithmic relationship if the level of mRNA in the transformant, which is one-tenth that in the wild type, is considered equivalent to a gene dosage one-tenth the wild type dose of 2, or 0.2. The periods of strains having various doses of mutant per alleles which shorten (pers) or lengthen (per1) the period can be fitted to the same logarithmic function. The analysis may provide an explanation for the partial dominance of pers over per+ and the dominance of per+ over per1, since it suggests that the per1 gene product is nearly inactive while the pers gene product is more than 34 times as active as the wild type product. Analysis of periods of strains heterozygous at the per locus suggests that the per gene product may be a multimeric protein. Three possible roles for the per gene product in circadian rhythmicity are discussed, including a role in synchronizing rhythm-producing cells.     

THE TOTAL LUMINOUS EFFICIENCY OF LUMINOUS BACTERIA

Methods are described for measuring the light emitted by an emulsion of luminous bacteria of given thickness, and calculating the light emitted by a single bacterium, measuring 1.1 x 2.2 micra, provided there is no absorption of light in the emulsion. At the same time, the oxygen consumed by a single bacterium was measured by recording the time for the bacteria to use up .9 of the oxygen dissolved in sea water from air (20 per cent oxygen). The luminescence intensity does not diminish until the oxygen concentration falls below 2 per cent, when the luminescence diminishes rapidly. Above 2 per cent oxygen (when the oxygen dissolving in sea water from pure oxygen at 760 mm. Hg pressure = 100 per cent) the bacteria use equal amounts of oxygen in equal times, while below 2 per cent oxygen it seems very likely that rate of oxygen absorption is proportional to oxygen concentration. By measuring the time for a tube of luminous bacteria of known concentration saturated with air (20 per cent oxygen) to begin to darken (2 per cent oxygen) we can calculate the oxygen absorbed by one bacterium per second. The bacteria per cc. are counted on a blood counting slide or by a centrifugal method, after measuring the volume of a single bacterium (1.695 x 10^–12 cc.). Both methods gave results in good agreement with each other. The maximum value for the light from a single bacterium was 24 x 10^–14 lumens or 1.9 x 10^–14 candles. The maximum value for lumen-seconds per mg. of oxygen absorbed was 14. The average value for lumen-seconds per mg. O₂ was 9.25. The maximum values were selected in calculating the efficiency of light production, since some of the bacteria counted may not be producing light, although they may still be using oxygen. The "diet" of the bacteria was 60 per cent glycerol and 40 per cent peptone. To oxidize this mixture each mg. of oxygen would yield 3.38 gm. calories or 14.1 watts per second. 1 lumen per watt is therefore produced by a normal bacterium which emits 14 lumen-seconds per mg. O₂ absorbed. Since the maximum lumens per watt are 640, representing 100 per cent efficiency, the total luminous efficiency if .00156. As some of the oxygen is used in respiratory oxidation which may have nothing to do with luminescence, the luminescence efficiency must be higher than 1 lumen per watt. Experiments with KCN show that this substance may reduce the oxygen consumption to 1/20 of its former value while reducing the luminescence intensity only ¼. A partial separation of respiratory from luminescence oxidations is therefore effected by KCN, and our efficiency becomes 5 lumens per watt, or .0078. This is an over-all efficiency, based on the energy value of the "fuel" of the bacteria, regarded as a power plant for producing light. It compares very favorably with the 1.6 lumens per watt of a tungsten vacuum lamp or the 3.9 lumens per watt of a tungsten nitrogen lamp, if we correct the usual values for these illuminants, based on watts at the lamp terminals, for a 20 per cent efficiency of the power plant converting the energy of coal fuel into electric current. The specific luminous emission of the bacteria is 3.14 x 10^–6 lumens per cm². One bacterium absorbs 215,000 molecules of oxygen per second and emits 1,280 quanta of light at λ_max = 510µµ. If we suppose that a molecule of oxygen uniting with luminous material gives rise to the emission of 1 quantum of light energy, only 1/168 of the oxygen absorbed is used in luminescence. On this basis the efficiency becomes 168 lumens per watt or 26.2 per cent.     

Microbiological Assay for Organic Compounds in Seawater

A method for the quantitative identification of organic compounds in seawater has been developed. When auxotrophic mutants of Serratia marinorubra were incubated at 21 to 24 C for 72 hr with constant agitation, standard bioassay reference curves were obtained. Sodium glycerophosphate (400 mg per liter), ammonium dibasic citrate (5 g per liter), and glycerol (25 ml per liter) supplied the needed nutrients for maximal growth with a limited concentration of the required metabolite. Data are presented for the microbiological assay for biotin in waters of the Gulf of Mexico and adjacent bays. The range of sensitivity for the biotin mutant A101V is 5 to 12 mmug per liter in seawater, with a growth response from 2 to 16 mmug per liter of seawater. The possible ecological and chemical significance of biotin occurrence in spring-summer off-shore water is discussed.     

Effects of polyploidy on photosynthesis

In polyploid plants the photosynthetic rate per cell is correlated with the amount of DNA per cell. The photosynthetic rate per unit leaf area is the product of the rate per cell times the number of photosynthetic cells per unit area. Therefore, the photosynthetic rate per unit leaf area will increase if there is a less than proportional increase in cell volume at higher ploidal levels, or if cell packing is altered to allow more cells per unit leaf area. In autopolyploids (Medicago sativa, C₃ species, and Pennisetum americanum, C₄ species) there is a doubling of photosynthesis per cell and of cell volume in the tetraploid compared to the diploid. However, there is a proportional decrease in number of cells per unit leaf area with this increase in ploidy such that the rate of photosynthesis per leaf area does not change. There is more diversity in the relationship between ploidal level (gene dosage) and photosynthetic rates per unit leaf area in allopolyploids. This is likely to reflect the effects of natural selection on leaf anatomy, and novel genetic interactions from contributed genomes which can occur with allopolyploidy. In allopolyploid wheat (C₃ species) a higher cell volume per unit DNA at the higher ploidal level is negatively correlated with photosynthesis rate per unit leaf area. Although photosynthesis per cell increases with ploidy, photosynthesis per leaf area decreases, being lowest in the allohexaploid, cultivated bread wheat (Triticum aestivum). Alternatively, doubling of photosynthetic rate per cell with doubling of DNA, with apparent natural selection for decreased cell volume per unit DNA, results in higher rates of photosynthesis per leaf area in octaploid compared to tetraploid Panicum virgatum (C₄) which may be a case of allopolyploidy. Similar responses probably occur in Festuca arundinacea. Therefore, in some systems anatomical factors affecting photosynthesis are also affected by ploidal level. It is important to evaluate that component as well as determining the effect on biochemical processes. Current information on polyploidy and photosynthesis in several species is discussed with respect to anatomy, biochemistry and bases for expressing photosynthetic rates.Abbreviations Chl chlorophyll - RuBPC ribulose-1,5-bisphosphate carboxylase     

Economic damage by Limothrips denticornis in rye, triticale and winter barley

Abstract:  Limothrips denticornis is a common thrips infesting rye, triticale and winter barley in Sweden. Field experiments with insecticides were carried out 1983–1996 in farmers' fields to investigate the damage to the plant and to evaluate the relationship between thrips density and crop yield losses. The total number of experiments was 99 in rye, 41 in triticale and nine in winter barley. The mean number of thrips per leaf sheath was around 8 in all three crops. The highest number found was 27 thrips per leaf sheath. The population density in the leaf sheath was correlated with the damage observed on the leaf sheath as percentage damaged surface. The effect on the leaf sheath alone contributed to a significant proportion of the yield loss. Thrips in the ear and aphids also contributed to the damage but with multiple regression methods it was possible to estimate the damage done solely by L. denticornis . The yield loss caused by L. denticornis was about the same in all three crops, with a variation between 21 and 26 kg per thrips per leaf sheath and hectare. Compared with the yield loss for aphids, which is about 40 kg per aphid per tiller and hectare, this is considerably lower. The economic injury level was found to be about 14 thrips per straw. The economic threshold for L. denticornis has to be decided when the females are flying into the crop and it was found to be 0.5 females per straw at earing. Economic damage by L. denticornis alone was estimated to be 20% of the total number of experiments for all three crops but economic damage for the three pests together was estimated at 40% of the total number of experiments.     

A novel circadianly expressed Drosophila melanogaster gene dependent on the period gene for its rhythmic expression.

The Drosophila melanogaster period (per) gene is required for expression of endogenous circadian rhythms of locomotion and eclosion. per mRNA is expressed with a circadian rhythm that is dependent on Per protein; this feedback loop has been proposed to be essential to the central circadian pacemaker. This model would suggest the Per protein also controls the circadian expression of other genetic loci to generate circadian behavior and physiology. In this paper we describe Dreg-5, a gene whose mRNA is expressed in fly heads with a circadian rhythm nearly identical to that of the per gene. Dreg-5 mRNA continues to cycle in phase with that of per mRNA in conditions of total darkness and also when the daily feeding time is altered. Like per mRNA, Dreg-5 mRNA is not expressed rhythmically in per null mutant flies. Dreg-5 encodes a novel 298 residue protein and Dreg-5 protein isoforms also oscillate in abundance with a circadian rhythm. The phase of Dreg-5 protein oscillation, however, is different from that of Per protein expression, suggesting that Dreg-5 and per have common translational but different post-translational control mechanisms. These results demonstrate that the per gene is capable of modulating the rhythmic expression of other genes; this activity may form the basis of the output of circadian rhythmicity in Drosophila.     

Meta-analysis of the impact of stocking rate on the productivity of pasture-based milk production systems

The objective of this study is to quantify the milk production response per cow and per hectare (ha) for an incremental stocking rate (SR) change, based on a meta-analysis of published research papers. Suitable experiments for inclusion in the database required a comparison of at least two SRs under the same experimental conditions in addition to details on experimental length and milk production results per cow and per ha. Each additional increased SR treatment was also described in terms of the relative milk production change per cow and per ha compared to the lower base SR (b_SR). A database containing 109 experiments of various lengths with 131 comparisons of SR was sub-divided into Type I experiments (common experimental lengths) and Type II experiments (variable experimental lengths). Actual and proportional changes in milk production according to SR change were analysed using linear mixed model procedures with study included as a random effect in the model. Low residual standard errors indicated a good precision of the predictive equations with the exception of proportional change in milk production per cow. For all milk yield variables analysed, the results illustrate that while production per cow is reduced, a strong positive relationship exists between SR and milk production per ha. An SR increase of one cow/ha resulted in a decrease in daily milk yield per cow of 7.4% and 8.7% for Type I and Type II data, respectively, whereas milk yield per ha increased by 20.1% and 19.6%, respectively. Within the Type II data set, a one cow/ha increase in SR also resulted in a 15.1% reduction in lactation length (equivalent to 42 days). The low predictability of proportional change in milk production per cow according to the classical SR definition of cows per ha over a defined period suggests that SR may be more appropriately defined in terms of the change in available feed offered per animal within each treatment.     

大豆小区产量及其相关性状QTL间的上位性和环境互作效应

以晋豆23栽培大豆(Glycine max)为母本、灰布支黑豆(ZDD2315,半野生大豆)为父本衍生出447个RIL群体,通过构建SSR遗传图谱及利用混合线性模型分析方法,对2年大豆小区产量及主要植物学性状进行QTL定位,并作加性效应、加性×加性上位互作效应及环境互作效应分析。结果显示,共检测到12个与小区产量、单株粒重、单株茎重、单株粒茎比、有效分枝、主茎节数、株高和结荚高度相关的QTL,分别位于A1、A2、H_1、I、J_2和M连锁群上。其中小区产量、株高、单株粒重、有效分枝和主茎节数均表现为遗传正效应,即增加其性状的等位基因来源于母本晋豆23。同时,检测到11对影响小区产量、单株粒重、单株茎重、株高和结荚高度的加性×加性上位互作效应及环境互作效应的QTL,发现22个QTL与环境存在互作。实验结果表明,上位效应和QE互作效应对大豆小区产量及主要农艺性状的遗传影响很大。进行大豆分子标记辅助育种时,既要考虑效应起主要作用的QTL,又要注重上位性QTL,这样有利于性状的稳定表达和遗传。     

Estimating mutation rate and generation time from longitudinal samples of DNA sequences

We present in this paper a simple method for estimating the mutation rate per site per year which also yields an estimate of the length of a generation when mutation rate per site per generation is known. The estimator, which takes advantage of DNA polymorphisms in longitudinal samples, is unbiased under a number of population models, including population structure and variable population size over time. We apply the new method to a longitudinal sample of DNA sequences of the env gene of human immunodeficiency virus type 1 (HIV-1) from a single patient and obtain 1.62 x 10(-2) as the mutation rate per site per year for HIV-1. Using an independent data set to estimate the mutation rate per generation, we obtain 1.8 days as the length of a generation of HIV-1, which agrees well with recent estimates based on viral load data. Our estimate of generation time differs considerably from a recent estimate by Rodrigo et al. when the same mutation rate per site per generation is used. Some factors that may contribute to the difference among different estimators are discussed.     

Comparison of two cacao (Theobroma cacao L.) clones for the effect of pollination intensity on fruit set and seed content

We compared the influence of pollination intensity (PI) on fruit set and seed number per pod in two cacao (Theobroma cacao L.) clones, IFC5 (Forastero Lower-Amazon Amelonado), which is self-compatible and known to produce a high number of seeds per pod under open pollination, and SCA6 (Forastero Upper-Amazon), which is self-incompatible and known to produce a low number of seeds per pod under open pollination. With both clones, PI had a positive effect on fruit set, with the maximum rate requiring more than 150 pollen grains per pod. One-half of the maximum rate of fruit set was reached with 39 pollen grains per pod for SCA6, and 78 for IFC5. With SCA6, a significant positive effect of PI on seed number per pod was also observed, with maximum seed number requiring more than 200 pollen grains per pod. In contrast, seed numbers with IFC5 were approximately equal over the PI range 100–800 pollen grains per pod. Patterns of seed number per pod were compared after: (1) open insect pollination, (2) low-intensity hand pollination and (3) high-intensity hand pollination. The patterns obtained with IFC5 under open pollination showed a peak of 40–50 seeds per pod, whereas the distribution patterns were more even with SCA6. The pattern of seed number under open pollination was similar to that obtained with high-intensity hand pollination for IFC5, and with low-intensity hand pollination for SCA6. We concluded that the high number of seeds per pod observed with IFC5 under natural insect pollination may be explained by a high number of compatible self-pollen grains on the stigma and by a severe drop of low-pollinated flowers eliminating potential lowfilled fruits. With SCA6, however, the number of compatible pollen grains deposited on the stigma was probably low under open pollination, and the flowers required lower pollen quantities to set fruit, which resulted in a high frequency of low seed numbers per fruit. This difference in the capacity to set low-seeded fruits might be considered as an adaptive trait related to the mode of reproduction.     

Growth of Chlorella in a Nitrate-limited Chemostat

Chlorella pyrenoidosa was grown in a continuous-flow chemostat under nitrogen-limited conditions. The population density tended to oscillate very significantly. Net specific growth rate was only approximately a hyperbolic function of nitrate concentration in the chemostat. The best estimate of the half-saturation constant for nitrate is 6 mug of nitrogen per liter and it is unlikely that the value is greater than 14 mug per liter or 1 mum nitrate.The dry weight production of cells per unit of nitrogen taken up is a linearly decreasing function of the net specific growth rate with a maximum of 27.1 mg per mg N and a minimum of about 9 mg per mg N. Thus there is considerable storage of nitrogen at high growth rates. Both the dark respiration rate and the rate of photosynthesis at light saturation increase with increasing net specific growth rate.     

MEASUREMENT OF THYROXIN SYNTHESIS WITH I131—A Test for Evaluation of Thyroid Function in Equivocal States

As the function of the thyroid gland is the synthesis and secretion of thyroxin, a test which correctly measures this process is best for diagnosis of thyroid disorder and for determining the success of therapy. The rate of secretion can be measured with a Geiger counter which indicates what proportion of radioactive iodine in a serum specimen is in the form of thyroxin. The normal proportion is 2 to 10 per cent; in hyperthyroidism the proportion is 50 to 70 per cent, and in hypothyroidism less than 1 per cent.The same test has served to detect metastases of thyroid carcinoma following total thyroidectomy.     

WHAT PSYCHIATRISTS THINK ABOUT ALCOHOLISM

The one approach most favored for alcoholism by psychiatrists in Southern California who answered a questionnaire is membership in Alcoholics Anonymous. Ninety-nine per cent of them approved Alcoholics Anonymous, and 80 per cent had referred patients to the organization. Yet they believed only 10 per cent of the persons who join A.A. remain sober for over two years. This against the claim of A.A. that 60 per cent or more of their fellowship are recovered emphasized the pessimism of the psychiatrists questioned.Ninety per cent of the psychiatrists who replied said they do not treat alcoholics or that they limit the number or the type they will accept for treatment. They obtain recovery, they said, of 10 per cent of patients, improvement of 50 per cent, and the rest are unchanged.The emphasis in psychiatry is on elimination of the anxieties leading to alcoholism; in Alcoholics Anonymous the emphasis is on the strength to bear these anxieties. Ninety per cent of the replies received were in favor of clinics for alcoholics, and the respondents felt that governmental agencies should support these clinics. Under such circumstances psychiatrists would combine their abilities with psychologists, social workers and Alcoholics Anonymous. Thirty-five per cent of psychiatrists said they are willing to work in a clinic, the majority without recompense.     

An improved model of root growth in structured soil

Summary The growth of roots of maize, sorghum and soybean is modelled through beds of spherical aggregates. Effects of aggregate size and strength, and effects of the spread or distribution of aggregate strengths are investigated.This is achieved by a combination of a statistical model for soil structure with a statistical model for the penetration behaviour of a root at a void/aggregate interface. It is shown that the behaviour of a root at such an interfac is dependent on the previous history of the root in its passage through the soil.It is concluded that the smaller the aggregate size, the greater is the nutrient availability per unit length of root. The influence of aggregate size decreases with increasing soil strength.An increase in aggregate strength reduces the availability of nutrients per unit length of root. However, the rate of nutrient uptake per root axis goes through a minimum at a strength (for maize) of around 80 per cent of the maximum limiting aggregate strength for root penetration. An increase in the spread of aggregate strengths usually results in a proportional increase in nutrient availability. This effect is more pronounced with smaller aggregate sizes.     

Trends in body size, diet and food availability in the Cook Islands in the second half of the 20th century

The body size of adult Cook Islanders on Rarotonga for the years 1952, 1966 and 1996 has been increasing. The rate of increase in stature of women aged 20-39 years was 0.5cm per decade across the period 1952-1966, and 0.8cm per decade for the period 1966-1996. The rate of increase of weight in the 20-29 years age group was 0.6kg per decade in period 1, and 7.3kg per decade in period 2. In the age group 30-39 years, the rates were 3.2kg per decade and 5.1kg per decade respectively. Changing food availability for the period 1961-2000 is used to compare estimates of dietary energy availability with estimates of physiological energy requirements. There has been reduced availability of traditional staples, a likely reduction in consumption of fish, increased consumption of meat, and a decline in the availability of dietary fats and oils. Daily per capita energy intakes in 1952 and 1966 greatly exceed an hypothetical physiological maximum value for energy expenditure, suggesting a large positive energy balance in 1952 and an even greater one in 1966, both predisposing to weight gain. Although daily per capita energy availability in 1996 is similar to the hypothetical physiological maximum value for energy expenditure, it exceeds the measured level of energy expenditure at that time. It is speculated that excessive energy intake relative to requirement is more likely to predispose to positive energy balance and weight gain than decline in energy expenditure, although to a lower extent than in 1966 and 1952.     

Molecular evolution of the period gene in Drosophila athabasca

We measured nucleotide variability within and between the three semispecies of the Drosophila athabasca complex, at the period (per) gene by using a polymerase chain reaction-based four-cutter restriction- enzyme analysis. The levels of polymorphism varied considerably between the three semispecies. Our results for per, combined with previous data for X-linked allozymes, suggest that the X chromosome in the western- northern semispecies is less variable than expected under an equilibrium-neutral model. Both the pattern of divergence between the semispecies and a cladistic clustering of per haplotypes support the previously hypothesized grouping of eastern A and eastern B as the two most recently diverged semispecies. A 21-bp in-frame segment in the region of per which shares sequence similarity with the neuronal development gene single minded is deleted in all eastern A and eastern B flies examined but is present in all of the western-northern flies and all other published per sequences. Despite these hints that there may be significant differences at the per gene between the semispecies, especially the western-northern group versus the two eastern groups, there is no compelling evidence that per is involved in the mating song differences between the semispecies.      

A RAPID METHOD FOR SELECTIVE SILVER STAINING OF NERVE FIBRES AND NERVE ENDINGS IN MOUNTED PARAFFIN SECTIONS

Abstract The staining described in this paper fundamentally is performed by two manipulations, namely (1) the treatment of deparaffinized sections for about fifteen minutes in a solution containing 15 per cent silver nitrate, 10 per cent potassium nitrate and 0.05 per cent glycine, and (2) the reduction for one minute in a solution of 1 per cent pyrogallol, 55 per cent ethyl alcohol and a trace (0.002 per cent) of nitric acid. After toning, dehydrating and mounting in the usual manner the sections generally are ready for examinations within less than an hour. The method is available for specimens fixed in the ordinary fixatives but those containing oxidizing metal compounds. The procedure is discussed from a theoretical point of view and some results are shown in photomicrographs.