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PubMed2003

Fertility estimation: a review of past experience and future prospects.

Fertility has many components and stages which require that males and females be functionally capable of carrying out all critical stages if each generational reproductive cycle is to be completed. To accomplish this, the male must produce and ejaculate normal fertile sperm. The female must produce, store and ovulate normal fertilizable oocytes. Furthermore, the female must provide a reproductive system compatible with sperm transport, capacitation, and fertilization of the oocytes, embryo and fetal development, and finally birth of healthy young. Reproductive success or failure at several of these points can be estimated quantitatively on a population basis, and in a few situations on an individual basis. It is important that fertility estimates be determined accurately and with precision to be most useful to researchers and managers of animal enterprises. Many studies have underestimated the biological relationship of fertility to other traits because the estimates lacked precision. Many in vitro manipulations of sperm in artificial insemination, of gametes in various assisted reproductive technologies, and of embryos in embryo transfer are utilized in animal breeding programs. Accurate estimation of reproductive efficiency of these in vitro procedures also is important. Conditions surrounding different sets of fertility estimates almost certainly will be different. These conditions should be described as precisely as possible, and appropriate controls included in all experiments. When possible, experiments should be replicated over time and place to determine the repeatability of the various criteria used to estimate fertility and reproductive efficiency. Advances in genomic information and molecular biology should facilitate characterizing more fully inherent potential fertility of animals at birth. In vitro tests will improve, and automated techniques will facilitate making multiple determinations possible on a large scale. Reliability of fertility estimates will increase, with the potential for enhanced animal reproductive performance through more accurate selection, genetic engineering, and enlightened animal care. Simultaneously, it is important to recognize that prediction of future fertility is more hazardous than estimating fertility, as a completely new set of circumstances may occur which are not predictable. Because fertility estimation may be applied under a myriad of conditions, principles and factors affecting fertility will be emphasized in this review as being more useful than a compilation of numerical examples.

Animals↗
PubMed2001

The protease inhibitors.

With the advent of newer antiretroviral agents for the treatment of patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), health care providers are faced with many options to optimize their patients' therapy. Currently, there are three groups of drugs available for the treatment of patients with HIV infection: nucleoside reverse transcriptase inhibitors (also known as nucleoside analogues), nonnucleoside reverse transcriptase inhibitors, and protease inhibitors (PIs). The preferred initial treatment regimen now consists of two nucleoside analogues and a PI. Protease inhibitors cause profound and sustained suppression of viral replication, increase time to first AIDS-defining illness, and reduce mortality. Each of the available PIs have distinct pharmacokinetic and metabolic properties that result in different dosing regimens and potential for interactions with food and other drugs. Patients with HIV infection typically receive several drugs; therefore, convenience of administration, optimal side-effect profile, and cost of the agents must also be considered along with the potential for drug interactions.A growing proportion of HIV patients worldwide are women. HIV-infected pregnant women should be offered antiretroviral prophylaxis to prevent perinatal HIV transmission as well as to optimize their own health. Zidovudine (ZDV) treatment has been the standard antiretroviral treatment during pregnancy; however, recent data has shown that combination regimens produce a more pronounced antiviral effect and may be more effective than ZDV monotherapy in preventing perinatal HIV transmission.

Journal Article↗
PubMed2000

Occupational Exposure in Nuclear Medicine and PET.

Purpose: With the increasing use of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for scanning in oncology in our center, a radiation dose survey was performed to determine the impact on staff exposure. Conventional nuclear medicine procedures such as gallium scan, bone scans, and sestamibi cardiac scans are used for comparative purposes.Procedure: Patients were measured using a hand-held radiation monitor (Victoreen 450-P) at various distances and times that replicate typical patient contact scenarios in the Diagnostic Imaging Department.Results: We present our findings from the survey and the implications these have on staff radiation exposure. The data suggest that emerging oncologic techniques such as PET, high dose gallium-67, and high dose Tl-201 do not represent a significantly greater occupational radiation hazard than conventional nuclear medicine procedures.

Journal Article↗
PubMed2005

Duration and temperature of culture medium equilibration affect frequency of blastocyst development.

Hamster 2-cell embryos were cultured in 50 microl drops of chemically defined medium (HECM-9) under oil in 60 mm Petri dishes. In the first experiment, the dishes were equilibrated with 5% O(2) /10% CO(2) /85% N(2) for 2 h either within sealed plastic bags or exposed directly to the same gas mixture in a tissue culture incubator. After culture of embryos for 48 h, there was no difference in development to the blastocyst stage. In the second experiment, the dishes were first equilibrated with 5% O(2) /10% CO(2) / 85% N(2) within sealed plastic bags, (A) at 4 degrees C overnight (16-18 h), or (B) at 37.5 degrees C overnight or (C) at 37.5 degrees C for 2 h. Dishes in treatment A were placed in the incubator at 37.5 degrees C for 2 h next day just before use. Two-cell embryos from a superovulated, mated female were equally distributed among the three treatments, then the dishes were sealed in fresh bags containing the same gas mixture and incubated at 37.5 degrees C for 48 h. This experiment was replicated 13 times with a total of 20 females and 268-275 embryos/treatment. There was no significant difference among the treatments for development to the (combined) morula/blastocyst stages. However, the percentage of blastocysts that developed in culture dishes that had been equilibrated overnight at 37.5 degrees C (treatment B) was significantly lower [50 +/- 14% (SEM)] than in treatments A and C, which were not different from one another (67 +/- 11 and 60 +/- 17% respectively). These results indicate that when culture medium is incubated at 37.5 degrees C overnight, chemical deterioration occurs that is detrimental to embryo development, and that this can be avoided by equilibrating dishes at 4 degrees C overnight, followed by a brief period at 37.5 degrees C to warm the medium before inserting embryos. This finding may have clinical relevance for human embryo culture. The study also demonstrates the utility and advantages of the sealed bag system for embryo culture.

Animals↗
PubMed2004

Gene amplification as a developmental strategy: isolation of two developmental amplicons in Drosophila.

Gene amplification is known to be critical for upregulating gene expression in a few cases, but the extent to which amplification is utilized in the development of diverse organisms remains unknown. By quantifying genomic DNA hybridization to microarrays to assay gene copy number, we identified two additional developmental amplicons in the follicle cells of the Drosophila ovary. Both amplicons contain genes which, following their amplification, are expressed in the follicle cells, and the expression of three of these genes becomes restricted to specialized follicle cells late in differentiation. Genetic analysis establishes that at least one of these genes, yellow-g, is critical for follicle cell function, because mutations in yellow-g disrupt eggshell integrity. Thus, during follicle cell differentiation the entire genome is overreplicated as the cells become polyploid, and subsequently specific genomic intervals are overreplicated to facilitate gene expression.

Animals↗
PubMed2003

Ontogenic variations of ascorbic acid and phenethyl isothiocyanate concentrations in watercress (Nasturtium officinale R.Br.) leaves.

Watercress (Nasturtium officinale R.Br.) is the richest source of glucosinolate nasturtiin, which on hydrolysis produces phenethyl isothiocyante (PEITC). Interest in growing watercress is stimulated since demonstration of the role of PEITC in protection against cancers associated with tobacco specific carcinogens. Twenty-one days old watercress seedlings were transplanted into growth chambers (16-h days/8-h nights of 25/22 degrees C and photosynthetic photon flux (PPF) of approximately 265 micromol m(-2) s(-)(1)). The study was replicated three times. Leaves were analyzed for PEITC and ascorbic acid concentrations at transplant, and harvested at 10-days intervals until 60 days after transplant. The PEITC and ascorbic acid concentrations were the highest in leaves harvested at 40 days and the lowest at transplant. Leaves harvested at 40 days produced about 150% higher PEITC concentrations compared to the leaves at transplant. Both PEITC and ascorbic acid concentrations of leaves increased linearly with age until 40 days after transplant after which there was no significant increase. Seedlings at transplant had the lowest dry mass and leaf area, while plants harvested at 60 days had the highest dry mass and leaf area.

Ascorbic Acid↗
PubMed2006

Quantitation of toxic arsenic species and arsenobetaine in Pacific oysters using an off-line process with hydride generation-atomic absorption spectroscopy.

An off-line process-based speciation technique was devised here to quantitatively determine toxic inorganic arsenic (iAs), methylarsonic acid (MA), dimethylarsinic acid (DMA), and the dominant, albeit virtually nontoxic, arsenobetaine (AB) in Pacific oysters (Crassostrea gigas). Oysters were extracted with fresh methanol-water (8+2), and this was replicated three times. They were then evaporated to near dryness and subsequently redissolved in pure water; defatting was then performed with a C18 cartridge. The trace hydride active arsenic species, that is, iAs, MA, and DMA, in the defatted solutions were determined with a sensitive hydride generation-packed coldfinger trap-atomic absorption spectrometric (HG-PCFT-AAS) coupled system. The arsenicals that were desorbed from the cation-exchange resin (Dowex 50W-X8) in the washings of 4 M NH3 were categorized on the basis of AB + DMA. The total quantity of arsenic in the recovered AB + DMA was determined with a commercial hydride generation-atomic absorption spectrometric (HG-AAS) system, and finally, AB was calculated from (AB + DMA) - DMA. The average concentrations of iAs, MA, DMA, AB, and total arsenic (TAs) in the oysters collected from six aquacultural sites along the west coast of Taiwan were, respectively, 0.15, 0.06, 0.64, 6.93, and 13.74 mg kg(-1) of dry weight. AB was the major species, whereas iAs (arsenite + arsenate) were the most toxic species, although the iAs made up only approximately 1% of the TAs in the oysters. The lifetime target cancer risk, as determined by the concentration of iAs on a fresh weight basis in the oysters, was well below the ordinary health protection criteria (10(-6)).

Animals↗
PubMed2001

Dose-dependent response and preliminary observations on attraction range of Ips typographus to pheromones at low release rates.

Responses of the European spruce bark beetle, 1. typographus (Coleoptera: Scolytidae), to low release-rate pheromones were investigated in two experiments in a spruce forest at Wellin, southern Belgium. Dose-response of the beetle was first examined in a trapping experiment in August 1999. The major pheromone components of L. typographus, (S)-cis-verbenol (cV) and 2-methyl-3-buten-2-ol (MB) were released from window traps. Five treatments were replicated five times: (1) blank trap, (2) 0.03 and 1.2, (3) 0.11 and 4.5, (4) 0.34 and 15.2 mg/day of cV and MB, respectively, and (5) Pheroprax. Trap catches increased linearly as a function of increasing release rates of cV and MB. A second study aimed at making preliminary observations on the attraction range of the pheromones as compared to Pheroprax. A release-recapture experiment was carried out in May 2000: four trap-trees located 50 m away from a central release platform were equipped with window traps baited with increasing release rates, tested in separate releases: 0.03 and 1.2; 0.11 and 4.5; 0.34 and 15.2 mg/day of cV and MB, respectively, and Pheroprax. Recaptures increased with the release rate. Trap catches were different at lower release rates, but not between the release rate of 15.2 mg/day of MB and Pheroprax. Variations in captures in relation to wind parameters showed persistently random flight at the lower release rates. Significant upwind flight was observed for Pheroprax only. These results imply that trap interference existed for Pheroprax and suggest that its attraction range may be greater than 50 m.

Animals↗
PubMed1989

Mutation rates differ among regions of the mammalian genome.

In the traditional view of molecular evolution, the rate of point mutation is uniform over the genome of an organism and variation in the rate of nucleotide substitution among DNA regions reflects differential selective constraints. Here we provide evidence for significant variation in mutation rate among regions in the mammalian genome. We show first that substitutions at silent (degenerate) sites in protein-coding genes in mammals seem to be effectively neutral (or nearly so) as they do not occur significantly less frequently than substitutions in pseudogenes. We then show that the rate of silent substitution varies among genes and is correlated with the base composition of genes and their flanking DNA. This implies that the variation in both silent substitution rate and base composition can be attributed to systematic differences in the rate and pattern of mutation over regions of the genome. We propose that the differences arise because mutation patterns vary with the timing of replication of different chromosomal regions in the germline. This hypothesis can account for both the origin of isochores in mammalian genomes and the observation that silent nucleotide substitutions in different mammalian genes do not have the same molecular clock.

Animals↗
PubMed2006

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗
PubMed2006

Chromatin signatures of pluripotent cell lines.

Epigenetic genome modifications are thought to be important for specifying the lineage and developmental stage of cells within a multicellular organism. Here, we show that the epigenetic profile of pluripotent embryonic stem cells (ES) is distinct from that of embryonic carcinoma cells, haematopoietic stem cells (HSC) and their differentiated progeny. Silent, lineage-specific genes replicated earlier in pluripotent cells than in tissue-specific stem cells or differentiated cells and had unexpectedly high levels of acetylated H3K9 and methylated H3K4. Unusually, in ES cells these markers of open chromatin were also combined with H3K27 trimethylation at some non-expressed genes. Thus, pluripotency of ES cells is characterized by a specific epigenetic profile where lineage-specific genes may be accessible but, if so, carry repressive H3K27 trimethylation modifications. H3K27 methylation is functionally important for preventing expression of these genes in ES cells as premature expression occurs in embryonic ectoderm development (Eed)-deficient ES cells. Our data suggest that lineage-specific genes are primed for expression in ES cells but are held in check by opposing chromatin modifications.

Animals↗
PubMed2006

How transcriptional and epigenetic programmes are played out on an individual mammalian gene cluster during lineage commitment and differentiation.

In the post-genomic era, a great deal of work has focused on understanding how DNA sequence is used to programme complex nuclear, cellular and tissue functions throughout differentiation and development. There are many approaches to these issues, but we have concentrated on understanding how a single mammalian gene cluster is activated or silenced as stem cells undergo lineage commitment, differentiation and maturation. In particular we have analysed the alpha globin cluster, which is expressed in a cell-type- and developmental stage-specific manner in the haemopoietic system. Our studies include analysis of the transcriptional programme that accompanies globin gene activation, focusing on the expression of relevant transcription factors and cofactors. Binding of these factors to the chromosomal domain containing the alpha globin cluster has been characterized by ChIP (chromatin immunoprecipitation). In addition, we have monitored the epigenetic modifications (e.g. nuclear position, timing of replication, chromatin modification, DNA methylation) that occur as the genes are activated (in erythroid cells) or silenced (e.g. in granulocytes) as haemopoiesis proceeds. Together, these observations provide a uniquely well-characterized model illustrating the mechanisms that regulate and memorize patterns of mammalian gene expression as stem cells undergo lineage specification, differentiation and terminal maturation.

Animals↗
PubMed1989

Adaptation and the masking of tinnitus.

The effect of adaptation on the masking of tinnitus was investigated. Six patients with tinnitus performed two 5-min tracking tasks, each replicated six times. The first task examined the masking of tinnitus by tracking the intensity of a pure tone required to mask the tinnitus. The second task examined adaptation of a suprathreshold tone by tracking the intensity of a pure tone required for constant loudness. For 3 patients, the change required for constant loudness did not differ from the change required for constant maskability. For 3 patients, however, these two changes were different. Possible implications of these results for determining the locus of tinnitus and for the use of tinnitus maskers are discussed.

Adaptation, Physiological↗
PubMed1999

Delayed nucleoid segregation in Escherichia coli.

To study the role of cell division in the process of nucleoid segregation, we measured the DNA content of individual nucleoids in isogenic Escherichia coli cell division mutants by image cytometry. In pbpB(Ts) and ftsZ strains growing as filaments at 42 degrees C, nucleoids contained, on average, more than two chromosome equivalents compared with 1.6 in wild-type cells. Because similar results were obtained with a pbpB recA strain, the increased DNA content cannot be ascribed to the occurrence of chromosome dimers. From the determination of the amount of DNA per cell and per individual nucleoid after rifampicin inhibition, we estimated the C and D periods (duration of a round of replication and time between termination and cell division respectively), as well as the D' period (time between termination and nucleoid separation). Compared with the parent strain and in contrast to ftsQ, ftsA and ftsZ mutants, pbpB(Ts) cells growing at the permissive temperature (28 degrees C) showed a long D' period (42 min versus 18 min in the parent) indicative of an extended segregation time. The results indicate that a defective cell division protein such as PbpB not only affects the division process but also plays a role in the last stage of DNA segregation. We propose that PbpB is involved in the assembly of the divisome and that this structure enhances nucleoid segregation.

Aztreonam↗
PubMed2005

Conserved interactions in the Staphylococcus aureus DNA PolC chromosome replication machine.

The PolC holoenzyme replicase of the Gram-positive Staphylococcus aureus pathogen has been reconstituted from pure subunits. We compared individual S. aureus replicase subunits with subunits from the Gram-negative Escherichia coli polymerase III holoenzyme for activity and interchangeability. The central organizing subunit, tau, is smaller than its Gram-negative homolog, yet retains the ability to bind single-stranded DNA and contains DNA-stimulated ATPase activity comparable with E. coli tau. S. aureus tau also stimulates PolC, although they do not form as stabile a complex as E. coli polymerase III.tau. We demonstrate that the extreme C-terminal residues of PolC bind to and function with beta clamps from different bacteria. Hence, this polymerase-clamp interaction is highly conserved. Additionally, the S. aureus delta wrench of the clamp loader binds to E. coli beta. The S. aureus clamp loader is even capable of loading E. coli and Streptococcus pyogenes beta clamps onto DNA. Interestingly, S. aureus PolC lacks functionality with heterologous beta clamps when they are loaded onto DNA by the S. aureus clamp loader, suggesting that the S. aureus clamp loader may have difficulty ejecting from heterologous clamps. Nevertheless, these overall findings underscore the conservation in structure and function of Gram-positive and Gram-negative replicases despite >1 billion years of evolutionary distance between them.

Bacterial Proteins↗
PubMed1983

Energy and nitrogen metabolism of lactating rabbits.

Twelve crossbred does (New Zealand White x California) were offered a diet of high protein and metabolizable energy content (249 g/kg dry matter (DM) and 13.6 MJ/kg DM respectively) throughout a 32 d lactation at one of four feeding levels (240, 280, 320 or 360 g/d). Each feeding level was replicated three times. Milk output was measured by weighing the does before and after their one daily suckling period. The lactation was divided into four consecutive 8-d periods. Each doe was placed in a direct calorimeter for 48 h around the mid-point of each of these periods and measurements of energy exchange were made. Nitrogen balance was also measured throughout the study period. Milk samples were taken from a parallel group of animals and the estimates of milk composition were applied to the main group of does. From the second period of lactation onwards nearly all does mobilized body tissue to support milk energy secretion, although there was no loss of weight. Multiple regression analyses were used to examine the apparent efficiency with which metabolizable energy and body-tissue energy were utilized for milk production. Overall, the relationship was described by the equation: (formula; see text) where Milk E is the milk energy output, ME intake is the metabolizable energy intake and Body ER is the body energy retention, all expressed in kJ/kg body-weight0.75 per d. All does appeared to be in positive N balance throughout lactation on this high-protein diet.

Animals↗