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Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

The swimming performance of hatchery-reared, juvenile shovelnose sturgeon Scaphirhynchus platorynchus and pallid sturgeon S. albus was studied in a laboratory swim tunnel at 20°C and 10°C. The mean 30-min critical swimming speed was not significantly different between species at either temperature (36.9 cm/s for shovelnose sturgeon and 35.9 cm/s for pallid sturgeon at 20°C, 19.4 cm/s for shovelnose sturgeon and 15.0 cm/s for pallid sturgeon at 10°C). Free swimming (swimming without contact with the substrate) was observed less than 18% of the time at speeds greater than 15 cm/s. As speed increased, pallid sturgeon swam significantly less in the water column at 20°C; however, speed had no effect on percent free swimming among shovelnose sturgeon at 20°C. The results of this study indicate that, over the temperature and size range tested, shovelnose sturgeon and pallid sturgeon probably do not segregate in rivers due to different swimming or station-holding abilities

Establishing causal relationships between environmental stressors and observed effects in natural systems is difficult due to the many intrinsic environmental factors that can hinder this process and because there are no widely accepted and proven approaches for determining such relationships. Several types of approaches or combinations of approaches, each with their own sets of advantages and limitations, have been applied in a variety of ecological systems to investigate possible causal relationships between stressors and effects. These include controlled laboratory studies (including acute and chronic bioassays), experimental field manipulations, field studies based on synoptic field surveys, mathematical simulation modeling, statistical associations, various combinations of laboratory, experimental, and field studies, and the ecoepidemiological (weight or evidence) approach. The use of ecoepidemiological (“forensic toxicology”) principles is becoming increasingly attractive as a method to help establi...

SummaryShort-day (SD) and long-day (LD) photoperiodic treatments were compared, at equal light integral, for their effects on the seedling growth of four bedding plant species: geranium, impatiens, pansy and petunia. Total leaf area was frequently increased by LD given either by day-extension lighting or night-break lighting, but this response was inconsistent and varied greatly between species and experiments. In contrast, leaf greenness measured using a SPAD-502 meter, a measure of chlorophyll content per unit area of leaf, was consistently and significantly increased in LD in all four species. However, night-break lighting may have been somewhat less effective than day-extension lighting. Increasing the day-extension lighting from 16 h to 24 h gave no further intensification of greenness. Consistent with increases in leaf greenness, total dry weight was generally increased in LD, and increases were of a similar magnitude to those given by doubling the daily light integral. The promotional effect of LD ...

Combined constraints from the CDF and D0 Collaborations on models of the Higgs boson with exotic spin J and parity P are presented and compared with results obtained assuming the standard model value J(P) = 0(+). Both collaborations analyzed approximately 10 fb(-1) of proton-antiproton collisions with a center-of-mass energy of 1.96 TeV collected at the Fermilab Tevatron. Two models predicting exotic Higgs bosons with J(P) = 0(-) and J(P) = 2(+) are tested. The kinematic properties of exotic Higgs boson production in association with a vector boson differ from those predicted for the standard model Higgs boson. Upper limits at the 95% credibility level on the production rates of the exotic Higgs bosons, expressed as fractions of the standard model Higgs boson production rate, are set at 0.36 for both the J(P) = 0(-) hypothesis and the J(P) = 2(+) hypothesis. If the production rate times the branching ratio to a bottom-antibottom pair is the same as that predicted for the standard model Higgs boson, then the exotic bosons are excluded with significances of 5.0 standard deviations and 4.9 standard deviations for the J(P) = 0(-) and J(P) = 2(+) hypotheses, respectively.

This chapter deals with the development and organization of different cell types and tissues of plants. Development includes processes such as cell division (including cell cycle), cell enlargement, differentiation, pattern formation and morphogenesis. A detailed account on cell cycle and its hormonal and genetic control has been provided. Differentiation of cells happens by modification of cell cycle events at specific control points. The laws of governing cell division, planes of cell division and asymmetric cell division are discussed in relation to specific morphogenesis of cell and tissue types. The relative importance of cell division and cell enlargement in overall morphogenesis, organ size and organ shape is highlighted. Differentiation, dedifferentiation, redifferentiation and transdifferentiation are distinguished and their importance in cell type production is emphasized. The importance of diffusion reaction of theory and positional information theory on morphogenesis of cells, tissues, organs and organisms is explained. Finally, the differentiation of various cell types is described.

Leaves are the most important organs of plants and carry out very vital physiological activities such as photosynthesis, respiration, transpiration, photoreception and synthesis and supply of signal compounds, including growth regulators. They are always associated with shoot apical meristems from which they arise. Leaves are arranged on the stem with very characteristic and non-mutagenic phyllotactic pattern characteristic of each plant. The various theories to explain this pattern are briefly described. The leaf primordia are initially with a leaf axis from which the lamina, petiole and phyllopodium regions of the mature leaf arise. This chapter deals with the genetic network that operates during various phases of leaf ontogeny. The genetic basis for shoot apical meristem (with indeterminate growth)–leaf primordium (with determinate growth) boundary is also discussed. This article also discusses the ontogenetic and genetic bases of the differences between simple and compound leaves. A short account each on heteroblasty, heterophylly, senescence and evolution of leaf is also provided.

This chapter deals with meristems and their importance in the organization of the primary and secondary plant body. The meristem concept is explained with particular reference to initials, stem cells and permanency of initials. A classification of meristems is provided, followed by the organization of SAM, RAM and vascular cambium. The genetic basis of the organization and behaviour of these three meristems is dealt with in detail along with their hormonal control. An account on intercalary meristem, metamers and modules, origin of nodes and internodes, axillary buds, apical dominance, primary and secondary thickening meristems and phellogen is also provided.

Five new isocyano/isothiocyanato sesquiterpenes (1-5) with tri- or bicyclic carbon skeletons have been characterized from Australian specimens of the nudibranch Phyllidia ocellata. Spectroscopic analyses at 900 MHz were informed by DFT calculations. The 1S, 5S, 8R configuration of 2-isocyanoclovene (1) was determined by X-ray crystallographic analysis of formamide 6. A biosynthetic pathway to clovanes 1 and 2 from epicaryolane precursors is proposed. Isocyanides 1, 2, and 4 showed activity against Plasmodium falciparum (IC50 0.26-0.30 ?M), while isothiocyanate 3 and formamide 6 had IC50 values of >10 ?M.

We present the final combination of CDF and D0 measurements of cross sections for single-top-quark production in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb(-1) per experiment. The t-channel cross section is measured to be sigma(t) = 2.25(-0.31)(+0.29) pb. We also present the combinations of the two-dimensional measurements of the s- vs t-channel cross section. In addition, we give the combination of the s + t channel cross section measurement resulting in sigma(s+t) = 3.30(-0.40)(+0.52) pb, without assuming the standard model value for the ratio sigma(s)/sigma(t). The resulting value of the magnitude of the top-to-bottom quark coupling is vertical bar V-tb vertical bar = 1.02(-0.05)(+0.06), corresponding to vertical bar V-tb vertical bar > 0.92 at the 95% C. L.

Peroxidase (EC 1.11.1.7)-mediated stiffening of cell walls within the fruit skin of tomato is hypothesized to regulate fruit growth. However, to date, there is no experimental evidence demonstrating that peroxidase affects the mechanical properties of skin tissue. Here, the mechanical properties of skin strips excised from a range of fruits at different ages were determined using an 'Instron' universal material testing instrument. The stiffness of tomato fruit skin strips increases 3-fold with increasing fruit age. Application of partially-purified peroxidase from the cell walls of mature tomato fruit skin significantly increased the stiffness of fruit skin irrespective of the age of fruit. Furthermore, the application of hydrogen peroxide significantly increased the stiffness of skin strips excised from fruit of an age when endogenous peroxidase isozymes associated with the termination of growth are first detected. The results support the hypothesis that the tomato fruit skin plays an integral role in the regulation of tomato fruit growth, and that changes in its mechanical properties may be mediated by peroxidase. As far as is known, this is the first demonstration that peroxidases alter the mechanical properties of the plant cell wall.

SummaryAn experiment was conducted to assess whether the severity of leaf removal or modifying night temperature set-points based upon the amount of solar radiation intercepted the previous day could affect tomato yields. A night temperature set-point of 16°C increasing linearly by 3 K for every 1000 klx h (˜ 67 mol m–2 d–1) was compared with a 19°C set-point which decreased by 5 K for every 1000 klx h. Similar mean diurnal temperatures were achieved in these two regimens and consequently there was little effect on the pattern of yield or cumulative yields for the whole season. When leaves were removed every week up to two trusses above the ripening truss (high leaf removal: HLR), fruits were warmer during the day and cooler at night, and ripened 1.2 d earlier than those on plants where leaves were removed up to two trusses below the ripening truss (low leaf removal: LLR). The leaf removal treatments had a similar pattern of yield and there was no significant difference in the cumulative yields for the se...

SummaryTo assess whether cycles in the weekly pattern of tomato yields were due to the pattern of fruit load on plants, truss-removal and truss-pruning treatments were applied to individual rows within glasshouse compartments. When the pattern of fruit load was stabilized by pruning all trusses to five fruits, fruit size increased although the pattern of yield was similar to that from control rows. Furthermore, imbalances in fruit load caused by truss removal did not cause cyclical fruit production. The effect of temperature on the pattern of yield was investigated by raising air temperature within compartments by about 4.5 K for one week on two occasions. High yields were initially recorded following the start of the high temperature pulse but low yields were subsequently recorded. Overall, there was no significant effect of the treatment on cumulative yields over the course of the experiment. The results show that changes in air temperature are important in determining the pattern of tomato yields. Frui...

The effect of coal ash exposure on fish health in freshwater communities is largely unknown. Given the large number of possible pathways of effects (e.g., toxicological effect of exposure to multiple metals, physical effects from ash exposure, and food web effects), measurement of only a few health metrics is not likely to give a complete picture. The authors measured a suite of 20 health metrics from 1100+ fish collected from 5 sites (3 affected and 2 reference) near a coal ash spill in east Tennessee over a 4.5-yr period. The metrics represented a wide range of physiological and energetic responses and were evaluated simultaneously using 2 multivariate techniques. Results from both hierarchical clustering and canonical discriminant analyses suggested that for most species × season combinations, the suite of fish health indicators varied more among years than between spill and reference sites within a year. In a few cases, spill sites from early years in the investigation stood alone or clustered together separate from reference sites and later year spill sites. Outlier groups of fish with relatively unique health profiles were most often from spill sites, suggesting that some response to the ash exposure may have occurred. Results from the 2 multivariate methods suggest that any change in the health status of fish at the spill sites was small and appears to have diminished since the first 2 to 3 yr after the spill.

A small series of histone deacetylase (HDAC) inhibitors (VI) are synthesized and evaluated together with previously described HDAC inhibitors for their antiplasmodial properties.

Therapies to prevent transmission of malaria parasites to the mosquito vector are a vital part of the global malaria elimination agenda. Primaquine is currently the only drug with such activity; however, its use is limited by side effects. The development of transmission-blocking strategies requires an understanding of sexual stage malaria parasite (gametocyte) biology and the identification of new drug leads. Lysine acetylation is an important posttranslational modification involved in regulating eukaryotic gene expression and other essential processes. Interfering with this process with histone deacetylase (HDAC) inhibitors is a validated strategy for cancer and other diseases, including asexual stage malaria parasites. Here we confirm the expression of at least one HDAC protein in Plasmodium falciparum gametocytes and show that histone and nonhistone protein acetylation occurs in this life cycle stage. The activity of the canonical HDAC inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA; Vorinostat) and a panel of novel HDAC inhibitors on early/late-stage gametocytes and on gamete formation was examined. Several compounds displayed early/late-stage gametocytocidal activity, with TSA being the most potent (50% inhibitory concentration, 70 to 90 nM). In contrast, no inhibitory activity was observed in P. falciparum gametocyte exflagellation experiments. Gametocytocidal HDAC inhibitors caused hyperacetylation of gametocyte histones, consistent with a mode of action targeting HDAC activity. Our data identify HDAC inhibitors as being among a limited number of compounds that target both asexual and sexual stage malaria parasites, making them a potential new starting point for gametocytocidal drug leads and valuable tools for dissecting gametocyte biology.

In mammals, it is believed that a portion of tissue metabolic rate is driven by counteraction of uncoupling, in which the energetically inefficient process of proton leak acts to diminish the mitochondrial electrochemical membrane potential. It is proposed that specific proteins associated with the mitochondrion catalyse uncoupling, and the biology of such putative uncoupling proteins (UCPs) is the subject of active research efforts. UCP4 and UCP5 are interesting in light of their abundant expression in the brain, which may signal an important metabolic function in thermogenesis or regulation of reactive oxygen species in that tissue. While each is expressed to various degrees outside of the brain, their impact on whole-animal metabolism remains to be clarified further. Transgenic mice expressing murine UCP5L, the long isoform of UCP5, using an inducible metallothionine promoter (to drive expression of the transgene in liver, testis, heart, lung, spleen, intestine, kidney and brain) did not display any overt metabolic phenotype, despite liver UCP5L mRNA expression equivalent to that of normal mouse brain. This highlights the need for further studies to examine the nature of UCP5 physiology. Evidence for uncoupling behaviour has recently emerged from studies of the human 2-oxoglutarate carrier (OGC), indicating that the possibility of physiological proton leak elicited by the OGC and other mitochondrial carriers warrants further experimental evaluation.

Tomato fruits ripened 95, 65, 46 and 42 d after flower opening when plants were grown under controlled environmental conditions at 14, 18, 22 and 26 °C, respectively. A similar response to temperature was observed when the temperature of individual trusses was modified while the plants were grown at 20 °C. These data were used to develop a thermal time model for fruit maturation. However, when buds/fruits were heated at different stages in their development, the thermal time model proved to be a poor predictor of the time of ripening. Fruits were more sensitive to elevated temperature in their later stages of maturation. Temperature also affected the rates of fruit growth in volume; these could be adequately described using a Gompertz function. Low temperatures reduced absolute volume growth rates and delayed the time at which the absolute growth rate became maximal. However, the response of fruit growth to temperature differed when only the temperature of the fruits was modified. There was a tendency towards small parthenocarpic fruits at both high (26 °C) and low (14 °C) temperature regimes which, combined with low flower numbers and poor fruit set at 26 °C, resulted in low fruit yields. Temperature also affected the shoot dry matter content and partitioning.

Fluorescent in situ hybridization and Southern blotting were used for showing the predominant absence of the Arabidopsis-type telomere repeat sequence (TRS) 5'-(TTTAGGG)(n)-3' (the 'typical' telomere) in a monocot clade which comprises up to 6300 species within Asparagales. Initially, two apparently disparate genera that lacked the typical telomere were identified. Here, we used the new angiosperm phylogenetic classification for predicting in which other related families such telomeres might have been lost. Our data revealed that 16 species in 12 families of Asparagales lacked typical telomeres. Phylogenetically, these were clustered in a derived clade, thereby enabling us to predict that the typical telomere was lost, probably as a single evolutionary event, following the divergence of Doryanthaceae ca. 80--90 million years ago. This result illustrates the predictive value of the new phylogeny, as the pattern of species lacking the typical telomere would be considered randomly placed against many previous angiosperm taxonomies. Possible mechanisms by which chromosome end maintenance could have evolved in this group of plants are discussed. Surprisingly, one genus, Ornithogalum (Hyacinthaceae), which is central to the group of plants that have lost the typical telomere, appears to have regained the sequences. The mechanism(s) by which such recovery may have occurred is unknown, but possibilities include horizontal gene transfer and sequence reamplification.

We isolated and characterized the entire coding sequence of a human gene encoding a protein that interacts with RPGR, a protein that is absent or mutant in many cases of X-linked retinitis pigmentosa. The newly identified gene, called “RPGRIP1” for RPGR-interacting protein (MIM 605446), is located within 14q11, and it encodes a protein predicted to contain 1,259 amino acids. Previously published work showed that both proteins, RPGR and RPGRIP1, are present in the ciliary structure that connects the inner and outer segments of rod and cone photoreceptors. We surveyed 57 unrelated patients who had Leber congenital amaurosis for mutations in RPGRIP1 and found recessive mutations involving both RPGRIP1 alleles in 3 (6%) patients. The mutations all create premature termination codons and are likely to be null alleles. Patients with RPGRIP1 mutations have a degeneration of both rod and cone photoreceptors, and, early in life, they experience a severe loss of central acuity, which leads to nystagmus.

Aquatic ecosystems can be chronically stressed by multiple environmental factors which originate from a variety of point and non-point sources. In addition, these stressors may vary both spatially and temporally, and, combined with synergestic and cumulative interactions of these stressors, complicate the interpretation and evaluation of stress responses in organisms. To help identify and differentiate between sources of anthropogenic stressors in aquatic systems, a diagnostic approach based on exposure-response profiles in sentinel organisms was developed from the known effects of various anthropogenic activities on biological systems. To generate these exposure-effects profiles, biomarkers of exposure were plotted against bioindicators of corresponding effects for several major anthropogenic activities including petrochemical, pulp and paper, domestic sewage, mining operations, land-development, and agricultural activities. Biomarkers of exposure to environmental stressors varied widely depending on the type of anthropogenic activity involved. Bioindicator effects, however, including histopathological lesions, bioenergetic status, growth, reproductive impairment, and community-level endpoints were similar among several of the major anthropogenic activities because responses at these higher levels are less specific to stressors than are biomarkers. This approach appears useful for helping to identify and diagnose sources of stress in environments impacted by multiple stressors. By identifying the types and sources of environmental stressors impacting key components of biological systems, aquatic ecosystems can be more effectively protected, regulated, and managed to help improve and maintain environmental quality and ecosystem fitness.

SummaryExperiments in glasshouse and controlled environment facilities investigated the effect of different fruit removal and lighting/shading treatments on the pattern of tomato yields. While the removal of flowering trusses resulted in a yield loss about eight weeks later, there was little loss in cumulative yield as assimilates were distributed to neighbouring trusses. In the growth room experiment, increased photosynthetic photon flux density (PPFD) for one week resulted in a period of increased yield from 4–6 weeks after the start of the treatment, followed by suppressed yields due to smaller fruits on subsequent trusses. However, neither fruit load nor assimilate availability appeared to be responsible for the fluctuations in yield recorded within the glasshouse crop. In this experiment fruit size remained fairly consistent (except when fruit removal treatments were applied), whereas the number of fruits picked per week exhibited much greater variability. This was the case even when all trusses were...

The Topeka shiner (Notropis topeka) is imperiled by extensive changes in stream hydrology. Responses of shiners to changes or variation in stream hydraulics, however, have not been quantified, hampering conservation efforts. We quantified swimming endurance and behavior for Topeka shiners in a laboratory swim tunnel. Sustained swimming (>200 min) was observed at water velocities of 30–40 cm/s. Prolonged and burst swimming (approximately 10 min to less than 0.1 min) was observed at water velocities of 40–75 cm/s and endurance was negatively correlated with water velocity. Larger individuals (4.4–5.5 cm standard length) exhibited greater sustained swimming ability than smaller individuals (3.0–4.2 cm standard length). Oral grasping of wire mesh within the swim tunnel was frequently employed at moderate water velocities (35–50 cm/s); this behavior may limit downstream displacement of shiners during freshets. Topeka shiners are capable of swimming speeds faster than water velocities which they typica...

The physical ends of chromosomes are protected and stabilised by telomeres. The sequence of telomeric DNA normally consists of a simple repeating unit that is conserved in many organisms. Most plants examined have been shown to possess Arabidopsis-type telomeres consisting of many repeat copies of the sequence 5'-TTTAGGG-3'. Using fluorescent in situ hybridisation, slot blotting and the asymmetric polymerase chain reaction we demonstrate an absence of Arabidopsis-type telomeres in the genus Aloe (family Asphodelaceae). The only other plant genera so far reported without such telomeres are Allium, Nothoscordum, and Tulbaghia (family Alliaceae). As these genera and Aloe are petaloid monocots in the Asparagales, it is suggested that an absence of Arabidopsis-type telomeres may be characteristic of this related group of plants.

Trovafloxacin, a recently-developed fourth-generation fluoroquinolone, is more potent than other quinolone drugs against a wide range of organisms including Toxoplasma gondii . We assessed the in vitro antimalarial activity of trovafloxacin against three laboratory-adapted Plasmodium falciparum isolates and compared the results with those of ciprofloxacin and norfloxacin. Synchronous and asynchronous cultures were exposed to a range of drug concentrations, and growth inhibition was assessed using 3 H-hypoxanthine incorporation. All isolates, both synchronous and asynchronous, exhibited comparable sensitivities with trovafloxacin (EC 50 range, 1.8×10 −5 to 3.7×10 −5 mol/l) and ciprofloxacin (2.0×10 −5 to 3.9×10 −5 mol/l), but were less sensitive to norfloxacin (5.4×10 −5 to 6.6×10 −4 mol/l). These results confirm that ciprofloxacin is twice as potent as norfloxacin against P. falciparum in vitro, but also show that trovafloxacin and ciprofloxacin have similar antimalarial potency. The EC 50 concentrations of all three drugs were generally higher than those achieved after conventional doses in humans, suggesting that their clinical application may be limited to combination therapy. Recent reports of hepatotoxicity with trovafloxacin may also prevent the use of this drug in humans. However, newer fourth-generation quinolones may prove safer and have similar antimalarial potency.

Effects of environmental stressors such as contaminants on the health of aquatic ecosystems usually involve a series of biological responses ranging from the biomolecular/biochemical to the population and community levels. To establish relationships and to determine the feasibility of extrapolating between higher and lower levels of biological organization, spatial patterns in fish responses to contaminant loading were investigated in a stream receiving point-source discharges of various contaminants near its headwaters. Relationships among fish responses at four major levels of biological organization (biochemical/physiological, individual, population, and community levels) were evaluated relative to patterns in contaminant loading along the spatial gradient of the stream. Both individual and integrated response analysis demonstrated that bioindicators at several levels of biological organization displayed similar downstream patterns in their response to contaminant loading within the stream. Some of the...

As sensitive and ecologically relevant measures of environmental conditions, bioindicators can be used to assess the health of aquatic ecosystems which may be compromised by a variety of environmental Stressors such as contaminants, sediments, nutrients, and varying temperature, salinity, and hydrologic regimes. The bioindicators approach is a proven bioassessment method that uses responses of key (sentinel) aquatic organisms both as integrators of stress effects and as sensitive response (early-warning) indicators of environmental health. This integrated approach involves measuring a suite of selected biological and ecological responses at several levels of biological organization from the biomolecular and biochemical to the community levels. When properly designed and applied in field situations, bioindicator studies can help identify causal mechanisms between environmental Stressors and population and community-level effects, and serve as a basis for which the effectiveness of remedial actions on the health of aquatic organisms can be evaluated. Rapidly-responding sensitive biomarkers, such as biomolecular and biochemical responses, and slower- response ecologically relevant bioindicators, such as population and community responses, can be included in field bioassessment programs to provide measurement endpoints for use in environmental compliance, regulatory decision-making, and ecological risk assessments. This bioindicators approach should be particularly relevant in helping to identify and diagnose sources of Stressors in environments impacted by multiple Stressors. To demonstrate use of bioindicators in addressing water quality issues, spatial and temporal patters in various biological responses are related to spatial and temporal patterns of contaminants in two aquatic systems compromised by different stressors.

Genotoxic responses (chromosomal damage, DNA strandbreakage) of redbreast sunfish (Lepomis auritis)populations exposed to industrial effluent andmutagenicity of the associated sediments weredetermined in order to compare them to changes incommunity structure. Data were collected from areference stream and East Fork Poplar Creek (EFPC), afirst-order stream which originates on the grounds ofthe Department of Energy Y-12 Plant at Oak Ridge, TN. This stream is contaminated with mercury, PCBs, andnumerous other compounds. Previous studies have shownthat sediment contaminant concentrations, as well asphysiological biomarker responses of the local fishpopulations, are highest at the headwaters of EFPC anddecrease with increasing distance from the DOEfacility as contaminant loading decreases. Chromosomal damage was measured by flow cytometry – asreflected by variation in cellular DNA content – andstrand breakage was determined by agarose gelelectrophoresis using blood as the source of DNA. Mutagenicity was determined by theSalmonella/microsome assay using organic solventextracts of sediment surface samples. Community levelresponses included community diversity and percentpollution-tolerant species. Biomarker responses andmutagenicity were found to be highest at theheadwaters of EFPC, and tended to decrease withincreasing distance from the effluent. In general,biomarker responses appeared to be correlated withmutagenicity of the sediment, and both of theserelated to fish community disturbance and level ofstream contamination. Because responses at severallevels of biological organization show similarpatterns of downstream effects, this suggests thatthere may be a causal relationship betweencontamination and biological effects.

The radial forearm free flap (RFFF) is a versatile flap offering many reconstructive options for head and neck defects. Its low bulk, ease of dissection, and excellent vascularity are among its advantages. Its low flap loss and complication rates offer the best choice for the reconstruction of oral, oropharyngeal, and hypopharyngeal lining. Evaluation of collateral circulation to the hand is important to avoid distal ischemia and donor site morbidity. Pulse oximetry can be used to augment Allen's test to assess collateral supply to the hand. This cost-neutral technique can be used in routine preoperative screening prior to RFFF surgery.

During early life stages, fish in the Mississippi River system may become stranded by shoreline drawdowns induced by the passage of commercial vessels. We examined the stranding of larval shovelnose sturgeon Scaphirhynchus platorynchus, paddlefish Polyodon spathula, and bigmouth buffalo Ictiobus cyprinellus and of juvenile blue catfish Ictalurus furcatus, largemouth bass Micropterus salmoides, and bluegill Lepomis macrochirus in a laboratory flume. Stranding was measured at three vertical drawdown rates (0.76, 0.46, and 0.21 cm/s) and two bank slopes (1:5 and 1:10). Blue catfish, shovelnose sturgeon, and paddlefish were not tested at both bank slopes. Susceptibility to stranding varied among species and was independent of drawdown rate. At a slope of 1:5, shovelnose sturgeons had the highest stranding percentage (66.7%), followed by paddlefish (38.0%), bluegills (20.0%), bigmouth buffalo (2.2%), and largemouth bass (0.0%). At 1:10, blue catfish had the highest stranding percentage (26.7%), follow...

Spatial distribution of contaminants in the sediments and biota of a large reservoir ecosystem were related to a variety of biological responses in fish populations and communities to determine possible relationships between contaminant loading in the environment and fish health. Much of the contaminant inventory in the Clinch River/Watts Bar Reservoir (CR/WBR) system has originated from three U.S. Department of Energy facilities on the Oak Ridge Reservation, which borders this system in its upper reaches. Fish sampled from areas of the CR/WBR system with the highest levels of contaminants in the sediments and biota, primarily mercury and PCBs, had the most dramatic bioindicator responses. The major changes observed were induction of detoxification enzymes, organ dysfunction, increased frequency of histopathological lesions, impaired reproduction, and reduced fish community integrity. Mercury, the dominant contaminant, displayed a decreasing concentration gradient from the upper reaches of Poplar Creek to the lower Clinch River, which was consistent with a downstream gradient in several of the biological responses. A multivariate analysis using all of the individual fish health responses at each site in a discriminant analysis procedure also revealed a downstream gradient in integrated fish health. In Poplar Creek where contaminant concentrations were the highest, statistical correlations were observed between individual bioindicator responses such as contaminant exposure indicators, organ dysfunction, histopathological damage, and reproductive impairment. Relationships between contaminant loading and fish community indices such as species richness and relative abundance, however, were more difficult to establish in Poplar Creek because of the possible dominating influence of food and habitat availability on fish community dynamics. Using a suite of bioindicators that encompass a range of levels of biological organization and response-sensitivity scales improves the probability of identifying cause (contaminant) and effect (biological response) and helps in distinguishing between natural and anthropogenic sources of stress in aquatic ecosystems.

Safety in medicine is a rapidly developing field. However, until recently it had been unclear how the skills and tools developed by human factors practitioners in other industries could be applied to medicine. This paper initially outlines the quality and safety programmes healthcare systems have traditionally used to improve quality of care, before turning our attention to the epidemiology of medical adverse events. The development of clinical risk management is explained, with a focus on how human factors methods could be used to assist safety management in healthcare. A formal and systematic method to investigate and analyse clinical adverse events and near misses is described, which is based on traditional human factors methodologies. The investigation of clinical adverse events utilises a semi-structured interview and performance influencing factor questionnaire, whilst Reason’s organisational accident causation model is used to analyse adverse events (Reason, J.T., 1993. The human factor in medical accidents. In: Vincent, C. (Ed.), Medical Accidents. Oxford Medical Publications, Oxford). An obstetrics case, concerning a post-partum haemorrhage is used to show how the investigative methods can be used by a clinical risk manager to build up an accurate and detailed description of what happened and the organisational accident causation model can be used to systematically identify why errors occurred. Finally, the applicability and necessary modifications of human factors methods for use in medicine are discussed.

Flowering in petunias is hastened by long days, but little is known about when the plants are most sensitive to photoperiod, or how light integral or temperature affect such phases of sensitivity. The effects of these factors on time to flowering was investigated using reciprocal transfer experiments between long (16 h d -1 ) and short days (8 h d -1 ). The effect of light integral on the phases of photoperiod sensitivity was examined using two sowing dates and a shading treatment (53% transmission). The effects of temperature were investigated by conducting reciprocal transfer experiments in glasshouse compartments at five temperature regimes (means of 13.7, 19.2, 22.3, 25.0 and 28.7 °C). The length of the photoperiod-insensitive juvenile phase of development, when flowering cannot be induced by any environmental stimulus, was sensitive to light integral; low light integrals prolonged this phase, from 23 d at 2.6 MJ m -2 d -1 to 36 d at 1.6 MJ m -2 d -1 (total solar radiation). The length of this development phase was shortest (12.5 d) at 21 °C; it was longer under cooler (21 d at 13.5 °C) and warmer temperatures (17.6 d at 28.3 °C). After this phase, time to flowering was influenced greatly by photoperiod, with long days hastening flowering by between 28 and 137 d, compared with short days. Plants also showed some sensitivity to both temperature and light integral during this phase, but the duration of the final phase of flower development, during which plants were photoperiod-insensitive, was dependent primarily on the temperature at which the plants were grown; at 14.5 °C, 33.9 d were required to complete this phase compared with 11.4 d at 25.5 °C. The experimental approach gave valuable information on the phases of sensitivity to photothermal environment during the flowering process, and could provide the basis of a more physiologically-based quantitative model of flowering than has hitherto been attempted. The information is also useful in the scheduling of lighting and temperature treatments to give optimal flowering times of high quality plants.

One-hundred ninety-five alcohol-using college students completed a questionnaire in early September, at the beginning of the fall semester, then completed a follow-up questionnaire in mid-November, near the end of the semester. The questionnaires included items on levels of alcohol use, the Eysenck I.7 measure of impulsiveness and venturesomeness, alcohol expectancies, perceived norms for alcohol use, reasons for drinking, and aspects of drinking game playing. As predicted, those students who were 18 years of age and younger, nearly all of them 1st-year students, significantly increased their levels of alcohol use during their first semester in college. While increases in reasons for drinking were significantly predictive of increased alcohol use and problems in first-year and older students, increases in expectancies of alcohol effects and in frequencies of drinking game playing were significantly predictive of increases in alcohol use and problems only for first-year students. The present results provide further evidence of the importance of drinking games in the socialization of college students into problematic alcohol use.

Synergy between HIV and malaria is being increasingly recognized. We examined the antimalarial activity of sera from subjects receiving chloroquine, no drugs or HAART. Sera from subjects taking ritonavir-boosted saquinavir or lopinavir significantly inhibited parasite growth (median of 55 and 69% inhibition, respectively). These results indicate that patients on protease inhibitors may be afforded some protection from malaria. The clinical relevance of these observations will require confirmation in controlled studies in malaria-endemic regions.

Although Osteospermum is a species which is known to require a period of chilling to induce flowering, the precise form of the relationships between temperature and photoperiod on the phases of flowering has not been quantified. This study aimed to investigate the effects of temperature and photoperiod on time to inflorescence commitment and on the rate of subsequent floral development in Osteospermum jucundum cv. Zulu. To assess how temperature and photoperiod affected the number of days needed for inflorescence commitment, plants were transferred from a range of photothermal environments to a non-inductive environment. The effect of temperature and photoperiod on subsequent inflorescence development was examined by transferring plants with initiated inflorescences to a range of photothermal environments. Inflorescence commitment occurred first in plants grown at a low average diurnal temperature (10.6°C), but no evidence was found to suggest that photoperiod affected the duration of this phase. Once initiated, high temperatures and long days hastened inflorescence development. The rate of progress to flowering from initiation increased linearly with photoperiod and temperature (up to an optimum of 23.5°C).

The relationships between temperature and time to inflorescence initiation and subsequent development in chrysanthemum cv. Snowdon (Chrysanthemum×morifolium Ramat.) were investigated. From pinching, flowering occurred most rapidly in plants grown at a mean temperature of 20.4°C, whilst those grown at 10.9°C had the lowest leaf number at flowering. The final leaf number, from the pinch to the inflorescence, increased with increasing temperature above 10.9°C. This could be attributed to a marked sigmoidal increase in the rate of leaf initiation with temperature, not delayed initiation. Above 20°C temperature had little effect on the time of floral initiation (plants initiating after 8–9 days), although temperatures below this led to a considerable delay in floral initiation (20.5 days at 9.6°C). Once initiated the inflorescences developed most rapidly at 20.2°C, however, unlike the process of flower initiation, subsequent flower development was delayed by both warmer and cooler temperature regimes.

Reciprocal transfer experiments can be used to describe the stages of photoperiod sensitivity in day-length-sensitive plants. However, there are inconsistencies in the literature concerning the techniques used and, more importantly, the assumptions made when analysing such data sets. This paper appraises the use of reciprocal transfer experiments, with chrysanthemum as a model (short day) plant. Experiments showed little evidence to suggest that axillary meristems were incapable of responding to a floral stimulus when released from apical dominance by pinching (even though the apex appeared vegetative). Five short days given after pinching resulted in sufficient induction to initiate an inflorescence, although seven short days were required to commit a plant to flower with a leaf number similar to plants grown in continuous short days. Floral initiation was then visible at the apex after nine short days. Once the inflorescence had been initiated, long days delayed the early stages of flower development. The results are discussed with reference to reciprocal transfer experiments in general, and specifically in relation to problems that arise when the length of a 'juvenile' phase is confounded with the number of inductive cycles for flower commitment.

The effects of temperature and sowing date on the time to first flowering were investigated in Petunia ×hybrida Vilm `Express Blush Pink' sown on three separate dates (8 Feb., 1 Mar. and 22 Mar. 1993) and grown in glasshouse compartments set to provide six air temperature regimes (minimum temperatures of 4, 10, 14, 18, 22, and 26 °C). Flowering was hastened under high temperatures and sowing later in the season (22 Mar.). To determine the extent to which this seasonal effect was due to photoperiod, a second experiment was conducted where plants were grown under controlled daylengths (8, 11, 14, and 17 h·d-1) within six temperature-controlled glasshouse compartments (set to provide minimum temperatures of 6, 10, 14, 18, 22, and 26 °C). The rate of progress to first flowering increased linearly with lengthening photoperiod up to a critical photoperiod of 14.4 h·d-1, while further increases in daylength had no further affect in hastening flowering. The rate of progress to flowering increased linearly with increasing temperature, however, the optimum temperature, at which the rate of progress to flowering was maximal, was lower under short days compared to long days. Furthermore, the rate of progress to flowering increased linearly with increasing photosynthetic photon flux (PPF). Data from both experiments were analyzed to construct a model to predict the effects of temperature, photoperiod, and PPF on time of flowering in petunia. This model accurately (r2 = 0.88) predicted the flowering times of a different set of plants sown on three dates and grown under six temperature regimes (6, 10, 14, 18, 22, and 26 °C).

Numerous studies have demonstrated how the performance physiology of fish may change when they are acclimated to designated laboratory temperatures, but few researchers have examined naturally occurring seasonal effects on several physiological parameters associated with swimming performance. Using field-acclimatized smallmouth buffalo (Ictiobus bubalus) collected each season, we report significant seasonal effects in the following variables: critical swimming speed (modified), metabolic rate (standard, active, and scope for activity), and swimming efficiency (total and net cost of transport). Underlying seasonal changes in performance was the reproductive cycle of buffalo, particularly the period of fall gonadal recrudescence. Compared with spring, fall buffalo had a significantly lower mean critical swimming speed (72%) and lower active metabolic rate (53%), even when tested at similar temperatures. During spring, buffalo had a high mean critical swimming speed and low net cost of transport in comparison with other seasons. Buffalo are known to participate in a spring migration and spawning that may require the increased performance and efficiency observed during that season. In addition, significant sex effects were detected in winter measurements of standard metabolic rate and net cost of transport, with females the more efficient swimmers.

To assess the in vitro effect of retinol on Plasmodium falciparum, the standard isolates 3D7, D10, W2 and K1 in continuous culture were exposed to retinol added in concentrations ranging from 10(-7) to 0.1 mumol/l. Parasite growth inhibition was assessed from 3H-hypoxanthine incorporation. Triplicate experiments were performed at physiological pH and in the case of D10, additional experiments were performed at pH 7.2 and 7.6. Final media retinol concentrations were assayed using high performance liquid chromatography. Retinol inhibited growth of both asynchronous and synchronous cultures of 3D7 and D10 and asynchronous cultures of W2 and K1. IC50 values determined from assayed media concentrations ranged from 0.2 to 3.9 mumol/l and were comparable to concentrations in normal human serum (1.0-3.0 mumol/l). IC50 values for asynchronous D10 cultures at pH 7.2 were lower than at pH 7.4 or 7.6 (0.5, 3.9 and 5.0 mumol/l, respectively); results from synchronous cultures were similar. These data suggest that P. falciparum is a retinol-sensitive parasite, especially at pH levels equivalent to those in an acidotic patient. Adjunctive retinol therapy may have a role in clinical management of malaria.

We describe a diffraction grating experiment for visible and microwave optics. The groove spacing for the visible-optics grating is determined through atomic force microscopy, so that an additional feature, the blaze angle, is revealed. From the blaze angle, students calculate the theoretical shift in the diffraction pattern and are then able to visualize this shift through measurements of a microwave diffraction pattern produced using a macroscopic grating. The experiment demonstrates the utility of an atomic force microscope in an engineering application and allows separation of diffraction pattern effects associated with slit width and slit spacing.

We report the first observation of single-top-quark production in the s channel through the combination of the CDF and D0 measurements of the cross section in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb(-1) per experiment. The measured cross section is sigma(s) = 1.29(-0.24)(+0.26) pb. The probability of observing a statistical fluctuation of the background to a cross section of the observed size or larger is 1.8 x 10(-10), corresponding to a significance of 6.3 standard deviations for the presence of an s-channel contribution to the production of single-top quarks.

The target of this study, the PfM18 aspartyl aminopeptidase (PfM18AAP), is the only AAP present in the genome of the malaria parasite Plasmodium falciparum. PfM18AAP is a metallo-exopeptidase that exclusively cleaves N-terminal acidic amino acids glutamate and aspartate. It is expressed in parasite cytoplasm and may function in concert with other aminopeptidases in protein degradation, of, for example, hemoglobin. Previous antisense knockdown experiments identified a lethal phenotype associated with PfM18AAP, suggesting that it is a valid target for new antimalaria therapies. To identify inhibitors of PfM18AAP function, a fluorescence enzymatic assay was developed using recombinant PfM18AAP enzyme and a fluorogenic peptide substrate (H-Glu-NHMec). This was screened against the Molecular Libraries Probe Production Centers Network collection of ∼292,000 compounds (the Molecular Libraries Small Molecule Repository). A cathepsin L1 (CTSL1) enzyme-based assay was developed and used as a counterscreen to identify compounds with nonspecific activity. Enzymology and phenotypic assays were used to determine mechanism of action and efficacy of selective and potent compounds identified from high-throughput screening. Two structurally related compounds, CID 6852389 and CID 23724194, yielded micromolar potency and were inactive in CTSL1 titration experiments (IC50 >59.6 μM). As measured by the Ki assay, both compounds demonstrated micromolar noncompetitive inhibition in the PfM18AAP enzyme assay. Both CID 6852389 and CID 23724194 demonstrated potency in malaria growth assays (IC50 4 μM and 1.3 μM, respectively). © 2014 Society for Laboratory Automation and Screening.

We combine six measurements of the inclusive top-quark pair (t(sic)) production cross section (sigma(t)(sic)) from data collected with the CDF and D0 detectors at the Fermilab Tevatron with proton-antiproton collisions at root s = 1.96 TeV. The data correspond to integrated luminosities of up to 8.8 fb(-1). We obtain a value of sigma tt = 7.60 +/- 0.41 pb for a top-quark mass of m(t) = 172.5 GeV. The contributions to the uncertainty are 0.20 pb from statistical sources, 0.29 pb from systematic sources, and 0.21 pb from the uncertainty on the integrated luminosity. The result is in good agreement with the standard model expectation of 7.35(-0.33)(+0.28) pb at next-to-next-to-leading order and next-to-next-to leading logarithms in perturbative QCD.