A physical model of sprinting.

A new physical model of all-out sprinting is presented. The first models for the applied forces in the block, drive and maintenance phases, as well as for braking forces, are proposed and are based on experimental observations. The applied forces and the aerodynamic drag forces along with the speed and position of the sprinter are calculated by the model as functions of time. The model's unknown parameters are physically relevant and are quantitatively comparable to quantities measured experimentally. A novel mathematical method, not based on curve fitting, is proposed along with the model which requires two observable quantities, time of first step and start of maintenance phase, and four time splits. The model was validated by modeling several elite sprints from available split data, as well as measured splits for non-elite sprinters, over 100 m and 200 m distances. Excellent agreement between the split times and the simulated times was obtained and the model was shown to accurately predict 100 m times from 60 m splits for non-elite runners and 200 m times from 100 m splits for elite sprinters. The model was also applied to the study of wind and altitude effects for elite sprinters in 100 and 200 m sprints. The model presented in this paper may also be useful as a coaching tool for non-elite sprinters by enabling comparisons with elite sprinters, the identification of weaknesses (comparing phases, braking coefficient) and by allowing predictions of 100 m times based on 60 m (indoor) performances and 200 m times based on 100 m splits.

Cell-to-cell variability in cell death: can systems biology help us make sense of it all?

One of the most common observations in cell death assays is that not all cells die at the same time, or at the same treatment dose. Here, using the perspective of the systems biology of apoptosis and the context of cancer treatment, we discuss possible sources of this cell-to-cell variability as well as its implications for quantitative measurements and computational models of cell death. Many different factors, both within and outside of the apoptosis signaling networks, have been correlated with the variable responses to various death-inducing treatments. Systems biology models offer us the opportunity to take a more synoptic view of the cell death process to identify multifactorial determinants of the cell death decision. Finally, with an eye toward 'systems pharmacology', we discuss how leveraging this new understanding should help us develop combination treatment strategies to compel cancer cells toward apoptosis by manipulating either the biochemical state of cancer cells or the dynamics of signal transduction.

Head capsule width as an instar indicator for larvae of the cranberry fruitworm (Lepidoptera: Pyralidae) in southeastern New Brunswick.

The objective of this study was to determine the number of instars of the cranberry fruitworm Acrobasis vaccinii Riley in southeastern New Brunswick based on the distribution of head capsule widths from field and laboratory observations. In 2000, head capsules from field samples were measured across their widest point, and the results were plotted against observed frequencies. The data from field samples suggested that A. vaccinii exhibited five instars in 2000. In 2001, larvae were reared in the laboratory until the final molt, and head capsules were counted and measured. The results were also plotted against observed frequencies. None of the laboratory specimens exhibited more than five instars, supporting the results of the previous year. Various factors are invoked to explain the difference between these results and those of a previous study conducted 50 yr earlier and 200 km away, in which six instars and larger head capsules were reported.

Characterization of PDZ-binding kinase, a mitotic kinase.

hDlg, the human homologue of the Drosophila Discs-large (Dlg) tumor suppressor protein, is known to interact with the tumor suppressor protein APC and the human papillomavirus E6 transforming protein. In a two-hybrid screen, we identified a 322-aa serine/threonine kinase that binds to the PDZ2 domain of hDlg. The mRNA for this PDZ-binding kinase, or PBK, is most abundant in placenta and absent from adult brain tissue. The protein sequence of PBK has all the characteristic protein kinase subdomains and a C-terminal PDZ-binding T/SXV motif. In vitro, PBK binds specifically to PDZ2 of hDlg through its C-terminal T/SXV motif. PBK and hDlg are phosphorylated at mitosis in HeLa cells, and the mitotic phosphorylation of PBK is required for its kinase activity. In vitro, cdc2/cyclin B phosphorylates PBK. This evidence shows how PBK could link hDlg or other PDZ-containing proteins to signal transduction pathways regulating the cell cycle or cellular proliferation.

[Psychosocial impact of the 1998 Québec Ice Storm.]. / Les impacts psychosociaux de la tempête de verglas au Québec.

Between January 5th and January 9th 1998, Quebec was struck by a natural disaster, an ice storm that disrupted the daily lives of millions of people. The ice accumulated on electric wires and installations caused the collapse of part of the system leaving millions of people without power for periods of up to a month. These events thus compelled many people to reorganize their daily lives in some of the most densely populated areas in Québec. Many elements make this disaster distinct from others. It is in this particular context that we must understand results of studies conducted for the Commission mandated by the Québec government to examine the consequences of the ice storm. These studies examined among other things, the psychosocial consequences of the disaster. By comparing the ice storm to other disasters, we see that the temporality of the phases of impact are somewhat different. The confusion between the phases of anticipation and the lengthy duration of the phase of impact are important characteristics which are also linked to some psychosocial impacts such as uncertainty and the more or less prolonged disorganization of daily life. The types of impact underlined in the studies lie in continuity with reactions generally expected in this area (stress, distress, vulnerability for example), and described in the literature but also reveal the specificity of a disaster occurring in a cold country. Here, there are no massive material destruction but help is diverse. However, as elsewhere, there is a context where some people are in a greater situation of vulnerability.

Metabolism of serotonin to N-acetylserotonin, melatonin, and 5-methoxytryptamine in hamster skin culture.

Biotransformation of [3H]serotonin by cultured hamster skin to 3H-metabolites corresponding to N-acetylserotonin (NAS), melatonin, and 5-methoxytryptamine (5-MT) was demonstrated. This process was time-dependent, with the highest production of radioactive NAS and melatonin metabolites after 3 and 5 h of incubation followed by a decrease in the rate of metabolite release into the media. Conversely, the formation of radioactive metabolite corresponding to 5-MT increased gradually during skin culture, reaching the highest level after 24 h of incubation. The production of 3H-metabolites, corresponding to NAS, melatonin, and 5-MT, was stimulated by forskolin with a maximum effect of forskolin at 10 microM concentration. The gas chromatographic/mass spectroscopy analysis of the fraction eluting at the retention time of NAS standard material showed that it contained NAS, further confirming production and release of NAS into the media by hamster skin. Therefore, we conclude that mammalian skin can acetylate serotonin to NAS and postulate that the NAS is further metabolized by the skin to form melatonin which is subsequently transformed to 5-MT.

Identification of arylamine N-acetyltransferase activity in the bovine lens.

Arylamine N-acetyltransferase (NAT) activity was identified and partially characterized in the bovine lens. According to size-exclusion HPLC, the molecular mass of the arylamine NAT is approximately 30-kDa. Based upon substrate specificity analysis, it is best described as an arylamine NAT which has some ability to N-acetylate arylalkylamines. This arylamine NAT acetylates para-aminobenzoic acid thereby demonstrating a monomorphic pattern of N-acetylation. It demonstrates low sensitivity to methotrexate inhibition as indicated by the relatively high IC50 value (470 microM). NAT could be involved in lenticular detoxification of both endogenous amines and exogenous drugs.

Differences in arylalkylamine N-acetyltransferase activity between inflammatory disease-susceptible Lewis and -resistant Fischer rats.

Lewis (LEW/N) and Fischer (F344/N) rats are histocompatible inbred strains characterized, respectively, by susceptibility and resistance to inflammatory disease. The susceptibility of LEW/N rats to inflammation has been associated with deficient corticotropin-releasing hormone (CRH), ACTH, and corticosterone responses to inflammatory stimuli, specifically attributed to a global impairment in hypothalamic CRH neuron function. In contrast to the LEW/N rats, F344/N rats demonstrate an intact hypothalamic-pituitary-adrenal (HPA) axis. Melatonin, a neurohormone initially isolated in the pineal gland, has been implicated with inhibition of the HPA axis. To investigate melatonin synthesis and secretion in LEW/N and F344/N rats, we examined the diurnal activity of pineal arylalkylamine N-acetyltransferase (NAT1), the rate-limiting enzyme in melatonin biosynthesis, which demonstrates circadian rhythmicity, as well as the diurnal levels of serum melatonin, in both strains. Arylamine N-acetyltransferase (NAT2), a related enzyme activity, thought not to be regulated in a circadian manner, was examined as a control of NAT1 activity. Pineal NAT1 activity peak was observed later and reached significantly higher levels in LEW/N than in F344/N rats. Serum melatonin levels reflected the circadian pattern of the NAT1 activity, without, however, showing any quantitative differences between the two strains. Time-course of pineal NAT1 activity response to beta-adrenergic stimulation was parallel in the two rat strains, whereas the magnitude of the response as greater in LEW/N than in F344/N rats. No circadian or major quantitative differences in NAT2 activity were found between the two strains. Size-exclusion HPLC chromatograms of NAT1 activity revealed similar patterns in both rat strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification and partial characterization of a proteinase specific for insulin-like growth factor binding protein-3 in aqueous and vitreous humors.

The IGFs (-I and -II) are normally found in serum and other extracellular fluids complexed to specific binding proteins (IGFBPs). While several IGFBPs have been identified in vitreous and aqueous humors, the major serum carrier of IGF, IGFBP-3, is notably absent from these fluids. To determine if this paucity could be due to an IGFBP-3 proteinase (IGFBP-3ase), samples of bovine vitreous or aqueous humor were mixed with serum and incubated at 37 degrees C for 4 h followed by western ligand blotting. In these experiments, a distinct loss of the 46 kDa band representing IGFBP-3 was observed while other bands present at 35, 28 and 25 kDa were unaltered. The IGFBP-3ase activity is temperature sensitive, has a pH optimum of about 8.0 and is inhibited by EDTA. Acid treatment of serum to remove endogenously bound IGF does not affect the specificity or activity of the IGFBP-3 proteinase. Size exclusion chromatography of bovine aqueous indicates an approximate molecular weight of 260 kDa. Incubation of recombinant IGFBP-3 or serum with partially-purified IGFBP-3ase results in the appearance of low molecular weight fragments of approximately 30 kDa. These fragments are undetectable by western ligand blotting but are readily visualized using an IGFBP-3 specific antibody. Comparison of normal and diabetic vitreous humor reveals the presence of an increased amount of IGFBP-3 proteolytic fragments in the diabetic as compared to control. These findings indicate the presence of a IGFBP-3 proteinase in aqueous and vitreous humors that may be important in regulating ocular homeostasis.

Judging personality traits of adolescents from photographs.

Previous research has indicated that individuals can accurately judge certain personality dispositions of unacquainted peers after viewing facial photographs of them. The present investigation attempted to replicate and extend this finding. In Study 1, American high school seniors watched a videotape containing a series of facial photographs of twenty-two 14-year-old boys, and judged the social adjustment, good-worker attributes, and aggressiveness of each of these boys, using a series of bipolar scales. These impressions were then correlated with objective measures of these factors that had been taken previously. The subjects judged social adjustment, but not the other two factors, accurately. A second study evaluated the reliability of these findings. College students who were unacquainted with these boys rank-ordered them on the same three dimensions, using photographs of their upper bodies. The results of Study 2 were identical to those of Study 1, despite the differences in the judges' ages, the stimulus materials, and the methods of measurement.

Identification and characterization of two isozymic forms of arylamine N-acetyltransferase in Syrian hamster skin.

Arylamine N-acetyltransferase (EC 2.3.1.5) activity was examined using skin from Syrian hamster. Two isozymes of arylamine N-acetyltransferase, designated NAT-1 and NAT-2, were detected on anion-exchange high-performance liquid chromatography analysis. Both enzyme activities had indistinguishable molecular masses (30 kDa), but differed significantly in their specificity toward the aromatic amines including serotonin, dopamine, methoxytryptamine, tryptamine, para-phenetidine, para-aminobenzoic acid, and sulphamethazine. Specifically, NAT-2 but not NAT-1 catalyzed acetylation of dopamine to N-acetyldopamine and acetylation of serotonin to form N-acetylserotonin, a direct precursor of melatonin. The two isozymes were also distinguishable based upon their sensitivity toward methotrexate inhibition (50% inhibiting dose for NAT-1 = 380 microM; NAT-2 > 2 mM). The presence of these two activities in the skin raises new questions about the physiologic role of this enzyme in general and in the skin-specific functions in particular.

Antibodies to quinolinic acid reveal localization in select immune cells rather than neurons or astroglia.

Polyclonal antibodies were produced against quinolinic acid. No immunoreactivity was observed in any cell type in carbodiimide-fixed brain tissue from control rats. When the antibodies were applied to carbodiimide-fixed spleen tissue, strong quinolinic acid immunoreactivity was observed in some cells with the appearance of macrophages and dendritic cells. These findings indicate an immune system origin for quinolinic acid, and implicate immune cells in excitotoxic CNS pathologies. These findings also raise the possibility that quinolinic acid is a unique cytokine in immune system signal transmission.

Differential regulation of arylamine and arylalkylamine N-acetyltransferases in human retinoblastoma (Y-79) cells.

For the first time, arylamine and arylalkylamine N-acetyltransferase (NAT) activities are shown to be differentially regulated. In a human retinoblastoma (Y-79) cell line, arylalkylamine NAT activity, but not arylamine NAT activity increased (3-5-fold) rapidly (1-3 h) in response to treatment with dibutyryl cAMP. In contrast, treatment with butyrate showed a delayed (3-5 days) increase (3-5-fold) in arylamine NAT activity but not in arylalkylamine NAT activity. The differential response to these agents in Y-79 cells provides a model system for future studies on the regulatory relationship between the two enzyme activities.

Identification and characterization of arylamine N-acetyltransferase activity from the bovine retinal pigment epithelium.

Arylamine N-acetyltransferase (NAT) activity was identified and characterized in bovine retinal pigment epithelium (RPE) cells. Upon examining the RPE supernatant for multiple ionic species, one major NAT activity peak was detected. Based upon its substrate specificity, it is best described as an arylamine NAT. However, there was detectable arylalkylamine NAT activity within this peak. Further purification via size-exclusion HPLC revealed multiple peaks of NAT activity, although the major peak (around 30 kDa) again predominantly exhibits arylamine NAT activity. However, substrate specificity studies indicate that this arylamine NAT activity is able to acetylate specific arylalkylamine substrates. This arylamine NAT demonstrates a monomorphic pattern of acetylation since it acetylates rho-aminobenzoic acid rather than sulfamethazine. It also demonstrates a low sensitivity to methotrexate inhibition indicated by the high IC50 value (570 microM). The mode of inhibition by methotrexate is uncompetitive as demonstrated by kinetic analysis.

Characterization of the brain family of aromatic amine N-acetyltransferases.

Arylamine and arylalkylamine N-acetyltransferase activities in the rat brain were isolated and partially characterized. A total of four N -acetyltransferase activities were identified using a combination of three separation procedures, ammonium sulfate fractionation, methotrexate affinity chromatography, and size-exclusion HPLC. Two of the N -acetyltransferase activities demonstrated preference for arylamines and differential sensitivity to inhibition by methotrexate. The other two activities were characterized as arylalkylamine N-acetyltransferase based on their preference for arylalkylamines such as serotonin and tryptamine. Potential functions of these enzyme activities in the brain are discussed.

Partial purification and characterization of arylamine N-acetyltransferase in bovine retina.

Arylamine N-acetyltransferase (NAT) activity was partially purified and characterized in bovine retina. Upon examining the retinal supernatant for multiple ionic species, only one NAT activity was detected. Based upon its substrate specificity, it is best described as an arylamine NAT. According to size-exclusion HPLC, the molecular mass of the arylamine NAT is approximately 30-kDa. This arylamine NAT acetylates p-aminobenzoic acid thereby demonstrating a monomorphic pattern of acetylation. The NAT activity demonstrated low sensitivity to methotrexate inhibition as indicated by a high IC50 value (480 microM).

Regional distribution of arylamine and arylalkylamine N-acetyltransferase activities in the rat brain.

Arylamine and arylalkylamine N-acetyltransferase (NAT) activities were measured separately in different areas of the rat brain using specific substrates. Relatively high levels of arylamine NAT activity were detected in all areas examined. Arylalkylamine NAT activity in these areas ranged from 2 to 5% of the arylamine NAT activity. The possibility that arylamine NAT may be involved in the control of kynurenine metabolism in the brain is discussed.