A feedforward model of suppressive and facilitatory habituation effects

 Simple exposure to repeatitive stimulation is known to induce short-term learning effects across a wide range of species. These effects can be both suppressive and facilitatory depending on stimulus conditions: repeatitive presentation of a weak stimulus decreases the strength of the response (habituation), whereas presentation of a tonic stimulus following a series of weak stimuli transiently increases the response strength (dishabituation). Although these phenomena have been comprehensively characterized at both behavioral and cellular levels, most existing models of nonassociative learning focus exclusively on the suppressive or facilitatory changes in response, and do not attempt to relate cellular events to behavior. I propose here a feedforward model of habituation effects that explains both suppressive and facilitatory changes in response relying on the interaction between excitatory and inhibitory processes that develop in parallel on two different timescales. The model's properties are used to explain the rate sensitivity property of habituation and recovery and stimulus dishabituation. Received: 1 June 2001 / Accepted in revised form: 4 December 2001     

Ethanol production from corn cob hydrolysates by <Emphasis Type="Italic">Escherichia coli</Emphasis> KO11

Corn cob hydrolysates, with xylose as the dominant sugar, were fermented to ethanol by recombinant Escherichia coli KO11. When inoculum was grown on LB medium containing glucose, fermentation of the hydrolysate was completed in 163 h and ethanol yield was 0.50 g ethanol/g sugar. When inoculum was grown on xylose, ethanol yield dropped, but fermentation was faster (113 h). Hydrolysate containing 72.0 g/l xylose and supplemented with 20.0 g/l rice bran was readily fermented, producing 36.0 g/l ethanol within 70 h. Maximum ethanol concentrations were not higher for fermentations using higher cellular concentration inocula. A simulation of an industrial process integrating pentose fermentation by E. coli and hexose fermentation by yeast was carried out. At the first step, E. coli fermented the hydrolysate containing 85.0 g/l xylose, producing 40.0 g/l ethanol in 94 h. Baker's yeast and sucrose (150.0 g/l) were then added to the spent fermentation broth. After 8 h of yeast fermentation, the ethanol concentration reached 104.0 g/l. This two-stage fermentation can render the bioconversion of lignocellulose to ethanol more attractive due to increased final alcohol concentration. Journal of Industrial Microbiology & Biotechnology (2002) 29, 124–128 doi:10.1038/sj.jim.7000287 Received 20 February 2002/ Accepted in revised form 04 June 2002     

NMR spectroscopic and theoretical study of the complexation of the inhibitor allosamidin in the binding pocket of the plant chitinase hevamine

Based on NMR spectroscopic information about the allosamidin-hevamine complex, ab initio MO calculations of the ring current effect of the aromatic moieties of Trp255, Tyr183 and Tyr6 of hevamine were carried out to investigate the role of these amino acid residues in binding interactions with allosamidin in solution. In addition, the intermolecular steric compression effect on the 13C chemical shifts of the allosamizoline carbon atoms and the hydrogen bonding to Glu127 was identified. It can be inferred that the binding forces are strongest in the allosamizoline moiety of allosamidin.     

Dynamics of Aboveground and Soil Carbon and Nitrogen Stocks and Cycling of Available Nitrogen along a Land-use Gradient in Rondônia,Brazil

High rates of deforestation in the Brazilian Amazon have the potential to alter the storage and cycling of carbon (C) and nitrogen (N) across this region. To investigate the impacts of deforestation, we quantified total aboveground biomass (TAGB), aboveground and soil pools of C and N, and soil N availability along a land-use gradient in Rondônia, Brazil, that included standing primary forest, slashed primary and secondary forest, shifting cultivation, and pasture sites. TAGB decreased substantially with increasing land use, ranging from 311 and 399 Mg ha^–1 (primary forests) to 63 Mg ha^–1 (pasture). Aboveground C and N pools declined in patterns and magnitudes similar to those of TAGB. Unlike aboveground pools, soil C and N concentrations and pools did not show consistent declines in response to land use. Instead, C and N concentrations were strongly related to percent clay content of soils. Concentrations of NO₃-N and NH₄-N generally increased in soils following slash-and-burn events along the land-use gradient and decreased with increasing land use. Increasing land use resulted in marked declines in NO₃-N pools relative to NH₄-N pools. Rates of net nitrification and N-mineralization were also generally higher in postfire treatments relative to prefire treatments along the land-use gradient and declined with increasing land use. Results demonstrate the linked responses of aboveground C and N pools and soil N availability to land use in the Brazilian Amazon; steady reductions in aboveground pools along the land-use gradient were accompanied by declines in inorganic soil N pools and transformation rates.     

Selective Pressures on RNA Hairpins In Vivo and In Vitro

Comparison of the most stable potential hairpins in the sequences of natural ribozymes with those in the randomized sequences has revealed that the hairpin loop energies are lower than expected by chance. Although these hairpins are not necessarily parts of functional structures, there is a selective pressure to diminish the destabilizing free energies of the hairpin loops. In contrast, no significant bias is observed in the stacking values of the most stable stems. In the ribozymes isolated in vitro the loops of potential hairpins are closer to random values, which can result in less efficient folding rates. Furthermore, the effects of kinetic traps seem to be more significant in the folding pathways of the in vitro isolates due to a potential to form stable stacks incompatible with the functional folds. Similarly to natural ribozyme sequences, the untranslated regions of viral RNAs also form hairpins with relatively low loop free energies. These evolutionary trends suggest ways for efficient engineering of improved RNA constructs on the basis of analysis of in vitro isolates and approaches for the search of regions coding for functional RNA structures in large genome sequences. Received: 12 January 2001 / Accepted: 21 May 2001     

Kinetic heterogeneity of an experimental tumour revealed by BrdUrd incorporation and mathematical modelling

In the present paper we propose a method of analysis of the cell kinetic characteristics of in vivo experimental tumours, that uses DNA-BrdUrd flow cytometry data at various times after the bromodeoxyuridine (BrdUrd) injection and mathematical modelling. The model of the cell population takes into account the cell-cell heterogeneity of the progression rate across cell cycle phases within the tumour, and assumes a strict correlation between the durations of S and G2M phases. The model also allows for a nonconstant DNA synthesis rate across S phase. In addition, the measurement process is modelled, considering the possibility of nonimpulsive labelling and providing a representation of the time course of the bivariate DNA-BrdUrd fluorescence distribution. Sequential DNA-BrdUrd distributions were obtained in vivo from a human ovarian carcinoma transplanted in mice and, for comparison, in vitro from a cell line of the same origin. From these data, that included the fractional density and the mean BrdUrd-fluorescence of BrdUrd-positive cells as a function of the DNA-fluorescence, kinetic parameters such as the potential doubling time (T _pot) and the mean and variance of the transit times in S and G2M phases, were estimated. This study revealed the presence of a substantial heterogeneity in S and G2M phases within the in vivo cell population and of a lower heterogeneity in the in vitro population. Moreover, our analysis suggests a nonnegligible effect of the BrdUrd pharmacokinetics in the in vivo cell labelling.     

FISH-mapping of a 100-kb terminal 22q13 deletion

Both cytogenetically visible and cryptic deletions of the terminal region of chromosome 22q are associated with a clinical phenotype including mental retardation, delay in expressive speech development, hypotonia, normal to accelerated growth and minor facial dysmorphic features. The genes responsible for the development of the phenotype have not yet been identified, but a distal localization is probable, since the cytogenetically visible and the cryptic deletions show a similar pattern of symptoms. We report a 33-year-old woman with a submicroscopic 22q13 deletion, mild mental retardation, speech delay, autistic symptoms and mild facial dysmorphic features. The deletion was mapped by FISH using cosmid probes from terminal 22q13, and the size of the deletion was estimated to be 100 kb. Three genes are affected by the deletion in this patient. ACR and RABL2B are deleted and proSAP2 is disrupted. This observation, together with recently published data, supports the notion that proSAP2 is the most important contributor to the 22q13 deletion phenotype.     

A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression

The cyclin-dependent kinase inhibitor, p27(Kip1), which regulates cell cycle progression, is controlled by its subcellular localization and subsequent degradation. p27(Kip1) is phosphorylated on serine 10 (S10) and threonine 187 (T187). Although the role of T187 and its phosphorylation by Cdks is well-known, the kinase that phosphorylates S10 and its effect on cell proliferation has not been defined. Here, we identify the kinase responsible for S10 phosphorylation as human kinase interacting stathmin (hKIS) and show that it regulates cell cycle progression. hKIS is a nuclear protein that binds the C-terminal domain of p27(Kip1) and phosphorylates it on S10 in vitro and in vivo, promoting its nuclear export to the cytoplasm. hKIS is activated by mitogens during G(0)/G(1), and expression of hKIS overcomes growth arrest induced by p27(Kip1). Depletion of KIS using small interfering RNA (siRNA) inhibits S10 phosphorylation and enhances growth arrest. p27(-/-) cells treated with KIS siRNA grow and progress to S/G(2 )similar to control treated cells, implicating p27(Kip1) as the critical target for KIS. Through phosphorylation of p27(Kip1) on S10, hKIS regulates cell cycle progression in response to mitogens.