bluuebunny/crossref_metadata_2025 huggingface dataset:
Ötzi's last meals: DNA analysis of the intestinal content of the Neolithic glacier mummy from the Alps
Authors: Rollo Franco , Ubaldi Massimo , Ermini Luca , Marota Isolina
Published: October 2002

Samples of the intestinal content were collected from the ileum and colon of the Neolithic glacier mummy popularly known as the Tyrolean Iceman, or Ötzi. DNA was extracted from the samples and PCR amplified, using a variety of primer pairs designed to bind to different genes (mammal mitochondrial 12S ribosomal RNA gene, plant/fungal nuclear 18S ribosomal RNA gene, plant chloroplast ribulose bisphosphate carboxylase large subunit gene). This made it possible to distinguish between animal and plant food residues (macroremains) and pollen (microremains). According to the DNA reconstruction, the man's last meal was composed of red deer (
Cervus elaphus
) meat, and, possibly, cereals; this meal had been preceded by another one based on ibex (
Capra ibex
), different species of dicots, and cereals. The DNA spectrum corresponding to pollen residues in the colon, on the other hand, fits with the hypothesis that the last journey of the Neolithic hunter/warrior was made through a subalpine coniferous forest to the site at over 3,200 m above sea level, where his mummified body was to be discovered 5,000 years later.
A push–pull approach to maximize vaccine efficacy: Abrogating suppression with an IL-13 inhibitor while augmenting help with granulocyte/macrophage colony-stimulating factor and CD40L
Authors: Ahlers Jeffrey D. , Belyakov Igor M. , Terabe Masaki , Koka Rima , Donaldson Debra D. , Thomas Elaine K. , Berzofsky Jay A.
Published: October 2002

Although a role for CD4+helper cells in CD8+cytotoxic T lymphocyte (CTL) induction by vaccines is widely recognized, much less is known about a counterbalancing role of CD4+T cells in down-modulating this response, or about ways to optimize vaccine responses through abrogation of this negative regulatory mechanism. Here, we discovered a synergistic enhancement of vaccine-mediated CTL induction and protection by the relief of suppression through depletion of regulatory CD4+cells, including CD4+NKT cells, or blockade of IL-13 made by these cells, combined with the cytokine granulocyte/macrophage colony-stimulating factor and the costimulatory molecule CD40L. Indeed, in the absence of helper epitopes, granulocyte/macrophage colony-stimulating factor and the helper-mimetic molecule CD40L are not sufficient to replace help to induce CTL without abrogation of CD4+T cell-mediated suppression, suggesting a role for T cell help in overcoming suppression. The increased CTL induction translated to striking protection against viral infection by a vaccine by using this synergistic combined approach. These results argue for a push–pull approach to maximize vaccine efficacy, especially for HIV and cancer.
Memory effects and oscillations in single-molecule kinetics
Authors: Vlad Marcel O. , Moran Federico , Schneider Friedemann W. , Ross John
Published: October 2002

An exactly solvable model for single-molecule kinetics is suggested, based on the following assumptions: (
i
) A single molecule can exist in different chemical states and the random transitions from one chemical state to another can be described by a local master equation with time-dependent transition rates. (
ii
) Because of conformational and other intramolecular fluctuations the rate coefficients in the master equation are random functions of time; their stochastic properties are represented in terms of a set of control parameters. We assume that the fluctuating rate coefficients fulfill a separability condition, that is, they are made up of the multiplicative contributions of two factors: (
a
) a universal factor, which depends on the vector of control parameters and is the same for all chemical transformation processes and (
b
) process-dependent factors, which depend on the initial and final chemical states of the molecule but are independent of the control parameters. For systems with two chemical states the condition of separability is automatically fulfilled. We introduce an intrinsic time scale, which makes it possible to compute theoretically various experimental observables, such as the correlation functions of the fluorescent signal. We analyze the connections between the condition of separability and detailed balance, and discuss the possible cause of chemical oscillations in single molecule kinetics. We show that the intrinsic dynamics of the molecule, expressed by the fluctuations of the control parameters, may lead to damped oscillations of the correlation functions of the fluorescent signal. The influence of the random fluctuations on the control parameters may be described by a renormalized master equation with nonfluctuating apparent rate coefficients. The apparent rate coefficients do not have to obey a condition of detailed balance, even though the real rate coefficients do obey such a condition. It follows that the renormalized master equation may have damped oscillatory solutions.
Untangling the wires: A strategy to trace functional interactions in signaling and gene networks
Authors: Kholodenko Boris N. , Kiyatkin Anatoly , Bruggeman Frank J. , Sontag Eduardo , Westerhoff Hans V. , Hoek Jan B.
Published: October 2002

Emerging technologies have enabled the acquisition of large genomics and proteomics data sets. However, current methodologies for analysis do not permit interpretation of the data in ways that unravel cellular networking. We propose a quantitative method for determining functional interactions in cellular signaling and gene networks. It can be used to explore cell systems at a mechanistic level or applied within a “modular” framework, which dramatically decreases the number of variables to be assayed. This method is based on a mathematical derivation that demonstrates how the topology and strength of network connections can be retrieved from experimentally measured network responses to successive perturbations of all modules. Importantly, our analysis can reveal functional interactions even when the components of the system are not all known. Under these circumstances, some connections retrieved by the analysis will not be direct but correspond to the interaction routes through unidentified elements. The method is tested and illustrated by using computer-generated responses of a modeled mitogen-activated protein kinase cascade and gene network.
Binding of the
Escherichia coli
response regulator CheY to its target measured
in vivo
by fluorescence resonance energy transfer
Authors: Sourjik Victor , Berg Howard C.
Published: October 2002

In
Escherichia coli
chemotaxis, signaling depends on modulation of the level of phosphorylation of CheY, a small protein that couples receptors and flagellar motors. Working
in vivo
, we used fluorescence resonance energy transfer (FRET) to measure the interaction of CheY∼P with its target, FliM. Binding of CheY∼P to FliM was found to be much less cooperative than motor switching; however, under the conditions of our experiment, most of the FliM appeared to be in the cytoplasm. We studied signal processing times in the chemotaxis pathway by measuring the changes in CheY∼P binding to FliM on flash release of caged chemoeffectors. Following sudden addition of attractant, the amount of CheY∼P bound to FliM decayed exponentially with a rate constant of about 2 s
−1
. Following sudden addition of repellent, FliM occupancy increased with a rate constant of about 20 s
−1
. Using these data, we were able to construct a simple model for the chemotactic pathway and to estimate values of rate constants for several key reactions.
Growth suppression of human carcinoma cells by reintroduction of the p300 coactivator
Authors: Suganuma Tamaki , Kawabata Masahiro , Ohshima Tomoko , Ikeda Masa-Aki
Published: October 2002

The p300 and closely related cAMP response element binding protein (CREB)-binding protein (CBP) acetyltransferases function as global transcriptional coactivators and play important roles in a broad spectrum of biological processes, including cell proliferation and differentiation. A role of p300/CBP in tumor suppression has been proposed from the fact that these coactivators are targeted by viral oncoproteins and that biallelic mutations of
p300
have been identified in carcinomas. Here, we show that transcriptional response to the transforming growth factor β (TGF-β), an inhibitor of epithelial cell growth, was severely impaired in human carcinoma cell lines carrying p300 mutations accompanied by inactivation of the second allele, and that wild-type expression restored TGF-β-dependent transcriptional activity. Furthermore, reintroduction of wild-type p300 suppressed the growth of p300-deficient carcinoma cells, whereas p300 did not inhibit the growth of carcinoma cells examined, which have no detectable alterations in p300 protein and retain the TGF-β-dependent transcriptional response. In addition, tumor-derived mutants missing the bromodomain or glutamine-rich region, which are respectively important for chromatin interaction and coactivator activities, lost the suppressive activity. In contrast, CBP exhibited no or reduced ability to suppress the growth of p300-deficient carcinoma cells. These results provide experimental evidence to show that p300 acts as a suppressor of tumor cell growth and suggest a distinct role of p300 in suppression of epithelial tumors.
Functional interaction of endothelial nitric oxide synthase with a voltage-dependent anion channel
Authors: Sun Jianxin , Liao James K.
Published: October 2002

Endothelium-derived nitric oxide (NO) is an important regulator of vascular function. NO is produced by endothelial NO synthase (eNOS) whose function is modulated, in part, by specific protein interactions. By coimmunoprecipitation experiments followed by MS analyses, we identified a human voltage-dependent anion/cation channel or porin as a binding partner of eNOS. The interaction between porin and eNOS was demonstrated by coimmunoprecipitation studies in nontransfected human endothelial cells and Cos-7 cells transiently transfected with eNOS and porin cDNAs.
In vitro
binding studies with glutathione
S
-transferase–porin indicated that porin binds directly to eNOS and that this interaction augmented eNOS activity. The calcium ionophore,
A23187
, and bradykinin, which are known to activate eNOS, markedly increased porin–eNOS interaction, suggesting a potential role of intracellular Ca
2+
in mediating this interaction. Theses results indicate that the interaction between a voltage-dependent membrane channel and eNOS may be important for regulating eNOS activity.
HecA, a member of a class of adhesins produced by diverse pathogenic bacteria, contributes to the attachment, aggregation, epidermal cell killing, and virulence phenotypes of
Erwinia chrysanthemi
EC16 on
Nicotiana clevelandii
seedlings
Authors: Rojas Clemencia M. , Ham Jong Hyun , Deng Wen-Ling , Doyle Jeff J. , Collmer Alan
Published: October 2002

Erwinia chrysanthemi
is representative of a broad class of bacterial pathogens that are capable of inducing necrosis in plants. The
E. chrysanthemi
EC16
hecA
gene predicts a 3,850-aa member of the
Bordetella pertussis
filamentous hemagglutinin family of adhesins. A
hecA
∷Tn
7
mutant was reduced in virulence on
Nicotiana clevelandii
seedlings after inoculation without wounding. Epifluorescence and confocal laser-scanning microscopy observations of
hecA
and wild-type cells expressing the green fluorescent protein revealed that the mutant is reduced in its ability to attach and then form aggregates on leaves and to cause an aggregate-associated killing of epidermal cells. Cell killing also depended on production of the major pectate lyase isozymes and the type II, but not the type III, secretion pathway in
E. chrysanthemi
. HecA homologs were found in bacterial pathogens of plants and animals and appear to be unique to pathogens and universal in necrogenic plant pathogens. Phylogenetic comparison of the conserved two-partner secretion domains in the proteins and the 16S rRNA sequences in respective bacteria revealed the two datasets to be fundamentally incongruent, suggesting horizontal acquisition of these genes. Furthermore,
hecA
and its two homologs in
Yersinia pestis
had a G+C content that was 10% higher than that of their genomes and similar to that of plant pathogenic
Ralstonia
,
Xylella
, and
Pseudomonas
spp. Our data suggest that filamentous hemagglutinin-like adhesins are broadly important virulence factors in both plant and animal pathogens.
Interaction of adjacent primase domains within the hexameric gene 4 helicase-primase of bacteriophage T7
Authors: Lee Seung-Joo , Richardson Charles C.
Published: October 2002

The interaction of primase monomers within the hexameric gene 4 helicase-primase of bacteriophage T7 has been examined by using two genetically distinct gene 4 proteins. The T7 56-kDa gene 4 protein differs from the full-length 63-kDa protein in that it lacks the N-terminal zinc motif essential for the recognition of primase recognition sites. A second gene 4 protein, gp4-K122A, is unable to catalyze the synthesis of phosphodiester bonds as the result of an amino acid change in the catalytic site. Although each protein alone is inactive, the two together catalyze the synthesis of RNA primers. Reconstitution of activity depends on hexamer formation. We propose that the zinc motif of one subunit in the hexamer interacts with the catalytic sites of adjacent subunits.
p53 and DNA damage-inducible expression of the xeroderma pigmentosum group C gene
Authors: Adimoolam Shanthi , Ford James M.
Published: October 2002

The p53 tumor suppressor gene product is a transcription factor involved in cell-cycle regulation, apoptosis, and DNA repair. We and others have shown that p53 is required for efficient nucleotide excision repair (NER) of UV-induced DNA lesions. p53-deficient cells are defective in the repair of UV photoproducts in genomic DNA but proficient for transcription-coupled repair. Therefore, we examined whether p53 regulates the expression of genes required for global genomic repair. In this study, we demonstrate that the mRNA and protein products of the xeroderma pigmentosum group C (
XPC
) gene are UV-inducible in a time- and dose-dependent manner in human WI38 fibroblasts and HCT116 colorectal cancer cells wild type for p53. However, no significant induction of XPC was observed in p53-deficient counterparts to these cells. Furthermore, regulated expression of wild-type p53 in p53 null Li–Fraumeni syndrome human fibroblasts significantly augmented the expression of XPC protein. Analysis of the human
XPC
gene sequence revealed a putative p53 response element in the
XPC
promoter that was capable of mediating sequence-specific DNA binding to p53
in vitro
. These results provide strong evidence that the NER gene
XPC
is a DNA damage-inducible and p53-regulated gene and likely plays a role in the p53-dependent NER pathway.
Conditional disruption of synaptic transmission induces male–male courtship behavior in
Drosophila
Authors: Kitamoto Toshihiro
Published: October 2002

It is reported here that male–male courtship behavior is evoked instantaneously in the fruit fly
Drosophila
by conditional disruption of synaptic transmission. A temperature-sensitive allele of the
Drosophila
dynamin gene
shibire
(
shi

ts1

) was expressed by using the GAL4/UAS system to disrupt synaptic transmission from GAL4-positive neurons in a temperature-dependent manner. An enhancer-trap GAL4 line C309 directing
shi

ts1

expression in central and peripheral neurons (C309/UAS-
shi

ts1

) initiated stereotypical precopulatory behavior toward other mature males immediately after a temperature shift from the permissive to restrictive temperature. At the restrictive temperature, C309/UAS-
shi

ts1

males formed “courtship chains” and exhibited abnormally high levels of head-to-head interactions. The temperature-induced male–male courtship is attributable not to an increase in sexual attractiveness but to an increase in sexual activity of C309/UAS-
shi

ts1

males. Interestingly, the temperature-induced increase in sexual activity is specific toward male partners, because C309/UAS-
shi

ts1

males courted receptive virgin females less vigorously and copulated less efficiently after shifted to the restrictive temperature. Among the GAL4-positive neurons in C309, conditional disruption of certain cholinergic neurons but not the mushroom body intrinsic neurons plays a critical role in the induction of male–male courtship. These neurons may be involved in inhibitory systems that normally suppress aberrant male–male courtship. The presented strategy that can induce behavioral abnormalities by disrupting synaptic transmission in an acute and noninvasive manner will allow further exploration as to how distinct neuronal groups control sexual orientation and other aspects of reproductive behavior in
Drosophila
.
Oscillations and chaos behind predator–prey invasion: mathematical artifact or ecological reality?
Authors: Sherratt Jonathan A. , Eagan Barry T. , Lewis Mark A.
Published: October 2002

A constant dilemma in theoretical ecology is knowing whether model predictions corrspond to real phenomena or whether they are artifacts of the modelling framework. The frequent absence of detailed ecological data against which models can be tested gives this issue particular importance. We address this question in the specific case of invasion in a predator–prey system with oscillatory population kinetics, in which both species exhibit local random movement. Given only these two basic qualitative features, we consider whether we can deduce any properties of the behaviour following invasion. To do this we study four different types of mathematical model, which have no formal relationship, but which all reflect our two qualitative ingredients. The models are: reaction–diffusion equations, coupled map lattices, deterministic cellular automata, and integrodifference equations. We present results of numerical simulations of the invasion of prey by predators for each model, and show that although there are certain differences, the main qualitative features of the behaviour behind invasion are the same for all the models. Specifically, there are either irregular spatiotemporal oscillations behind the invasion, or regular spatiotemporal oscillations with the form of a periodic travelling ‘wake’, depending on parameter values. The observation of this behaviour in all types of model strongly suggests that it is a direct consequence of our basic qualitative assumptions, and as such is an ecological reality which will always occur behind invasion in actual oscillatory predator–prey systems.
The toughness of secondary cell wall and woody tissue
Authors: Lucas P.W. , Tan H. T. W. , Cheng P. Y.
Published: October 2002

The ‘across grain’ toughness of 51 woods has been determined on thin wet sections using scissors. The moisture content of sections and the varying sharpness of the scissor blades had little effect on the results. In thin sections (< 0.6 mm), toughness rose linearly with section thickness. The intercept toughness at zero thickness, estimated from regression analysis, was proportional to relative density, consistent with values reported for non–woody plant tissues. Extrapolation of the intercept toughness of these woods and other plant tissues/materials to a relative density of 1.0 predicted a toughness of 3.45kJ m
−2
, which we identify with the intrinsic toughness of the cell wall. This quantity appears to predict published results from
K
IC
tests on woods and is related to the propensity for crack deflection. The slope of the relationship between section thickness and toughness, describing the work of plastic buckling of cells, was not proportional to relative density, the lightest (balsa) and heaviest (lignum vitae) woods fracturing with less plastic work than predicted. The size of the plastic zone around the crack tip was estimated to be 0.5 mm in size. From this, the hypothetical overall toughness of a thick (> 1 mm) block of solid cell wall material was calculated as 39.35 kJ m
−2
, due to both cell wall resistance (10 %) and the plastic buckling of cells (90 %). This value successfully predicts the toughness of most commercial woods (of relative densities between 0.2 and 0.8) from ‘work area’ tests in tension and bending. Though density was the most important factor, both fibre width/fibre length (in hardwoods) and lignin/cellulose ratios were negatively correlated with the work of plastic buckling, after correcting for density. At low densities the work of plastic buckling in the longitudinal radial (LR) direction exceeded that in longitudinal tangential (LT), but the reverse was true for relative densities above 0.25. This could be attributed to the direction of rays. Density for density, the toughness of temperate hardwoods tested was about 20 % lower than that of tropical hardwoods. This is probably due to the much greater number of vessels in temperate hardwoods. Vessels appear either not to display buckling behaviour during fracture at all or to collapse cheaply. These general results have applications to other plant tissues.
Why the chameleon has spiral–shaped muscle fibres in its tongue
Authors: Van Leeuwen Johan L.
Published: October 2002

The intralingual accelerator muscle is the primary actuator for the remarkable ballistic tongue projection of the chameleon. At rest, this muscle envelopes the elongated entoglossal process, a cylindrically shaped bone with a tapering distal end. During tongue projection, the accelerator muscle elongates and slides forward along the entoglossal process until the entire muscle extends beyond the distal end of the process. The accelerator muscle fibres are arranged in transverse planes (small deviations are possible), and form (hitherto unexplained) spiral–shaped arcs from the peripheral to the internal boundary. To initiate tongue projection, the muscle fibres probably generate a high intramuscular pressure. The resulting negative pressure gradient (from base to tip) causes the muscle to elongate and to accelerate forward. Effective forward sliding is made possible by a lubricant and a relatively low normal stress exerted on the proximal cylindrical part of the entoglossal process. A relatively high normal stress is, however, probably required for an effective acceleration of muscle tissue over the tapered end of the process. For optimal performance, the fast extension movement should occur without significant (energy absorbing) torsional motion of the tongue. In addition, the tongue extension movement is aided by a close packing of the muscles fibres (required for a high power density) and a uniform strain and work output in every cross–section of the muscle. A quantitative model of the accelerator muscle was developed that predicts internal muscle fibre arrangements based on the functional requirements above and the physical principle of mechanical stability. The curved shapes and orientations of the muscle fibres typically found in the accelerator muscle were accurately predicted by the model. Furthermore, the model predicts that the reduction of the entoglossal radius towards the tip (and thus the internal radius of the muscle) tends to increase the normal stress on the entoglossal bone.
Measurements of tissue viability in transplantation
Authors: Thorniley M. S. , Simpkin S. , Balogun E. , Khaw K. , Shurey C. , Burton K. , Green C. J.
Published: October 2002

Near–infrared spectroscopy has primarily been used in monitoring changes in cerebral haemoglobin oxygenatiuon and haemodynamics. However its use as a method for the assessment of tissue viability following transplantation has recently been explored experimentally in our laboratory.

The ability to measure changes in oxygenation and perfusion during harvesting and following transplantation of organs or transfer of free and pedicled flaps is potentially important in reconstructive surgery. We have found that near–infrared spectroscopy is extremely useful in detecting vaso–occlusive events and can accurately and reliably distinguish between arterial, venous or total occlusions. Venous congestion indicated by raised levels of deoxygenated haemoglobin with a concomitant increase in blood volume and the presence and magnitude of reactive hyperaemia are both easily recognizable features by near–infrared spectroscopy. We have shown that near–infrared spectroscopy measurements of venous congestion in kidneys (and other tissues) following prolonged storage correlate with medullary vascular congestion confirmed by angiographical and histological analysis of intrarenal perfusion.

Clinically we have shown that flap perfusion can be improved by altering fluid replacement regimes and the addition of ionotropes. Cerebral near–infrared spectroscopy measurements in a liver transplant model showed statistically significant differences within minutes after the anhepatic phase in cerebral perfusion and oxygenation, between animals transplanted with ischaemically damaged livers compared to those isografted with minimally stored livers. Similarly we have found that near–infrared spectroscopy can be used as a monitor to assess the adequacy of fluid or blood replacement in haemorrhagic and hypovolaemic models. We believe that near–infrared spectroscopy provides a sensitive and reliable postoperative method for the assessment of tissue viability following the transfer of free and pedicled flaps and organs.
Cerebral haemoglobin oxygenation during sustained visual stimulation – a near–infrared spectroscopy study
Authors: Heekeren H. R. , Obrig H. , Wenzel R. , Eberle K. , Ruben J. , Villringer K. , Kurth R. , Villringer A.
Published: October 2002

Using near–infrared spectroscopy, we investigated the time–course of the concentrations of oxygenated haemoglobin, [oxy–Hb], and deoxygenated haemoglobin, [deoxy–Hb], in the occipital cortex of healthy human adults during sustained visual stimulation. Within a few seconds after stimulation (coloured dodecahedrons) we observed a decrease in [deoxy–Hb], peaking after 13 s (‘initial undershoot’). In the subsequent 1–2 min, in seven out of ten subjects, [deoxy–Hb] gradually returned to a plateau closer to the baseline level. After cessation of stimulation, there was a ‘post–stimulus overshoot’ in the concentration of deoxyhaemoglobin. There was a statistically significant correlation between the size of the ‘initial undershoot’ and the ‘post–stimulus overshoot’.

The concentration of oxyhaemoglobin increased upon functional activation. However, in the mean across all subjects there was no initial overshoot. After approximately 19 s it reached a plateau and remained constantly elevated throughout the activation period. After cessation of activation there was a ‘post–stimulus undershoot’ of oxyhaemoglobin.

It is important to consider the time–course of haemoglobin oxygenation when interpreting functional activation data, especially those data obtained with oxygenation–sensitive methods, such as BOLD contrast fMRI.
The knowledge used in vision and where it comes from
Authors: Barlow Horace B.
Published: October 2002

Knowledge is often thought to be something brought from outside to act upon the visual messages received from the eye in a ‘top–down’ fashion, but this is a misleadingly narrow view. First, the visual system is a multilevel heterarchy with connections acting in all directions so it has no ‘top’; and second, knowledge is provided through innately determined structure and by analysis of the redundancy in sensory messages themselves, as well as from outside. This paper gives evidence about mechanisms analysing sensory redundancy in biological vision. Automatic gain controls for luminance and contrast depend upon feedback from the input, and there are strong indications that the autocorrelation function, and other associations between input variables, affect the contrast sensitivity function and our subjective experience of the world. The associative structure of sensory messages can provide much knowledge about the world we live in, and neural mechanisms that discount established associative structure in the input messages by recoding them can improve survival by making new structure more easily detectable. These mechanisms may be responsible for illusions, such as those produced by a concave face–mask, that are classically attributed to top–down influences.
Adaptation to contingencies in macaque primary visual cortex
Authors: Carandini Matteo , Barlow Horace B. , O'keefe Lawrence P. , Poirson Allen B. , Movshon J. Anthony
Published: October 2002

We tested the hypothesis that neurons in the primary visual cortex adapt selectively to contingencies in the attributes of visual stimuli. We recorded from single neurons in macaque V1 and measured the effects of adaptation either to the sum of two gratings (compound stimulus) or to the individual gratings. According to our hypothesis, there would be a component of adaptation that is specific to the compound stimulus. In a first series of experiments, the two gratings differed in orientation. One grating had optimal orientation and the other was orthogonal to it, and therefore did not activate the neuron under study. These experiments provided evidence in favour of our hypothesis. In most cells adaptation to the compound stimulus reduced responses to the compound stimulus more than it reduced responses to the optimal grating, and adaptation to the optimal grating reduced responses to the optimal grating more than it reduced responses to the compound stimulus. This suggests that a component of adaptation was specific to (and caused by) the simultaneous presence of the two orientations in the compound stimulus. To test whether V1 neurons could adapt to other contingencies in the stimulus attributes, we performed a second series of experiments, in which the component gratings were parallel but differed in spatial frequency, and were both effective in activating the neuron under study. These experiments failed to reveal convincing contingent effects of adaptation, suggesting that neurons cannot adapt equally well to all types of contingency.
Robotic and neuronal simulation of the hippocampus and rat navigation
Authors: Burgess Neil , Donnett James G. , Jeffery Kathryn J. , O–keefe John
Published: October 2002

The properties of hippocampal place cells are reviewed, with particular attention to the nature of the internal and external signals that support their firing. A neuronal simulation of the firing of place cells in open–field environments of varying shape is presented. This simulation is coupled with an existing model of how place–cell firing can be used to drive navigation and is tested by implementation as a miniature mobile robot. The sensors on the robot provide visual, odometric and short–range proximity data, which are combined to estimate the distance of the walls of the enclosure from the robot and the robot's current heading direction. These inputs drive the hippocampal simulation, in which the robot's location is represented as the firing of place cells. If a goal location is encountered, learning occurs in connections from the concurrently active place cells to a set of ‘goal cells’, which guide subsequent navigation, allowing the robot to return to an unmarked location. The system shows good agreement with actual place–cell firing, and makes predictions regarding the firing of cells in the subiculum, the effect of blocking long–term synaptic changes, and the locus of search of rats after deformation of their environment.
Development and regeneration of the retinotectal map in goldfish: a computational study
Authors: Weber Cornelius , Ritter Helge , Cowan Jack , Obermayer Klaus
Published: October 2002

We present a simple computational model to study the interplay of activity-dependent and intrinsic processes thought to be involved in the formation of topographic neural projections. Our model consists of two input layers which project to one target layer. The connections between layers are described by a set of synaptic weights. These weights develop according to three interacting developmental rules: (i) an intrinsic fibre-target interaction which generates chemospecific adhesion between afferent fibres and target cells; (ii) an intrinsic fibre-fibre interaction which generates mutual selective adhesion between the afferent fibres; and (iii) an activity-dependent fibre-fibre interaction which implements Hebbian learning. Additionally, constraints are imposed to keep synaptic weights finite. The model is applied to a set of eleven experiments on the regeneration of the retinotectal projection in goldfish. We find that the model is able to reproduce the outcome of an unprecedented range of experiments with the same set of model parameters, including details of the size of receptive and projective fields. We expect this mathematical framework to be a useful tool for the analysis of developmental processes in general.
Memory and anxiety disorders
Authors:   The American Association for Research into Nervous and Mental Diseases, McNally Richard J.
Published: October 2002

Experimental psychopathologists have identified varying patterns in memory bias in people with depressive and anxiety disorders. Individuals suffering from depression tend to exhibit explicit memory deficits for positively-valanced material, and sometimes exhibit biases for retrieving negative self-relevant information as well. Most studies, however, provide scant evidence for implicit memory biases in depression. In contrast to depression, anxiety disorders are rarely associated with enhanced esplicit memory for threat-related information (with the exception of panic disorder). Evidence for implicit memory biases for threat in these syndromes is mixed. After providing an overview of findings on memory abnormalities in depressive and anxiety disorders, data from several new studies bearing on posttraumatic stress disorder (PTSD) in Vietnam combat veterans and in women with histories of childhood sexual abuse are presented. Involving directed forgetting, implicit memory and autobiographical cueing paradigms, these experiments point to a pattern of abnormalities linked to PTSD rather than to trauma per se.
Ageing and physiological functions
Authors: Young Archie
Published: October 2002

In youth, most physiological functions have generous spare capacity. Even in health, however, increasing age is characterized by progressive erosion of these ‘safety margins’. Examples include the decline of bone mass (towards a threshold for likelihood of fracture), of glomerular filtration rate (towards a threshold for susceptibility to clinical renal failure), of renal tubular function (towards a threshold for clinically important susceptibility to dehydration), of hepatic function (towards a thresholds for accumulation following conventional ‘young adult’ doses of common medications), or of lower limb explosive power (towards thresholds for impaired functional mobility).

Increasing age is also characterized by a rising prevalence of chronic pathologies, complicating attempts to determine the rate or the mechanism of the age–related decline in a physiological function. Nevertheless, it is clear that in many organs the loss of function is largely attributable to the loss of functioning cells, even in the absence of overt disease. This apparently fundamental aspect of ageing remains poorly understood.
Economic and social structure for an ageing population
Authors: Fogel Robert W.
Published: October 2002

The driving force behind the improvement in the quality of life, the rising standard of living, improving health, and increasing longevity, is a process called‘technophysio evolution’, which began about 300 years ago, accelerated during the twentieth century, and is still in progress. Increased spending on health care and on pensions is an appropriate concomitant of technophysio evolution, and should be welcomed. Only wasteful medical services should be restricted. The resources available now and in the future can provide increasingly long and healthy lives of relative luxury for all. However, methods of financing health care and retirement need to be modernized. In the future luxury will be defined increasingly in terms of spiritual rather than material resources. The test of well–being in the future for both young and old will be measured increasingly in terms of the quality of health and the opportunity for self–realization.
Intracellular motility and the evolution of the actin cytoskeleton during development of the male gametophyte of wheat (Triticum aestivumL.)
Authors: Heslop-Harrison J. , Heslop-Harrison Y.
Published: October 2002

The uniaperturate pollen of wheat is dispersed in a partially hydrated condition. Amyloplasts are concentrated in the apertural hemisphere where they surround the two sperms, while vigorously moving polysaccharide–containing wall precursor bodies (P–particles) together with the vegetative nucleus occupy the other. This disposition is the product of a post–meiotic developmental sequence apparently peculiar to the grasses. During vacuolation of the spore after release from the tetrad, the nucleus is displaced to the pole of the cell opposite the site of the germination aperture, already defined in the tetrad. Following pollen mitosis, the vegetative nucleus migrates along the wall of the vegetative cell towards the aperture, leaving the generative cell at the opposite pole isolated by a callose wall. As the vacuole is resorbed, the generative cell rounds up, loses its wall and follows the vegetative nucleus, passing along the wall of the vegetative cell towards the aperture where it eventually divides to produce the two sperms. Throughout this period of nucleus and cell manoeuvrings, minor inclusions of the vegetative cell cytoplasm, including mitochondria, lipid globuli and developing amyloplasts, move randomly. Coordinated vectorial movement begins after the main period of starch accumulation, when the amyloplasts migrate individually into the apertural hemisphere of the grain, a final redistribution betokening the attainment of germinability. In the present paper we correlate aspects of the evolution of the actin cytoskeleton with these events in the developing grain, and relate the observations to published evidence from another monocotyledonous species concerning the timing of the expression of actin genes during male gametophyte development, as revealed in the synthesis of actin mRNA.
Differential chromatin structure within a tandem array 100 kb upstream of the maize b1 locus is associated with paramutation
Authors: Stam Maike , Belele Christiane , Dorweiler Jane E. , Chandler Vicki L.
Published: October 2002

Recombination mapping defined a 6-kb region, 100 kb upstream of the transcription start site, that is required for B-I enhancer activity and paramutation—a stable, heritable change in transcription caused by allele interactions in maize (Zea mays). In this region, B-I and B‘ (the only b1 alleles that participate in paramutation) have seven tandem repeats of an 853-bp sequence otherwise unique in the genome; other alleles have one. Examination of recombinant alleles with different numbers of tandem repeats indicates that the repeats are required for both paramutation and enhancer function. The 6-kb region is identical in B-I andB‘, showing that epigenetic mechanisms mediate the stable silencing associated with paramutation. This is the first endogenous gene for which sequences required for paramutation have been defined and examined for methylation and chromatin structure. The tandem repeat sequences are more methylated in B-I (high expressing) relative to B‘ (low expressing), opposite of the typical correlation. Furthermore, the change in repeat methylation follows establishment of the B‘ epigenetic state. B-I has a more open chromatin structure in the repeats relative to B‘. The nuclease hypersensitivity differences developmentally precede transcription, suggesting that the repeat chromatin structure could be the heritable imprint distinguishing the two transcription states.
Distinct requirements for Ras oncogenesis in human versus mouse cells
Authors: Hamad Nesrin M. , Elconin Joel H. , Karnoub Antoine E. , Bai Wenli , Rich Jeremy N. , Abraham Robert T. , Der Channing J. , Counter Christopher M.
Published: October 2002

The spectrum of tumors associated with oncogenic Ras in humans often differs from those in mice either treated with carcinogens or engineered to sporadically express oncogenic Ras, suggesting that the mechanism of Ras transformation may be different in humans. Ras stimulates primarily three main classes of effector proteins, Rafs, PI3-kinase, and RalGEFs, with Raf generally being the most potent at transforming murine cells. Using oncogenic Ras mutants that activate single effectors as well as constitutively active effectors, we find that the RalGEF, and not the Raf or PI3-kinase pathway, is sufficient for Ras transformation in human cells. Thus, oncogenic Ras may transform murine and human cells by distinct mechanisms, and the RalGEF pathway—previously deemed to play a secondary role in Ras transformation—could represent a new target for anti-cancer therapy.
Memory Consolidation for the Discrimination of Frequency-Modulated Tones in Mongolian Gerbils Is Sensitive to Protein-Synthesis Inhibitors Applied to the Auditory Cortex
Authors: Kraus Michaela , Schicknick Horst , Wetzel Wolfram , Ohl Frank , Staak Sabine , Tischmeyer Wolfgang
Published: October 2002

Differential conditioning of Mongolian gerbils to linearly frequency-modulated tones (FM) has recently received experimental attention. In the study of the role of cerebral protein synthesis for FM discrimination memory, gerbils received post-training bilateral injections of anisomycin into the auditory cortex under light halothane anesthesia. Compared with saline-treated controls, anisomycin-treated gerbils showed a discrimination decrement during the subsequent three days of training. They markedly improved their performance within training sessions, but started each session at low levels. When repeatedly trained gerbils received post-session injections of anisomycin, discrimination performance during subsequent sessions was similar to the pre-injection performance, indicating that retention, retrieval, reconsolidation, and expression of the established reaction were not affected. However, the improvement of a partially established discrimination reaction was impaired after this treatment. Intracortical injections of emetine confirmed this finding. Neither drug affected FM discrimination learning when given several days before the initial training. Our results suggest that protein-synthesis inhibitors applied to the auditory cortex of gerbils during the post-acquisition phase interfered with learning and memory-related aspects of FM processing. The resulting deficit was evident for a number of post-injection training days. This effect was probably due to impaired consolidation, i.e., processes required for long-term stabilization or retrieval of the memory trace while leaving short-term memory intact.
Rapid Adaptation to Auditory-Visual Spatial Disparity
Authors: Lewald Jörg
Published: October 2002

The so-called ventriloquism aftereffect is a remarkable example of rapid adaptative changes in spatial localization caused by visual stimuli. After exposure to a consistent spatial disparity of auditory and visual stimuli, localization of sound sources is systematically shifted to correct for the deviation of the sound from visual positions during the previous adaptation period. In the present study, this aftereffect was induced by presenting, within 17 min, 1800 repetitive noise or pure-tone bursts in combination with synchronized, and 20° disparate flashing light spots, in total darkness. Post-adaptive sound localization, measured by a method of manual pointing, was significantly shifted 2.4° (noise), 3.1° (1 kHz tones), or 5.8° (4 kHz tones) compared with the pre-adaptation condition. There was no transfer across frequencies; that is, shifts in localization were insignificant when the frequencies used for adaptation and the post-adaptation localization test were different. It is hypothesized that these aftereffects may rely on shifts in neural representations of auditory space with respect to those of visual space, induced by intersensory spatial disparity, and may thus reflect a phenomenon of neural short-term plasticity.
Fatty Acid Export from the Chloroplast. Molecular Characterization of a Major Plastidial Acyl-Coenzyme A Synthetase from Arabidopsis
Authors: Schnurr Judy A. , Shockey Jay M. , de Boer Gert-Jan , Browse John A.
Published: October 2002

Acyl-coenzyme A (CoA) synthetases (ACSs, EC 6.2.1.3) catalyze the formation of fatty acyl-CoAs from free fatty acid, ATP, and CoA. Essentially all de novo fatty acid synthesis occurs in the plastid. Fatty acids destined for membrane glycerolipid and triacylglycerol synthesis in the endoplasmic reticulum must be first activated to acyl-CoAs via an ACS. Within a family of nine ACS genes from Arabidopsis, we identified a chloroplast isoform,LACS9. LACS9 is highly expressed in developing seeds and young rosette leaves. Both in vitro chloroplast import assays and transient expression of a green fluorescent protein fusion indicated that the LACS9 protein is localized in the plastid envelope. A T-DNA knockout mutant (lacs9-1) was identified by reverse genetics and these mutant plants were indistinguishable from wild type in growth and appearance. Analysis of leaf lipids provided no evidence for compromised export of acyl groups from chloroplasts. However, direct assays demonstrated thatlacs9-1 plants contained only 10% of the chloroplast long-chain ACS activity found for wild type. The residual long-chain ACS activity in mutant chloroplasts was comparable with calculated rates of fatty acid synthesis. Although another isozyme contributes to the activation of fatty acids during their export from the chloroplast, LACS9 is a major chloroplast ACS.
ACTIN2 Is Essential for Bulge Site Selection and Tip Growth during Root Hair Development of Arabidopsis
Authors: Ringli Christoph , Baumberger Nicolas , Diet Anouck , Frey Beat , Keller Beat
Published: October 2002

Root hairs develop as long extensions from root epidermal cells. After the formation of an initial bulge at the distal end of the epidermal cell, the root hair structure elongates by tip growth. Because root hairs are not surrounded by other cells, root hair formation provides an excellent system for studying the highly complex process of plant cell growth. Pharmacological experiments with actin filament-interfering drugs have provided evidence that the actin cytoskeleton is an important factor in the establishment of cell polarity and in the maintenance of the tip growth machinery at the apex of the growing root hair. However, there has been no genetic evidence to directly support this assumption. We have isolated an Arabidopsis mutant, deformed root hairs 1 (der1), that is impaired in root hair development. The DER1locus was cloned by map-based cloning and encodes ACTIN2 (ACT2), a major actin of the vegetative tissue. The three der1alleles develop the mutant phenotype to different degrees and are all missense mutations, thus providing the means to study the effect of partially functional ACT2. The detailed characterization of theder1 phenotypes revealed that ACT2 is not only involved in root hair tip growth, but is also required for correct selection of the bulge site on the epidermal cell. Thus, the der1mutants are useful tools to better understand the function of the actin cytoskeleton in the process of root hair formation.