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PubMed2005

Allometry for sexual size dimorphism: testing two hypotheses for Rensch's rule in the water strider Aquarius remigis.

Within any given clade, male size and female size typically covary, but male size often varies more than female size. This generates a pattern of allometry for sexual size dimorphism (SSD) known as Rensch's rule. I use allometry for SSD among populations of the water strider Aquarius remigis (Hemiptera, Gerridae) to test the hypothesis that Rensch's rule evolves in response to sexual selection on male secondary sexual traits and an alternative hypothesis that it is caused by greater phenotypic plasticity of body size in males. Comparisons of three populations reared under two temperature regimes are combined with an analysis of allometry for genital and somatic components of body size among 25 field populations. Contrary to the sexual-selection hypothesis, genital length, the target of sexual selection, shows the lowest allometric slope of all the assayed traits. Instead, the results support a novel interpretation of the differential-plasticity hypothesis: that the traits most closely associated with reproductive fitness (abdomen length in females and genital length in males) are "adaptively canalized." While this hypothesis is unlikely to explain Rensch's rule among species or higher clades, it may explain widespread patterns of intraspecific variation in SSD recently documented for many insect species.

Animals↗

PubMed1999

Pathway alignment: application to the comparative analysis of glycolytic enzymes.

Comparative analysis of metabolic pathways in different genomes yields important information on their evolution, on pharmacological targets and on biotechnological applications. In this study on glycolysis, three alternative ways of comparing biochemical pathways are combined: (1) analysis and comparison of biochemical data, (2) pathway analysis based on the concept of elementary modes, and (3) a comparative genome analysis of 17 completely sequenced genomes. The analysis reveals a surprising plasticity of the glycolytic pathway. Isoenzymes in different species are identified and compared; deviations from the textbook standard are detailed. Several potential pharmacological targets and by-passes (such as the Entner-Doudoroff pathway) to glycolysis are examined and compared in the different species. Archaean, bacterial and parasite specific adaptations are identified and described.

Enzymes↗

PubMed2005

Synaptic plasticity disruption by amyloid beta protein: modulation by potential Alzheimer's disease modifying therapies.

AD (Alzheimer's disease) is characterized by a progressive and devastating mental decline that is usually presaged by impairment of a form of memory dependent on medial temporal lobe structures, including the hippocampus. The severity of clinical dementia correlates positively with the cerebral load of the AD-related protein Abeta (amyloid beta), particularly in its soluble form rather than the insoluble fibrillar Abeta found in amyloid plaques. Recent research in animal models of AD has pointed to a potentially important role for rapid disruptive effects of soluble species of Abeta on neural function in causing a relatively selective impairment of memory early in the disease. Our experiments assessing the mechanisms of Abeta inhibition of LTP (long-term potentiation), a correlate of memory-related synaptic plasticity, in the rodent hippocampus showed that low-n oligomers were the soluble Abeta species primarily responsible for the disruption of synaptic plasticity in vivo. Exogenously applied and endogenously generated anti-Abeta antibodies rapidly neutralized and prevented the synaptic plasticity disrupting effects of these very potent Abeta oligomers. This suggests that active or passive immunotherapeutic strategies for early AD should target Abeta oligomers in the brain. The ability of agents that reduce nitrosative/oxidative stress or antagonize stress-activated kinases to prevent Abeta inhibition of LTP in vitro points to a key role of these cellular mechanisms at very early stages in Abeta-induced neuronal dysfunction. A combination of antibody-mediated inactivation of Abeta oligomers and pharmacological prevention of cellular stress mechanisms underlying their synaptic plasticity disrupting effects provides an attractive strategy in the prevention of early AD.

Alzheimer Disease↗

PubMed1986

Distribution of altered hippocampal neurons and axons immunoreactive with antisera against neuropeptide Y in Alzheimer's-type dementia.

This paper provides detailed information on the distribution of neuropeptide tyrosine (neuropeptide Y; NPY) immunoreactive neurons and fibers in the hippocampal region of eight neuropathologically confirmed cases of Alzheimer's-type dementia (ATD) at postmortem. These neuronal networks are detected by a polyclonal antibody raised against the unconjugated peptide and controls were obtained by using liquid phase absorption immunocytochemistry. The description covers the subfields area dentata, CA3 and CA1, the subicular complex, and the entorhinal area. The hippocampal regions in which the NPY-i neuron networks are most severely affected are the hilus, CA1, the parasubiculum, and the entorhinal cortex. Less obvious reductions occurred in CA3, subiculum, and the presubiculum. Parallel semiquantitative estimates were made of the numbers of neuritic plaques and neurofibrillary tangles in the other hippocampus of the brains in every ATD case. The areas of heaviest pathological changes by these indices are CA1 and the entorhinal cortex. The subicular complex CA3 and the area dentata are less affected. These findings show that the areas with the most severe loss of NPY-i neurons and axons, CA1 and the entorhinal cortex, are the same as those areas most severely affected by the other indices of ATD. Thus NPY-i networks are involved in the ATD disease process. However, other NPY-i networks survive, in some subfields better than in others. The cumulative evidence suggests a population of hippocampal peptide neurons that are remarkably resistant in terminal neurological disease. These neurons have the capability to participate in the maintenance of minimal functioning circuits in target areas of the disease and as such hold significant links for our understanding of synaptic plasticity in disease.

Aged↗

PubMed1995

A Green's function method for heavy ion beam transport.

The use of Green's function has played a fundamental role in transport calculations for high-charge high-energy (HZE) ions. Two recent developments have greatly advanced the practical aspects of implementation of these methods. The first was the formulation of a closed-form solution as a multiple fragmentation perturbation series. The second was the effective summation of the closed-form solution through nonperturbative techniques. The nonperturbative methods have been recently extended to an inhomogeneous, two-layer transport media to simulate the lead scattering foil present in the Lawrence Berkeley Laboratories (LBL) biomedical beam line used for cancer therapy. Such inhomogeneous codes are necessary for astronaut shielding in space. The transport codes utilize the Langley Research Center atomic and nuclear database. Transport code and database evaluation are performed by comparison with experiments performed at the LBL Bevalac facility using 670 A MeV 20Ne and 600 A MeV 56Fe ion beams. The comparison with a time-of-flight and delta E detector measurement for the 20Ne beam and the plastic nuclear track detectors for 56Fe show agreement up to 35%-40% in water and aluminium targets, respectively.

Aluminum↗

PubMed2005

Molecular mechanisms of hormonal activity. II. Kinase systems. Systems with intracellular receptors. Transactivation of STS.

Hormone receptors and other components, functional mechanisms, and biological role of analyzed signal transduction systems (STS) are described. The recently revealed module principle of the structure and STS transactivation providing diversity and plasticity of regulation are highlighted. STS activities are significantly changed in many diseases. Novel promising pharmaceuticals targeted to certain components of STS increase in number from year to year. The data published by the beginning of January 2004 are summarized in this review.

Animals↗

PubMed2005

Changing the specificity of a bacterial chemoreceptor.

The methyl-accepting chemotaxis proteins are a family of receptors in bacteria that mediate chemotaxis to diverse signals. To explore the plasticity of these proteins, we have developed a simple method for selecting cells that swim to target attractants. The procedure is based on establishing a diffusive gradient in semi-soft agar plates and does not require that the attractant be metabolized or degraded. We have applied this method to select for variants of the Escherichia coli aspartate receptor, Tar, that have a new or improved response to different amino acids. We found that Tar can be readily mutated to respond to new chemical signals. However, the overall change in specificity depended on the target compound. A Tar variant that could detect cysteic acid still showed a strong sensitivity to aspartate, indicating that the new receptor had a broadened specificity relative to wild-type Tar. Tar variants that responded to phenylalanine or N-methyl aspartate, or that had an increased sensitivity to glutamate showed a strong decrease in their response to aspartate. In at least some of the cases, the maximal level of sensitivity that was obtained could not be attributed solely to substitutions within the binding pocket. The new tar alleles and the techniques described here provide a new approach for exploring the relationship between ligand binding and signal transduction by chemoreceptors and for engineering new receptors for applications in biotechnology.

Amino Acid Sequence↗

PubMed2004

Regulation of FOXO3a by brain-derived neurotrophic factor in differentiated human SH-SY5Y neuroblastoma cells.

FOXO3a is a ubiquitously expressed mammalian forkhead transcription factor with a high expression level in adult brain. The activity of FOXO3a is inhibited by growth factors through activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling, which phosphorylates FOXO3a and decreases the level of FOXO3a in the nucleus. In the present study, we examined the regulation of FOXO3a by brain-derived neurotrophic factor (BDNF) in retinoic acid (RA)-differentiated human SH-SY5Y neuroblastoma cells. BDNF caused a rapid and time-dependent decrease of nuclear FOXO3a with a corresponding increase of cytosolic FOXO3a. The rate of the BDNF-induced nuclear/cytosolic redistribution was consistent with the time course of BDNF-induced threonine32-phosphorylation of FOXO3a, and was mediated by the PI3K/Akt signaling pathway. Active FOXO3a rapidly increased the level of Bcl-2-interacting mediator (bim) in differentiated SH-SY5Y cells, and BDNF decreased the FOXO3a-induced increase of bim through activation of both PI3K/Akt and Erk signaling pathways. Thapsigargin, an endoplasmic reticulum (ER) stress-inducing agent, significantly decreased threonine32-phosphorylation of FOXO3a, and increased nuclear and decreased cytosolic FOXO3a, suggesting that thapsigargin activates FOXO3a. Treatment with BDNF completely reversed and blocked the thapsigargin-induced dephosphorylation and nuclear accumulation of FOXO3a. In addition, protein phosphatase 1/2A inhibitors increased threonine32-phosphorylation of FOXO3a, decreased nuclear FOXO3a, and blocked thapsigargin-induced activity of FOXO3a. The regulatory effect of BDNF on FOXO3a and its target genes may play a significant role in the BDNF-mediated neuronal survival, differentiation, and plasticity.

Apoptosis Regulatory Proteins↗

PubMed2001

Neurosteroids in learning and memory processes.

The discovery that neurosteroids could be synthesized de novo in the brain independent from the periphery and display neuronal actions led to great enthusiasm for the study of their physiological role. Pharmacological studies suggest that neurosteroids may be involved in several physiological processes, such as learning and memory. This chapter summarizes the effects of the administration of neurosteroids on learning and memory capabilities in rodents and in models of amnesia. We address the central mechanisms involved in mediating the modulation of learning and memory processes by neurosteroids. In this regard, the neurosteroid-modulated neurotransmitter systems, such as gamma-aminobutyric acid type A, N-methyl-D-aspartate, and cholinergic and sigma opioid systems, appear to be potential targets for the rapid memory alteration actions of neurosteroids. Moreover, given that some neurosteroids affect neuronal plasticity, this neuronal change could be involved in the long-term modulation of learning and memory processes. To understand the role of endogeneous neurosteroids in learning and memory processes, we present some physiological studies in rodents and humans. However, the latter do not successfully prove a role of endogenous neurosteroids in age-related memory impairments. Finally, we discuss the relative implication of a given neurosteroid vs its metabolites. For this question, a new approach using the quantitative determination of traces of neurosteroids by mass spectrometry seems to have potential for examining the role of each neurosteroid in discrete brain areas in learning and memory alterations, as observed during aging.

Animals↗

PubMed2001

The mismatch negativity in evaluating central auditory dysfunction in dyslexia.

The mismatch negativity (MMN), a brain response elicited by a discriminable change in any repetitive aspect of auditory stimulation even in the absence of attention, has been widely used in both basic and clinical research during recent years. The fact that the MMN reflects the accuracy of auditory discrimination and that it can be obtained even from unattentive subjects makes it an especially attractive tool for studying various central auditory-system dysfunctions both in adults and children. In this review, we will discuss the applicability of the MMN to studies in dyslexia, which is currently thought, in the majority of the cases, to primarily result either from a dysfunction of the phonological system or a more general auditory deficit. Recent evidence indicates that the MMN enables one to determine which aspects of auditory information are deficiently processed in dyslexia. The MMN might also be helpful in the early definition of the dyslexia type, which would make it possible to start correctly-targeted training programmes before any major learning delays occur. Furthermore, the MMN holds promise of showing plastic changes in the brain of dyslexic individuals underlying the alleviation or remediation of dyslexia in the course of a successful training programme.

Acoustic Stimulation↗

PubMedDate not supplied

Intravascular MR-monitored balloon angioplasty: an in vivo feasibility study.

PURPOSE: To develop a new method for monitoring balloon angioplasty by using an intravascular magnetic resonance (MR) imaging technique. MATERIALS AND METHODS: Nine New Zealand White rabbits were used: seven for technique refinement, including surgery, device insertion, stenosis creation, and MR protocol development; and two for the final MR imaging of the balloon angioplasty. The in vivo experimental method involved insertion of a catheter antenna and a balloon catheter, via femoral arteriotomies bilaterally, into the target site of the upper abdominal aorta, where a stenosis was artificially created by binding a plastic cable tie. Then, the entire process of the dilation of the stenosis with balloon inflation was monitored under MR fluoroscopy. RESULTS: Catheter insertions were successful, and a 5-mm-long stenosis of the aorta was produced in all nine rabbits. Eight complete balloon angioplasty procedures were satisfactorily monitored and recorded, showing clearly the stenosis of the aorta at the beginning of the procedure, the dilation of the stenosis during the balloon inflation, and the complete opening of the stenosis after balloon dilation. CONCLUSION: Preliminary results of in vivo balloon angioplasty monitored with intravascular MR imaging are presented. MR fluoroscopy, based on the intravascular MR imaging technique, may represent a potential alternative to x-ray fluoroscopy for guiding interventional treatment of cardiovascular diseases.

Angioplasty, Balloon↗

PubMed2006

Activity-dependent dynamics and sequestration of proteasomes in dendritic spines.

The regulated degradation of proteins by the ubiquitin proteasome pathway is emerging as an important modulator of synaptic function and plasticity. The proteasome is a large, multi-subunit cellular machine that recognizes, unfolds and degrades target polyubiquitinated proteins. Here we report NMDA (N-methyl-D-aspartate) receptor-dependent redistribution of proteasomes from dendritic shafts to synaptic spines upon synaptic stimulation, providing a mechanism for local protein degradation. Using a proteasome-activity reporter and local perfusion, we show that synaptic stimulation regulates proteasome activity locally in the dendrites. We used restricted photobleaching of individual spines and dendritic shafts to reveal the dynamics that underlie proteasome sequestration, and show that activity modestly enhances the entry rate of proteasomes into spines while dramatically reducing their exit rate. Proteasome sequestration is persistent, reflecting an association with the actin-based cytoskeleton. Together, our data indicate that synaptic activity can promote the recruitment and sequestration of proteasomes to locally remodel the protein composition of synapses.

Actins↗

PubMed2005

A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity?

alpha-RIMs and Munc13s are active zone proteins that control priming of synaptic vesicles to a readily releasable state, and interact with each other via their N-terminal sequences. The alpha-RIM N-terminal sequence also binds to Rab3s (small synaptic vesicle GTPases), an interaction that regulates presynaptic plasticity. We now demonstrate that alpha-RIMs contain adjacent but separate Munc13- and Rab3-binding sites, allowing formation of a tripartite Rab3/RIM/Munc13 complex. Munc13 binding is mediated by the alpha-RIM zinc-finger domain. Elucidation of the three-dimensional structure of this domain by NMR spectroscopy facilitated the design of a mutation that abolishes alpha-RIM/Munc13 binding. Selective disruption of this interaction in the calyx of Held synapse decreased the size of the readily releasable vesicle pool. Our data suggest that the ternary Rab3/RIM/Munc13 interaction approximates synaptic vesicles to the priming machinery, providing a substrate for presynaptic plasticity. The modular architecture of alpha-RIMs, with nested binding sites for Rab3 and other targets, may be a general feature of Rab effectors that share homology with the alpha-RIM N-terminal sequence.

Amino Acid Sequence↗

PubMed2005

Genetic variance in female condition predicts indirect genetic variance in male sexual display traits.

During sexual encounters, individuals often use signals, such as display traits, to attract mates. If individuals alter their display traits with respect to the genotype of potential mates, indirect genetic effects (IGEs) may occur in which the genes of one individual influence the phenotype of another. Although IGEs between related individuals have received much attention, their occurrence between unrelated individuals during sexual encounters has not. Here, we demonstrate that in the Australian fruit fly Drosophila serrata, males assess females by using both visual and olfactory cues, resulting in a rapid plastic response (within minutes) in male cuticular hydrocarbons (CHCs), a display trait that is an important target of mate choice. Several CHCs in males exhibited significant IGEs, and IGEs were inducible on both males reared in the laboratory and on field-caught individuals. A vector describing genetic variance in multiple CHCs in females was found to be almost identical to a vector describing indirect genetic variance in male CHCs, suggesting that males might assess female CHCs during courtship. This vector displayed contributions from all female CHCs in the same direction and of similar magnitude, suggesting that female condition may be the underlying casual trait that males are assessing. Consistent with this interpretation, when measured directly in a separate experiment, genetic variance in female condition accounted for 19.8% of the indirect genetic variance in male CHCs. These indirect genetic effects have the potential to alter the response to selection of male sexual display traits.

Animals↗

PubMed1977

Determination of some parameters for pion radiobiology studies.

An experimental investigation of the central axis depth-dose and stopping rate distribution of the SIN biomedical pion beam is reported. The pion stopping rate in a thin disc of tissue-equivalent plastic was determined using a counter telescope. The dose rate at the position of this dic 'target' was measured using a specially designed parallel-plate tissue-equivalent ionization chamber. Both dose rate and pion stopping rate are given as a function of depth for beams of two different momenta spread. The energy deposition required per pion stop to fit the measured dose rate curves was calculated and found to be between 37 and 40 MeV. From the stopping rate measurements the depth-dose distribution of pion interaction dose (star-dose) and the dose due to the pion slowing down have been evaluated. The maximum star-dose is found at a depth of about 2 g cm-2 beyound the maximum of the ionization dose.

Elementary Particles↗

PubMed2006

Evolution of small nucleolar RNAs in nematodes.

In contrast to mRNAs, which are templates for translating proteins, non-protein coding (npc) RNAs (also known as 'non-coding' RNA, ncRNA), exhibit various functions in different compartments and developmental stages of the cell. Small nucleolar RNAs (snoRNAs), one of the largest classes of npcRNAs, guide post-transcriptional modifications of other RNAs that are crucial for appropriate RNA folding as well as for RNA-RNA and RNA-protein interactions. Although snoRNA genes comprise a significant fraction of the eutherian genome, identifying and characterizing large numbers of them is not sufficiently accessible by classical computer searches alone. Furthermore, most previous investigations of snoRNAs yielded only limited indications of their evolution. Using data obtained by a combination of high-throughput cDNA library screening and computational search strategies based on a modified DNAMAN program, we characterized 151 npcRNAs, and in particular 121 snoRNAs, from Caenorhabditis elegans and extensively compared them with those in the related, Caenorhabditis briggsae. Detailed comparisons of paralog snoRNAs in the two nematodes revealed, in addition to trans-duplication, a novel, cis-duplication distribution strategy with insertions near to the original loci. Some snoRNAs coevolved with their modification target sites, demonstrating the close interaction of complementary regions. Some target sites modified by snoRNAs were changed, added or lost, documenting a high degree of evolutionary plasticity of npcRNAs.

Animals↗

PubMed1996

Neural competition and statistical mechanics.

Computational models of activity-dependent competitive neural plasticity typically impose competition in networks in which plasticity is accommodated by permitting changes in the efficacies of synapses in an anatomically fixed network. This is despite the fact that much evidence suggests that neurons compete for neurotrophins, during both target innervation and activity-dependent synaptic re-arrangement, which influence the sprouting and retraction of axonal processes. We therefore present a new approach to the computational modelling of competitive neural plasticity which permits neurons to compete explicitly for neurotrophins. This competition is associated with the sprouting and retraction of axonal processes. Because there is much uncertainty regarding the basic mechanisms, we adopt the powerful machinery of statistical mechanics to avoid the need to address these issues. We show that such an approach can readily account for a wide range of plasticity phenomena in a range of systems, including the results of various pharmacological manipulations.

Animals↗

PubMedDate not supplied

Long-lasting modifications of saccadic eye movements following adaptation induced in the double-step target paradigm.

The adaptation of saccadic eye movements to environmental changes occurring throughout life is a good model of motor learning and motor memory. Numerous studies have analyzed the behavioral properties and neural substrate of oculomotor learning in short-term saccadic adaptation protocols, but to our knowledge, none have tested the persistence of the oculomotor memory. In the present study, the double-step target protocol was used in five human subjects to adaptively decrease the amplitude of reactive saccades triggered by a horizontally-stepping visual target. We tested the amplitude of visually guided saccades just before and at different times (up to 19 days) after the adaptation session. The results revealed that immediately after the adaptation session, saccade amplitude was significantly reduced by 22% on average. Although progressively recovering over days, this change in saccade gain was still statistically significant on days 1 and 5, with an average retention rate of 36% and 19%, respectively. On day 11, saccade amplitude no longer differed from the pre-adaptation value. Adaptation was more effective and more resistant to recovery for leftward saccades than for rightward ones. Lastly, modifications of saccade gain related to adaptation were accompanied by a decrease of both saccade duration and peak velocity. A control experiment indicated that all these findings were specifically related to the adaptation protocol, and further revealed that no change in the main sequence relationships could be specifically related to adaptation. We conclude that in humans, the modifications of saccade amplitude that quickly develop during a double-step target adaptation protocol can remain in memory for a much longer period of time, reflecting enduring plastic changes in the brain.

Adaptation, Physiological↗