CiteULike: Author Cardenas

Costly Punishment Across Human Societies

Joseph Henrich — 2006-06-26T21:04:14-00:00

Science, Vol. 312, No. 5781. (23 June 2006), pp. 1767-1770.

Recent behavioral experiments aimed at understanding the evolutionary foundations of human cooperation have suggested that a willingness to engage in costly punishment, even in one-shot situations, may be part of human psychology and a key element in understanding our sociality. However, because most experiments have been confined to students in industrialized societies, generalizations of these insights to the species have necessarily been tentative. Here, experimental results from 15 diverse populations show that (i) all populations demonstrate some willingness to administer costly punishment as unequal behavior increases, (ii) the magnitude of this punishment varies substantially across populations, and (iii) costly punishment positively covaries with altruistic behavior across populations. These findings are consistent with models of the gene-culture coevolution of human altruism and further sharpen what any theory of human cooperation needs to explain. 10.1126/science.1127333

Real wealth and experimental cooperation: experiments in the field lab

Juan-Camilo Cardenas — 2008-05-14T19:45:27-00:00

Journal of Development Economics, Vol. 70, No. 2. (April 2003), pp. 263-289.

This paper explores how wealth and inequality can affect self-governed solutions to commons dilemmas by constraining group cooperation. It reports a series of experiments in the field where subjects are actual commons users. Household data about the participants' context explain statistically the usually observed wide variation found within and across groups in similar experiments. Participants' wealth and inequality reduced cooperation when groups were allowed to have face-to-face communication between rounds. There are implications for a greater awareness of nonpayoff asymmetries affecting cooperation in heterogeneous groups, apart from heterogeneity in the payoffs structure of the game.

miRNApath: a database of miRNAs, target genes and metabolic pathways.

AO Chiromatzo — 2008-05-10T08:30:40-00:00

Genetics and molecular research : GMR, Vol. 6, No. 4. (2007), pp. 859-865.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression and hence play important roles in metabolic pathways. Recent studies have evidenced the interrelation of miRNAs with cell proliferation, differentiation, development, and diseases. Since they are involved in gene regulation, they are intrinsically related to metabolic pathways. This leads to questions that are particularly interesting for investigating medical and laboratorial applications. We developed an miRNApath online database that uses miRNA target genes to link miRNAs to metabolic pathways. Currently, databases about miRNA target genes (DIANA miRGen), genomic maps (miRNAMap) and sequences (miRBase) do not provide such correlations. Additionally, miRNApath offers five search services and a download area. For each search, there is a specific type of input, which can be a list of target genes, miRNAs, or metabolic pathways, which results in different views, depending upon the input data, concerning relationships between the target genes, miRNAs and metabolic pathways. There are also internal links that lead to a deeper analysis and cross-links to other databases with more detailed information. miRNApath is being continually updated and is available at http://lgmb.fmrp.usp.br/mirnapath.

Dynamic structures of Bacillus subtilis RecN-DNA complexes.

H Sanchez — 2008-04-30T03:31:16-00:00

Nucleic acids research, Vol. 36, No. 1. (January 2008), pp. 110-120.

Genetic and cytological evidences suggest that Bacillus subtilis RecN acts prior to and after end-processing of DNA double-strand ends via homologous recombination, appears to participate in the assembly of a DNA repair centre and interacts with incoming single-stranded (ss) DNA during natural transformation. We have determined the architecture of RecN-ssDNA complexes by atomic force microscopy (AFM). ATP induces changes in the architecture of the RecN-ssDNA complexes and stimulates inter-complex assembly, thereby increasing the local concentration of DNA ends. The large CII and CIII complexes formed are insensitive to SsbA (counterpart of Escherichia coli SSB or eukaryotic RPA protein) addition, but RecA induces dislodging of RecN from the overhangs of duplex DNA molecules. Reciprocally, in the presence of RecN, RecA does not form large RecA-DNA networks. Based on these results, we hypothesize that in the presence of ATP, RecN tethers the 3'-ssDNA ends, and facilitates the access of RecA to the high local concentration of DNA ends. Then, the resulting RecA nucleoprotein filaments, on different ssDNA segments, might promote the simultaneous genome-wide homology search.

Isotopic and Elemental Variations of Carbon and Nitrogen in a Mangrove Estuary

LA Cifuentes — 2008-04-14T18:06:28-00:00

Estuarine, Coastal and Shelf Science, Vol. 43, No. 6. (December 1996), pp. 781-800.

Variations in elemental and isotopic ratios of suspended particulate matter (SPM) were investigated in the Guayas River Estuary Ecosystem (GREE) that empties into the Gulf of Guayaquil, Ecuador. Detritus in the system was identified on the basis of extremely high carbon:chlorophyll aratios (>1000). This material had mean [delta]13C of -26·4±0·3, [delta]15N of +4·8±0·2, and (C:N)atomicof 14·1±0·9. The isotopic data were comparable to measurements reported for fresh and degrading mangrove leaves, whereas the elemental ratio was comparatively enriched in nitrogen. Isotope measurements of SPM throughout the GREE were more similar to values for riverine material and detritus compared with that for the coastal end-member. Values indicative ofin situproduced algae, sewage and shrimp pond effluent were only found at selected sites. Bacterial bioassays, which were used to document potential sources of dissolved organic matter in the GREE, were isotopically similar to SPM. This correspondence coupled with the relatively low (C:N)aof SPM could be explained by bacterial immobolization of nitrogen onto detritus. Finally, tidal variations of (C:N)aand [delta]13C at a brackish mangrove site were similar in magnitude to spatial variations encountered throughout the GREE. Based on these results, the authors caution that care must be taken when samples are taken for food-web studies in these systems.

Inhibition of cytoplasmic mRNA stress granule formation by a viral proteinase.

JP White — 2008-04-10T13:28:18-00:00

Cell host & microbe, Vol. 2, No. 5. (15 November 2007), pp. 295-305.

Mammalian cells form dynamic cytoplasmic mRNA stress granules (SGs) in response to environmental stresses including viral infections. SGs are involved in regulating host mRNA function and metabolism, although their precise role during viral infection is unknown. SGs are thought to assemble based on functions of the RNA-binding proteins TIA-1/TIAR or Ras-GAP SH3 domain-binding protein (G3BP). Here, we investigated the relationship between a prototypical plus-strand RNA virus and SGs. Early during poliovirus infection, SG formation is induced, but as infection proceeds this ability is lost, and SGs disperse. Infection resulted in cleavage of G3BP, but not TIA-1 or TIAR, by poliovirus 3C proteinase. Expression of a cleavage-resistant G3BP restored SG formation during poliovirus infection and significantly inhibited virus replication. These results elucidate a mechanism for viral interference with mRNP metabolism and gene regulation and support a critical role of G3BP in SG formation and restriction of virus replication.

The ribosomal database project (RDP-II): introducing myRDP space and quality controlled public data.

JR Cole — 2007-03-03T22:33:39-00:00

Nucleic Acids Res, Vol. 35, No. Database issue. (January 2007)

Substantial new features have been implemented at the Ribosomal Database Project in response to the increased importance of high-throughput rRNA sequence analysis in microbial ecology and related disciplines. The most important changes include quality analysis, including chimera detection, for all available rRNA sequences and the introduction of myRDP Space, a new web component designed to help researchers place their own data in context with the RDP's data. In addition, new video tutorials describe how to use RDP features. Details about RDP data and analytical functions can be found at the RDP-II website (http://rdp.cme.msu.edu/).

Local Environmental Control and Institutional Crowding-Out

Juan Cardenas — 2008-03-25T23:20:06-00:00

World Development, Vol. 28, No. 10. (October 2000), pp. 1719-1733.

Regulations that are designed to improve social welfare typically begin with the premise that individuals are purely self-interested. Experimental evidence shows, however, that individuals do not typically behave this way; instead, they tend to strike a balance between self and group interests. From experiments performed in rural Colombia, we found that a regulatory solution for an environmental dilemma that standard theory predicts would improve social welfare clearly did not. This occurred because individuals confronted with the regulation began to exhibit less other-regarding behavior and made choices that were more self-interested; that is, the regulation appeared to crowd out other-regarding behavior.

How Do Groups Solve Local Commons Dilemmas? Lessons from Experimental Economics in the Field

Juan-Camilo Cardenas — 2008-03-25T23:15:26-00:00

Environment, Development and Sustainability, Vol. 2, No. 3. (2000), pp. 305-322.

The use of experimental settings to observe human behaviour in a controlled environment of incentives, rules and institutions, has been widely used by the behavioural sciences for sometime now, particularly by psychology and economics. In most cases the subjects are college students recruited for one to two hour decision making exercises in which, depending on their choices, they earn cash averaging US$ 20. In such exercises players face a set of feasible actions, rules and incentives (payoffs) involving different forms of social exchange with other people, and that in most cases involve some kind of externalities with incomplete contracts, such as in the case of common-pool resources situations. Depending on the ecological and institutional settings, the resource users face a set of feasible levels of extraction, a set of rules regarding the control or monitoring of individual use, and sometimes ways of imposing material or non-material costs or rewards to those breaking or following the rules. We brought the experimental lab to the field and invited about two hundred users of natural resources in three Colombian rural villages to participate in such decision making exercises and through these and other research instruments we learned about the ways they solve - or fail to - tragedies of the commons with different social institutions. Further, bringing the lab to the field allowed us to explore some of the limitations of existing models about human behaviour and its consequences for designing policies for conserving ecosystems and improving social welfare.

Control strategies for voltage control of a boost type PWM converter

RS Pena — 2008-03-11T05:26:34-00:00

Power Electronics Specialists Conference, 2001. PESC. 2001 IEEE 32nd Annual, Vol. 2 (2001), pp. 730-735 vol.2.

This paper addresses the nonlinear problem of regulating the DC link voltage, in a vector controlled three-phase boost type PWM converter with particular emphasis on applications in wind energy systems. The AC side current control is performed in a synchronously rotating reference frame. An analysis of the system is provided and several alternative DC link voltage controller designs are investigated and compared. Fuzzy controllers augmented using a feedforward compensation technique are found to provide excellent performance. A 3 kW experimental set up has been built and experimental results are provided to validate the control designs

A cage induction generator using back to back PWM converters for variable speed grid connected wind energy system

R Pena — 2008-03-11T05:15:56-00:00

Industrial Electronics Society, 2001. IECON '01. The 27th Annual Conference of the IEEE, Vol. 2 (2001), pp. 1376-1381 vol.2.

A new control scheme of a variable speed grid connected wind energy generation system is presented. The scheme uses a cage induction generator driven by an emulated wind turbine with two back-to-back voltage-fed PWM inverters to interface the generator and the grid. The machine currents are controlled using an indirect vector control technique. The generator torque is controlled to drive the machine to the speed for maximum wind turbine aerodynamic efficiency. The supply side converter currents are also controlled using a vector approach using a reference frame aligned with stator voltage vector. The DC link voltage of the power electronics interface is controlled acting upon the supply active power current component using a nonlinear control and a fuzzy based interpolation of linear PI controllers to improve the disturbance rejection and meet noise considerations in steady state. Experimental validation of the proposed control scheme on an emulated 3.2 kW wind energy system is shown

Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus

Sarah Highlander — 2007-11-07T21:43:29-00:00

BMC Microbiology, Vol. 7 (06 November 2007), 99.

Cellulat: an agent-based intracellular signalling model

Pedro Gonzalez — 2008-03-03T16:24:04-00:00

Biosystems, Vol. 68, No. 2-3. ( 2003), pp. 171-185.

The theory of behaviour-based systems (or autonomous agents) constitutes a useful approach for the modelling of intracellular signalling networks. In this sense, a cell can be seen as an adaptive autonomous agent or as a society of such agents, where each can exhibit a particular behaviour depending on its cognitive capabilities. We present an intracellular signalling model obtained by integrating several computational techniques into an agent-based paradigm. Cellulat, the model, takes into account two essential aspects of the intracellular signalling networks: (1) cognitive capacities, which are modelled as the agent abilities to interact with the surrounding medium and (2) a spatial organisation, this last obtained using a shared data structure through which the agents communicate between them. We propose a methodology for the modelling of intracellular signalling pathway using Cellulat and we discuss the goal of a virtual laboratory based on our model and presently under development.

Different roles of P1 and P2 Saccharomyces cerevisiae ribosomal stalk proteins revealed by cross-linking

Qiu — 2006-10-27T11:51:06-00:00

Molecular Microbiology, Vol. 62, No. 4. (November 2006), pp. 1191-1202.

Tracking multiple topics for finding interesting articles

Raymond Pon — 2008-01-29T18:04:47-00:00

(2007), pp. 560-569.

iScore: Measuring the Interestingness of Articles in a Limited User Environment

RK Pon — 2008-01-26T17:35:46-00:00

Computational Intelligence and Data Mining, 2007. CIDM 2007. IEEE Symposium on (2007), pp. 354-361.

Search engines, such as Google, assign scores to news articles based on their relevancy to a query. However, not all relevant articles for the query may be interesting to a user. For example, if the article is old or yields little new information, the article would be uninteresting. Relevancy scores do not take into account what makes an article interesting, which would vary from user to user. Although methods such as collaborative filtering have been shown to be effective in recommendation systems, in a limited user environment there are not enough users that would make collaborative filtering effective. We present a general framework for defining and measuring the "interestingness" of articles, incorporating user-feedback. We show 21% improvement over traditional IR methods

Muscarine reduces calcium-dependent electrical activity in substantia nigra dopaminergic neurons.

RS Scroggs — 2007-11-23T09:06:18-00:00

J Neurophysiol, Vol. 86, No. 6. (December 2001), pp. 2966-2972.

The effect of muscarine on Ca2+ dependent electrical activity was studied in dopamine (DA) neurons located in the substantia nigra pars compacta (SNc) in brain slices from young rats, using sharp electrodes. In most DA neurons tested, muscarine (50 microM) reduced the amplitude of spontaneous oscillatory potentials and evoked Ca2+-dependent potentials recorded in the presence of TTX. Muscarine also reduced the amplitude of the slow afterhyperpolarization (sAHP) following action potentials in most DA neurons. These data suggest that muscarine reduces Ca2+ entry in SNc DA neurons. The reduction of the amplitude of the sAHP by muscarine in DA neurons may facilitate bursting initiated by glutamatergic input by increasing the frequency at which DA neurons can fire. The reduction of the sAHP via activation of muscarinic receptors in vivo may provide a mechanism whereby cholinergic inputs to DA neurons from the tegmental peduncular pontine nucleus could modulate dopamine release at dopaminergic targets in the brain.

Dunes, turbulent eddies, and interfacial exchange with permeable sediments

Bayani Cardenas — 2007-10-09T16:34:52-00:00

Water Resources Research, Vol. 43 (11 August 2007), W08412.

Self-organization at the origin of life

Athel Cornish-Bowden — 2007-10-02T07:48:10-00:00

Journal of Theoretical Biology, Vol. In Press, Corrected Proof

The concept of an (M,R) system with organizational invariance allows one to understand how a system may be able to maintain itself indefinitely if it is coupled to an external source of energy and materials. However, although this constitutes an important step towards understanding the difference between a living and a non-living system, it is not clear that an (M,R) system with organizational invariance is sufficient to define a living system. To take a further step towards defining what it means to be alive it is necessary to add to a simple (M,R) system some property that represents its identity, and which can be maintained and modified in subsequent generations.

5HT4 Receptors Couple Positively to Tetrodotoxin-Insensitive Sodium Channels in a Subpopulation of Capsaicin-Sensitive Rat Sensory Neurons

Carla Cardenas — 2007-09-13T16:30:32-00:00

J. Neurosci., Vol. 17, No. 19. (1 October 1997), pp. 7181-7189.

Exchange across a sediment-water interface with ambient groundwater discharge

Bayani Cardenas — 2007-09-01T07:41:22-00:00

Journal of Hydrology, Vol. In Press, Accepted Manuscript

Sensing the environment: lessons from fungi

Yong-Sun Bahn — 2006-12-16T00:06:36-00:00

Nature Reviews Microbiology, Vol. 5, No. 1., pp. 57-69.

The genetic signature of (astronomically induced) life extinctions

Robersy Sanchez — 2007-06-26T15:03:45-00:00

(24 Sep 2005)

The current understanding of supernova and gamma-ray burst events suggests important effects on the biosphere if one of more of them happened to strike the earth in the past. In this paper we evaluate the possibility that life extinctions which probably occurred due to excess of radiation occurring in the geologic past might have left a genetic signature on surviving species. We emphasize the signatures of these extinctions, proposing a quantitative model to evaluate the surviving probability of the species, based on kinetic aspects of the frequency of mutations and the DNA repair rate.

PIRSF: family classification system at the Protein Information Resource.

CH Wu — 2005-12-23T08:34:39-00:00

Nucleic Acids Res, Vol. 32, No. Database issue. (1 January 2004)

The Protein Information Resource (PIR) is an integrated public resource of protein informatics. To facilitate the sensible propagation and standardization of protein annotation and the systematic detection of annotation errors, PIR has extended its superfamily concept and developed the SuperFamily (PIRSF) classification system. Based on the evolutionary relationships of whole proteins, this classification system allows annotation of both specific biological and generic biochemical functions. The system adopts a network structure for protein classification from superfamily to subfamily levels. Protein family members are homologous (sharing common ancestry) and homeomorphic (sharing full-length sequence similarity with common domain architecture). The PIRSF database consists of two data sets, preliminary clusters and curated families. The curated families include family name, protein membership, parent-child relationship, domain architecture, and optional description and bibliography. PIRSF is accessible from the website at http://pir.georgetown.edu/pirsf/ for report retrieval and sequence classification. The report presents family annotation, membership statistics, cross-references to other databases, graphical display of domain architecture, and links to multiple sequence alignments and phylogenetic trees for curated families. PIRSF can be utilized to analyze phylogenetic profiles, to reveal functional convergence and divergence, and to identify interesting relationships between homeomorphic families, domains and structural classes.

Using automated morphometry to detect associations between ERP latency and structural brain MRI in normal adults

Valerie Cardenas — 2007-03-02T16:55:27-00:00

Human Brain Mapping, Vol. 25, No. 3. (2005), pp. 317-327.

Despite the clinical significance of event-related potential (ERP) latency abnormalities, little attention has focused on the anatomic substrate of latency variability. Volume conduction models do not identify the anatomy responsible for delayed neural transmission between neural sources. To explore the anatomic substrate of ERP latency variability in normal adults using automated measures derived from magnetic resonance imaging (MRI), ERPs were recorded in the visual three-stimulus oddball task in 59 healthy participants. Latencies of the P3a and P3b components were measured at the vertex. Measures of local anatomic size in the brain were estimated from structural MRI, using tissue segmentation and deformation morphometry. A general linear model was fitted relating latency to measures of local anatomic size, covarying for intracranial vault volume. Longer P3b latencies were related to contractions in thalamus extending superiorly into the corpus callosum, white matter (WM) anterior to the central sulcus on the left and right, left temporal WM, the right anterior limb of the internal capsule extending into the lenticular nucleus, and larger cerebrospinal fluid volumes. There was no evidence for a relationship between gray matter (GM) volumes and P3b latency. Longer P3a latencies were related to contractions in left temporal WM, and left parietal GM and WM near the interhemispheric fissure. P3b latency variability is related chiefly to WM, thalamus, and lenticular nucleus, whereas P3a latency variability is not related as strongly to anatomy. These results imply that the WM connectivity between generators influences P3b latency more than the generators themselves do. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc.

Challenges and progress toward quantitative deformation morphometry of gyral anatomy

C Studholme — 2007-03-02T16:52:27-00:00

Biomedical Imaging: Macro to Nano, 2004. IEEE International Symposium on (2004), pp. 599-602 Vol. 1.

This paper examines recent work toward quantitative mapping of cross-sectional structural differences in gyral anatomy. Taking the approach of deformation based morphometry, it examines an alternative method of calibrating the spatial filtering used in the statistical analysis of maps of relative tissue volume. This differs fundamentally from many common studies based on voxel morphometry. Rather than applying spatial filtering to simply create a significant statistical effect, filtering can be applied in a way which optimizes the qualitative accuracy of the maps with respect to structures of interest, allowing inferences to be made about the effect of a degenerative disease on the amount of tissue on a given region of anatomy. Results using this approach are included from a recent cross sectional study of semantic dementia.

A physical map of the chicken genome

John Wallis — 2004-12-08T23:22:57-00:00

Nature, Vol. 432, No. 7018. (09 December 2004), pp. 761-764.

Deformation-based morphometry of brain changes in alcohol dependence and abstinence

Valerie Cardenas — 2007-02-27T23:41:28-00:00

NeuroImage, Vol. 34, No. 3. (1 February 2007), pp. 879-887.

Brain atrophy associated with chronic alcohol consumption is partially reversible after cessation of drinking. Recovering alcoholics (RA, 45 +/- 8 years) were studied with MRI within 1 week of entering treatment, with follow-up at 8 months. Light drinkers (LD) were studied with MRI twice 1 year apart. For each participant, deformation maps of baseline structure and longitudinal size changes between baseline and follow-up scans were created using nonlinear registration techniques. ANCOVA assessed group differences and regression methods examined relationships between deformation maps and measures of drinking severity or baseline atrophy. At baseline, RA showed significant atrophy in the frontal and temporal lobes. Longitudinally, abstainers recovered tissue volumes significantly faster than LD in parietal and frontal lobes. When comparing abstainers to relapsers, additional regions with significantly greater recovery in abstainers were temporal lobes, thalamus, brainstem, cerebellum, corpus callosum, anterior cingulate, insula, and subcortical white matter. Gray matter volume at baseline predicted volume recovery during abstinence better than white matter. Drinking severity was not significantly related to brain structural changes assessed with this method. Longitudinally, deformation-based morphometry confirmed tissue recovery in RAs who maintain long-term sobriety. Abstinence-associated tissue volume gains are significant in focal parts of the fronto-ponto-cerebellar circuit that is adversely affected by heavy drinking.

Geochemical Rate-RNA Integration Study: Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Gene Transcription and Photosynthetic Capacity of Planktonic Photoautotrophs

Jorge Corredor — 2007-02-14T14:24:27-00:00

Appl. Environ. Microbiol., Vol. 70, No. 9. (1 September 2004), pp. 5459-5468.

A pilot field experiment to assess the relationship between traditional biogeochemical rate measurements and transcriptional activity of microbial populations was carried out at the LEO 15 site off Tuckerton, N.J. Here, we report the relationship between photosynthetic capacity of autotrophic plankton and transcriptional activity of the large subunit gene (rbcL) for ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), the enzyme responsible for primary carbon fixation during photosynthesis. Similar diel patterns of carbon fixation and rbcL gene expression were observed in three of four time series, with maxima for photosynthetic capacity (Pmax) and rbcL mRNA occurring between 10 a.m. and 1 p.m.. The lowest Pmax and rbcL levels were detected between 6 p.m. and 10:30 p.m.. A significant correlation was found between Pmax and form ID rbcL mRNA (R2 = 0.56) and forms IA and IB (R2 = 0.41 and 0.47, respectively). The correlation between the abundance of "diatom" rbcL and Pmax mRNA was modest (R2 = 0.49; n = 12) but improved dramatically (R2 = 0.97; n = 10) upon removal of two outliers which represented afternoon samples with high Pmax but lower mRNA levels. Clone libraries from reverse transcription-PCR-amplified rbcL mRNA indicated the presence of several chromophytic algae (diatoms, prymnesiophytes, and chrysophytes) and some eukaryotic green flagellates. Analogous results were obtained from amplified small rRNA sequences and secondary pigment analysis. These results suggest that diatoms were a major contributor to carbon fixation at LEO 15 at the time of sampling and that photosynthetic carbon fixation was partially controlled by transcriptional regulation of the RubisCO gene.

Co-analysis of Maps of Atrophy Rate and Atrophy State in Neurodegeneration

Valerie Cardenas — 2007-02-02T22:30:51-00:00

: Medical Image Computing and Computer-Assisted Intervention â MICCAI 2004 (2004), pp. 680-687.

Deformation-based mapping of volume change from serial brain MRI in the presence of local tissue contrast change

C Studholme — 2007-01-26T23:20:36-00:00

Medical Imaging, IEEE Transactions on, Vol. 25, No. 5. (2006), pp. 626-639.

This paper is motivated by the analysis of serial structural magnetic resonance imaging (MRI) data of the brain to map patterns of local tissue volume loss or gain over time, using registration-based deformation tensor morphometry. Specifically, we address the important confound of local tissue contrast changes which can be induced by neurodegenerative or neurodevelopmental processes. These not only modify apparent tissue volume, but also modify tissue integrity and its resulting MRI contrast parameters. In order to address this confound we derive an approach to the voxel-wise optimization of regional mutual information (RMI) and use this to drive a viscous fluid deformation model between images in a symmetric registration process. A quantitative evaluation of the method when compared to earlier approaches is included using both synthetic data and clinical imaging data. Results show a significant reduction in errors when tissue contrast changes locally between acquisitions. Finally, examples of applying the technique to map different patterns of atrophy rate in different neurodegenerative conditions is included.

Comparison of methods for measuring longitudinal brain change in cognitive impairment and dementia

VA Cardenas — 2006-10-16T16:20:41-00:00

Neurobiology of Aging, Vol. 24, No. 4. ( 2003), pp. 537-544.

Purpose: The goal of this project was to compare MRI measures of hippocampal, entorhinal cortex (ERC), and whole brain longitudinal change in cognitively normal elderly controls (C), non-demented subjects with cognitive impairment (CI), and demented (D) subjects.Methods: 16 C, 6 CI, and 7 D subjects of comparable age were studied with MRI twice, at least 1 year apart. Longitudinal change in total brain size was measured by several methods, including computerized segmentation, non-linear warping, and change in the fluid/tissue boundaries between cerebrospinal fluid (CSF) and brain. Change in hippocampal volume was measured by semi-automated methods, and ERC volumes were manually measured.Results: The annual rate of atrophy was greater in D versus C and D versus CI for cortical gray matter (cGM) (P=0.009 and 0.002), hippocampus (P=0.0001 and 0.002), and for the change in the fluid/tissue boundary (P=0.03 and 0.03). The annual rate of atrophy of ERC was greater in both CI and D versus C (P=0.01 and 0.0002). No significant differences between groups were found using non-linear warping.Conclusions: In CI, the greatest annual rates of atrophy were in ERC, while in D the greatest annual rates of atrophy were in hippocampus and cortex. Progressive ERC atrophy was observed with a greater degree of cognitive impairment, while hippocampal and cortical atrophy were only observed in demented subjects.

An intensity consistent filtering approach to the analysis of deformation tensor derived maps of brain shape.

C Studholme — 2006-04-01T17:12:36-00:00

Neuroimage, Vol. 19, No. 4. (August 2003), pp. 1638-1649.

Deformation tensor morphometry makes use of the derivatives of spatial transformations between anatomies, to provide highly localized volumetric maps of relative anatomical size. The analysis of such maps, however, has the challenge of describing the data in a way that allows the spatial scale and extent of the local shape properties to match those induced by the disease process being studied. This study examines an approach to the spatial filtering of transformation Jacobian maps created in multisubject studies of brain anatomy, which constrains the filter neighborhood within common structural boundaries present in the spatially normalized image data. The filtering incorporates information derived from the spatial normalization process, using a statistical framework to introduce a measure of uncertainty in local regional intensity correspondence following spatial normalisation. The proposed filtering approach is compared to the use of spatially invariant Gaussian filtering in the analysis of Jacobian determinant maps of brain shape and shape change in Alzheimer's disease and normal aging. Results show significantly improved delineation of fine scale patterns of shape difference (in cross-sectional studies) and shape change (from multiple serial magnetic resonance imaging studies).

Deformation tensor morphometry of semantic dementia with quantitative validation.

C Studholme — 2006-04-01T17:11:59-00:00

Neuroimage, Vol. 21, No. 4. (April 2004), pp. 1387-1398.

High-resolution structural MRI scans of 20 subjects diagnosed with semantic dementia were compared against scans of 20 cognitively normal control subjects using whole brain deformation tensor morphometry to study spatially consistent differences in local anatomical size. A fine lattice free-form volume registration algorithm was used to estimate a continuous mapping from a reference MRI to each individual subject MRI. The Jacobian of these transformations at each voxel were used to quantitatively map relative anatomical size in each individual brain. Intensity consistent filtering was applied to the determinant of these Jacobians. A careful validation using manually traced gyral anatomy was carried out and used to select an optimal deformation tensor filter scale at which to examine the anatomical size maps. General linear modeling at each voxel was used to decompose the influence of age and head size from the primary diagnosis. Maps of the T statistic of the diagnosis across the 40 subjects highlighted significant (P < 0.01 Bonferroni corrected) focal tissue contraction effects related to dementia diagnosis in the left temporal pole extending into the hippocampus, occipitotemporal gyrus and parahippocampal gyrus. Some evidence of greater focal contraction in gray over white matter was also apparent. Contraction effects were also seen, but with reduced significance in the right temporal anatomy, focused toward the temporal pole and hippocampal regions. Additional lower significance findings (P < 0.05 permutation corrected) were detected in the left superior frontal gyrus, left orbital gyrus and left parietal lobe.

Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron toxicity in cells derived from the substantia nigra

Irmgard Paris — 2005-02-13T11:36:44-00:00

Journal of Neurochemistry, Vol. 92, No. 5. (March 2005), pp. 1021-1032.

The TOR kinases link nutrient sensing to cell growth.

J Rohde — 2005-05-04T12:12:03-00:00

J Biol Chem, Vol. 276, No. 13. (30 March 2001), pp. 9583-9586.

Rapamycin is an immunosuppressive natural product that inhibits the proliferation of T-cells in response to nutrients and growth factors. Rapamycin binds to the peptidyl-prolyl isomerase FKBP12 and forms protein-drug complexes that inhibit signal transduction by the TOR kinases. The FKBP12 and TOR proteins are conserved from fungi to humans, and in both organisms the TOR signaling pathway plays a role in nutrient sensing. In response to nitrogen sources or amino acids, TOR regulates both transcription and translation, enabling cells to appropriately respond to growth-promoting signals. Rapamycin is having a profound impact on clinical medicine and was approved as an immunosuppressant for transplant recipients in 1999. Ongoing clinical studies address new clinical applications for rapamycin as an antiproliferative drug for chemotherapy and invasive cardiology.

Tor and Cyclic AMP-Protein Kinase A: Two Parallel Pathways Regulating Expression of Genes Required for Cell Growth.

SA Zurita-Martinez — 2005-01-13T09:09:02-00:00

Eukaryot Cell, Vol. 4, No. 1. (January 2005), pp. 63-71.

In the budding yeast Saccharomyces cerevisiae, the Tor and cyclic AMP-protein kinase A (cAMP-PKA) signaling cascades respond to nutrients and regulate coordinately the expression of genes required for cell growth, including ribosomal protein (RP) and stress-responsive (STRE) genes. The inhibition of Tor signaling by rapamycin results in repression of the RP genes and induction of the STRE genes. Mutations that hyperactivate PKA signaling confer resistance to rapamycin and suppress the repression of RP genes imposed by rapamycin. By contrast, partial inactivation of PKA confers rapamycin hypersensitivity but only modestly affects RP gene expression. Complete inactivation of PKA impairs RP gene expression and concomitantly enhances STRE gene expression; remarkably, this altered transcriptional pattern is still sensitive to rapamycin and thus subject to Tor control. These findings illustrate how the Tor and cAMP-PKA signaling pathways respond to nutrient signals to govern gene expression required for cell growth via two parallel routes, and they have broad implication for our understanding of analogous regulatory networks in normal and neoplastic mammalian cells.