bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixture Models Based on Neural Network Averaging
Authors: Focke Walter W.
Published: November 2005

A modified version of the single hidden-layer perceptron architecture is proposed for modeling mixtures. A particular flexible mixture model is obtained by implementing the Box-Cox transformation as transfer function. In this case, the network response can be expressed in closed form as a weighted power mean. The quadratic Scheffé K-polynomial and the exponential Wilson equation turn out to be special forms of this general mixture model. Advantages of the proposed network architecture are that binary data sets suffice for “training” and that it is readily extended to incorporate additional mixture components while retaining all previously determined weights.
Bayesian Population Decoding of Motor Cortical Activity Using a Kalman Filter
Authors: Wu Wei , Gao Yun , Bienenstock Elie , Donoghue John P. , Black Michael J.
Published: November 2005

Effective neural motor prostheses require a method for decoding neural activity representing desired movement. In particular, the accurate reconstruction of a continuous motion signal is necessary for the control of devices such as computer cursors, robots, or a patient's own paralyzed limbs. For such applications, we developed a real-time system that uses Bayesian inference techniques to estimate hand motion from the firing rates of multiple neurons. In this study, we used recordings that were previously made in the arm area of primary motor cortex in awake behaving monkeys using a chronically implanted multielectrode microarray. Bayesian inference involves computing the posterior probability of the hand motion conditioned on a sequence of observed firing rates; this is formulated in terms of the product of a likelihood and a prior. The likelihood term models the probability of firing rates given a particular hand motion. We found that a linear gaussian model could be used to approximate this likelihood and could be readily learned from a small amount of training data. The prior term defines a probabilistic model of hand kinematics and was also taken to be a linear gaussian model. Decoding was performed using a Kalman filter, which gives an efficient recursive method for Bayesian inference when the likelihood and prior are linear and gaussian.In off-line experiments, the Kalman filter reconstructions of hand trajectory were more accurate than previously reported results.The resulting decoding algorithm provides a principled probabilistic model of motor-cortical coding, decodes hand motion in real time, provides an estimate of uncertainty, and is straightforward to implement. Additionally the formulation unifies and extends previous models of neural coding while providing insights into the motor-cortical code.
On Consistency of Bayesian Inference with Mixtures of Logistic Regression
Authors: Ge Yang , Jiang Wenxin
Published: November 2005

This is a theoretical study of the consistency properties of Bayesian inference using mixtures of logistic regression models. When standard logistic regression models are combined in a mixtures-of-experts setup, a flexible model is formed to model the relationship between a binary (yes-no) response y and a vector of predictors x. Bayesian inference conditional on the observed data can then be used for regression and classification. This letter gives conditions on choosing the number of experts (i.e., number of mixing components) k or choosing a prior distribution for k, so that Bayesian inference is consistent, in the sense of often approximating the underlying true relationship between y and x. The resulting classification rule is also consistent, in the sense of having near-optimal performance in classification. We show these desirable consistency properties with a nonstochastic k growing slowly with the sample size n of the observed data, or with a random k that takes large values with nonzero but small probabilities.
Facial Attractiveness: Beauty and the Machine
Authors: Eisenthal Yael , Dror Gideon , Ruppin Eytan
Published: November 2005

This work presents a novel study of the notion of facial attractiveness in a machine learning context. To this end, we collected human beauty ratings for data sets of facial images and used various techniques for learning the attractiveness of a face. The trained predictor achieves a significant correlation of 0.65 with the average human ratings. The results clearly show that facial beauty is a universal concept that a machine can learn. Analysis of the accuracy of the beauty prediction machine as a function of the size of the training data indicates that a machine producing human-like attractiveness rating could be obtained given a moderately larger data set.
Turning the Whole Soul: The Educational Dialectic of a Sand County Almanac
Authors: Callicott J. Baird
Published: November 2005

A Sand County Almanac by Aldo Leopold is arguably the most influential text for the contemporary environmental movement. It is designed to entice readers to seek direct and sustained experience of nature and to structure that experience through the lens of ecology and evolutionary biology. Part I implicitly conveys the evolutionary-ecological worldview through descriptive prose; in Part II it is expressed in more abstract, conceptual terms; Part III explores its normative implications. The wisdom of this project is problematic. Environmental education in the form of worldview remediation should be encouraged at the post-secondary level of education, but should be complemented by an effort to express positive environmental attitudes and values in terms of popular, pre-scientific worldviews—such as that of the Judeo-Christian-Islamic tradition.
The Flowering of Environmental Roots and the Four Elements in Presocratic Philosophy: From Empedocles to Deleuze and Guattari
Authors: Macauley David
Published: November 2005

I examine the Presocratic thinker Empedocles' philosophical, poetic and religious works—Peri Phuseous (On Nature) and Katharmoi (Purifications)—in terms of their orientations, attitudes and sensibilities toward the natural environment. Through the development of an ethical and material framework centered upon the four rhizomata (roots or elements) of earth, fire, air and water, Empedocles provides an early but important understanding of ideas and issues that remain ecologically relevant today, including conceptions of pollution, the treatment of nonhuman animals, descriptions of organic processes, and the speculative underpinnings of evolutionary theory. I suggest that we can reasonably view Empedocles as kind of shaman-naturalist who is keenly aware of and empathetic with the workings of the physical world even if he is not strictly an "ancient environmentalist". Finally, I point to the post-structuralist work of Deleuze and Guattari, where we can find a critical exploration of the kind of "roots" Empedocles identifies and a defense of the notion of "rhizomes" that enables us both to observe continuities with the Presocratic philosopher and to make creative or constructive links with our modern environment.
The development of behaviour: trends since Tinbergen (1963)
Authors: Hogan Jerry , Bolhuis Johan
Published: November 2005

Niko Tinbergen (1963) put behavioural development on the map as one of the four main problems in behavioural biology. Developmental research at the time was still in the grip of the nature/nurture debate. In his discussion, Tinbergen advocated an interactionist approach to development, which has been the main point of view in developmental research since then. In this paper, we review research in a number of different areas, including imprinting, song learning, motivational systems, human language, and attachment. It has become clear that sensitive periods are important in all these areas, and that some aspects of development are generally irreversible; but these phenomena are not as rigid as was thought previously. Similarly, predispositions, or biases, play an important role in perceptual development, but here too there is much more flexibility than is sometimes suggested. Learning mechanisms underlying imprinting and song acquisition are very similar to those underlying other forms of associative learning. Cognitive concepts such as neural representations and behaviour systems are becoming more common in the analysis of developmental questions. Finally, there are numerous parallels between developmental processes in humans and other animals.
Do ideas about function help in the study of causation?
Authors: Sherry David
Published: November 2005

One of Tinbergen's most lasting contributions to the study of behaviour was the distinction he drew between causal, functional, developmental, and evolutionary questions about behaviour. More recently, behavioural ecologists have claimed that understanding the function of behaviour is an important step towards understanding its causes. This claim has, in turn, been criticised for confusing the fundamental distinction that Tinbergen defined. The study of behaviour, however, usually begins by identifying units of behaviour functionally and only then proceeds to causal analysis. Research carried out on four phenomena — disassortative mating by MHC loci, memory for cache sites in food-storing birds, auditory localisation of prey by barn owls, and magnetic orientation — illustrates the contributions made to causal research through understanding the function of behaviour. Understanding function, and sometimes simply a hypothesis about function, defines the causal questions that are asked, identifies novel questions for causal investigation, and sets the criteria that causal explanations must satisfy.
Causation: the study of behavioural mechanisms
Authors: Hogan Jerry
Published: November 2005

This paper describes current work on the causal analysis of behaviour systems. It is noted that while causal work investigating the neural, hormonal, and genetic bases of behaviour is flourishing, work being conducted at a strictly behavioural level of analysis has declined greatly over the past 40 years. Nonetheless, most recent research on animal cognition and applied ethology is still being carried out at a behavioural level of analysis and examples of both types of research are presented: memory mechanisms of food-storing birds and decisions of spider-eating jumping spiders, as well as feather pecking in fowl and animal welfare issues, are all briefly discussed. Finally, I discuss the similarities between neural network modelling and early ethological models of motivation, and then show how a modern version of Lorenz's model of motivation can account for current research findings on dustbathing in chickens and sleep in humans. I conclude that valuable information can still be obtained by research at a behavioural level of analysis.
Function and mechanism in neuroecology: looking for clues
Authors: Bolhuis Johan
Published: November 2005

The four questions that Niko Tinbergen identified for behavioural biology — evolution, function, development and causation — are all important and should be studied in their own right. Recently, there has been a debate as to whether these four questions should be investigated separately or whether they should be integrated. Integration of the four questions has been attempted in novel research disciplines such as cognitive ecology, evolutionary psychology and neuroecology. Euan Macphail and I have criticised these integrative approaches, suggesting that they are fundamentally flawed as they confound function and mechanism. Investigating the function or evolutionary history of a behaviour or cognitive system is important and entirely legitimate. However, such investigations cannot provide us with answers to questions about the mechanisms underlying behaviour or cognition. At most, functional or evolutionary considerations can provide clues that may be useful for a causal analysis of the underlying mechanisms. However, these clues can be misleading and are often wrong, as is illustrated with examples from song learning and food storing in birds. After summarising the main issues in the neuroecology debate, I discuss some misunderstandings that were apparent in the responses to our critique, as well as some recent relevant data. Recent results do not support the neuroecological approach. Finally, I suggest that the way forward is a cautious and critical use of functional and evolutionary clues in the study of the mechanisms of behaviour.
The evolution of behaviour, and integrating it towards a complete and correct understanding of behavioural biology
Authors: Ryan Michael
Published: November 2005

Tinbergen suggested there are four major aims or questions in ethology. All of these contribute to the larger single question of why animals behave as they do. Here, I emphasise one aim, to understand the evolution of behaviour. Using studies of sexual communication in túngara frogs (Physalaemus pustulosus) I attempt to illustrate how an analysis of the past evolution of behaviour can contribute to our understanding of its current function and the details of the mechanisms guiding it. I argue that integration of Tinbergen's four questions not only give us a more complete understanding of the biology of behaviour, it might be necessary to give us a correct understanding.
Parameterization of Eddy Effects on Mixed Layers and Tracer Transport: A Linearized Eddy Perspective
Authors: Killworth Peter D.
Published: November 2005

Two aspects of the effects of eddies on ocean circulation have proven difficult to parameterize: eddy effects in regions of neutrally stable (or convecting) fluid and the mixing of passive tracers. The effects of linearized eddies, although a restrictive parameter regime, can be straightforwardly computed in these cases. The eddy effects in areas of neutral stability—for example, mixed layers—blend naturally into those in the stably stratified water below, although losing the concept of bolus velocity. Instead, the mixed layer density is advected by an extra overturning velocity and is diffused laterally by a diffusion that is the same as the eddy diffusion at the top of the stably stratified fluid. Passive tracers are advected by the bolus velocity and mixed by the same diffusivity as is used to compute the bolus velocity at that location, so that two different diffusivities are not needed.
Water Mass Transformation and Subduction in the South Atlantic
Authors: Donners J. , Drijfhout S. S. , Hazeleger W.
Published: November 2005

The transformation of water masses induced by air–sea fluxes in the South Atlantic Ocean is calculated with a global ocean model, Ocean Circulation and Climate Advanced Modeling (OCCAM), and has been compared with several observational datasets. Air–sea interaction supplies buoyancy to the ocean at almost all density levels. The uncertainty of the estimates of water mass transformations is at least 10 Sv (Sv ≡ 106 m3 s−1), largely caused by the uncertainties in heat fluxes. Further analysis of the buoyancy budget of the mixed layer in the OCCAM model shows that diffusion extracts buoyancy from the water column at all densities. In agreement with observations, water mass formation of surface water by air–sea interaction is completely balanced by consumption from diffusion. There is a large interocean exchange with the Indian and Pacific Oceans. Intermediate water is imported from the Pacific, and light surface water is imported from the Indian Ocean. South Atlantic Central Water and denser water masses are exported to the Indian Ocean. The air–sea formation rate is only a qualitative estimate of the sum of subduction and interocean exchange. Subduction generates teleconnections between the South Atlantic and remote areas where these water masses reemerge in the mixed layer. Therefore, the subduction is analyzed with a Lagrangian trajectory analysis. Surface water obducts in the South Atlantic, while all other water masses experience net subduction. The subducted Antarctic Intermediate Water and Subantarctic Mode Water reemerge mainly in the Antarctic Circumpolar Current farther downstream. Lighter waters reemerge in the eastern tropical Atlantic. As a result, the extratropical South Atlantic has a strong link with the tropical Atlantic basin and only a weak direct link with the extratropical North Atlantic. The impact of the South Atlantic on the upper branch of the thermohaline circulation is indirect: water is significantly transformed by air–sea fluxes and mixing in the South Atlantic, but most of it reemerges and subducts again farther downstream.
Estimating Eddy Stresses by Fitting Dynamics to Observations Using a Residual-Mean Ocean Circulation Model and Its Adjoint
Authors: Ferreira David , Marshall John , Heimbach Patrick
Published: November 2005

A global ocean circulation model is formulated in terms of the “residual mean” and used to study eddy–mean flow interaction. Adjoint techniques are used to compute the three-dimensional eddy stress field that minimizes the departure of the coarse-resolution model from climatological observations of temperature. The resulting 3D maps of eddy stress and residual-mean circulation yield a wealth of information about the role of eddies in large-scale ocean circulation. In eddy-rich regions such as the Southern Ocean, the Kuroshio, and the Gulf Stream, eddy stresses have an amplitude comparable to the wind stress, of order 0.2 N m−2, and carry momentum from the surface down to the bottom, where they are balanced by mountain form drag. From the optimized eddy stress, 3D maps of horizontal eddy diffusivity κ are inferred. The diffusivities have a well-defined large-scale structure whose prominent features are 1) large values of κ (up to 4000 m2 s−1) in the western boundary currents and on the equatorial flank of the Antarctic Circumpolar Current and 2) a surface intensification of κ, suggestive of a dependence on the stratification N 2. It is shown that implementation of an eddy parameterization scheme in which the eddy diffusivity has an N 2 dependence significantly improves the climatology of the ocean model state relative to that obtained using a spatially uniform diffusivity.
Deep Cyclonic Circulation in the Gulf of Mexico
Authors: DeHaan Christopher J. , Sturges Wilton
Published: November 2005

The anticyclonic Loop Current dominates the upper-layer flow in the eastern Gulf of Mexico, with a weaker mean anticyclonic pattern in the western gulf. There are reasons, however, to suspect that the deep mean flow should actually be cyclonic. Topographic wave rectification and vortex stretching contribute to this cyclonic tendency, as will the supply of cold incoming deep water at the edges of the basin. The authors find that the deep mean flow is cyclonic both in the eastern and western gulf, with speeds on the order of 1–2 cm s−1 at 2000 m. Historical current-meter mooring data, as well as profiling autonomous Lagrangian circulation explorer (PALACE) floats (at 900 m), suggest that vertical geostrophic shear relative to 1000 m gives a surprisingly accurate result in the interior of the basin. The temperature around the edges of the basin at 2000 m is coldest near the Yucatan Channel, where Caribbean Sea water is colder by ∼0.1°C. The temperature increases steadily with distance in the counterclockwise direction from the Yucatan, consistent with a deep mean cyclonic boundary flow.
Effects of the Pacific Diapycnal Mixing and Wind Stress on the Global and Pacific Meridional Overturning Circulation*
Authors: Furue Ryo , Endoh Masahiro
Published: November 2005

Numerical experiments are conducted using an idealized basin to investigate roles of the deep vertical diffusivity and wind stress of the Pacific Ocean in the global and Pacific meridional overturning circulation. The Pacific middepth diffusivity is found to be enhancing the global meridional overturning circulation; when this part of diffusivity is reduced to the background value, not only is the layered circulation of the Pacific greatly weakened, but also the production of the North Atlantic Deep Water (NADW) and Antarctic Bottom Water (AABW) is significantly reduced. The deeper part of the Pacific diffusivity is found to be enhancing the production of the AABW in the model. When the wind stress is turned off in the Pacific, the deep meridional overturning circulation of the Pacific is reduced and the production of the NADW and AABW is also significantly reduced. This is likely due to the reduction of the wind-enhanced upwelling in the subpolar and equatorial regions. These results suggest the importance of the diapycnal diffusion and sea surface conditions in the Pacific not only to the circulation within the Pacific but also to the global meridional overturning circulation.
Spectral Characteristics of the Response of the Meridional Overturning Circulation to Deep-Water Formation
Authors: Deshayes Julie , Frankignoul Claude
Published: November 2005

The response of the upper limb of the meridional overturning circulation to the variability of deep-water formation is investigated analytically with a linear, reduced-gravity model in basins of simple geometry. The spectral characteristics of the model response are first derived by prescribing white-noise fluctuations in the meridional transport at the northern boundary. Although low-frequency basin modes are solutions to the eigenproblem, they are too dissipative to be significantly excited by the boundary forcing, and the thermocline depth response has a red spectrum with no prevailing time scale other than that of a high-frequency equatorial mode, only flattening at the millennial time scale because of vertical diffusivity. The meridional transport is asymmetric about the equator because the northern part of the basin is directly influenced by the boundary forcing while the southern part is mostly set in motion by long Rossby waves. This results in the equator acting as a low-pass filter for the Southern Hemisphere, which clarifies the so-called buffering effect of the equator. In a basin connected by a southern circumpolar channel, the thermocline depth and the transport spectra are redder than in the forced basin and, when a somewhat more realistic stochastic forcing derived from general circulation model simulations is considered, the variability is strongly reduced at high frequency. The linear model qualitatively explains several features of the low-frequency variability of the meridional overturning circulation in climate models, such as its red spectrum and its larger intensity in the North Atlantic Ocean.
Stratified Tidal Flow over a Bump
Authors: Dewey Richard , Richmond David , Garrett Chris
Published: November 2005

The interaction of a stratified flow with an isolated topographic feature can introduce numerous disturbances into the flow, including turbulent wakes, internal waves, and eddies. Measurements made near a “bump” east of Race Rocks, Vancouver Island, reveal a wide range of phenomena associated with the variable flow speeds and directions introduced by the local tides. Upstream and downstream flows were observed by placing two acoustic Doppler current profilers (ADCPs) on one flank of the bump. Simultaneous shipboard ADCP surveys corroborated some of the more striking features. Froude number conditions varied from subcritical to supercritical as the tidal velocities varied from 0.2 to 1.5 m s−1. During the strong ebb, when the moored ADCPs were located on the lee side, a persistent full-water-depth lee wave was detected in one of the moored ADCPs and the shipboard ADCP. However, the placement of the moorings would suggest that, by the time it appears in the moored ADCP beams, the lee wave has been swept downstream or has separated from the bump. Raw ADCP beam velocities suggest enhanced turbulence during various phases of the tide. Many of the three-dimensional flow characteristics are in good agreement with laboratory studies, and some characteristics, such as shear in the bottom boundary layer, are not.
Assessing the precision of high-throughput computational and laboratory approaches for the genome-wide identification of protein subcellular localization in bacteria
Authors: Rey Sébastien , Gardy Jennifer L , Brinkman Fiona SL
Published: November 2005

Background

Identification of a bacterial protein's subcellular localization (SCL) is important for genome annotation, function prediction and drug or vaccine target identification. Subcellular fractionation techniques combined with recent proteomics technology permits the identification of large numbers of proteins from distinct bacterial compartments. However, the fractionation of a complex structure like the cell into several subcellular compartments is not a trivial task. Contamination from other compartments may occur, and some proteins may reside in multiple localizations. New computational methods have been reported over the past few years that now permit much more accurate, genome-wide analysis of the SCL of protein sequences deduced from genomes. There is a need to compare such computational methods with laboratory proteomics approaches to identify the most effective current approach for genome-wide localization characterization and annotation.

Results

In this study, ten subcellular proteome analyses of bacterial compartments were reviewed. PSORTb version 2.0 was used to computationally predict the localization of proteins reported in these publications, and these computational predictions were then compared to the localizations determined by the proteomics study. By using a combined approach, we were able to identify a number of contaminants and proteins with dual localizations, and were able to more accurately identify membrane subproteomes. Our results allowed us to estimate the precision level of laboratory subproteome studies and we show here that, on average, recent high-precision computational methods such as PSORTb now have a lower error rate than laboratory methods.

Conclusion

We have performed the first focused comparison of genome-wide proteomic and computational methods for subcellular localization identification, and show that computational methods have now attained a level of precision that is exceeding that of high-throughput laboratory approaches. We note that analysis of all cellular fractions collectively is required to effectively provide localization information from laboratory studies, and we propose an overall approach to genome-wide subcellular localization characterization that capitalizes on the complementary nature of current laboratory and computational methods.
Evaluation of potential reference genes in real-time RT-PCR studies of Atlantic salmon
Authors: Olsvik Pål A , Lie Kai K , Jordal Ann-Elise O , Nilsen Tom O , Hordvik Ivar
Published: November 2005

Background

Salmonid fishes are among the most widely studied model fish species but reports on systematic evaluation of reference genes in qRT-PCR studies is lacking.

Results

The stability of six potential reference genes was examined in eight tissues of Atlantic salmon (Salmo salar), to determine the most suitable genes to be used in quantitative real-time RT-PCR analyses. The relative transcription levels of genes encoding 18S rRNA, S20 ribosomal protein, β-actin, glyceraldehyde-3P-dehydrogenase (GAPDH), and two paralog genes encoding elongation factor 1A (EF1AA and EF1AB) were quantified in gills, liver, head kidney, spleen, thymus, brain, muscle, and posterior intestine in six untreated adult fish, in addition to a group of individuals that went through smoltification. Based on calculations performed with the geNorm VBA applet, which determines the most stable genes from a set of tested genes in a given cDNA sample, the ranking of the examined genes in adult Atlantic salmon was EF1AB>EF1AA>β-actin>18S rRNA>S20>GAPDH. When the same calculations were done on a total of 24 individuals from four stages in the smoltification process (presmolt, smolt, smoltified seawater and desmoltified freshwater), the gene ranking was EF1AB>EF1AA>S20>β-actin>18S rRNA>GAPDH.

Conclusion

Overall, this work suggests that the EF1AA and EF1AB genes can be useful as reference genes in qRT-PCR examination of gene expression in the Atlantic salmon.
Membrane testosterone binding sites in prostate carcinoma as a potential new marker and therapeutic target: Study in paraffin tissue sections
Authors: Dambaki Constantina , Kogia Christina , Kampa Marilena , Darivianaki Katherine , Nomikos Michael , Anezinis Ploutarchos , Theodoropoulos Panayiotis A , Castanas Elias , Stathopoulos Efstathios N
Published: November 2005

Background

Steroid action is mediated, in addition to classical intracellular receptors, by recently identified membrane sites, that generate rapid non-genomic effects. We have recently identified a membrane androgen receptor site on prostate carcinoma cells, mediating testosterone rapid effects on the cytoskeleton and secretion within minutes.

Methods

The aim of this study was to investigate whether membrane androgen receptors are differentially expressed in prostate carcinomas, and their relationship to the tumor grade. We examined the expression of membrane androgen receptors in archival material of 109 prostate carcinomas and 103 benign prostate hyperplasias, using fluorescein-labeled BSA-coupled testosterone.

Results

We report that membrane androgen receptors are preferentially expressed in prostate carcinomas, and they correlate to their grade using the Gleason's microscopic grading score system.

Conclusion

We conclude that membrane androgen receptors may represent an index of tumor aggressiveness and possibly specific targets for new therapeutic regimens.
Abnormal expression and processing of the proprotein convertases PC1 and PC2 in human colorectal liver metastases
Authors: Tzimas George N , Chevet Eric , Jenna Sarah , Nguyên Duc Thang , Khatib Abdel M , Marcus Victoria , Zhang Yi , Chrétien Michel , Seidah Nabil , Metrakos Peter
Published: November 2005

Background

The family of proprotein convertases has been recently implicated in tumorigenesis and metastasis in animal models. However, these studies have not yet been completely corroborated in human tumors.

Methods

Using RT PCR, immunoblot and immunohistochemistry we assessed the presence and the processing patterns of the convertases PC1 and PC2 as well as the PC2 specific chaperone 7B2 in human liver metastases originating from colorectal cancer and compared them to unaffected and normal liver. Furthermore, we assessed the presence and processing profiles of PC1, PC2 and 7B2 in primary colon cancers.

Results

mRNA, protein expression, and protein cleavage profiles of proprotein convertases 1 and 2 are altered in liver colorectal metastasis, compared to unaffected and normal liver. Active PC1 protein is overexpressed in tumor, correlating with its mRNA profile. Moreover, the enhanced PC2 processing pattern in tumor correlates with the overexpression of its specific binding protein 7B2. These results were corroborated by immunohistochemistry. The specific and uniform convertase pattern observed in the metastases was present only in a fraction of primary colon cancers.

Conclusion

The uniformly altered proprotein convertase profile in liver metastases is observed only in a fraction of primary colon cancers, suggesting possible selection processes involving PCs during metastasis as well as an active role of PCs in liver metastasis. In addition, the exclusive presence of 7B2 in metastatic tumors may represent a new target for early diagnosis, prognosis and/or treatment.
The International Classification of Functioning as an explanatory model of health after distal radius fracture: A cohort study
Authors: Harris Jocelyn E , MacDermid Joy C , Roth James
Published: November 2005

Background

Distal radius fractures are common injuries that have an increasing impact on health across the lifespan. The purpose of this study was to identify health impacts in body structure/function, activity, and participation at baseline and follow-up, to determine whether they support the ICF model of health.

Methods

This is a prospective cohort study of 790 individuals who were assessed at 1 week, 3 months, and 1 year post injury. The Patient Rated Wrist Evaluation (PRWE), The Wrist Outcome Measure (WOM), and the Medical Outcome Survey Short-Form (SF-36) were used to measure impairment, activity, participation, and health. Multiple regression was used to develop explanatory models of health outcome.

Results

Regression analysis showed that the PRWE explained between 13% (one week) and 33% (three months) of the SF-36 Physical Component Summary Scores with pain, activities and participation subscales showing dominant effects at different stages of recovery. PRWE scores were less related to Mental Component Summary Scores, 10% (three months) and 8% (one year). Wrist impairment scores were less powerful predictors of health status than the PRWE.

Conclusion

The ICF is an informative model for examining distal radius fracture. Difficulty in the domains of activity and participation were able to explain a significant portion of physical health. Post-fracture rehabilitation and outcome assessments should extend beyond physical impairment to insure comprehensive treatment to individuals with distal radius fracture.
Inhibition of HIV derived lentiviral production by TAR RNA binding domain of TAT protein
Authors: Mi Michael Y , Zhang Jiying , He Yukai
Published: November 2005

Background

A critical step in the production of new HIV virions involves the TAT protein binding to the TAR element. The TAT protein contains in close proximity its TAR RNA binding domain and protein transduction domain (PTD). The PTD domain of TAT has been identified as being instrumental in the protein's ability to cross mammalian cell and nuclear membranes. All together, this information led us to form the hypothesis that a protein containing the TAR RNA binding domain could compete with the native full length TAT protein and effectively block the TAR RNA binding site in transduced HIV infected cells.

Results

We synthesized a short peptide named Tat-P, which contained the TAR RNA binding and PTD domains to examine whether the peptide has the potential of inhibiting TAT dependent HIV replication. We investigated the inhibiting effects of Tat-P in vitro using a HIV derived lentiviral vector model. We found that the TAT PTD domain not only efficiently transduced test cells, but also effectively inhibited the production of lentiviral particles in a TAT dependent manner. These results were also supported by data derived from the TAT activated LTR-luciferase expression model and RNA binding assays.

Conclusion

Tat-P may become part of a category of anti-HIV drugs that competes with full length TAT proteins to inhibit HIV replication. In addition, this study indicates that the HIV derived lentiviral vector system is a safe and reliable screening method for anti-HIV drugs, especially for those targeting the interaction of TAT and TAR RNAs.
Memory and selective learning in children with spina bifida-myelomeningocele and shunted hydrocephalus: A preliminary study
Authors: Vachha Behroze , Adams Richard C
Published: November 2005

Background

Selective learning is the ability to select items of relevance from among less important items. Limited evidence exists regarding the efficiency with which children with spina bifida-myelomeningocele and shunted hydrocephalus (SB/SH) are able to learn information. This report describes initial data related to components of learning and metacognitive skills in children with SB/SH.

Methods

Twenty six children with SB/SH and 26 controls (age: 7 – 16 y) with average intelligence, and monolingual English-speaking backgrounds participated in the study. Exclusion criteria for the SB/SH group were: prior history of shunt infection, history of seizure or shunt malfunction within the previous three months, prior diagnoses of attention disorders and/or clinical depression. Children were presented lists of words with equal exemplars each of two distinct semantic categories (e.g. fruits, animals), and told to make as high a score as possible by learning the words. The value of the words was designated by category membership (e.g. animals = low value; fruits = high value). The total number of words learned across three learning trials was used to determine memory span. Selective learning efficiency (SLE) was computed as the efficiency with which items of greater value were selectively learned across three trials.

Results

Children with SB/SH did worse than controls on memory span (P< 0.05). Although SLE was not significantly different between groups, when asked what strategy was used in the selective learning tasks, 65% of the SB/SH children said they tried to remember all words (inefficient strategy). In contrast, 85% of controls said they tried to remember the higher value words – the more efficient strategy.

Conclusion

Success in school is often dependent on the ability to recall important facts selectively and ignore less important information. Children with SB/SH in our study had a poor memory span and were unable to monitor and report an efficient and workable metacognitive strategy required to remember a list of words. Preliminary findings may begin to explain our previous clinical and research findings wherein children with SB/SH often focus on extraneous details, but demonstrate difficulty remembering the main gist of a story/event.
THR0921, a novel peroxisome proliferator-activated receptor gamma agonist, reduces the severity of collagen-induced arthritis
Authors: Tomita Tetsuya , Kakiuchi Yoshimi , Tsao Philip S
Published: November 2005

THR0921 is a novel peroxisome proliferator-activated receptor gamma (PPARγ) agonist with potent anti-diabetic properties. Because of the proposed role of PPARγ in inflammation, we investigated the potential of orally active THR0921 to inhibit the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in DBA/1J mice by the injection of bovine type II collagen in complete Freund's adjuvant on days 0 and 21. Mice were treated with THR0921 (50 mg/kg/day) starting on the day of the booster injection and throughout the remaining study period. Both clinical disease activity scores as well as histological scores of joint destruction were significantly reduced in mice treated with THR0921 compared to untreated mice. Proliferation of isolated spleen cells, as well as circulating levels of IgG antibody to type II collagen, was decreased by THR0921. Moreover, spleen cell production of IFN-γ, tumor necrosis factor (TNF)-α and IL-1β in response to exposure to lipopolysaccharide or type II collagen was reduced by in vivo treatment with THR0921. Steady state mRNA levels of TNF-α, IL-1β, monocyte chemotactic protein-1 and receptor activator of nuclear factor κB ligand (RANKL) in isolated joints were all decreased in mice treated with THR0921. Finally, THR0921 inhibited osteoclast differentiation of bone marrow-derived cells stimulated with macrophage colony-stimulating factor and RANKL. In conclusion, THR0921 attenuates collagen-induced arthritis in part by reducing the immune response. As such, PPARγ may be an important therapeutic target for rheumatoid arthritis.
The roles of FGF signaling in germ cell migration in the mouse
Authors: Takeuchi Yutaka , Molyneaux Kathleen , Runyan Chris , Schaible Kyle , Wylie Chris
Published: November 2005

Fibroblast growth factor (FGF) signaling is thought to play a role in germ cell behavior. FGF2 has been reported to be a mitogen for primordial germ cells in vitro, whilst combinations of FGF2, steel factor and LIF cause cultured germ cells to transform into permanent lines of pluripotent cells resembling ES cells. However, the actual function of FGF signaling on the migrating germ cells in vivo is unknown. We show, by RT-PCR analysis of cDNA from purified E10.5 germ cells, that germ cells express two FGF receptors: Fgfr1-IIIc and Fgfr2-IIIb. Second, we show that FGF-mediated activation of the MAP kinase pathway occurs in germ cells during their migration, and thus they are potentially direct targets of FGF signaling. Third, we use cultured embryo slices in simple gain-of-function experiments,using FGF ligands, to show that FGF2, a ligand for FGFR1-IIIc, affects motility, whereas FGF7, a ligand for FGFR2-IIIb, affects germ cell numbers. Loss of function, using a specific inhibitor of FGF signaling, causes increased apoptosis and inhibition of cell shape change in the migrating germ cells. Lastly, we confirm in vivo the effects seen in slice cultures in vitro,by examining germ cell positions and numbers in embryos carrying a loss-of-function allele of FGFR2-IIIb. In FGFR2-IIIb-/- embryos,germ cell migration is unaffected, but the numbers of germ cells are significantly reduced. These data show that a major role of FGF signaling through FGFR2-IIIb is to control germ cell numbers. The data do not discriminate between direct and indirect effects of FGF signaling on germ cells, and both may be involved.
Cell-to-cell movement of the CAPRICE protein inArabidopsisroot epidermal cell differentiation
Authors: Kurata Tetsuya , Ishida Tetsuya , Kawabata-Awai Chie , Noguchi Masahiro , Hattori Sayoko , Sano Ryosuke , Nagasaka Ryoko , Tominaga Rumi , Koshino-Kimura Yoshihiro , Kato Tomohiko , Sato Shusei , Tabata Satoshi , Okada Kiyotaka , Wada Takuji
Published: November 2005

CAPRICE (CPC), a small, R3-type Myb-like protein, is a positive regulator of root hair development in Arabidopsis. Cell-to-cell movement of CPC is important for the differentiation of epidermal cells into trichoblasts(root hair cells). CPC is transported from atrichoblasts (hairless cells),where it is expressed, to trichoblasts, and generally accumulates in their nuclei. Using truncated versions of CPC fused to GFP, we identified a signal domain that is necessary and sufficient for CPC cell-to-cell movement. This domain includes the N-terminal region and a part of the Myb domain. Amino acid substitution experiments indicated that W76 and M78 in the Myb domain are critical for targeted transport, and that W76 is crucial for the nuclear accumulation of CPC:GFP. To evaluate the tissue-specificity of CPC movement,CPC:GFP was expressed in the stele using the SHR promoter and in trichoblasts using the EGL3 promoter. CPC:GFP was able to move from trichoblasts to atrichoblasts but could not exit from the stele, suggesting the involvement of tissue-specific regulatory factors in the intercellular movement of CPC. Analyses with a secretion inhibitor, Brefeldin A, and with an rhd3 mutant defective in the secretion process in root epidermis suggested that intercellular CPC movement is mediated through plasmodesmata. Furthermore, the fusion of CPC to tandem-GFPs defined the capability of CPC to increase the size exclusion limit of plasmodesmata.
Growth and cell survival are unevenly impaired inpixiemutant wing discs
Authors: Coelho Carmen M. A. , Kolevski Benjamin , Bunn Caroline , Walker Cherryl , Dahanukar Anupama , Leevers Sally J.
Published: November 2005

It is largely unknown how growth slows and then stops in vivo. Similar to most organs, Drosophila imaginal discs undergo a fast,near-exponential growth phase followed by a slow growth phase before final target size is reached. We have used a genetic approach to study the role of an ABC-E protein, Pixie, in wing disc growth. pixie mutants, like mutants in ribosomal proteins genes (known as Minutes), show severe developmental delay with relatively mild alterations in final body size. Intriguingly, pixie mutant wing imaginal discs show complex regional and temporal defects in growth and cell survival that are compensated to result in near-normal final size. In S2 cells, Pixie, like its yeast homolog RLI1, is required for translation. However, a comparison of the growth of eukaryotic translation initiation factor eIF4A and pixiemutant clones in wing discs suggests that only a subset of translation regulators, including pixie, mediate regional differences in growth and cell survival in wing discs. Interestingly, some of the regional effects on pixie mutant clone growth are enhanced in a Minutebackground. Our results suggest that the role of Pixie is not merely to allow growth, as might be expected for a translation regulator. Instead, Pixie also behaves as a target of putative constraining signals that slow disc growth during late larval life. We propose a model in which a balance of growth inhibitors and promoters determines tissue growth rates and cell survival. An alteration in this balance slows growth before final disc size is reached.
Distinct roles forXenopusTcf/Lef genes in mediating specific responses to Wnt/β-catenin signalling in mesoderm development
Authors: Liu Fei , van den Broek Olaf , Destrée Olivier , Hoppler Stefan
Published: November 2005

Tcf/Lef transcription factors and β-catenin mediate canonical Wnt signalling, which plays remarkably diverse roles in embryonic development,stem cell renewal and cancer progression. To investigate the molecular mechanisms allowing for these diverse yet specific functions, we studied the several distinct roles for Wnt/β-catenin signalling in early Xenopus development: establishing the dorsal body axis; regulating mesoderm induction; and subsequent ventrolateral patterning. Our previous experiments and the expression patterns of Tcf/Lef factors during these embryonic stages led us to examine whether different Tcf/Lef factors mediate these distinct events downstream of canonical Wnt/β-catenin signalling. By manipulating gene expression with morpholino-driven gene knockdown and capped RNA-mediated rescue, we show that genes encoding different Tcf/Lef transcription factors mediate distinct responses to Wnt signalling in early Xenopus development: Tcf1 and Tcf3 genes are non-redundantly required in mesoderm induction for mediating primarily transcriptional activation and repression, respectively; while ventrolateral patterning requires both Tcf1 and Lef1 genes to express sufficient levels of transcription-activating Tcf factors. Our investigation further identifies that motifs within their central domain, rather than their C-terminus, determine the particular molecular function of Tcf/Lef factors. These findings suggest that Tcf/Lef genes encode factors of different activities, which function together in antagonistic or synergistic ways to modulate the intensity and outcome of Wnt/β-catenin signalling and to trigger tissue-specific responses.
Non-cell-autonomous role forCriptoin axial midline formation during vertebrate embryogenesis
Authors: Chu Jianhua , Ding Jixiang , Jeays-Ward Katherine , Price Sandy M. , Placzek Marysia , Shen Michael M.
Published: November 2005

Several membrane-associated proteins are known to modulate the activity and range of potent morphogenetic signals during development. In particular,members of the EGF-CFC family encode glycosyl-phosphatidylinositol(GPI)-linked proteins that are essential for activity of the transforming growth factor β (TGFβ) ligand Nodal, a factor that plays a central role in establishing the vertebrate body plan. Genetic and biochemical studies have indicated that EGF-CFC proteins function as cell-autonomous co-receptors for Nodal; by contrast, cell culture data have suggested that the mammalian EGF-CFC protein Cripto can act as a secreted signaling factor. Here we show that Cripto acts non-cell-autonomously during axial mesendoderm formation in the mouse embryo and may possess intercellular signaling activity in vivo. Phenotypic analysis of hypomorphic mutants demonstrates that Criptois essential for formation of the notochordal plate, prechordal mesoderm and foregut endoderm during gastrulation. Remarkably, Cripto null mutant cells readily contribute to these tissues in chimeras, indicating non-cell-autonomy. Consistent with these loss-of-function analyses,gain-of-function experiments in chick embryos show that exposure of node/head process mesoderm to soluble Cripto protein results in alterations in cell fates toward anterior mesendoderm, in a manner that is dependent on Nodal signaling. Taken together, our findings support a model in which Cripto can function in trans as an intercellular mediator of Nodal signaling activity.