bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive strategies in seedlings of three co-occurring, ecologically distinct northern coniferous tree species across an elevational gradient
Authors: Green D Scott
Published: May 2005

The inherent clinal responses of four quantitative traits thought to be adaptive for trees in cold-limited environments (i.e., height-growth cessation, growth rate, resource allocation to aboveground and belowground tissues, and resource allocation to photosynthetic and nonphotosynthetic tissues in the shoot) were characterized under nonlimiting conditions in a controlled glasshouse study for seedlings of three ecologically distinct and co-occurring northern tree species (Pinus contorta Dougl. var. latifolia Engelm. (lodgepole pine), Picea glauca (Moench) Voss × Picea engelmannii Parry ex Engelm. (interior spruce), and Abies lasiocarpa (Hook.) Nutt. (subalpine fir)). For each species, clinal trends were quantified among populations adapted to increasingly cold-limited climates across an elevation gradient approaching the tree line. In subalpine fir seedlings, strong clinal variation for all the quantitative traits indicated an increasingly conservative response to climate moving toward harsher conditions. Variation in lodgepole pine and interior spruce seedlings suggested a more plastic strategy, favoring competitive traits across a wide range of climate conditions. Study findings suggest that ecologically distinct species may exhibit different strategies in adapting to local climates.
Snag longevity under alternative silvicultural regimes in mixed-species forests of central Maine
Authors: Garber Sean M , Brown John P , Wilson Duncan S , Maguire Douglas A , Heath Linda S
Published: May 2005

Predictions of snag longevity, defined here as the probability of snag survival to a given age, are key to designing silvicultural regimes that ensure their availability for wildlife and form an important component of carbon flow models. Species, diameter at breast height, stand density, management regime, and agent of tree mortality were assessed for their effect on snag longevity in a long-term silvicultural study on the Penobscot Experimental Forest in central Maine. Snag recruitment and fall data from USDA Forest Service inventories between 1981 and 1997 were analyzed using parametric survival analysis. A Weibull model fit the data best, indicating a significant lag time followed by rapid fall rates. Half-times varied among species, with Thuja occidentalis L. having the longest (10 years) and Picea species the shortest (6 years). Snag longevity was significantly greater with increasing diameter and decreased with increasing stand density. Agent of mortality and silvicultural treatment were also significant. Two models were developed for estimating probability of snag survival over time, one that included predictor variables unique to the silvicultural systems study on the Penobscot Experimental Forest and one using predictor variables available in most standard inventories. Snag survival models can easily be incorporated into comprehensive forest dynamics models to facilitate estimates of wildlife habitat structure and carbon flow.
Models for predicting product recovery using selected tree characteristics of black spruce
Authors: Liu Chuangmin , Zhang S Y
Published: May 2005

The artificial neural network (ANN) model and five traditional statistical regression models were used to predict four parameters of simulated product recovery (lumber volume, lumber value, chip volume, and total product value) from the stud mill simulation based on three basic tree characteristics of black spruce (i.e., diameter at breast height (DBH), tree height, and tree taper). The ANN model (i.e., the three-layer perceptron with error back-propagation algorithm) performed as well as or better than the five statistical regression models in terms of statistical criteria such as R2, root mean square error, and mean absolute error of predictions. The second-order polynomial with both DBH and tree height predicted the four product recoveries as accurately as the ANN model. This study showed that the ANN model, the second-order polynomial function, and the power function were suitable for the prediction of product recovery using the selected tree characteristics. The models developed in this study allow the estimation of the product recovery of individual trees and of a forest stand before it is harvested. It is evident that these models would be valuable tools for forest resource managers.
Growth and nutrient dynamics of western hemlock with conventional or exponential greenhouse fertilization and planting in different fertility conditions
Authors: Hawkins B J , Burgess D , Mitchell A K
Published: May 2005

In many northern forests, low nutrient availability constrains growth of young trees. We tested the efficacy of exponential nutrient application to load western hemlock (Tsuga heterophylla (Raf.) Sarg.) seedlings with nutrients to enhance field performance. Seedlings were grown with conventional, constant-rate fertilization (100 mg N·L1) or with exponentially increasing fertilization at rates of 2% and 3% per day in a greenhouse. Growth and nutrient allocation were characterized. Seedlings from the three greenhouse treatments were then planted in an outdoor nursery experiment for 2 years with NPK fertilizer applied at 10, 25, or 100 mg N·L1, and in a 3-year field experiment with and without slow-release fertilizer. Seedling height, biomass, and nutrient concentration did not differ greatly among exponential or constant-rate fertilization treatments in the greenhouse. The influence of postplanting fertility, both in the nursery and in the field, outweighed the effect of greenhouse exponential nutrient application. In the outdoor nursery, seedlings from all greenhouse treatments showed increased growth with higher rates of fertilization. In the field, there were no differences in growth among seedlings from the three greenhouse treatments, but fertilization at planting increased growth. The capacity for nutrient loading in container-grown western hemlock was likely exceeded because large quantities of N were applied in all treatments.
How resilient are southwestern ponderosa pine forests after crown fires?
Authors: Savage Melissa , Mast Joy Nystrom
Published: May 2005

The exclusion of low-severity surface fire from ponderosa pine (Pinus ponderosa P. & C. Lawson) forests of the Southwest has changed ecosystem structure and function such that severe crown fires are increasingly causing extensive stand mortality. This altered fire regime has resulted from the intersection of natural drought cycles with human activities that have suppressed natural fires for over a century. What is the trajectory of forest recovery after such fires? This study explores the regeneration response of ponderosa pine and other species to crown fires that occurred in the region from the late 1940s to the mid-1970s. We address two main questions: (1) What is the success of ponderosa regeneration and establishment, and (2) Can these sites, burned in stand-destroying fires, be "captured" by other species on the scale of decades? Two main trajectories of recovery were found: (1) establishment of unnaturally dense ponderosa pine stands vulnerable to further crown fire and (2) establishment of nonforested grass or shrub communities.
COMPUTING TRANSPORT PROPERTIES OF HETEROGENEOUS MEDIA BY AN OPTIMIZATION METHOD
Authors: VAEZ ALLAEI S. M. , SAHIMI MUHAMMAD
Published: May 2005

The problem of computing the effective transport and mechanical properties of disordered materials, modeled by random or correlated percolation networks, is studied as an optimization problem. We show that calculating an optimal distribution of the potentials (voltages, displacements, etc.) throughout a disordered material that minimizes its total energy reduces the computation times for calculating the effective properties by a factor that depending on the morphology of the system, ranges from 3 to 73. Hence, this offers significant speed-up over the most efficient numerical methods currently available.
Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency
Authors: Koopman Werner J. H. , Visch Henk-Jan , Verkaart Sjoerd , van den Heuvel Lambertus W. P. J. , Smeitink Jan A. M. , Willems Peter H. G. M.
Published: May 2005

Complex I (NADH:ubiquinone oxidoreductase) is the largest multisubunit assembly of the oxidative phosphorylation system, and its malfunction is associated with a wide variety of clinical syndromes ranging from highly progressive, often early lethal, encephalopathies to neurodegenerative disorders in adult life. The changes in mitochondrial structure and function that are at the basis of the clinical symptoms are poorly understood. Video-rate confocal microscopy of cells pulse-loaded with mitochondria-specific rhodamine 123 followed by automated analysis of form factor (combined measure of length and degree of branching), aspect ratio (measure of length), and number of revealed marked differences between primary cultures of skin fibroblasts from 13 patients with an isolated complex I deficiency. These differences were independent of the affected subunit, but plotting of the activity of complex I, normalized to that of complex IV, against the ratio of either form factor or aspect ratio to number revealed a linear relationship. Relatively small reductions in activity appeared to be associated with an increase in form factor and never with a decrease in number, whereas relatively large reductions occurred in association with a decrease in form factor and/or an increase in number. These results demonstrate that complex I activity and mitochondrial structure are tightly coupled in human isolated complex I deficiency. To further prove the relationship between aberrations in mitochondrial morphology and pathological condition, fibroblasts from two patients with a different mutation but a highly fragmented mitochondrial phenotype were fused. Full restoration of the mitochondrial network demonstrated that this change in mitochondrial morphology was indeed associated with human complex I deficiency.
Integrin αIIbβ3 signals lead cofilin to accelerate platelet actin dynamics
Authors: Falet Hervé , Chang Gregory , Brohard-Bohn Brigitte , Rendu Francine , Hartwig John H.
Published: May 2005

Cofilin, in its Ser3 dephosphorylated form, accelerates actin filament turnover in cells. We report here the role of cofilin in platelet actin assembly. Cofilin is primarily phosphorylated in the resting platelet as evidenced by a specific antibody directed against its Ser3 phosphorylated form. After stimulation with thrombin under nonstirring conditions, cofilin is reversibly dephosphorylated and transiently incorporates into the actin cytoskeleton. Its dephosphorylation is maximal 1–2 min after platelet stimulation, shortly after the peak of actin assembly occurs. Cofilin rephosphorylation begins 2 min after activation and exceeds resting levels by 5–10 min. Cofilin is dephosphorylated with identical kinetics but fails to become rephosphorylated when platelets are stimulated under stirring conditions. Cofilin is normally rephosphorylated when platelets are stimulated in the presence of Arg-Gly-Asp-Ser (RGDS) peptide or wortmannin to block αIIbβ3 cross-linking and signaling or in platelets isolated from a patient with Glanzmann thrombasthenia, which express only 2–3% of normal αIIbβ3 levels. Furthermore, actin assembly and Arp2/3 complex incorporation in the platelet actin cytoskeleton are decreased when αIIbβ3 is engaged. Our results suggest that cofilin is essential for actin dynamics mediated by outside-in signals in activated platelets.
Anti-tumor necrosis factor-α therapies attenuate adaptive arteriogenesis in the rabbit
Authors: Grundmann Sebastian , Hoefer Imo , Ulusans Susann , van Royen Niels , Schirmer Stephan H. , Ozaki C. Keith , Bode Christoph , Piek Jan J. , Buschmann Ivo
Published: May 2005

The specific antagonists of tumor necrosis factor-α (TNF-α), infliximab and etanercept, are established therapeutic agents for inflammatory diseases such as rheumatoid arthritis and Crohn’s disease. Although the importance of TNF-α in chronic inflammatory diseases is well established, little is known about its implications in the cardiovascular system. Because proliferation of arteriolar connections toward functional collateral arteries (arteriogenesis) is an inflammatory-like process, we tested in vivo the hypothesis that infliximab and etanercept have antiarteriogenic actions. Sixty-three New Zealand White rabbits underwent femoral artery occlusion and received infliximab, etanercept, or vehicle according to clinical dosage regimes. After 1 wk, collateral conductance, assessed with fluorescent microspheres, revealed significant inhibition of arteriogenesis (collateral conductance): 52.4 (SD 8.1), 35.2 (SD 7.7), and 33.3 (SD 10.1) ml·min−1·100 mmHg−1 with PBS, infliximab, and etanercept, respectively ( P < 0.001). High-resolution angiography showed no significant differences in number of collateral arteries, but immunohistochemical analysis demonstrated a decrease in mean collateral diameter, proliferation of vascular smooth muscle cells, and reduction of leukocyte accumulation around collateral arteries in treated groups. Infliximab and etanercept bound to infiltrating leukocytes, which are important mediators of arteriogenesis. Infliximab induced monocyte apoptosis, and neither substance affected monocyte expression of the adhesion molecule Mac-1. We demonstrated that TNF-α serves as a pivotal modulator of arteriogenesis, which is attenuated by treatment with TNF-α inhibitors. Reduction of collateral conductance is most likely due to inhibition of perivascular leukocyte infiltration and subsequent lower vascular smooth muscle cell proliferation. This is the first report showing a negative influence of TNF-α inhibitors on collateral artery growth.
Population Coding of Self-Motion: Applying Bayesian Analysis to a Population of Visual Interneurons in the Fly
Authors: Karmeier Katja , Krapp Holger G. , Egelhaaf Martin
Published: May 2005

Coding of sensory information often involves the activity of neuronal populations. We demonstrate how the accuracy of a population code depends on integration time, the size of the population, and noise correlation between the participating neurons. The population we study consists of 10 identified visual interneurons in the blowfly Calliphora vicina involved in optic flow processing. These neurons are assumed to encode the animal's head or body rotations around horizontal axes by means of graded potential changes. From electrophysiological experiments we obtain parameters for modeling the neurons' responses. From applying a Bayesian analysis on the modeled population response we draw three major conclusions. First, integration of neuronal activities over a time period of only 5 ms after response onset is sufficient to decode accurately the rotation axis. Second, noise correlation between neurons has only little impact on the population's performance. And third, although a population of only two neurons would be sufficient to encode any horizontal rotation axis, the population of 10 vertical system neurons is advantageous if the available integration time is short. For the fly, short integration times to decode neuronal responses are important when controlling rapid flight maneuvers.
Distinct Brain Systems for Processing Concrete and Abstract Concepts
Authors: Binder J. R. , Westbury C. F. , McKiernan K. A. , Possing E. T. , Medler D. A.
Published: May 2005

Behavioral and neurophysiological effects of word imageability and concreteness remain a topic of central interest in cognitive neuroscience and could provide essential clues for understanding how the brain processes conceptual knowledge. We examined these effects using event-related functional magnetic resonance imaging while participants identified concrete and abstract words. Relative to nonwords, concrete and abstract words both activated a left-lateralized network of multimodal association areas previously linked with verbal semantic processing. Areas in the left lateral temporal lobe were equally activated by both word types, whereas bilateral regions including the angular gyrus and the dorsal prefrontal cortex were more strongly engaged by concrete words. Relative to concrete words, abstract words activated left inferior frontal regions previously linked with phonological and verbal working memory processes. The results show overlapping but partly distinct neural systems for processing concrete and abstract concepts, with greater involvement of bilateral association areas during concrete word processing, and processing of abstract concepts almost exclusively by the left hemisphere.
Method Matters: An Empirical Study of Impact in Cognitive Neuroscience
Authors: Fellows Lesley K. , Heberlein Andrea S. , Morales Dawn A. , Shivde Geeta , Waller Sara , Wu Denise H.
Published: May 2005

A major thrust of cognitive neuroscience is the elucidation of structure-function relationships in the human brain. Over the last several years, functional neuroimaging has risen in prominence relative to the lesion studies that formed the historical core of work in this field. These two methods have different strengths and weaknesses. Among these is a crucial difference in the nature of evidence each can provide. Lesion studies can provide evidence for necessity claims, whereas functional neuroimaging studies do not. We hypothesized that lesion studies will continue to have greater scientific impact even as the relative proportion of such studies in the cognitive neuroscience literature declines. Using methods drawn from systematic literature review, we identified a set of original cognitive neuroscience articles that employed either functional imaging or lesion techniques, published at one of two time points in the 1990s, and assessed the effect of the method used on each article's impact across the decade. Functional neuro-imaging studies were cited three times more often than lesion studies throughout the time span we examined. This effect was in large part due to differences in the influence of the journals publishing the two methods; functional neuroimaging studies appeared disproportionately more often in higher impact journals. There were also differences in the degree to which articles using one method cited articles using the other method. Functional neuroimaging articles were less likely to include such cross-method citations.
Covert Speech Arrest Induced by rTMS over Both Motor and Nonmotor Left Hemisphere Frontal Sites
Authors: Aziz-Zadeh Lisa , Cattaneo Luigi , Rochat Magali , Rizzolatti Giacomo
Published: May 2005

Blocking the capacity to speak aloud (overt speech arrest, SA) may be induced by repetitive transcranial magnetic stimulation (rTMS). The possibility, however, of blocking internal speech (covert SA) has not been explored. To investigate this issue, we conducted two rTMS experiments. In the first experiment, we stimulated two left frontal lobe sites. The first was a motor site (left posterior site) and the second was a nonmotor site located in correspondence to the posterior part of the inferior frontal gyrus (IFG) (left anterior site). The corresponding right hemisphere nonmotor SA site was stimulated as a control. In the second experiment, we focused on the right hemisphere and stimulated a right hemisphere motor site (right posterior site), and, as control sites, a right hemisphere nonmotor site corresponding to the IFG (right anterior site) and a left hemisphere anteromedial site (left control). For both experiments, participants performed a syllable counting task both covertly and overtly for each stimulation site. Longer latencies in this task imply the occurrence of an overt and/or covert SA.

All participants showed significantly longer latencies when stimulation was either over the left posterior or the left anterior site, as compared with the right hemisphere site (Experiment 1). This result was observed for the overt and covert speech task alike. During stimulation of the posterior right hemisphere site, a dissociation for overt and covert speech was observed. An overt SA was observed but there was no evidence for a covert SA (Experiment 2). Taken together, the results show that rTMS can induce a covert SA when applied to areas over the brain that are pertinent to language. Furthermore, both the left posterior/motor site and the left anterior/IFG site appear to be essential to language elaboration even when motor output is not required.
Reading Fluent Speech from Talking Faces: Typical Brain Networks and Individual Differences
Authors: Hall Deborah A. , Fussell Clayton , Summerfield A. Quentin
Published: May 2005

Listeners are able to extract important linguistic information by viewing the talker's face—a process known as “speechreading.” Previous studies of speechreading present small closed sets of simple words and their results indicate that visual speech processing engages a wide network of brain regions in the temporal, frontal, and parietal lobes that are likely to underlie multiple stages of the receptive language system. The present study further explored this network in a large group of subjects by presenting naturally spoken sentences which tap the richer complexities of visual speech processing. Four different baselines (blank screen, static face, nonlinguistic facial gurning, and auditory speech) enabled us to determine the hierarchy of neural processing involved in speechreading and to test the claim that visual input reliably accesses sound-based representations in the auditory cortex.

In contrast to passively viewing a blank screen, the static-face condition evoked activation bilaterally across the border of the fusiform gyrus and cerebellum, and in the medial superior frontal gyrus and left precentral gyrus (p < .05, whole brain corrected). With the static face as baseline, the gurning face evoked bilateral activation in the motion-sensitive region of the occipital cortex, whereas visual speech additionally engaged the middle temporal gyrus, inferior and middle frontal gyri, and the inferior parietal lobe, particularly in the left hemisphere. These latter regions are implicated in lexical stages of spoken language processing. Although auditory speech generated extensive bilateral activation across both superior and middle temporal gyri, the group-averaged pattern of speechreading activation failed to include any auditory regions along the superior temporal gyrus, suggesting that fluent visual speech does not always involve sound-based coding of the visual input.

An important finding from the individual subject analyses was that activation in the superior temporal gyrus did reach significance (p < .001, small-volume corrected) for a subset of the group. Moreover, the extent of the left-sided superior temporal gyrus activity was strongly correlated with speech-reading performance. Skilled speechreading was also associated with activations and deactivations in other brain regions, suggesting that individual differences reflect the efficiency of a circuit linking sensory, perceptual, memory, cognitive, and linguistic processes rather than the operation of a single component process.
Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy
Authors: Zappia Emanuela , Casazza Simona , Pedemonte Enrico , Benvenuto Federica , Bonanni Ivan , Gerdoni Ezio , Giunti Debora , Ceravolo Antonella , Cazzanti Francesco , Frassoni Francesco , Mancardi Gianluigi , Uccelli Antonio
Published: May 2005

We studied the immunoregulatory features of murine mesenchymal stem cells (MSCs) in vitro and in vivo. MSCs inhibited T-cell receptor (TCR)-dependent and -independent proliferation but did not induce apoptosis on T cells. Such inhibition was paired with a decreased interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha production and was partially reversed by interleukin-2 (IL-2). Thus, we used MSCs to treat myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice. We injected intravenously 1 × 106 MSCs before disease onset (preventive protocol) and at different time points after disease occurrence (therapeutic protocol). MSC administration before disease onset strikingly ameliorated EAE. The therapeutic scheme was effective when MSCs were administered at disease onset and at the peak of disease but not after disease stabilization. Central nervous system (CNS) pathology showed decreased inflammatory infiltrates and demyelination in mice that received transplants of MSCs. T-cell response to MOG and mitogens from MSC-treated mice was inhibited and restored by IL-2 administration. Upon MSC transfection with the enhanced green fluorescent protein (eGFP), eGFP+ cells were detected in the lymphoid organs of treated mice. These data suggest that the immunoregulatory properties of MSCs effectively interfere with the autoimmune attack in the course of EAE inducing an in vivo state of T-cell unresponsiveness occurring within secondary lymphoid organs. (Blood. 2005; 106:1755-1761)
Effects of lesions of the nucleus accumbens core on choice between small certain rewards and large uncertain rewards in rats
Authors: Cardinal Rudolf N , Howes Nathan J
Published: May 2005

Background

Animals must frequently make choices between alternative courses of action, seeking to maximize the benefit obtained. They must therefore evaluate the magnitude and the likelihood of the available outcomes. Little is known of the neural basis of this process, or what might predispose individuals to be overly conservative or to take risks excessively (avoiding or preferring uncertainty, respectively). The nucleus accumbens core (AcbC) is known to contribute to rats' ability to choose large, delayed rewards over small, immediate rewards; AcbC lesions cause impulsive choice and an impairment in learning with delayed reinforcement. However, it is not known how the AcbC contributes to choice involving probabilistic reinforcement, such as between a large, uncertain reward and a small, certain reward. We examined the effects of excitotoxic lesions of the AcbC on probabilistic choice in rats.

Results

Rats chose between a single food pellet delivered with certainty (p= 1) and four food pellets delivered with varying degrees of uncertainty (p= 1, 0.5, 0.25, 0.125, and 0.0625) in a discrete-trial task, with the large-reinforcer probability decreasing or increasing across the session. Subjects were trained on this task and then received excitotoxic or sham lesions of the AcbC before being retested. After a transient period during which AcbC-lesioned rats exhibited relative indifference between the two alternatives compared to controls, AcbC-lesioned rats came to exhibit risk-averse choice, choosing the large reinforcer less often than controls when it was uncertain, to the extent that they obtained less food as a result. Rats behaved as if indifferent between a single certain pellet and four pellets atp= 0.32 (sham-operated) or atp= 0.70 (AcbC-lesioned) by the end of testing. When the probabilities did not vary across the session, AcbC-lesioned rats and controls strongly preferred the large reinforcer when it was certain, and strongly preferred the small reinforcer when the large reinforcer was very unlikely (p= 0.0625), with no differences between AcbC-lesioned and sham-operated groups.

Conclusion

These results support the view that the AcbC contributes to action selection by promoting the choice of uncertain, as well as delayed, reinforcement.
Medical students who decompress during the M-1 year outperform those who fail and repeat it: A study of M-1 students at the University of Illinois College of Medicine at Urbana-Champaign 1988–2000
Authors: Kies Susan M , Freund Gregory G
Published: May 2005

Background

All medical schools must counsel poor-performing students, address their problems and assist them in developing into competent physicians. The objective of this study was to determine whether students with academic deficiencies in their M-1 year graduate more often, spend less time to complete the curriculum, and need fewer attempts at passing USMLE Step 1 and Step 2 by entering the Decompressed Program prior to failure of the M-1 year than those students who fail the M-1 year and then repeat it.

Method

The authors reviewed the performance of M-1 students in the Decompressed Program and compared their outcomes to M-1 students who failed and fully repeated the M-1 year. To compare the groups upon admission, t-Tests comparing the Cognitive Index of students and MCAT scores from both groups were performed. Performance of the two groups after matriculation was also analyzed.

Results

Decompressed students were 2.1 times more likely to graduate. Decompressed students were 2.5 times more likely to pass USMLE Step 1 on the first attempt than the repeat students. In addition, 46% of those in the decompressed group completed the program in five years compared to 18% of the repeat group.

Conclusion

Medical students who decompress their M-1 year prior to M-1 year failure outperform those who fail their first year and then repeat it. These findings indicate the need for careful monitoring of M-1 student performance and early intervention and counseling of struggling students.
Nanotechnology for the biologist
Authors: McNeil Scott E
Published: May 2005

Nanotechnology refers to research and technology development at the atomic, molecular, and macromolecular scale, leading to the controlled manipulation and study of structures and devices with length scales in the 1- to 100-nanometers range. Objects at this scale, such as “nanoparticles,” take on novel properties and functions that differ markedly from those seen in the bulk scale. The small size, surface tailorability, improved solubility, and multifunctionality of nanoparticles open many new research avenues for biologists. The novel properties of nanomaterials offer the ability to interact with complex biological functions in new ways—operating at the very scale of biomolecules. This rapidly growing field allows cross-disciplinary researchers the opportunity to design and develop multifunctional nanoparticles that can target, diagnose, and treat diseases such as cancer. This article presents an overview of nanotechnology for the biologist and discusses “nanotech” strategies and constructs that have already demonstrated in vitro and in vivo efficacy.
Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing
Authors: Shirakata Yuji , Kimura Rina , Nanba Daisuke , Iwamoto Ryo , Tokumaru Sho , Morimoto Chie , Yokota Koichi , Nakamura Masanori , Sayama Koji , Mekada Eisuke , Higashiyama Shigeki , Hashimoto Koji
Published: May 2005

Members of the epidermal growth factor (EGF) family are the most important growth factors involved in epithelialization during cutaneous wound healing. Heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF family, is thought to play an important role in skin wound healing. To investigate the in vivo function of HB-EGF in skin wound healing, we generated keratinocyte-specific HB-EGF-deficient mice using Cre/loxP technology in combination with the keratin 5 promoter. Studies of wound healing revealed that wound closure was markedly impaired in keratinocyte-specific HB-EGF-deficient mice. HB-EGF mRNA was upregulated at the migrating epidermal edge, although cell growth was not altered. Of the members of the EGF family, HB-EGF mRNA expression was induced the most rapidly and dramatically as a result of scraping in vitro. Combined, these findings clearly demonstrate, for the first time, that HB-EGF is the predominant growth factor involved in epithelialization in skin wound healing in vivo and that it functions by accelerating keratinocyte migration, rather than proliferation.
Polarity of the ascidian egg cortex and relocalization of cER and mRNAs in the early embryo
Authors: Prodon François , Dru Philippe , Roegiers Fabrice , Sardet Christian
Published: May 2005

The mature ascidian oocyte is a large cell containing cytoplasmic and cortical domains polarized along a primary animal-vegetal (a-v) axis. The oocyte cortex is characterized by a gradient distribution of a submembrane monolayer of cortical rough endoplasmic reticulum (cER) and associated maternal postplasmic/PEM mRNAs (cER-mRNA domain). Between fertilization and first cleavage, this cER-mRNA domain is first concentrated vegetally and then relocated towards the posterior pole via microfilament-driven cortical contractions and spermaster-microtubule-driven translocations. The cER-mRNA domain further concentrates in a macroscopic cortical structure called the centrosome attracting body (CAB), which mediates a series of asymmetric divisions starting at the eight-cell stage. This results in the segregation of determinant mRNAs and their products in posterior cells of the embryo precursors of the muscle and germ line.

Using two species of ascidians (Ciona intestinalis and Phallusia mammillata), we have pursued and amplified the work initiated in Halocynthia roretzi. We have analysed the cortical reorganizations in whole cells and in cortical fragments isolated from oocytes and from synchronously developing zygotes and embryos. After fertilization, we observe that a cortical patch rich in microfilaments encircles the cER-mRNA domain, concentrated into a cortical cap at the vegetal/contraction pole (indicating the future dorsal pole). Isolated cortices also retain microtubule asters rich in cER (indicating the future posterior pole). Before mitosis, parts of the cER-mRNA domain are detected, together with short microtubules, in isolated posterior (but not anterior) cortices. At the eight-cell stage, the posteriorly located cER-mRNA domain undergoes a cell-cycle-dependant compaction into the CAB. The CAB with embedded centrosomal microtubules can be isolated with cortical fragments from eight-cell-stage embryos.

These and previous observations indicate that cytoskeleton-driven repositioning and compaction of a polarized cortical domain made of rough ER is a conserved mechanism used for polarization and segregation of cortical maternal mRNAs in embryos of evolutionarily distant species of ascidians.
Differential regulation of Cdc2 and Aurora-A in Xenopus oocytes: a crucial role of phosphatase 2A
Authors: Maton Gilliane , Lorca Thierry , Girault Jean-Antoine , Ozon René , Jessus Catherine
Published: May 2005

The success of cell division relies on the activation of its master regulator Cdc2-cyclin B, and many other kinases controlling cellular organization, such as Aurora-A. Most of these kinase activities are regulated by phosphorylation. Despite numerous studies showing that okadaic acid-sensitive phosphatases regulate both Cdc2 and Aurora-A activation, their identity has not yet been established in Xenopus oocytes and the importance of their regulation has not been evaluated. Using an oocyte cell-free system, we demonstrate that PP2A depletion is sufficient to lead to Cdc2 activation, whereas Aurora-A activation depends on Cdc2 activity. The activity level of PP1 does not affect Cdc2 kinase activation promoted by PP2A removal. PP1 inhibition is also not sufficient to lead to Aurora-A activation in the absence of active Cdc2. We therefore conclude that in Xenopus oocytes, PP2A is the key phosphatase that negatively regulates Cdc2 activation. Once this negative regulator is removed, endogenous kinases are able to turn on the activator Cdc2 system without any additional stimulation. In contrast, Aurora-A activation is indirectly controlled by Cdc2 activity independently of either PP2A or PP1. This strongly suggests that in Xenopus oocytes, Aurora-A activation is mainly controlled by the specific stimulation of kinases under the control of Cdc2 and not by downregulation of phosphatase.
Localization of all seven messenger RNAs for the actin-polymerization nucleator Arp2/3 complex in the protrusions of fibroblasts
Authors: Mingle Lisa A. , Okuhama Nataly N. , Shi Jian , Singer Robert H. , Condeelis John , Liu Gang
Published: May 2005

The actin-related protein 2/3 (Arp2/3) complex is a crucial actin polymerization nucleator and is localized to the leading protrusions of migrating cells. However, how the multiprotein complex is targeted to the protrusions remains unknown. Here, we demonstrate that mRNAs for the seven subunits of the Arp2/3 complex are localized to the protrusions in fibroblasts, supporting a hypothesis that the Arp2/3 complex is targeted to its site of function by mRNA localization. Depletion of serum from culture medium inhibits Arp2/3-complex mRNA localization to the protrusion, whereas serum stimulation leads to significant mRNA localization within 30 minutes. The effect of serum suggests that Arp2/3-complex mRNA localization is a cellular response to extracellular stimuli. The localization of the Arp2/3 complex mRNAs is dependent on both actin filaments and microtubules, because disruption of either cytoskeletal system (with cytochalasin D and colchicine, respectively) inhibited the localization of all seven subunit mRNAs. In addition, myosin inhibitors significantly inhibit Arp2 mRNA localization in chicken embryo fibroblasts, suggesting a myosin motor dependent mechanism for Arp2/3-complex mRNA localization.
Mapping of the interface between leptin and the leptin receptor CRH2 domain
Authors: Iserentant Hannes , Peelman Frank , Defeau Delphine , Vandekerckhove Joël , Zabeau Lennart , Tavernier Jan
Published: May 2005

Despite the impact of the leptin system on body weight and other physiologic processes, little is known about the binding of leptin to its receptor. The extracellular domain of the leptin receptor consists of two cytokine receptor homology (CRH) domains separated by an immunoglobulin-like domain, and followed by two juxtamembrane fibronectin type III modules. The CRH2 domain functions as a high-affinity binding site for leptin, and we previously demonstrated interaction with helices A and C of leptin. In this work, we constructed a homology model for the leptin/CRH2 complex and performed a detailed mutation analysis of the CRH2/leptin interface. Using both cell-based and in vitro binding assays using the isolated CRH2 domain, we show the critical role of hydrophobic interactions between Leu 13 and Leu 86 of leptin and Leu 504 in CRH2 in leptin binding and signalling. This binding pattern closely resembles the interaction of other four-helix bundle long chain cytokines with the CRH domain of their cognate receptors.
Close encounters: regulation of vertebrate skeletal myogenesis by cell-cell contact
Authors: Krauss Robert S. , Cole Francesca , Gaio Ursula , Takaesu Giichi , Zhang Wei , Kang Jong-Sun
Published: May 2005

Cells of the vertebrate skeletal muscle lineage develop in a highly ordered process that includes specification, migration and differentiation into multinucleated myofibers. The changes in gene expression and cell morphology that occur during myogenic differentiation must be coordinated with each other in a spatiotemporal fashion; one way that this might occur is through regulation of these processes by cell-cell adhesion and resultant signaling. The past several years have witnessed the identification of molecules that are likely to be mediators of the promyogenic effects of cell-cell contact and some of the mechanisms by which they work. These include: the community factor, embryonic fibroblast growth factor (eFGF); classical cadherins, which mediate both adhesion and signaling; and cadherin-associated immunoglobulin superfamily members such as CDO, BOC and neogenin. Genetic evidence for the promyogenic roles of some of these factors is emerging. In other cases, potential compensatory or redundant functions necessitate future construction of double or triple mutants. Mechanistic studies in vitro indicate that specific cadherins and immunoglobulin superfamily proteins exert some of their effects in an interdependent fashion by signaling from a multiprotein complex found at sites of cell-cell contact.
Microbiology and antimicrobial management of sinusitis
Authors: Brook Itzhak
Published: May 2005

Sinusitis generally develops as a complication of viral or allergic inflammation of the upper respiratory tract. The bacterial pathogens in acute sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, while anaerobic bacteria and Staphylococcus aureus are predominant in chronic sinusitis. Pseudomonas aeruginosa has emerged as a potential pathogen in immunocompromised patients and in those who have nasal tubes or catheters, or are intubated. Many of these organisms recovered from sinusitis became resistant to penicillins either through the production of beta-lactamase (H. influenzae, M. catarrhalis, S. aureus, Fusobacterium spp., and Prevotella spp) or through changes in the penicillin-binding protein (S. pneumoniae). The pathogenicity of beta-lactamase-producing bacteria is expressed directly through their ability to cause infections, and indirectly through the production of betalactamase. The indirect pathogenicity is conveyed not only by surviving penicillin therapy, but also by ‘shielding’ penicillin-susceptible pathogens from the drug. The direct and indirect virulent characteristics of these bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections. The antimicrobials that are the most effective in management of acute sinusitis are amoxycillin-clavulanate (given in a high dose), the newer quinolones (gatifloxacin, moxifloxacin) and the second generation cephalosporins (cefuroxime, cefpodoxime, cefprozil or cefdinir). The antimicrobials that are the most effective in management of chronic sinusitis are amoxycillinclavulanate, clindamycin and the combination of metronidazole and a penicillin.
Cutaneous metastases from a hypopharyngeal malignancy
Authors: Durvasula V S P , Mahendran S , Grant J W , Jani P
Published: May 2005

We present an unusual case of carcinoma of the piriform fossa, presenting with cutaneous metastases. These metastases are very rare, present in the late stages of disease, and are usually associated with distant metastases and poor prognosis. They often suggest aggressive disease. We believe that cutaneous metastases from a malignancy in the piriform fossa are more unusual than those from other sites of the head and neck.
Deep neck abscess: a prospective study of 54 cases
Authors: Meher Ravi , Jain Anubhav , Sabharwal Anup , Gupta Bulbul , Singh Ishwar , Agarwal A K
Published: May 2005

Deep neck abscesses (DNAs) continue to be commonly encountered in developing countries like India. This study was conducted to determine the changing trends within our population with respect to presentation, aetiology, location and microbiology of DNAs. Fifty-four patients with DNAs who were managed at the Department of ORL and H&N Surgery in our hospital between May 2002 and December 2002 formed the basis of the study. We observed that the high incidence of DNAs could be attributed to lack of awareness, illiteracy and poverty among patients, along with the poor primary health infrastructure. We also recommend early surgical intervention in these cases to decrease the prevalence of complications.
Simultaneous reconstruction of large skin and mucosal defect following head and neck surgery with a single skin paddle pectoralis major myocutaneous flap
Authors: Chaturvedi P , Pai P S , Pathak K A , Chaukar D A , Deshpande M S , D’Cruz A K
Published: May 2005

The pectoralis major myocutaneous (PMMC) flap is commonly used for head and neck reconstruction especially in impoverished nations. PMMC is a sturdy pedicled flap with relatively fewer complications, the learning curve is short and no specialized training in microvascular surgery is needed in order to use this flap. In a defect that requires a large skin and mucosal lining the authors routinely use either a bi-paddle PMMC or a combination of PMMC (for the mucosal lining) and a delto-pectoral flap (for the skin defect). It is indisputable that free tissue transfer is a better way of reconstruction for the majority of most such defects. Unfortunately, not all patients can be offered this form of reconstruction due to the cost, time, expertise and infrastructural constraints in high volume centres such as ours. Bi-paddling of PMMC is hazardous in obese males and most female patients. In such patients the skin defect is reconstructed usually by the delto-pectoral (DP) flap but this, for obvious reasons, is less welcomed by the patients. The authors suggest a technique wherein mucosal lining is created by the myofascial lining (inner surface) of the flap and the skin defect is reconstructed by the skin paddle of the single paddle PMMC. It should be considered wherever a DP flap is unacceptable, or bi-paddling or free tissue transfer is not possible.
GRASP with Path Relinking for Three-Index Assignment
Authors: Aiex Renata M. , Resende Mauricio G. C. , Pardalos Panos M. , Toraldo Gerardo
Published: May 2005

This paper proposes and tests variants of GRASP (greedy randomized adaptive search procedure) with path relinking for the three-index assignment problem (AP3). GRASP is a multistart metaheuristic for combinatorial optimization. It usually consists of a construction procedure based on a greedy randomized algorithm and of a local search. Path relinking is an intensification strategy that explores trajectories that connect high-quality solutions. Several variants of the heuristic are proposed and tested. Computational results show clearly that this GRASP for AP3 benefits from path relinking and that the variants considered in this paper compare well with previously proposed heuristics for this problem. GRASP with path relinking was able to improve the solution quality of heuristics proposed by Balas and Saltzman (1991), Burkard et al. (1996), and Crama and Spieksma (1992) on all instances proposed in those papers. We show that the random variable “time to target solution,” for all proposed GRASP with path-relinking variants, fits a two-parameter exponential distribution. To illustrate the consequence of this, one of the variants of GRASP with path relinking is shown to benefit from parallelization.
A New Pricing Model for Competitive Telecommunications Services Using Congestion Discounts
Authors: Keon Neil , Anandalingam G. “Anand”
Published: May 2005

We propose a two-stage pricing approach that enables providers of telecommunications services to guarantee quality of service (QoS) to their customers. The scheme is intended to shift demand during congestion periods to periods of lower demand by offering price discounts as an incentive to users to delay service during the high-demand periods. The price-discount offers act as a congestion-avoidance scheme that also balances communication traffic across different time periods. To get the scheme to work, we provide methods to evaluate when to offer the discounting scheme, estimate what proportion of customers accept the discounts, and how much the price discounts should be. In addition to offering a novel pricing structure, we show the optimal solution to the problem can be computed in a sequential manner from one period to the next, greatly simplifying implementation. Furthermore, we develop the model under uncertainty to emphasize the key implementation features of simple computations that can be performed in real time using sampled information online. We use simulations to demonstrate the scheme’s usefulness in regulating peak period demand.