bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchronization of Ca2+oscillations: a coupled oscillator‐based mechanism in smooth muscle
Authors: Imtiaz Mohammad S. , von der Weid Pierre‐Yves , van Helden Dirk F.
Published: November 2009

Entrained oscillations in Ca2+underlie many biological pacemaking phenomena. In this article, we review a long‐range signaling mechanism in smooth muscle that results in global outcomes of local interactions. Our results are derived from studies of the following: (a) slow‐wave depolarizations that underlie rhythmic contractions of gastric smooth muscle; and (b) membrane depolarizations that drive rhythmic contractions of lymphatic smooth muscle. The main feature of this signaling mechanism is a coupled oscillator‐based synchronization of Ca2+oscillations across cells that drives membrane potential changes and causes coordinated contractions. The key elements of this mechanism are as follows: (a) the Ca2+release–refill cycle of endoplasmic reticulum Ca2+stores; (b) Ca2+‐dependent modulation of membrane currents; (c) voltage‐dependent modulation of Ca2+store release; and (d) cell–cell coupling through gap junctions or other mechanisms. In this mechanism, Ca2+stores alter the frequency of adjacent stores through voltage‐dependent modulation of store release. This electrochemical coupling is many orders of magnitude stronger than the coupling through diffusion of Ca2+or inositol 1,4,5‐trisphosphate, and thus provides an effective means of long‐range signaling.
Synchronization of Ca2+ oscillations: involvement of ATP release in astrocytes
Authors: Koizumi Schuichi
Published: November 2009

Glial cells, especially astrocytes, are not merely supportive cells, but are important partners to neighboring cells, including neurons, vascular cells, and other glial cells. Although glial cells are not excitable in terms of electrophysiology, they have been shown to generate synchronized Ca2+ transients (Ca2+ oscillations) through mechanisms of chemical coupling. Until recently, Ca2+ transients in astrocytes were thought to be totally dependent on neuronal activities, because astrocytes express a large variety of receptors for neurotransmitters and surround almost all synapses at which neurotransmitters are spilled over to stimulate astrocytes. In addition, however, astrocytes have been shown to release diffusible substances, so‐called ‘gliotransmitters’, and Ca2+ transients in astrocytes are therefore also triggered by astrocytic activities, leading to propagation of Ca2+ transients or Ca2+ waves. In these processes, the gliotransmitter ATP and activation of P2Y receptors play central roles. Interestingly, astrocytes evoke Ca2+ transients when neurons are not present, suggesting that astrocytes themselves can initiate and control Ca2+ transients. Astrocytic Ca2+ transients are observed even in vivo, through mechanisms of chemical coupling by gliotransmitters, but they are less frequent and synchronous than those in vitro. Although we have not yet clarified their significance in the central nervous system, astrocytic Ca2+ transients are dramatically affected by pathological conditions, suggesting that, in addition to physiological events, they might be closely involved in disorders in the central nervous system.
Synchronization of Ca2+ oscillations: a capacitative (AC) electrical coupling model in neuroepithelium
Authors: Yamashita Masayuki
Published: November 2009

Increases in intracellular [Ca2+] occur synchronously between cells in the neuroepithelium. If neuroepithelial cells were capable of generating action potentials synchronized by gap junctions (direct current electrical coupling), the influx of Ca2+ through voltage‐activated Ca2+ channels would lead to a synchronous increase in intracellular [Ca2+]. However, no action potential is generated in neuroepithelial cells, and the [Ca2+] increase is instead produced by the release of Ca2+ from intracellular Ca2+ stores. Recently, synchronous fluctuations in the membrane potential of Ca2+ stores were recorded using an organelle‐specific voltage‐sensitive dye. On the basis of these recordings, a capacitative [alternating current (AC)] electrical coupling model for the synchronization of voltage fluctuations of Ca2+ store potential was proposed [Yamashita M (2006) FEBS Lett580, 4979–4983; Yamashita M (2008) FEBS J275, 4022–4032]. Ca2+ efflux from the Ca2+ store and K+ counterinflux into the store cause alternating voltage changes across the store membrane, and the voltage fluctuation induces ACs. In cases where the store membrane is closely apposed to the plasma membrane and the cells are tightly packed, which is true of neuroepithelial cells, the voltage fluctuation of the store membrane is synchronized between the cells by the AC currents through the series capacitance of these membranes. This article provides a short review of the model and its relationship to the structural organization of the Ca2+ store. This is followed by a discussion of how the mode of synchronization of [Ca2+] increase may change during central nervous system development and new molecular insights into the synchronicity of [Ca2+] increase.
Parentage analysis in Gabonese colonies of soil‐feeding termites belonging to theCubitermessp.affinis subarquatuscomplex of species (Termitidae: Termitinae)
Authors: Roy Virginie , Dupont Lise , Harry Myriam
Published: November 2009

Abstract Cubitermesspp. are widely distributed soil‐feeding termite species in sub‐Saharan Africa which play a fundamental role in soil structure and fertility. A complex of at least four cryptic species (i.e.,Cubitermessp.affinis subarquatuscomplex of species) has been recently described using molecular markers. In order to investigate the breeding system of these species, five microsatellite markers were used to carry out parentage and relatedness analyses in 15 Gabonese colonies. Monogamy was confirmed as the predominant reproductive organization inCubitermesspp. (76% of the colonies). Within 30% of these monogamous colonies, a high relatedness between reproductives was shown, suggesting that mating between related individuals occurs. However,Cubitermescolonies can deviate from monogamy. Indeed, parental contributions by at least two related reproductives of the same sex were revealed in four colonies and polyandry was demonstrated in two of them. Infiltration of reproductives in the colony is the most plausible explanation for such cases of polygamy inCubitermesspp.
Contraction‐induced changes in skeletal muscle Na+,K+ pump mRNA expression – importance of exercise intensity and Ca2+‐mediated signalling
Authors: Nordsborg N. B. , Kusuhara K. , Hellsten Y. , Lyngby S. , Lundby C. , Madsen K. , Pilegaard H.
Published: November 2009

Aim:  To investigate if exercise intensity and Ca2+ signalling regulate Na+,K+ pump mRNA expression in skeletal muscle.

Methods:  The importance of exercise intensity was evaluated by having trained and untrained humans perform intense intermittent and prolonged exercise. The importance of Ca2+ signalling was investigated by electrical stimulation of rat soleus and extensor digitorum longus (EDL) muscles in combination with studies of cell cultures.

Results:  Intermittent cycling exercise at ∼85% of VO2peak increased (P < 0.05) α1 and β1 mRNA expression ∼2‐fold in untrained and trained subjects. In trained subjects, intermittent exercise at ∼70% of VO2peak resulted in a less (P < 0.05) pronounced increase (∼1.4‐fold; P < 0.05) for α1 and no change in β1 mRNA. Prolonged low intensity exercise increased (P < 0.05) mRNA expression of α1 ∼3.0‐fold and α2 ∼1.8‐fold in untrained but not in trained subjects. Electrical stimulation of rat soleus, but not EDL, muscle increased (P < 0.05) α1 mRNA expression, but not when combined with KN62 and cyclosporin A incubation. Ionomycin incubation of cultured primary rat skeletal muscle cells increased (P < 0.05) α1 and reduced (P < 0.001) α2 mRNA expression and these responses were abolished (P < 0.05) by co‐incubation with cyclosporin A or KN62.

Conclusion:  (1) Exercise‐induced increases in Na+,K+ pump α1 and β1 mRNA expression in trained subjects are more pronounced after high‐ than after moderate‐ and low‐intensity exercise. (2) Both prolonged low and short‐duration high‐intensity exercise increase α1 mRNA expression in untrained subjects. (3) Ca2+i regulates α1 mRNA expression in oxidative muscles via Ca2+/calmodulin‐dependent protein kinase (CaMK) and calcineurin signalling pathways.
Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy
Authors: Cartier Nathalie , Hacein-Bey-Abina Salima , Bartholomae Cynthia C. , Veres Gabor , Schmidt Manfred , Kutschera Ina , Vidaud Michel , Abel Ulrich , Dal-Cortivo Liliane , Caccavelli Laure , Mahlaoui Nizar , Kiermer Véronique , Mittelstaedt Denice , Bellesme Céline , Lahlou Najiba , Lefrère François , Blanche Stéphane , Audit Muriel , Payen Emmanuel , Leboulch Philippe , l’Homme Bruno , Bougnères Pierre , Von Kalle Christof , Fischer Alain , Cavazzana-Calvo Marina , Aubourg Patrick
Published: November 2009

Slowing Brain Disease with Gene Therapy

X-linked adrenoleukodystrophy (ALD), the hereditary brain demyelinating disorder that was featured in the movie “
Lorenzo's Oil
,” is typically treated by transplantation of bone marrow from matched donors. This treatment slows progression of the disease by introducing cells that differentiate into myelin-producing cells.

Cartier
et al.

(p.
818
; see Perspective by

Naldini

) tested an alternative gene therapy–based approach in two young patients without matched donors. A lentiviral vector was used to introduce a wild-type copy of the ALD gene into the patients' hematopoietic stem cells ex vivo. The modified cells were then infused back into the patients. Expression of the transferred gene was still detectable in the patients' blood cells 2 years later, and both patients showed neurological improvement and a delay in disease progression comparable to that seen with bone marrow transplants.
Ecological Restoration in the Light of Ecological History
Authors: Jackson Stephen T. , Hobbs Richard J.
Published: November 2009

Ecological history plays many roles in ecological restoration, most notably as a tool to identify and characterize appropriate targets for restoration efforts. However, ecological history also reveals deep human imprints on many ecological systems and indicates that secular climate change has kept many targets moving at centennial to millennial time scales. Past and ongoing environmental changes ensure that many historical restoration targets will be unsustainable in the coming decades. Ecological restoration efforts should aim to conserve and restore historical ecosystems where viable, while simultaneously preparing to design or steer emerging novel ecosystems to ensure maintenance of ecological goods and services.
Phenology Feedbacks on Climate Change
Authors: Peñuelas Josep , Rutishauser This , Filella Iolanda
Published: November 2009

A longer growing season as a result of climate change will in turn affect climate through biogeochemical and biophysical effects.
MafB/c-Maf Deficiency Enables Self-Renewal of Differentiated Functional Macrophages
Authors: Aziz Athar , Soucie Erinn , Sarrazin Sandrine , Sieweke Michael H.
Published: November 2009

Self-Renewing Macrophages

The capacity for self-renewal is associated with progenitor cell populations and is lost upon differentiation.

Aziz
et al.

(p.
867
) discovered an exception to this rule when mouse monocytes and macrophages deficient in the transcription factors MafB and c-Maf were cultured in the presence of the growth factor, macrophage colony-stimulating factor (M-CSF). Under these conditions, MafB/c-Maf–deficient cells were able to divide continuously while maintaining the phenotype and function of mature cells. Unexpectedly, when these in vitro–cultured cells were transferred into mice, they did not induce tumors, despite continuing to divide, but rather incorporated themselves into tissues and adopted normal macrophage functions. Suppression of two genes involved in the self-renewal capacity of inducible pluripotent stem cells, KLF4 and c-Myc, inhibited the ability of MafB/c-Maf–deficient macrophages to self-renew. Such long-term propagation of a differentiated cell population that does not result in transformation when reintroduced in vivo has exciting therapeutic potential.
Shifts in Lake N:P Stoichiometry and Nutrient Limitation Driven by Atmospheric Nitrogen Deposition
Authors: Elser James J. , Andersen Tom , Baron Jill S. , Bergström Ann-Kristin , Jansson Mats , Kyle Marcia , Nydick Koren R. , Steger Laura , Hessen Dag O.
Published: November 2009

Nitrogen Overload

The cycling of essential nutrients in terrestrial ecosystems has been altered by human activities.

Elser
et al.

(p.
835
) report a comparative analysis of lakes in Norway, Sweden, and in the United States that suggests that this is also true in aquatic ecosystems such as lakes. Deposition of anthropogenically derived atmospheric nitrogen controls whether N or P is growth-limiting for phytoplankton. Under elevated conditions of atmospheric N inputs, lake phytoplankton become consistently P-limited because the N:P ratio is strongly distorted. This is in contrast to conditions of low N deposition when lake phytoplankton are N-limited. These effects are even observed in remote lakes, demonstrating the indirect yet wide-ranging effects of humans on global food webs.
Bridging the Montreal-Kyoto Gap
Authors: Cohen Jeff , Rau Alex , Brüning Kristian
Published: November 2009

Using carbon markets to eliminate substances that deplete stratospheric ozone could pay huge dividends in combating global warming.
Building on No Child Left Behind
Authors: Hanushek Eric A.
Published: November 2009

A federally mandated system of test-based accountability for U.S. education can be made even better.
Moving Past No Child Left Behind
Authors: Koretz Daniel
Published: November 2009

No Child Left Behind is a poorly designed program, with serious side effects and little evidence of benefit, in need of fundamental changes.
Small-Molecule Activators of a Proenzyme
Authors: Wolan Dennis W. , Zorn Julie A. , Gray Daniel C. , Wells James A.
Published: November 2009

Small-Molecule Protease Activator

Human proteases regulate numerous biological processes. Most are stored as inactive proenzymes that are activated either by upstream processes or by self-proteolysis.

Wolan
et al.

(p.
853
) have identified a small molecule that activates the apoptotic procaspases-3 and -6. These caspases are homodimers, and the compound probably competitively inhibits one active site, but stabilizes an on-state conformation that promotes self-cleavage by the unoccupied site. It may thus be possible to find other small-molecule activators for other proenzymes that should facilitate functional and mechanistic studies.
A Single Peptide–MHC Complex Positively Selects a Diverse and Specific CD8 T Cell Repertoire
Authors: Wang Baomei , Primeau Tina M. , Myers Nancy , Rohrs Henry W. , Gross Michael L. , Lybarger Lonnie , Hansen Ted H. , Connolly Janet M.
Published: November 2009

Goldilocks Immunology

T cells are carefully calibrated in the thymus to react to invading pathogens and to ignore the self. This occurs through interactions between the T cell receptor and major histocompatibility complexes (MHCs) expressing self-peptides. A Goldilocks-like selection process is carried out whereby T cells that do not react or react too strongly to self-peptide MHCs are deleted, whereas those with interactions that are “just right” are allowed to survive. The result is T cells highly specific for a particular foreign peptide-MHC complex. Receipt of survival signals from “just-right” interactions (positive selection) and deletion of cells that are too reactive (negative selection) are spatially and temporally segregated in the thymus, and it is unclear at which stage T cells acquire their high degree of peptide-MHC specificity. By using mice expressing a single peptide-MHC complex,

Wang
et al.

(p.
871
) now show that this single complex is sufficient for selection of a CD8
+
T cell repertoire with a broad range of specificity. Importantly, recognition of peptide MHC by these cells was highly specific, demonstrating that peptide-MHC specificity is acquired during positive selection in the thymus.
Chemically Accurate Simulation of a Prototypical Surface Reaction: H
2
Dissociation on Cu(111)
Authors: Díaz C. , Pijper E. , Olsen R. A. , Busnengo H. F. , Auerbach D. J. , Kroes G. J.
Published: November 2009

Simulating Surfaces

Although modern computational chemistry can often match or even exceed experimental accuracy in modeling gas phase reactions, the surface-bound processes involved in most practical catalysis pose a substantially greater challenge to theory (see the Perspective by

Hasselbrink

).

Díaz
et al.

(p.
832
) show that a modification to standard density functional methods can predict reaction barrier heights to within 1 kilocalorie per mole for the widely studied dissociative adsorption of dihydrogen on copper. In a complementary study,

Shenvi
et al.

(p.
829
) apply an efficient algorithmic framework to model transitions among multiple electronic states at a metal surface and successfully account for the complex dependence of nitric oxide scattering on the small molecule's vibrations and rotations.
Biodiversity and Climate Change
Authors: Willis Kathy J. , Bhagwat Shonil A.
Published: November 2009

Efforts to elucidate the effect of climate change on biodiversity with detailed data sets and refined models reach novel conclusions.
Abiotic Gas Formation Drives Nitrogen Loss from a Desert Ecosystem
Authors: McCalley Carmody K. , Sparks Jed P.
Published: November 2009

Desert Balancing Act

Ecosystem nutrient budgets are often difficult to estimate given the variety of processes and organisms that influence their flux. In deserts, for example, the loss of nitrogen—a limiting nutrient for growth—is often thought to be mediated by the generation of trace gases from biological activity.
McCalley and Sparks
(p.
837
) present results from the Mojave Desert that suggest most nitrogen is instead driven off by the Sun at high temperatures that inhibit microbial activity. This requires a reevaluation of the desert nitrogen budget both now and in the future when climate change may drive increased abiotic emissions in arid ecosystems.
Polymorphic Butterfly Reveals the Missing Link in Ecological Speciation
Authors: Chamberlain Nicola L. , Hill Ryan I. , Kapan Durrell D. , Gilbert Lawrence E. , Kronforst Marcus R.
Published: November 2009

Butterfly Apartheid

Heliconius
butterflies show differences in mimetic color patterns across geographic races associated with patterns of assortative mating, suggesting that ecological speciation may be ongoing.

Chamberlain
et al.

(p.
847
) demonstrate assortative mating on the basis of color pattern mimicry that generates reproductive isolation between
Heliconius cydno
species and subspecies within polymorphic populations in Ecuador. Furthermore, it appears that these traits are controlled by a single gene that affects color pigment in wing pattern formation and vision. Thus, these butterflies are indeed in the early stages of reproductive isolation that is being driven by an ecological trait, allowing observation of an incipient speciation event.
Darwin Is Dead—Long Live Evolution

Stephen Jay Gould and the Politics of Evolution
by David F. Prindle

Prometheus, Amherst, NY, 2009. 249 pp. $26.98, £22.50. ISBN 9781591027188.
Authors: Smocovitis Vassiliki Betty
Published: November 2009

Exploring Gould's science, politics, and their intersections, Prindle holds that they constitute a consistent whole.
Population Structure Mediates Sexual Conflict in Water Striders
Authors: Eldakar Omar Tonsi , Dlugos Michael J. , Pepper John W. , Wilson David Sloan
Published: November 2009

When water striders can disperse among groups, females select for reduced male aggression.
Electronic Structure Controls Reactivity of Size-Selected Pd Clusters Adsorbed on TiO
2
Surfaces
Authors: Kaden William E. , Wu Tianpin , Kunkel William A. , Anderson Scott L.
Published: November 2009

Cluster Electronics and Catalysis

Many practical catalysts consist of small metal clusters on oxide supports, and the activity of these clusters usually varies with their size. In order to sort out some of the competing effects that lead to such variations,

Kaden
et al.

(p.
826
) size-selected palladium clusters (from single atoms to clusters up to 25 atoms) and deposited them on a crystal face of the rutile phase of titanium dioxide. X-ray photoemission studies and temperature-programmed reaction measurements showed that the activity of these model catalysts for CO oxidation was related to the electronic energy, which was reflected in the Pd 3d electron binding energy. Ion-scattering studies showed that the clusters formed flat single- or double-layer islands.
An Unusually Fast-Evolving Supernova
Authors: Poznanski Dovi , Chornock Ryan , Nugent Peter E. , Bloom Joshua S. , Filippenko Alexei V. , Ganeshalingam Mohan , Leonard Douglas C. , Li Weidong , Thomas Rollin C.
Published: November 2009

We Are Stardust

Supernovae form as the result of stellar explosions and are classified according to the properties of their spectra.

Poznanski
et al.

(p.
58
, published online 5 November) present a peculiar supernova that is characterized by extremely fast temporal evolution and unusual spectroscopic features, such that it defies classification. SN2002bj appears to be a member of a new class of supernovae, possibly formed by a helium detonation on a white dwarf ejecting a small envelope of material.
A Comeback for Gene Therapy
Authors: Naldini Luigi
Published: November 2009

A lentivirus was used as a vector in hemato-poietic stem cells to treat a neurodegenerative disease in a clinical gene therapy trial.
Development and Climate Change
Authors: Bierbaum Rosina M. , Zoellick Robert B.
Published: November 2009

No country is immune to climate change, but the developing world will bear the brunt of the effects, including some 75 to 80% of the costs of anticipated damages. Millions in densely populated coastal areas and in island nations will lose their homes as the sea level rises, while poor people will face crop failures, reduced agricultural productivity, and increased hunger, malnutrition, and disease. Extreme events such as droughts, floods, and forest fires will become more frequent, making it even harder for developing countries to attain the United Nations' Millennium Development Goals of 2015. A “climate-smart” world is possible in our time. But to ensure a safe and sustainable future, all nations must act now, act together, and act differently.
Moving Beyond DNA
Authors: Gitig Diana
Published: November 2009

Scientists have been playing with nucleic acids for decades. Now, with so many newly discovered molecules to explore--no longer just genomic DNA and mRNA but mitochondrial DNA, microRNA, small interfering RNA--companies and even individual researchers are coming up with newer and better ways to purify and store nucleic acids for various downstream applications. And some even have technologies that preclude the need for purification altogether.
Who Needs Labels?: Macromolecular Interaction Sans Labels
Authors: Perkel Jeffrey
Published: November 2009

When it comes to monitoring biological interactions, whether of nucleic acids, proteins,small molecules, or cells, labels are essential for detection, right? Researchers certainly have embraced detection modalities based on tagging with radioisotopes, fluorescent dyes, and conjugated enzymes. Yet in many cases such molecular baggage is unnecessary, and possibly detrimental. But there is another way. Whether based on optical, mechanical, or electrical detection, label-free methods can probe molecular pas de deux in their native, unadulterated states. As a result, they are faster, simpler, and more physiological than their labeled counterparts.
RNAI Therapeutics: A Two-Year Update
Authors: Perkel Jeffrey
Published: November 2009

Two years is a long time in the world of RNAi therapeutics. Since Science last covered the topic in 2007, the first Phase 3 human clinical trial of an siRNA drug has been prematurely terminated; new off-target effects have been identified; and the first miRNA-based therapeutic entered clinical trials. Yet much remains the same, especially the biggest challenge: delivery. As researchers struggle to overcome these obstacles, optimism persists undiminished.
Helium-3 Shortage Could Put Freeze On Low-Temperature Research
Authors: Cho Adrian
Published: November 2009

A shortfall of helium-3, the lighter isotope of the most inert element, threatens several research fields, and the Department of Energy, the major supplier, is releasing the gas, which is used in neutron detectors that help prevent the smuggling of plutonium and other radioactive materials into the country, only to researchers with U.S. funding.
Why So Few East German Directors?
Authors: Vogel Gretchen
Published: November 2009

The reunification of Germany was a mixed blessing for East German scientists. For many, especially the younger ones, it was a great opportunity (see p.
792
). But others were set adrift when entire preexisting eastern institutes were closed or cut to a fraction of their original size.
Big Dreams Come True
Authors: Curry Andrew
Published: November 2009

An East German family of scientists reflects on life before and after 1989. The Hübners have become a dynamic demonstration of how the lives of scientists in the former East Germany have changed over the past 2 decades.
Catastrophic injuries among young athletes
Authors: Zemper E D
Published: November 2009

While very rare, catastrophic injuries in youth sports have a major impact on athletes and their families when they do occur. This article reviews and summarises the sparse research on direct catastrophic injuries in youth sports, a direct catastrophic sports injury being defined as a sport injury that resulted from participation in the skills of the sport, and resulted in a fatality or in a non-fatal brain or spinal cord injury, or skull or spinal fracture. While an electronic database search was completed to assemble the articles reviewed here, much of the data come from the National Center for Catastrophic Injury Research at the University of North Carolina, which has the most extensive and complete data set on this issue. This article reviews and summarises what is known about the rate of occurrence of these injuries in various youth sports, the risk factors for these injuries, injury mechanisms and what can be done to prevent them in various youth sports.
Switching to “lighter” cigarettes and quitting smoking
Authors: Tindle H A , Shiffman S , Hartman A M , Bost J E
Published: November 2009

Objective:

Smokers who switch to “lighter” cigarettes may be diverted from quitting smoking. We assessed factors associated with switching and the association between switching and (1) making a quit attempt, and (2) recent quitting, yielding a measure of net quitting (attempts × recent quitting).

Design:

In 2003, a total of 30 800 ever-smokers who smoked in the past year provided history of switching and 3 reasons for switching: harm reduction, quitting smoking and flavour. Among those who made a past-year quit attempt, recent quitting was defined as ⩾90-day abstinence when surveyed. Multivariable logistic regression identified determinants of outcomes.

Results:

In all, 12 009 (38%) of ever-smokers switched. Among switchers, the most commonly cited reasons were flavour only (26%) and all 3 reasons (18%). Switchers (vs non-switchers) were more likely to make a quit attempt between 2002 and 2003 (51% vs 41%, p<0.001, adjusted odds ratio (AOR) 1.58, (95% confidence interval (CI) 1.48 to 1.69)), but less likely to have recently quit (9% vs 17%, p<0.001; AOR 0.40 (95% CI 0.35 to 0.45)), yielding lower overall net quitting (4.3% vs 7.0%, p<0.001; AOR 0.54, (95% CI 0.47 to 0.61)). The effects of switching on outcomes were most pronounced for reasons including quitting smoking, whereas switching for harm reduction alone had no association with outcomes.

Conclusion:

Compared with no switching, a history of switching was associated with 46% lower odds of net quitting.
Hybridization and introgression between a rare and a common lady’s slipper orchid,Cypripedium candidumandC. parviflorum(Orchidaceae)
Authors: Worley Anne C. , Sawich Lauren , Ghazvini Habibollah , Ford Bruce A.
Published: November 2009

Extinction through hybridization can threaten endangered species when hybrids are vigorous and fertile. We studied hybridization between the endangered small white lady’s slipper ( Cypripedium candidum Muhlenberg ex Willdenow) and the common yellow lady’s slipper ( Cypripedium parviflorum Salisbury var. makasin (Farwell) Sheviak and C. parviflorum var. pubescens (Willdenow) O.W. Knight) in four Manitoban populations. We used 8 morphological characters and 1061 amplified fragment length polymorphism (AFLP) loci to characterize variation in 182 plants. Canonical correlation analysis indicated that morphology was highly predictive of genetic composition. Ordination analyses of morphological and genetic data, and Bayesian clustering analysis of the genetic data, all clearly distinguished the two parental species. The two varieties of C. parviflorum were morphologically divergent but occupied the same genetic cluster in both ordination and Bayesian analyses. Putative hybrids had considerable morphological overlap with parental species but were mostly genetically intermediate. Five of 79 individuals assigned to C. candidum and 15 of 71 individuals assigned to C. parviflorum had genetic profiles consistent with mixed ancestry. These results suggest that some introgression has occurred, but genetic assimilation of endangered C. candidum by the more common C. parviflorum does not seem imminent. The high local abundance of C. candidum may reduce its susceptibility to gene flow from C. parviflorum.
Chloroplast DNA phylogeography ofRhodiola alsia(Crassulaceae) in the Qinghai–Tibet Plateau
Authors: Gao Qingbo , Zhang Dejun , Chen Shengyun , Duan Yizhong , Zhang Faqi , Li Yinghu , Chen Shilong
Published: November 2009

We studied the phylogeography of Rhodiola alsia (Fröderström) S.H. Fu, which is a perennial herbaceous plant endemic to the Qinghai–Tibet (Q–T) Plateau, by sequencing one intergenic chloroplast spacer, rpl20–rps12 (844 bp). The sampling design included 18 populations and 315 individuals, and spanned the entire distribution range of the species. Thirty-one haplotypes were characterized, and polymorphism was observed both within and among populations. Most haplotypes were restricted to single sites or to neighbouring populations, suggesting an extremely low level of long distance gene flow via seeds. Only three haplotypes were common and widespread throughout the distributional range of R. alsia. The present geographical distribution of haplotypes probably reflects an ancient geographical pattern between the platform and southeastern margin of the Q–T Plateau identified as genetic hotspot areas. We suggest that populations of R. alsia survived in isolated refugia located in the platform and the southeastern margin of the Q–T Plateau during the Quaternary glaciation, at least during the last glaciation maximum (LGM, 32 000–16 000 years ago). The populations of R. alsia were geographically isolated by a subsequent local range expansion and independent evolution. The genetic structure of R. alsia is very different from previous phylogeographical studies of Q–T Plateau alpine plants and illustrates the importance of species-specific characteristics such as distribution areas and life-history traits which are mainly responsible for different patterns of genetic variation. Our investigation thus provides a new pattern of several refugia on the plateau platform.
Sénescence d’un pied de maïs : évolution de la floraison à la récolte
Authors: Combe Laurette , Escobar-Gutiérrez Abraham J.
Published: November 2009

Chez les espèces monocarpiques telles que le maïs, la sénescence des feuilles est coordonnée avec celle de la plante entière et sous l’influence du fonctionnement reproductif. L’objectif de ce travail était de décrire l’évolution de la sénescence du maïs selon deux axes : (1) l’axe de la plante entière, où les différents étages foliaires sont considérés chacun comme une entité, et (2) l’axe foliaire, où la dynamique de trois symptômes macroscopiques de la sénescence sur chaque feuille prise individuellement, selon des zones allant de la pointe vers la base du limbe de la feuille, a été prise en considération. Sur une culture au champ, des pieds et des feuilles de maïs ont été suivis ou échantillonnés de la floraison à la récolte. Les dynamiques des teneurs en eau, en matière sèche et en chlorophylle sont différentes, aussi bien le long d’une feuille qu’entre les rangs de feuilles. De plus, la teneur en chlorophylle dans la plante suit une dynamique plus complexe que celles de l’eau et de la matière sèche. À partir du suivi de la décoloration le long des feuilles de 15 plantes sur toute leur hauteur, nous avons établi des relations fonctionnelles décrivant la progression du front de sénescence pour chaque rang des feuilles 7 à terminales (15 ou 16). Cette description quantitative peut être utilisée directement pour compléter des modèles de culture et des modèles de type structure–fonction. Cela permettrait d’estimer l’impact de la sénescence des feuilles sur l’interception du rayonnement et donc sur la photosynthèse et le rendement. Nos résultats peuvent servir aussi à l’interprétation des mesures de réflectance des couverts de maïs faites par télédétection.
Peripheral peptide YY inhibits propulsive colonic motor function through Y2receptor in conscious mice
Authors: Wang Lixin , Gourcerol Guillaume , Yuan Pu-Qing , Wu S. Vincent , Million Mulugeta , Larauche Muriel , Taché Yvette
Published: November 2009

Peptide YY (PYY) antisecretory effect on intestinal epithelia is well established, whereas less is known about its actions to influence colonic motility in conscious animals. We characterized changes in basal function and stimulated colonic motor function induced by PYY-related peptides in conscious mice. PYY3–36, PYY, and neuropeptide Y (NPY) (8 nmol/kg) injected intraperitoneally inhibited fecal pellet output (FPO) per hour during novel environment stress by 90%, 63%, and 57%, respectively, whereas the Y1-preferring agonists, [Pro34]PYY and [Leu31,Pro34]NPY, had no effect. Corticotrophin-releasing factor 2 receptor antagonist did not alter PYY3–36inhibitory action. PYY and PYY3–36significantly reduced restraint-stimulated defecation, and PYY3–36inhibited high-amplitude distal colonic contractions in restrained conscious mice for 1 h, by intraluminal pressure with the use of a microtransducer. PYY suppression of intraperitoneal 5-hydroxytryptophan induced FPO and diarrhea was blocked by the Y2antagonist, BIIE0246, injected intraperitoneally and mimicked by PYY3–36, but not [Leu31,Pro34]NPY. PYY3–36also inhibited bethanechol-stimulated FPO and diarrhea. PYY3–36inhibited basal FPO during nocturnal feeding period and light phase in fasted/refed mice for 2–3 h, whereas the reduction of food intake lasted for only 1 h. PYY3–36delayed gastric emptying after fasting-refeeding by 48% and distal colonic transit time by 104%, whereas [Leu31,Pro34]NPY had no effect. In the proximal and distal colon, higher Y2mRNA expression was detected in the mucosa than in muscle layers, and Y2immunoreactivity was located in nerve terminals around myenteric neurons. These data established that PYY/PYY3–36potently inhibits basal and stress/serotonin/cholinergic-stimulated propulsive colonic motor function in conscious mice, likely via Y2receptors.
Multiple abnormalities of myocardial insulin signaling in a porcine model of diet-induced obesity
Authors: Lee Jenny , Xu Ya , Lu Li , Bergman Bryan , Leitner J. Wayne , Greyson Clifford , Draznin Boris , Schwartz Gregory G.
Published: November 2009

Heightened cardiovascular risk among patients with systemic insulin resistance is not fully explained by the extent of atherosclerosis. It is unknown whether myocardial insulin resistance accompanies systemic insulin resistance and contributes to increased cardiovascular risk. This study utilized a porcine model of diet-induced obesity to determine if myocardial insulin resistance develops in parallel with systemic insulin resistance and investigated potential mechanisms for such changes. Micropigs ( n = 16) were assigned to control (low fat, no added sugars) or intervention (25% wt/wt coconut oil and 20% high-fructose corn syrup) diet for 7 mo. Intervention diet resulted in obesity, hypertension, and dyslipidemia. Systemic insulin resistance was manifest by elevated fasting glucose and insulin, abnormal response to intravenous glucose tolerance testing, and blunted skeletal muscle phosphatidylinositol-3-kinase (PI 3-kinase) activation and protein kinase B (Akt) phosphorylation in response to insulin. In myocardium, insulin-stimulated glucose uptake, PI 3-kinase activation, and Akt phosphorylation were also blunted in the intervention diet group. These findings were explained by increased myocardial content of p85α (regulatory subunit of PI 3-kinase), diminished association of PI 3-kinase with insulin receptor substrate (IRS)-1 in response to insulin, and increased serine-307 phosphorylation of IRS-1. Thus, in a porcine model of diet-induced obesity that recapitulates many characteristics of insulin-resistant patients, myocardial insulin resistance develops along with systemic insulin resistance and is associated with multiple abnormalities of insulin signaling.
Predictive value of electrical restitution in hypokalemia-induced ventricular arrhythmogenicity
Authors: Osadchii Oleg E. , Larsen Anders Peter , Olesen Soren Peter
Published: November 2009

The ventricular action potential (AP) shortens exponentially upon a progressive reduction of the preceding diastolic interval. Steep electrical restitution slopes have been shown to promote wavebreaks, thus contributing to electrical instability. The present study was designed to assess the predictive value of electrical restitution in hypokalemia-induced arrhythmogenicity. We recorded monophasic APs and measured effective refractory periods (ERP) at distinct ventricular epicardial and endocardial sites and monitored volume-conducted ECG at baseline and after hypokalemic perfusion (2.5 mM K+ for 30 min) in isolated guinea pig heart preparations. The restitution of AP duration measured at 90% repolarization (APD90) was assessed after premature extrastimulus application at variable coupling stimulation intervals, and ERP restitution was assessed by measuring refractoriness over a wide range of pacing rates. Hypokalemia increased the amplitude of stimulation-evoked repolarization alternans and the inducibility of tachyarrhythmias and reduced ventricular fibrillation threshold. Nevertheless, these changes were associated with flattened rather than steepened APD90 restitution slopes and slowed restitution kinetics. In contrast, ERP restitution slopes were significantly increased in hypokalemic hearts. Although epicardial APD90 measured during steady-state pacing (S1-S1 = 250 ms) was prolonged in hypokalemic hearts, the left ventricular ERP was shortened. Consistently, the epicardial ERP measured at the shortest diastolic interval achieved upon a progressive increase in pacing rate was reduced in the hypokalemic left ventricle. In conclusion, this study highlights the superiority of ERP restitution at predicting increased arrhythmogenicity in the hypokalemic myocardium. The lack of predictive value of APD90 restitution is presumably related to different mode of changes in ventricular repolarization and refractoriness in a hypokalemic setting, whereby APD90 prolongation may be associated with shortened ERP.
Combining neuropeptide Y and mesenchymal stem cells reverses remodeling after myocardial infarction
Authors: Wang Yigang , Zhang Dongsheng , Ashraf Muhammad , Zhao Tiemin , Huang Wei , Ashraf Atif , Balasubramaniam Ambikaipakan
Published: November 2009

Neuropeptide Y (NPY) induced reentry of differentiated rat neonatal and adult cardiomyocytes into the cell cycle. NPY also induced differentiation of bone marrow-derived mesenchymal stem cells (MSC) into cardiomyocytes following transplantation into infarcted myocardium. Rat neonatal and adult cardiomyocytes were treated in vitro with vehicle, NPY, fibroblast growth factor (FGF; 100 ng/ml), or FGF plus NPY. DNA synthesis, mitosis, and cytokinesis were determined by immunocytochemistry. NPY-induced MSC gene expression, cell migration, tube formation, and endothelial cell differentiation were analyzed. Male rat green fluorescent protein-MSC (2 × 106), pretreated with either vehicle or NPY (10−8 M) for 72 h, were injected into the border zone of the female myocardium following left anterior descending artery ligation. On day 30, heart function was assessed, and hearts were harvested for histological and immunohistochemical analyses. NPY increased 5-bromo-2′-deoxy-uridine incorporation and promoted both cytokinesis and mitosis in rat neonatal and adult myocytes. NPY also upregulated several genes required for mitosis in MSC, including aurora B kinase, FGF-2, cycline A2, eukaryotic initiation factor 4 E, and stromal cell-derived factor-1α. NPY directly induced neonatal and adult cardiomyocyte cell-cycle reentry and enhanced the number of differentiated cardiomyocytes from MSC in the infarcted myocardium, which corresponded to improved cardiac function, reduced fibrosis, ventricular remodeling, and increased angiomyogenesis. It is concluded that a combined treatment of NPY with MSC is a novel approach for cardiac repair.
Lower strength of the human posterior patellar tendon seems unrelated to mature collagen cross-linking and fibril morphology
Authors: Hansen Philip , Haraldsson Bjarki Thor , Aagaard Per , Kovanen Vuokko , Avery Nicholas C. , Qvortrup Klaus , Larsen Jytte Overgaard , Krogsgaard Michael , Kjaer Michael , Peter Magnusson S.
Published: November 2009

The human patellar tendon is frequently affected by tendinopathy, but the etiology of the condition is not established, although differential loading of the anterior and posterior tendon may be associated with the condition. We hypothesized that changes in fibril morphology and collagen cross-linking would parallel differences in material strength between the anterior and posterior tendon. Tendon fascicles were obtained from elective ACL surgery patients and tested micromechanically. Transmission electron microscopy was used to assess fibril morphology, and collagen cross-linking was determined by HPLC and calorimetry. Anterior fascicles were markedly stronger (peak stress: 54.3 ± 21.2 vs. 39.7 ± 21.3 MPa; P < 0.05) and stiffer (624 ± 232 vs. 362 ± 170 MPa; P < 0.01) than posterior fascicles. Notably, mature pyridinium type cross-links were less abundant in anterior fascicles (hydroxylysylpyridinoline: 0.859 ± 0.197 vs. 1.416 ± 0.250 mol/mol, P = 0.001; lysylpyridinoline: 0.023 ± 0.006 vs. 0.035 ± 0.006 mol/mol, P < 0.01), whereas pentosidine and pyrrole concentrations showed no regional differences. Fibril diameters tended to be larger in anterior fascicles (7.819 ± 2.168 vs. 4.897 ± 1.434 nm2; P = 0.10). Material properties did not appear closely related to cross-linking or fibril morphology. These findings suggest region-specific differences in mechanical, structural, and biochemical properties of the human patellar tendon.
Inhibition of calpain prevents muscle weakness and disruption of sarcomere structure during hindlimb suspension
Authors: Salazar Jay J. , Michele Daniel E. , Brooks Susan V.
Published: November 2009

Unloading skeletal muscle results in atrophy and weakness. Inhibition of calpain activity during unloading reduced atrophy, but the impact on force generation has not been determined. Our hypothesis was that inhibition of calpain, through muscle-specific overexpression of calpastatin, would prevent the disruption of sarcomere structure and decreased specific force (kN/m2) observed during unloading. Calpastatin-overexpressing ( cp) and wild-type ( wt) mice were subjected to 3, 9, or 14 days of hindlimb suspension (HS). Compared with soleus muscles of non-suspended control mice, soleus muscles of wt mice showed a 25% decline in mass after 14 days of HS while maximum isometric force (Po) decreased by 40%, resulting in a specific Pothat was 35% lower than control values. Over the same time period, muscles of cp mice demonstrated 25% declines in both mass and Pobut no change in specific Po. Consistent with the preservation of specific force during HS, soleus muscles of cp mice also maintained a high degree of order in sarcomere structure, in contrast to wt muscles that demonstrated misalignment of z-lines and decreased uniformity of thick filament lengths. Susceptibility to lengthening contraction-induced injury increased with the duration of HS and was not different for muscles of cp and wt mice. We conclude that inhibition of calpain activity during unloading preserves sarcomere structure such that the isometric force-generating capability is not diminished, while the effects of unloading on lengthening contraction-induced injury likely occur through calpain-independent mechanisms.
Joint Involvement Associated with Inflammatory Bowel Disease
Authors: De Vos M.
Published: November 2009

Joint involvement associated with inflammatory bowel disease (IBD) belongs to the concept of spondyloarthritis (SpA) and includes two types of arthritis: a peripheral arthritis characterized by the presence of pauciarticular asymmetrical arthritis affecting preferentially joints of lower extremities and an axial arthropathy including inflammatory back pain, sacroiliitis and ankylosing spondylitis (AS). Treatment of arthritis includes a short-term use of NSAIDs associated with optimized treatment of gut inflammation. Safety concerns mean that long-term treatment with NSAIDs is best avoided if possible. Salazopyrine can be recommended for treatment of peripheral arthritis. Methotrexate and azathioprine are generally ineffective. Finally, efficacy of anti-TNF therapy (infliximab and adalimumab) is well established. However, use of etanercept is not recommended because of the increased risk for intestinal disease relapse. Pathogenesis of gut-joint iteropathy is not elucidated. Both inflammations are tightly related as suggested by human evidence of gut inflammation in patients with other forms of SpA and animal evidence of gut and joint inflammation in HLA-B27/human β2-microglobulin transgenic rat model and TNFΔARE mice. Several clues for the linkage between gut and joint inflammation have been put forward including an altered recognition and handling of bacterial antigens, an aberrant trafficking of CD8+ T cells with an impaired T-helper type 1 cytokine profile and expression of aEb7 integrin, an altered trafficking of macrophages expressing CD163 and evidence of an increased angiogenesis. A transcriptome analysis of mucosal biopsies identified a set of 95 genes that are differentially expressed in both CD and SpA as compared with healthy controls suggesting common pathways. TNF plays a key role in the pathogenesis of various arthritic diseases and IBD. Mesenchymal/myofibroblast-like cells may represent the local primary targets of TNF in the induction of gut and joint pathology. Selective expression of TNFRI on these cells seems to be sufficient to orchestrate the complete development of SpA-related pathologies at least in TNFΔARE mice. Finally, genetic susceptibility is probably required to develop these pathologies. Genotyping of AS patients provided evidence for an important overlap between determinants of inherited predisposition to CD and AS. The best documented common association is with an IL-23R polymorphism, although the exact role remains unexplored. In addition, evidence suggests that a number of recently identified CD-susceptibility loci are associated with AS. Clinical, genetical, immunological and therapeutic evidence support the tight junction between gut and joint inflammation in two linked diseases, IBD and SpA, belonging to the ‘immune-mediated inflammatory diseases’.