bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping wildlife: integrating stakeholder knowledge with modelled patterns of deer abundance by using participatory GIS
Authors: Austin Z. , Cinderby S. , Smart J. C. R. , Raffaelli D. , White P. C. L.
Published: October 2009

Context. Some species that are perceived by certain stakeholders as a valuable resource can also cause ecological or economic damage, leading to contrasting management objectives and subsequent conflict between stakeholder groups. There is increasing recognition that the integration of stakeholder knowledge with formal scientific data can enhance the information available for use in management. This is especially true where scientific understanding is incomplete, as is frequently the case for wide-ranging species, which can be difficult to monitor directly at the landscape scale.
Aims. The aim of the research was to incorporate stakeholder knowledge with data derived from formal quantitative models to modify predictions of wildlife distribution and abundance, using wild deer in the UK as an example.
Methods. We use selected predictor variables from a deer–vehicle collision model to estimate deer densities at the 10-km square level throughout the East of England. With these predictions as a baseline, we illustrate the use of participatory GIS as a methodological framework for enabling stakeholder participation in the refinement of landscape-scale deer abundance maps.
Key results. Stakeholder participation resulted in modifications to modelled abundance patterns for all wild deer species present in the East of England, although the modifications were minor and there was a high degree of consistency among stakeholders in the adjustments made. For muntjac, roe and fallow deer, the majority of stakeholder changes represented an increase in density, suggesting that populations of these species are increasing in the region.
Conclusions. Our results show that participatory GIS is a useful technique for enabling stakeholders to contribute to incomplete scientific knowledge, especially where up-to-date species distribution and abundance data are needed to inform wildlife research and management.
Implications. The results of the present study will serve as a valuable information base for future research on deer management in the region. The flexibility of the approach makes it applicable to a range of species at different spatial scales and other wildlife conflict issues. These may include the management of invasive species or the conservation of threatened species, where accurate spatial data and enhanced community involvement are necessary in order to facilitate effective management.
Domestic goat grazing disturbance enhances tree seed removal and caching by small rodents in a warm-temperate deciduous forest in China
Authors: Zhang Hongmao , Wang Yu , Zhang Zhibin
Published: October 2009

Context. Grazing by large herbivores may have a considerable influence on ground vegetation as well as on the species composition and abundance of granivors (e.g. small rodents) and this may affect forest regeneration. Very few studies have focussed on the effects of herbivore disturbance on forest regeneration by looking at the modified seed-hoarding behaviour of small rodents.
Aims. To test the indirect effects that grazing disturbance by domestic animals has on seed dispersal through the modified seed-hoarding behaviour of small rodents.
Methods. We looked at the differences in seed removal and caching of Liaodong oak (Quercus liaotungensis) by small rodents between a plot that was grazed and a plot that was ungrazed by domestic goats in a warm-temperate forest in northern China in 2006 (a non-mast-seeding year) and 2008 (a mast-seeding year).
Key results. Seed removal and caching by small rodents were significantly higher in the grazed plots, especially in the mast-seeding year (2008). Significantly more seeds were buried in soil during the mast-seeding year (2008) compared with the non-mast-seeding year (2006).
Conclusions. Grazing-induced disturbance might stimulate hoarding efforts by seed-caching rodents. Mast seeding benefits seed survival and forest regeneration.
Implications. The presence of large herbivores is likely to benefit early seed dispersal in forests by increasing the hoarding activities of rodents.
Basic mechanism for abrupt monsoon transitions
Authors: Levermann Anders , Schewe Jacob , Petoukhov Vladimir , Held Hermann
Published: October 2009

Monsoon systems influence the livelihood of hundreds of millions of people. During the Holocene and last glacial period, rainfall in India and China has undergone strong and abrupt changes. Though details of monsoon circulations are complicated, observations reveal a defining moisture-advection feedback that dominates the seasonal heat balance and might act as an internal amplifier, leading to abrupt changes in response to relatively weak external perturbations. Here we present a minimal conceptual model capturing this positive feedback. The basic equations, motivated by observed relations, yield a threshold behavior, robust with respect to addition of other physical processes. Below this threshold in net radiative influx,
R

c

, no conventional monsoon can develop; above
R

c

, two stable regimes exist. We identify a nondimensional parameter
l
that defines the threshold and makes monsoon systems comparable with respect to the character of their abrupt transition. This dynamic similitude may be helpful in understanding past and future variations in monsoon circulation. Within the restrictions of the model, we compute
R

c

for current monsoon systems in India, China, the Bay of Bengal, West Africa, North America, and Australia, where moisture advection is the main driver of the circulation.
Sexual dimorphism and directional sexual selection on aposematic signals in a poison frog
Authors: Maan Martine E. , Cummings Molly E.
Published: October 2009

It is commonly assumed that natural selection imposed by predators is the prevailing force driving the evolution of aposematic traits. Here, we demonstrate that aposematic signals are shaped by sexual selection as well. We evaluated sexual selection for coloration brightness in populations of the poison frog
Oophaga [Dendrobates] pumilio
in Panama's Bocas del Toro archipelago. We assessed female preferences for brighter males by manipulating the perceived brightness of spectrally matched males in two-way choice experiments. We found strong female preferences for bright males in two island populations and weaker or ambiguous preferences in females from mainland populations. Spectral reflectance measurements, coupled with an
O. pumilio
-specific visual processing model, showed that
O. pumilio
coloration was significantly brighter in island than in mainland morphs. In one of the island populations (Isla Solarte), males were significantly more brightly colored than females. Taken together, these results provide evidence for directional sexual selection on aposematic coloration and document sexual dimorphism in vertebrate warning coloration. Although aposematic signals have long been upheld as exemplars of natural selection, our results show that sexual selection should not be ignored in studies of aposematic evolution.
A theory for the evolution of other-regard integrating proximate and ultimate perspectives
Authors: Akçay Erol , Van Cleve Jeremy , Feldman Marcus W. , Roughgarden Joan
Published: October 2009

Although much previous work describes evolutionary mechanisms that promote or stabilize different social behaviors, we still have little understanding of the factors that drive animal behavior proximately. Here we present a modeling approach to answer this question. Our model rests on motivations to achieve objectives as the proximate determinants of behavior. We develop a two-tiered framework by first modeling the dynamics of a social interaction at the behavioral time scale and then find the evolutionarily stable objectives that result from the outcomes these dynamics produce. We use this framework to ask whether “other-regarding” motivations, which result from a kind of nonselfish objective, can evolve when individuals are engaged in a social interaction that entails a conflict between their material payoffs. We find that, at the evolutionarily stable state, individuals can be other-regarding in that they are motivated to increase their partners' payoff as well as their own. In contrast to previous theories, we find that such motivations can evolve because of their direct effect on fitness and do not require kin selection or a special group structure. We also derive general conditions for the evolutionary stability of other-regarding motivations. Our conditions indicate that other-regarding motivations are more likely to evolve when social interactions and behavioral objectives are both synergistic.
The dynamics of adaptation on correlated fitness landscapes
Authors: Kryazhimskiy Sergey , Tkačik Gašper , Plotkin Joshua B.
Published: October 2009

Evolutionary theory predicts that a population in a new environment will accumulate adaptive substitutions, but precisely how they accumulate is poorly understood. The dynamics of adaptation depend on the underlying fitness landscape. Virtually nothing is known about fitness landscapes in nature, and few methods allow us to infer the landscape from empirical data. With a view toward this inference problem, we have developed a theory that, in the weak-mutation limit, predicts how a population's mean fitness and the number of accumulated substitutions are expected to increase over time, depending on the underlying fitness landscape. We find that fitness and substitution trajectories depend not on the full distribution of fitness effects of available mutations but rather on the expected fixation probability and the expected fitness increment of mutations. We introduce a scheme that classifies landscapes in terms of the qualitative evolutionary dynamics they produce. We show that linear substitution trajectories, long considered the hallmark of neutral evolution, can arise even when mutations are strongly selected. Our results provide a basis for understanding the dynamics of adaptation and for inferring properties of an organism's fitness landscape from temporal data. Applying these methods to data from a long-term experiment, we infer the sign and strength of epistasis among beneficial mutations in the
Escherichia coli
genome.
Numbering the hairs on our heads: The shared challenge and promise of phenomics
Authors: Houle David
Published: October 2009

Evolution and medicine share a dependence on the genotype–phenotype map. Although genotypes exist and are inherited in a discrete space convenient for many sorts of analyses, the causation of key phenomena such as natural selection and disease takes place in a continuous phenotype space whose relationship to the genotype space is only dimly grasped. Direct study of genotypes with minimal reference to phenotypes is clearly insufficient to elucidate these phenomena. Phenomics, the comprehensive study of phenotypes, is therefore essential to understanding biology. For all of the advances in knowledge that a genomic approach to biology has brought, awareness is growing that many phenotypes are highly polygenic and susceptible to genetic interactions. Prime examples are common human diseases. Phenomic thinking is starting to take hold and yield results that reveal why it is so critical. The dimensionality of phenotypic data are often extremely high, suggesting that attempts to characterize phenotypes with a few key measurements are unlikely to be completely successful. However, once phenotypic data are obtained, causation can turn out to be unexpectedly simple. Phenotypic data can be informative about the past history of selection and unexpectedly predictive of long-term evolution. Comprehensive efforts to increase the throughput and range of phenotyping are an urgent priority.
Natural selection in a contemporary human population
Authors: Byars Sean G. , Ewbank Douglas , Govindaraju Diddahally R. , Stearns Stephen C.
Published: October 2009

Our aims were to demonstrate that natural selection is operating on contemporary humans, predict future evolutionary change for specific traits with medical significance, and show that for some traits we can make short-term predictions about our future evolution. To do so, we measured the strength of selection, estimated genetic variation and covariation, and predicted the response to selection for women in the Framingham Heart Study, a project of the National Heart, Lung, and Blood Institute and Boston University that began in 1948. We found that natural selection is acting to cause slow, gradual evolutionary change. The descendants of these women are predicted to be on average slightly shorter and stouter, to have lower total cholesterol levels and systolic blood pressure, to have their first child earlier, and to reach menopause later than they would in the absence of evolution. Selection is tending to lengthen the reproductive period at both ends. To better understand and predict such changes, the design of planned large, long-term, multicohort studies should include input from evolutionary biologists.
LACTB is a filament-forming protein localized in mitochondria
Authors: Polianskyte Zydrune , Peitsaro Nina , Dapkunas Arvydas , Liobikas Julius , Soliymani Rabah , Lalowski Maciej , Speer Oliver , Seitsonen Jani , Butcher Sarah , Cereghetti Grazia M. , Linder Matts D. , Merckel Michael , Thompson James , Eriksson Ove
Published: October 2009

LACTB is a mammalian active-site serine protein that has evolved from a bacterial penicillin-binding protein. Penicillin-binding proteins are involved in the metabolism of peptidoglycan, the major bacterial cell wall constituent, implying that LACTB has been endowed with novel biochemical properties during eukaryote evolution. Here we demonstrate that LACTB is localized in the mitochondrial intermembrane space, where it is polymerized into stable filaments with a length extending more than a hundred nanometers. We infer that LACTB, through polymerization, promotes intramitochondrial membrane organization and micro-compartmentalization. These findings have implications for our understanding of mitochondrial evolution and function.
Interdependence of movement and anatomy persists when amputees learn a physiologically impossible movement of their phantom limb
Authors: Moseley G. Lorimer , Brugger P.
Published: October 2009

The feeling we have of our own body, sometimes called “body image,” is fundamental to self-awareness. However, by altering sensory input, the body image can be modified into impossible configurations. Can impossible movements of the body image be conjured solely via internally generated mechanisms, and, if so, do the structural characteristics of the body image modify to accommodate the new movements? We encouraged seven amputees with a vivid phantom arm to learn to perform a phantom wrist movement that defied normal anatomical constraints. Four reported success. Learning the impossible movement coincided in time with a profound change in the body image of the arm, including a sense of ownership and agency over a modified wrist joint. Remarkably, some previous movements and functional tasks involving the phantom arm became more difficult once the shift in body image had occurred. Crucially, these introspective reports were corroborated by robust empirical data from motor imagery tasks, about which amputees were naïve and to which assessors were blind. These results provide evidence that: a completely novel body image can be constructed solely by internally generated mechanisms; that the interdependence between movement repertoire and structural constraints of the body persists even when the structural constraints imparted by the body do not—the body image we construct still constrains imagined movements; and that motor learning does not necessarily need sensory feedback from the body or external feedback about task performance.
Cultural evolution and individual development of openness and conservatism
Authors: Acerbi Alberto , Enquist Magnus , Ghirlanda Stefano
Published: October 2009

We present a model of cultural evolution in which an individual's propensity to engage in social learning is affected by social learning itself. We assume that individuals observe cultural traits displayed by others and decide whether to copy them based on their overall preference for the displayed traits. Preferences, too, can be transmitted between individuals. Our results show that such cultural dynamics tends to produce conservative individuals, i.e., individuals who are reluctant to copy new traits. Openness to new information, however, can be maintained when individuals need significant time to acquire the cultural traits that make them effective cultural models. We show that a gradual enculturation of young individuals by many models and a larger cultural repertoire to be acquired are favorable circumstances for the long-term maintenance of openness in individuals and groups. Our results agree with data about lifetime personality change, showing that openness to new information decreases with age. Our results show that cultural remodeling of cultural transmission is a powerful force in cultural evolution, i.e., that cultural evolution can change its own dynamics.
Message-passing algorithms for compressed sensing
Authors: Donoho David L. , Maleki Arian , Montanari Andrea
Published: October 2009

Compressed sensing aims to undersample certain high-dimensional signals yet accurately reconstruct them by exploiting signal characteristics. Accurate reconstruction is possible when the object to be recovered is sufficiently sparse in a known basis. Currently, the best known sparsity–undersampling tradeoff is achieved when reconstructing by convex optimization, which is expensive in important large-scale applications. Fast iterative thresholding algorithms have been intensively studied as alternatives to convex optimization for large-scale problems. Unfortunately known fast algorithms offer substantially worse sparsity–undersampling tradeoffs than convex optimization. We introduce a simple costless modification to iterative thresholding making the sparsity–undersampling tradeoff of the new algorithms equivalent to that of the corresponding convex optimization procedures. The new iterative-thresholding algorithms are inspired by belief propagation in graphical models. Our empirical measurements of the sparsity–undersampling tradeoff for the new algorithms agree with theoretical calculations. We show that a state evolution formalism correctly derives the true sparsity–undersampling tradeoff. There is a surprising agreement between earlier calculations based on random convex polytopes and this apparently very different theoretical formalism.
A sequence-compatible amount of native burial information is sufficient for determining the structure of small globular proteins
Authors: Pereira de Araujo Antonio F. , Onuchic José N.
Published: October 2009

Protein tertiary structures are known to be encoded in amino acid sequences, but the problem of structure prediction from sequence continues to be a challenge. With this question in mind, recent simulations have shown that atomic burials, as expressed by atom distances to the molecular geometrical center, are sufficiently informative for determining native conformations of small globular proteins. Here we use a simple computational experiment to estimate the amount of this required burial information and find it to be surprisingly small, actually comparable with the stringent limit imposed by sequence statistics. Atomic burials appear to satisfy, therefore, minimal requirements for a putative dominating property in the folding code because they provide an amount of information sufficiently large for structural determination but, at the same time, sufficiently small to be encodable in sequences. In a simple analogy with human communication, atomic burials could correspond to the actual “language” encoded in the amino acid “script” from which the complexity of native conformations is recovered during the folding process.
MCL-1–dependent leukemia cells are more sensitive to chemotherapy than BCL-2–dependent counterparts
Authors: Brunelle Joslyn K. , Ryan Jeremy , Yecies Derek , Opferman Joseph T. , Letai Anthony
Published: October 2009

Myeloid cell leukemia sequence 1 (MCL-1) and B cell leukemia/lymphoma 2 (BCL-2) are anti-apoptotic proteins in the BCL-2 protein family often expressed in cancer. To compare the function of MCL-1 and BCL-2 in maintaining cancer survival, we constructed complementary mouse leukemia models based on Eμ-Myc expression in which either BCL-2 or MCL-1 are required for leukemia maintenance. We show that the principal anti-apoptotic mechanism of both BCL-2 and MCL-1 in these leukemias is to sequester pro-death BH3-only proteins rather than BAX and BAK. We find that the MCL-1–dependent leukemias are more sensitive to a wide range of chemotherapeutic agents acting by disparate mechanisms. In common across these varied treatments is that MCL-1 protein levels rapidly decrease in a proteosome-dependent fashion, whereas those of BCL-2 are stable. We demonstrate for the first time that two anti-apoptotic proteins can enable tumorigenesis equally well, but nonetheless differ in their influence on chemosensitivity.
Identity of the elusive IgM Fc receptor (FcμR) in humans
Authors: Kubagawa Hiromi , Oka Satoshi , Kubagawa Yoshiki , Torii Ikuko , Takayama Eiji , Kang Dong-Won , Gartland G. Larry , Bertoli Luigi F. , Mori Hiromi , Takatsu Hiroyuki , Kitamura Toshio , Ohno Hiroshi , Wang Ji-Yang
Published: October 2009

Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been extensively characterized, FcR for IgM (FcμR) has defied identification. By retroviral expression and functional cloning, we have identified a complementary DNA (cDNA) encoding a bona fide FcμR in human B-lineage cDNA libraries. FcμR is defined as a transmembrane sialoglycoprotein of ∼60 kD, which contains an extracellular Ig-like domain homologous to two other IgM-binding receptors (polymeric Ig receptor and Fcα/μR) but exhibits an exclusive Fcμ-binding specificity. The cytoplasmic tail of FcμR contains conserved Ser and Tyr residues, but none of the Tyr residues match the immunoreceptor tyrosine-based activation, inhibitory, or switch motifs. Unlike other FcRs, the major cell types expressing FcμR are adaptive immune cells, including B and T lymphocytes. After antigen-receptor ligation or phorbol myristate acetate stimulation, FcμR expression was up-regulated on B cells but was down-modulated on T cells, suggesting differential regulation of FcμR expression during B and T cell activation. Although this receptor was initially designated as Fas apoptotic inhibitory molecule 3, or TOSO, our results indicate that FcμR per se has no inhibitory activity in Fas-mediated apoptosis and that such inhibition is only achieved when anti-Fas antibody of an IgM but not IgG isotype is used for inducing apoptosis.
A Successful Mandatory Influenza Vaccination Campaign Using an Innovative Electronic Tracking System
Authors: Palmore Tara N. , Vandersluis J. Patrick , Morris Joan , Michelin Angela , Ruprecht Lisa M. , Schmitt James M. , Henderson David K.
Published: October 2009

Background.

Although influenza vaccination of healthcare workers reduces influenza-like illness and overall mortality among patients, national rates of vaccination for healthcare providers are unacceptably low. We report the implementation of a new mandatory vaccination policy by means of a streamlined electronic enrollment and vaccination tracking system at the National Institutes of Health (NIH) Clinical Center.

Objective.

To evaluate the outcome of a new mandatory staff influenza vaccination program.

Methods.

A new hospital policy endorsed by all the component NIH institutes and the Clinical Center departments mandated that employees who have patient contact either be vaccinated annually against influenza or sign a declination specifying the reason(s) for refusal. Those who fail to comply would be required to appear before the Medical Executive Committee to explain their rationale. We collected in a database the names of all physician and nonphysician staff who had patient contact. When a staff member either was vaccinated or declined vaccination, a simple system of badge scanning and bar-coded data entry captured essential data. The database was continuously updated, and it provided a list of noncompliant employees with whom to follow up.

Results.

By February 12, 2009, all 2,754 identified patient-care employees either were vaccinated or formally declined vaccination. Among those, 2,424 (88%) were vaccinated either at the NIH or elsewhere, 36 (1.3%) reported medical contraindications, and 294 (10.7%) declined vaccination for other reasons. Among the 294 employees without medical contraindications who declined, the most frequent reason given for declination was concern about side effects.

Conclusions.

Implementation of a novel vaccination tracking process and a hospital policy requiring influenza vaccination or declination yielded dramatic improvement in healthcare worker vaccination rates and likely will result in increased patient safety in our hospital.
Epidemiology and Impact of Imipenem Resistance in Acinetobacter baumannii
Authors: Lautenbach Ebbing , Synnestvedt Marie , Weiner Mark G. , Bilker Warren B. , Vo Lien , Schein Jeff , Kim Myoung
Published: October 2009

Background.

Acinetobacter baumannii is an emerging gram-negative pathogen that can cause healthcare-acquired infections among patients. Treatment is complicated for cases of healthcare-acquired infection with A. baumannii resistant to imipenem.

Objective.

To elucidate the risk factors for imipenem-resistant A. baumannii (IRAB) infection or colonization and to identify the effect of resistance on clinical and economic outcomes.

Methods.

We analyzed data from 2 medical centers of the University of Pennsylvania. Longitudinal trends in the prevalence of IRAB clinical isolates were characterized during the period from 1989 through 2004. For A. baumannii isolates obtained from 2001 through 2006, a case-control study was conducted to investigate the association between prior carbapenem use and IRAB infection or colonization, and a cohort study was performed to identify the effect of IRAB infection or colonization on mortality, length of stay after culture, and hospital cost after culture.

Results.

From 1989 through 2004, the annual prevalence of IRAB isolates ranged from 0% to 21%. During the period from 2001 through 2006, there were 386 unique patients with A. baumannii isolates, and 89 (23.1%) had IRAB isolates. Prior carbapenem use was independently associated with IRAB infection or colonization (adjusted odds ratio, 3.04 [95% confidence interval, 1.07–8.65]). There was a borderline significant association between IRAB infection or colonization and mortality, although this association was limited to isolates recovered from blood samples (adjusted odds ratio, 5.30 [95% confidence interval, 0.81–34.59]). Compared with patients with imipenem-susceptible A. baumannii infection or colonization, patients with IRAB infection or colonization had a longer hospital stay after culture (median, 21 vs 16 days; P = .07) and greater hospital charges after culture (mean, $334,516 vs $276,059; P = .03). After controlling for patient location in an intensive care unit, transfer from another facility, and length of hospital stay before culture, there was no longer an independent association between IRAB infection or colonization and higher cost after culture and length of stay after positive culture result.

Conclusions.

Many A. baumannii isolates exhibit imipenem resistance, which is strongly associated with prior use of carbapenems. Given the high mortality rate associated with A. baumannii infection or colonization, interventions to curb further emergence of cases of IRAB infection and strategies to optimize therapy are needed.
Impact of Hurricane Ike on Texas Poison Center Calls
Authors: Forrester Mathias B.
Published: October 2009

On September 13, 2008, Hurricane Ike made landfall in Texas, resulting in the mandatory evacuation of 8 counties before landfall and the declaration of disaster areas in 29 counties afterward. This study evaluated whether Hurricane Ike affected the pattern of Texas poison center calls. Texas poison center calls received from the disaster area counties were identified for 3 time periods: August 12 to September 10, 2008 (preevacuation), September 11 to 13, 2008 (evacuation and hurricane landfall), and September 14 to 30, 2008 (postevacuation). For selected types of calls, the mean daily call volume during time periods 2 and 3 was compared with a baseline range (BR) derived from the mean daily call volume during time period 1. During the evacuation and landfall period, gasoline exposure calls were higher than expected (mean 3, BR −1 to 2). During the postevacuation period, higher than expected numbers of calls were observed for gasoline exposures (mean 5, BR −1 to 2) and carbon monoxide exposures (mean 3, BR –1–1). During an evacuation, certain calls such as those involving gasoline exposures may increase. After a hurricane, calls such as those involving carbon monoxide and gasoline exposures may increase. (Disaster Med Public Health Preparedness. 2009;3:151–157)
Correction for Braendle
et al.
, Genetic variation for an aphid wing polyphenism is genetically linked to a naturally occurring wing polymorphism
Authors: Braendle Christian , Friebe Ilvy , Caillaud Marina C. , Stern David L.
Published: October 2009

Correction for ‘Genetic variation for an aphid wing polyphenism is genetically linked to a naturally occurring wing polymorphism’ by Christian Braendle, Ilvy Friebe, Marina C. Caillaud and David L. Stern (Proc. R. Soc. B
272
, 657–664.
(doi:
10.1098/rspb.2004.2995
)).

Figure 2 in the print version of this paper is incorrect; the correct figure is as follows.
Genome-wide mapping of alternative splicing in Arabidopsis thaliana
Authors: Filichkin Sergei A. , Priest Henry D. , Givan Scott A. , Shen Rongkun , Bryant Douglas W. , Fox Samuel E. , Wong Weng-Keen , Mockler Todd C.
Published: October 2009

Alternative splicing can enhance transcriptome plasticity and proteome diversity. In plants, alternative splicing can be manifested at different developmental stages, and is frequently associated with specific tissue types or environmental conditions such as abiotic stress. We mapped the Arabidopsis transcriptome at single-base resolution using the Illumina platform for ultrahigh-throughput RNA sequencing (RNA-seq). Deep transcriptome sequencing confirmed a majority of annotated introns and identified thousands of novel alternatively spliced mRNA isoforms. Our analysis suggests that at least ∼42% of intron-containing genes in Arabidopsis are alternatively spliced; this is significantly higher than previous estimates based on cDNA/expressed sequence tag sequencing. Random validation confirmed that novel splice isoforms empirically predicted by RNA-seq can be detected in vivo. Novel introns detected by RNA-seq were substantially enriched in nonconsensus terminal dinucleotide splice signals. Alternative isoforms with premature termination codons (PTCs) comprised the majority of alternatively spliced transcripts. Using an example of an essential circadian clock gene, we show that intron retention can generate relatively abundant PTC+ isoforms and that this specific event is highly conserved among diverse plant species. Alternatively spliced PTC+ isoforms can be potentially targeted for degradation by the nonsense mediated mRNA decay (NMD) surveillance machinery or regulate the level of functional transcripts by the mechanism of regulated unproductive splicing and translation (RUST). We demonstrate that the relative ratios of the PTC+ and reference isoforms for several key regulatory genes can be considerably shifted under abiotic stress treatments. Taken together, our results suggest that like in animals, NMD and RUST may be widespread in plants and may play important roles in regulating gene expression.
Detection of nonneutral substitution rates on mammalian phylogenies
Authors: Pollard Katherine S. , Hubisz Melissa J. , Rosenbloom Kate R. , Siepel Adam
Published: October 2009

Methods for detecting nucleotide substitution rates that are faster or slower than expected under neutral drift are widely used to identify candidate functional elements in genomic sequences. However, most existing methods consider either reductions (conservation) or increases (acceleration) in rate but not both, or assume that selection acts uniformly across the branches of a phylogeny. Here we examine the more general problem of detecting departures from the neutral rate of substitution in either direction, possibly in a clade-specific manner. We consider four statistical, phylogenetic tests for addressing this problem: a likelihood ratio test, a score test, a test based on exact distributions of numbers of substitutions, and the genomic evolutionary rate profiling (GERP) test. All four tests have been implemented in a freely available program called phyloP. Based on extensive simulation experiments, these tests are remarkably similar in statistical power. With 36 mammalian species, they all appear to be capable of fairly good sensitivity with low false-positive rates in detecting strong selection at individual nucleotides, moderate selection in 3-bp elements, and weaker or clade-specific selection in longer elements. By applying phyloP to mammalian multiple alignments from the ENCODE project, we shed light on patterns of conservation/acceleration in known and predicted functional elements, approximate fractions of sites subject to constraint, and differences in clade-specific selection in the primate and glires clades. We also describe new “Conservation” tracks in the UCSC Genome Browser that display both phyloP and phastCons scores for genome-wide alignments of 44 vertebrate species.
Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo
Authors: Bai Yu , Mao Qi‐Qi , Qin Jie , Zheng Xiang‐Yi , Wang Yun‐Bin , Yang Kai , Shen Hua‐Feng , Xie Li‐Ping
Published: October 2009

Resveratrol, a naturally occurring polyphenolic antioxidant compound present in grapes and red wine, has been reported to hold various biochemical responses. In this preliminary study, we evaluate the chemopreventive potential of resveratrol against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with resveratrol resulted in a significant decrease in cell viability. Resveratrol induced apoptosis through the modulation of Bcl‐2 family proteins and activation of caspase 9 and caspase 3 followed by poly(ADP‐ribose) polymerase degradation. Treatment with resveratrol led to G1 phase cell cycle arrest in T24 cells by activation of p21 and downregulation of cyclin D1, cyclin‐dependent kinase 4, and phosphorylated Rb. Resveratrol also inhibited the phosphorylation of Akt, whereas the phosphorylation of p38 MAPK was enhanced. In addition, resveratrol treatment decreased the expression of vascular endothelial growth factor and fibroblast growth factor‐2, which might contribute to the inhibition of tumor growth on the bladder cancer xenograft model. These findings suggest that reveratrol could be an important chemoprevention agent for bladder cancer. (Cancer Sci 2009)
Effect of siRNA‐mediated silencing of Bmi‐1 gene expression on HeLa cells
Authors: Jiang Yue , Su Benli , Meng Xiuxiang , Liu Chunqing , Liu Ben , Liu Dandan , Fan Ying , Yang Hong
Published: October 2009

B‐cell‐specific Moloney murine leukemia virus insertion site 1 (Bmi‐1) is highly expressed in several malignant tumors and its expression level is positively correlated with tumor invasion, distant metastasis, prognosis, and recurrence. In the present study, the biological effect of small interfering RNA (siRNA) that targeted Bmi‐1 expression was studied in human cervical carcinoma cell line HeLa cells. Bmi‐1 siRNA inhibited the expression of Bmi‐1 at the mRNA and protein levels in HeLa cells, which significantly affected proliferation, colony formation, and migration of HeLa cells in vitro and in vivo. Therefore, silencing Bmi‐1 may be a potential therapeutic option for the management of some human cancers. (Cancer Sci 2009)
Exaggerated adrenarche in a cohort of Scottish children: clinical features and biochemistry
Authors: Paterson W. F. , Ahmed S. F. , Bath L. , Donaldson M. D. C. , Fleming R. , Greene S. A. , Hunter I. , Kelnar C. J. H. , Mayo A. , Schulga J. S. , Shapiro D. , Smail P. J. , Wallace A. M.
Published: October 2009

Objective  To investigate the reported association between exaggerated adrenarche (EA) and reduced foetal growth and to identify possible risk factors for future morbidity in Scottish children with clinical features of EA.

Design  Three‐year prospective study.

Measurements  Auxology, blood pressure (BP), biochemical analysis of blood and urine, pelvic ultrasound in girls.

Results  Fifty‐two patients were recruited of whom one girl had nonclassical congenital adrenal hyperplasia (17‐OHP 17 nmol/l) and one had insufficient blood for analysis. The final cohort comprised 42 girls of mean (SD) age 7·7 (0·99) and eight boys of 8·8 (0·67) years. Mean (SD) birth weight was 3·27 (0·49) and 3·10 (0·76) kg in girls and boys respectively. Height/weight SDS were 1·13/1·69 in girls and 1·69/1·88 in boys. Mean systolic/diastolic BP was 107·8/60·4 (50th–75th centile) in girls and 115·5/63·9 (75th–91st centile) in boys. Uterine and ovarian development was prepubertal. Median serum dehydroepiandrosterone sulphate (DHEAS) was 2·1 and 4·1 μmol/l, androstenedione 3·1 and 3·8 nmol/l in girls and boys respectively, with DHEAS within the reference range/undetectable in 18/2 and androstenedione in 12/6 patients. Fasting insulin was 9·0 and 15·0 mU/l in girls and boys respectively, with concomitant low normal SHBG. Anti‐Mullerian hormone (AMH) was 15·7 pmol/l in 27 girls, compared with 5·0 pmol/l in normal girls aged 5–8 years.

Conclusions  Our Scottish EA cohort showed female predominance, no evidence of reduced foetal growth, a tendency to overweight with commensurate mild hyperinsulinaemia and modest elevation of serum androgens in some patients. We have found raised AMH levels in the girls, indicating advanced ovarian follicular development.
Utility of liquid‐based cytology in endometrial pathology: diagnosis of endometrial carcinoma
Authors: Norimatsu Y. , Kouda H. , Kobayashi T. K. , Shimizu K. , Yanoh K. , Tsukayama C. , Miyake Y. , Ohno E.
Published: October 2009

Objective:  The purpose of this study was to examine the utility of SurePath‐liquid‐based cytology (LBC) compared to conventional cytological preparations (CCP) in the identification of endometrial carcinoma.

Methods:  During a 13‐month period, direct endometrial samples were collected from 120 patients using the Uterobrush. The material comprised 30 cases each of endometrial carcinoma, proliferative endometrium, secretory endometrium and atrophic endometrium. The following points were investigated:(i) the frequency of cell clumps in endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei.

Results:  (i) Comparison of the frequency of cell clumps with irregular protrusion pattern and papillo‐tubular pattern showed no statistically significant difference in either type of cell clump between CCP and LBC. (ii) Comparison of the nuclear area of cells showed a sequential decrease from endometrial carcinoma to secretory endometrium, to proliferative endometrium and to atrophic endometrium, which was significant in CCP and LBC. (iii) Nuclear area was significantly lower with LBC compared with CCP in endometrial carcinoma, secretory endometrium and proliferative endometrium but not atrophic endometrium. (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease from endometrial carcinoma to proliferative endometrium, to secretory endometrium and to atrophic endometrium, which was significant in both CCP and LBC. (v) Comparison of the degree of overlapping nuclei between CCP and LBC showed no significant difference for normal types of endometrium, but LBC had significantly higher values (P < 0.0001) in endometrial carcinoma than in CCP.

Conclusions:  The results of this study revealed that applying diagnostic criteria used in CCP to LBC was easy to achieve, because LBC had excellent cytoarchitectural preservation and cells were well presented. Although we have not examined all cytological features of malignancy and have not considered atypical hyperplasia, we believe that this method may be a useful tool in the diagnosis of endometrial cytology.
Extraction and identification of anthocyanin from purple corn (Zea mays L.)
Authors: Yang Zhendong , Chen Zhijie , Yuan Shulin , Zhai Weiwei , Piao Xiangshu , Piao Xianglan
Published: October 2009

An efficient extraction of anthocyanin from purple corn (Zea mays L.) was investigated in this paper. Tristimulus colourimetry was used to evaluate the process quantitatively and qualitatively. Purple corn anthocyanin was extracted with 1 n HCl–95% ethanol (15:85, v/v) at different extraction temperatures (30–70 °C), times (60–120 min) and solid–liquid ratio (1:20–1:40). The combined effects of extraction conditions on anthocyanin yield and colour attributes were studied using a three‐level three‐factor Box–Behnken design. The results showed that the highest yield of anthocyanin from purple corn (6.02 mg g−1) were obtained at 70 °C, extraction time 73 min, and solid–liquid ratio 1:25. Three kinds of non‐acylated anthocyanins were detected and characterised as cyanidin‐3‐glucoside, pelargonidin‐3‐glucoside and peonidin‐3‐glucoside by HPLC‐MS.
Polyphenols: food sources, properties and applications – a review
Authors: El Gharras Hasna
Published: October 2009

There is currently much interest in phytochemicals as bioactive compounds of food. The roles of fruit, vegetables and red wine in disease prevention have been attributed, in part, to the antioxidant properties of their constituent polyphenols (vitamins E and C, and the carotenoids). Recent studies have shown that many dietary polyphenolic constituents derived from plants are more effective antioxidants in vitro than vitamins E or C, and thus might contribute significantly to the protective effects in vivo. Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Dietary polyphenols show a great diversity of structures, ranging from rather simple molecules (monomers and oligomers) to polymers. Higher‐molecular‐weight structures (with molecular weights of ∼500) are usually designated as tannins, which refers to their ability to interact with proteins. Among them, condensed tannins (proanthocyanidins) are particularly important because of their wide distribution in plants and their contributions to major food qualities. This paper focuses on polyphenols; we illustrate their sources from food, properties and their beneficial uses.
Trial‐generated profiles for implantation of electrical devices in outpatients with heart failure: real‐world prevalence and 1‐year outcome
Authors: Boriani Giuseppe , Rapezzi Claudio , Diemberger Igor , Gonzini Lucio , Gorini Marco , Lucci Donata , Sinagra Gianfranco , Cooke Robin M. T. , Di Pasquale Giuseppe , Tavazzi Luigi , Maggioni Aldo P.
Published: October 2009

Background  Randomized controlled trials have generated strong evidence on the efficacy of electrical device therapy in selected patients with heart failure (HF). The enrolment criteria of these three trials generated patient profiles that helped to shape current guidelines on chronic heart failure (CHF) treatment and sudden cardiac death (SCD) prevention. We investigated the prevalence of trial‐generated profiles for implantable defibrillator or cardiac resynchronization therapy candidacy among HF outpatients; we explored differences between real‐world and trial populations and we evaluated 1‐year survival without device treatment.

Methods  We reviewed Italian Network on Congestive Heart Failure (IN‐CHF) registry patients (n = 4977) enrolled in a period (1995–2000) roughly concurrent with the MADIT‐II and SCD‐HeFT trials.

Results  Regarding device eligibility, 14.5% IN‐CHF patients at entry satisfied MADIT‐II criteria, 6.8% satisfied CARE‐HF criteria and as many as 47.9% fulfilled SCD‐HeFT criteria. One‐year overall mortality among non‐implanted patients was 1.5 to 2‐fold higher in each of these subgroups than in control arms of the corresponding trials. Among registry patients, different trial‐profile combinations were associated with a wide range of 1‐year outcomes (mortality, 8–35%; SCD/total mortality ratio, 0.35–0.57). Despite clear differences between registry and trial patients in pharmacological therapy (and clinical characteristics), none of the main drug classes independently predicted 1‐year mortality in any of the IN‐CHF subgroups.

Conclusions  As many as half the IN‐CHF outpatients fulfilled current criteria for device implantation. Various subgroups had higher 1‐year mortality than patients in trial control arms – a finding that may not be entirely attributable to differences in drug therapy (especially beta blockers).
Four‐dimensional telomere analysis in recordings of living human cells acquired with Controlled Light Exposure Microscopy
Authors: DE VOS W.H. , JOSS G.H. , HAFFMANS W. , HOEBE R.A. , MANDERS E.M.M. , VAN OOSTVELDT P.
Published: October 2009

Telomeres are the complex end structures that confer functional integrity and positional stability to human chromosomes. Telomere research has long been dominated by length measurements and biochemical analyses. Recently, interest has shifted towards the role of their three‐dimensional organization and dynamics within the nuclear volume. In the mammalian interphase nucleus, there is increasing evidence for a telomeric configuration that is non‐random and is cell cycle and cell type dependent. This has functional implications for genome stability. Objective and reproducible representation of the spatiotemporal organization of telomeres, under different experimental conditions, requires quantification by reliable automated image processing techniques. In this paper, we describe methods for quantitative telomere analysis in cell nuclei of living human cells expressing telomere‐binding fusion proteins. We present a toolbox for determining telomere positions within the nucleus with subresolution accuracy and tracking telomeres in 4D controlled light exposure microscopy (CLEM) recordings. The use of CLEM allowed for durable imaging and thereby improved segmentation performance considerably. With minor modifications, the underlying algorithms can be expanded to the analysis of other intranuclear features, such as nuclear bodies or DNA double stranded break foci.