bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling yield response of a traditional and a modern barley cultivar to different water and nitrogen levels in two contrasting soil types
Authors: Abeledo L. Gabriela , Calderini Daniel F. , Slafer Gustavo A.
Published: April 2011

The importance of yield improvement at farm conditions is highly dependent on the interaction between genotype and environment. The aim of the present work was to assess the attainable yield of a traditional and a modern malting barley cultivar growing under a wide range of soil nitrogen (N) availabilities and different water scenarios (low, intermediate and high rainfall conditions during the fallow period and throughout the crop cycle) considering a 25-year climate dataset for two sites (a shallow and a deep soil) in the Pampas, Argentina. For that purpose, a barley model was first calibrated and validated and then used to expand field research information to a range of conditions that are not only much wider but also more realistic than experiments on experimental farms. Yield of the modern cultivar was at least equal to (under the lowest yielding conditions) or significantly higher (under most growing conditions) than that of the traditional cultivar. Averaged across all the scenarios, yield was ~20% higher in the modern than in the traditional cultivar. The average attainable yield represented 42% of the yield potential in the shallow and 79% in the deep soil profiles. Yield advantage of the high yielding cultivar was based on using N more efficiently, which not only determined higher attainable yields but also reduced the requirements of soil N to achieve a particular yield level. Farmers would face little risk in adopting higher yielding cultivars in both high and low yielding environments and even in the latter ones N fertilisation could be beneficial in most years.
The use of conjoint analysis to determine the relative importance of specific traits as selection criteria for the improvement of perennial pasture species in Australia
Authors: Smith K. F. , Fennessy P. F.
Published: April 2011

Despite the large number of active programs breeding improved forage plants, relatively little is known about the weightings that breeders consciously or subconsciously give to specific traits when selecting individual plants or that agronomists and producers use when assessing the relative merits of contrasting cultivars. This is in contrast to most modern animal breeding programs where the relative merits of novel genetics may be assessed against an index-based breeding objective. These technologies have not been widely used in crop or forage plant breeding but their use in forest tree breeding is relatively common. We have assessed the usefulness of discrete choice experiment techniques in the development of weightings for specific traits in forage plant improvement based on the views of an expert panel (plant breeders and non-breeders – agronomists, nutritionists, senior managers in breeding companies and consultants) asked to consider the requirements in four species (white clover, lucerne, perennial ryegrass and tall fescue). The results indicate that criteria related to abiotic stress tolerance, adaptation or the costs of pasture (root growth, drought tolerance, persistence, resistance to invertebrate pests, tolerance of hostile soil conditions) were deemed to be particularly important for white clover, while the highest-rated criteria for lucerne were not dissimilar, being tolerance of hostile soil conditions, persistence and tolerance of transient water-logging. For perennial ryegrass, three of the five highest-weighted criteria (drought tolerance, root growth, rate of recovery of pasture after water) are related to yield in environments where too much or too little water is a problem, highlighting the importance that the experts placed on the ability of the plant to withstand this important abiotic stress. For tall fescue, the highest-rated criteria were seedling vigour, drought tolerance, and persistence. Overall the preference weightings tended to reflect the perceived limitations of the various species, such as the priority of seedling vigour in tall fescue. This focus on the importance of abiotic stress is especially interesting as previous attempts to identify priorities have focused on the forage quality traits rather than analysing their importance relative to traits related to herbage yield or stress tolerance. This study highlights the importance of further work to help determine the focus of breeding objectives and selection criteria for different pasture species across production systems.
Temporal increase in organic mercury in an endangered pelagic seabird assessed by century-old museum specimens
Authors: Vo Anh-Thu E. , Bank Michael S. , Shine James P. , Edwards Scott V.
Published: April 2011

Methylmercury cycling in the Pacific Ocean has garnered significant attention in recent years, especially with regard to rising mercury emissions from Asia. Uncertainty exists concerning whether increases in anthropogenic emissions over time may have caused increased mercury bioaccumulation in the biota. To address this, we measured total mercury and, for a subset of samples, methylmercury (the bioaccumulated form of mercury) in museum feathers from an endangered seabird, the black-footed albatross (Phoebastria nigripes), spanning a 120-y period. We analyzed stable isotopes of nitrogen (δ15N) and carbon (δ13C) to control for temporal changes in trophic structure and diet. In post-1940 and -1990 feathers, we detected significantly higher mean methylmercury concentrations and higher proportions of samples exhibiting above deleterious threshold levels (∼40,000 ng·g−1) of methylmercury relative to prior time points, suggesting that mercury toxicity may undermine reproductive effort in the species. We also found higher levels of (presumably curator-mediated) inorganic mercury in older specimens of albatross as well as two nonpelagic species lacking historical exposure to bioavailable mercury, patterns suggesting that studies on bioaccumulation should measure methylmercury rather than total mercury when using museum collections. δ15N contributed substantially to models explaining the observed methylmercury variation. After simultaneously controlling for significant trends in δ13C over time and δ15N with methylmercury exposure, year remained a significant independent covariate with feather methylmercury levels among the albatrosses. These data show that remote seabird colonies in the Pacific basin exhibit temporal changes in methylmercury levels consistent with historical global and recent regional increases in anthropogenic emissions.
Mechanisms of perceptual organization provide auto-zoom and auto-localization for attention to objects
Authors: Mihalas Stefan , Dong Yi , von der Heydt Rüdiger , Niebur Ernst
Published: April 2011

Visual attention is often understood as a modulatory field acting at early stages of processing, but the mechanisms that direct and fit the field to the attended object are not known. We show that a purely spatial attention field propagating downward in the neuronal network responsible for perceptual organization will be reshaped, repositioned, and sharpened to match the object's shape and scale. Key features of the model are grouping neurons integrating local features into coherent tentative objects, excitatory feedback to the same local feature neurons that caused grouping neuron activation, and inhibition between incompatible interpretations both at the local feature level and at the object representation level.
Chemical methodology as a source of small-molecule checkpoint inhibitors and heat shock protein 70 (Hsp70) modulators
Authors: Huryn Donna M. , Brodsky Jeffrey L. , Brummond Kay M. , Chambers Peter G. , Eyer Benjamin , Ireland Alex W. , Kawasumi Masaoki , LaPorte Matthew G. , Lloyd Kayla , Manteau Baptiste , Nghiem Paul , Quade Bettina , Seguin Sandlin P. , Wipf Peter
Published: April 2011

Unique chemical methodology enables the synthesis of innovative and diverse scaffolds and chemotypes and allows access to previously unexplored “chemical space.” Compound collections based on such new synthetic methods can provide small-molecule probes of proteins and/or pathways whose functions are not fully understood. We describe the identification, characterization, and evolution of two such probes. In one example, a pathway-based screen for DNA damage checkpoint inhibitors identified a compound, MARPIN (AT
M
and
A
T
R
p
athway
in
hibitor) that sensitizes p53-deficient cells to DNA-damaging agents. Modification of the small molecule and generation of an immobilized probe were used to selectively bind putative protein target(s) responsible for the observed activity. The second example describes a focused library approach that relied on tandem multicomponent reaction methodologies to afford a series of modulators of the heat shock protein 70 (Hsp70) molecular chaperone. The synthesis of libraries based on the structure of MAL3-101 generated a collection of chemotypes, each modulating Hsp70 function, but exhibiting divergent pharmacological activities. For example, probes that compromise the replication of a disease-associated polyomavirus were identified. These projects highlight the importance of chemical methodology development as a source of small-molecule probes and as a drug discovery starting point.
Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure
Authors: Chung Amy W. , Isitman Gamze , Navis Marjon , Kramski Marit , Center Rob J. , Kent Stephen J. , Stratov Ivan
Published: April 2011

Effective immunity to HIV is poorly understood. In particular, a role for antibody-dependent cellular cytotoxicity (ADCC) in controlling HIV is controversial. We hypothesized that significant pressure from HIV-specific ADCC would result in immune-escape variants. A series of ADCC epitopes in HIV-infected subjects to specific consensus strain HIV peptides were mapped using a flow cytometric assay for natural killer cell activation. We then compared the ADCC responses to the same peptide epitope derived from the concurrent HIV sequence(s) expressed in circulating virus. In 9 of 13 epitopes studied, ADCC antibodies were unable to recognize the concurrent HIV sequence. Our studies suggest ADCC responses apply significant immune pressure on the virus. This result has implications for the induction of ADCC responses by HIV vaccines.
Humans and monkeys share visual representations
Authors: Fize Denis , Cauchoix Maxime , Fabre-Thorpe Michèle
Published: April 2011

Conceptual abilities in animals have been shown at several levels of abstraction, but it is unclear whether the analogy with humans results from convergent evolution or from shared brain mechanisms inherited from a common origin. Macaque monkeys can access “non-similarity–based concepts,” such as when sorting pictures containing a superordinate target category (animal, tree, etc.) among other scenes. However, such performances could result from low-level visual processing based on learned regularities of the photographs, such as for scene categorization by artificial systems. By using pictures of man-made objects or animals embedded in man-made or natural contexts, the present study clearly establishes that macaque monkeys based their categorical decision on the presence of the animal targets regardless of the scene backgrounds. However, as is found with humans, monkeys performed better with categorically congruent object/context associations, especially when small object sizes favored background information. The accuracy improvements and the response-speed gains attributable to superordinate category congruency in monkeys were strikingly similar to those of human subjects tested with the same task and stimuli. These results suggest analogous processing of visual information during the activation of abstract representations in both humans and monkeys; they imply a large overlap between superordinate visual representations in humans and macaques as well as the implicit use of experienced associations between object and context.
Crystal structure of the
Vibrio cholerae
cytolysin heptamer reveals common features among disparate pore-forming toxins
Authors: De Swastik , Olson Rich
Published: April 2011

Pore-forming toxins (PFTs) are potent cytolytic agents secreted by pathogenic bacteria that protect microbes against the cell-mediated immune system (by targeting phagocytic cells), disrupt epithelial barriers, and liberate materials necessary to sustain growth and colonization. Produced by gram-positive and gram-negative bacteria alike, PFTs are released as water-soluble monomeric or dimeric species, bind specifically to target membranes, and assemble transmembrane channels leading to cell damage and/or lysis. Structural and biophysical analyses of individual steps in the assembly pathway are essential to fully understanding the dynamic process of channel formation. To work toward this goal, we solved by X-ray diffraction the 2.9-Å structure of the 450-kDa heptameric
Vibrio cholerae
cytolysin (VCC) toxin purified and crystallized in the presence of detergent. This structure, together with our previously determined 2.3-Å structure of the VCC water-soluble monomer, reveals in detail the architectural changes that occur within the channel region and accessory lectin domains during pore formation including substantial rearrangements of hydrogen-bonding networks in the pore-forming amphipathic loops. Interestingly, a ring of tryptophan residues forms the narrowest constriction in the transmembrane channel reminiscent of the phenylalanine clamp identified in anthrax protective antigen [Krantz BA, et al. (2005)
Science
309:777–781]. Our work provides an example of a β-barrel PFT (β-PFT) for which soluble and assembled structures are available at high-resolution, providing a template for investigating intermediate steps in assembly.
Conserved, developmentally regulated mechanism couples chromosomal looping and heterochromatin barrier activity at the homeobox gene A locus
Authors: Kim Yoon Jung , Cecchini Katharine R. , Kim Tae Hoon
Published: April 2011

Establishment and segregation of distinct chromatin domains are essential for proper genome function. The insulator protein CCCTC-binding factor (CTCF) is involved in creating boundaries that segregate chromatin and functional domains and in organizing higher-order chromatin structures by promoting chromosomal loops across the vertebrate genome. Here, we investigate the insulation properties of CTCF at the human and mouse homeobox gene A (
HOXA
) loci. Although cohesin loading at the CTCF binding site is required for looping, we found that cohesin is dispensable for chromatin barrier activity at that site. Using mouse embryonic stem cells in both a pluripotent and differentiated neuronal progenitor state, we determined that embryonic stem cell pluripotency factor OCT4 antagonizes cohesin loading at the CTCF binding site. Loss of OCT4 in the committed and differentiated neuronal progenitor cells results in loading of cohesin and chromosome looping, which contributes to heterochromatin partitioning and selective gene activation across the
HOXA
locus. Our analysis reveals that chromatin barrier activity of CTCF is evolutionarily conserved and is responsible for the coordinated establishment of chromatin structure, higher-order architecture, and developmental expression of the
HOXA
locus.
Dose–response curve slope is a missing dimension in the analysis of HIV-1 drug resistance
Authors: Sampah Maame Efua S. , Shen Lin , Jilek Benjamin L. , Siliciano Robert F.
Published: April 2011

HIV-1 drug resistance is a major clinical problem. Resistance is evaluated using in vitro assays measuring the fold change inIC50caused by resistance mutations. Antiretroviral drugs are used at concentrations aboveIC50, however, and inhibition at clinical concentrations can only be predicted fromIC50if the shape of the dose–response curve is also known. Curve shape is influenced by cooperative interactions and is described mathematically by the slope parameter or Hill coefficient (m). Implicit in current analysis of resistance is the assumption that mutations shift dose–response curves to the right without affecting the slope. We show here thatmis altered by resistance mutations. For reverse transcriptase and fusion inhibitors, single resistance mutations affect both slope andIC50. For protease inhibitors, single mutations primarily affect slope. For integrase inhibitors, onlyIC50is affected. Thus, there are fundamental pharmacodynamic differences in resistance to different drug classes. Instantaneous inhibitory potential (IIP), the log inhibition of single-round infectivity at clinical concentrations, takes into account both slope andIC50, and thus provides a direct measure of the reduction in susceptibility produced by mutations and the residual activity of drugs against resistant viruses. The standard measure, fold change inIC50, does not correlate well with changes inIIPwhen mutations alter slope. These results challenge a fundamental assumption underlying current analysis of HIV-1 drug resistance and suggest that a more complete understanding of how resistance mutations reduce antiviral activity requires consideration of a previously ignored parameter, the dose–response curve slope.
Phantom percepts: Tinnitus and pain as persisting aversive memory networks
Authors: De Ridder Dirk , Elgoyhen Ana Belen , Romo Ranulfo , Langguth Berthold
Published: April 2011

Phantom perception refers to the conscious awareness of a percept in the absence of an external stimulus. On the basis of basic neuroscience on perception and clinical research in phantom pain and phantom sound, we propose a working model for their origin. Sensory deafferentation results in high-frequency, gamma band, synchronized neuronal activity in the sensory cortex. This activity becomes a conscious percept only if it is connected to larger coactivated “(self-)awareness” and “salience” brain networks. Through the involvement of learning mechanisms, the phantom percept becomes associated to distress, which in turn is reflected by a simultaneously coactivated nonspecific distress network consisting of the anterior cingulate cortex, anterior insula, and amygdala. Memory mechanisms play a role in the persistence of the awareness of the phantom percept, as well as in the reinforcement of the associated distress. Thus, different dynamic overlapping brain networks should be considered as targets for the treatment of this disorder.
Light-dependent gene regulation by a coenzyme B
12
-based photoreceptor
Authors: Ortiz-Guerrero Juan Manuel , Polanco María Carmen , Murillo Francisco J. , Padmanabhan S. , Elías-Arnanz Montserrat
Published: April 2011

Cobalamin (B
12
) typically functions as an enzyme cofactor but can also regulate gene expression via RNA-based riboswitches. B
12
-directed gene regulatory mechanisms via protein factors have, however, remained elusive. Recently, we reported down-regulation of a light-inducible promoter in the bacterium
Myxococcus xanthus
by two paralogous transcriptional repressors, of which one, CarH, but not the other, CarA, absolutely requires B
12
for activity even though both have a canonical B
12
-binding motif. Unanswered were what underlies this striking difference, what is the specific cobalamin used, and how it acts. Here, we show that coenzyme B
12
(5′-deoxyadenosylcobalamin, AdoB
12
), specifically dictates CarH function in the dark and on exposure to light. In the dark, AdoB
12
-binding to the autonomous domain containing the B
12
-binding motif foments repressor oligomerization, enhances operator binding, and blocks transcription. Light, at various wavelengths at which AdoB
12
absorbs, dismantles active repressor oligomers by photolysing the bound AdoB
12
and weakens repressor–operator binding to allow transcription. By contrast, AdoB
12
alters neither CarA oligomerization nor operator binding, thus accounting for its B
12
-independent activity. Our findings unveil a functional facet of AdoB
12
whereby it serves as the chromophore of a unique photoreceptor protein class acting in light-dependent gene regulation. The prevalence of similar proteins of unknown function in microbial genomes suggests that this distinct B
12
-based molecular mechanism for photoregulation may be widespread in bacteria.
Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA
Authors: Winther Kristoffer S. , Gerdes Kenn
Published: April 2011

Eukaryotic PIN (PilT N-terminal) domain proteins are ribonucleases involved in quality control, metabolism and maturation of mRNA and rRNA. The majority of prokaryotic PIN-domain proteins are encoded by the abundant
vapBC
toxin—antitoxin loci and inhibit translation by an unknown mechanism. Here we show that enteric VapCs are site-specific endonucleases that cleave tRNA
fMet
in the anticodon stem-loop between nucleotides +38 and +39 in vivo and in vitro. Consistently, VapC inhibited translation in vivo and in vitro. Translation-reactions could be reactivated by the addition of VapB and extra charged tRNA
fMet
. Similarly, ectopic production of tRNA
fMet
counteracted VapC in vivo. Thus, tRNA
fMet
is the only cellular target of VapC. Depletion of tRNA
fMet
by
vapC
induction was bacteriostatic and stimulated ectopic translation initiation at elongator codons. Moreover, addition of chloramphenicol to cells carrying
vapBC
induced VapC activity. Thus, by cleavage of tRNA
fMet
, VapC simultaneously may regulate global cellular translation and reprogram translation initiation.
Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation
Authors: Katayama Kei-ichi , Melendez Jaime , Baumann Jessica M. , Leslie Jennifer R. , Chauhan Bharesh K. , Nemkul Niza , Lang Richard A. , Kuan Chia-Yi , Zheng Yi , Yoshida Yutaka
Published: April 2011

The organization of neural progenitors in the developing mammalian neuroepithelium is marked by cadherin-based adherens junctions. Whereas RhoA, a founding member of the small Rho GTPase family, has been shown to play important roles in epithelial adherens junctions, its physiological roles in neural development remain uncertain due to the lack of specific loss-of-function studies. Here, we show that RhoA protein accumulates at adherens junctions in the developing mouse brain and colocalizes to the cadherin–catenin complex. Conditional deletion ofRhoAin midbrain and forebrain neural progenitors using Wnt1-Cre and Foxg1-Cre mice, respectively, disrupts apical adherens junctions and causes massive dysplasia of the brain. Furthermore,RhoA-deficient neural progenitor cells exhibit accelerated proliferation, reduction of cell- cycle exit, and increased expression of downstream target genes of the hedgehog pathway. Consequently, both lines of conditionalRhoA-deficient embryos exhibit expansion of neural progenitor cells and exencephaly-like protrusions. These results demonstrate a critical role of RhoA in the maintenance of apical adherens junctions and the regulation of neural progenitor proliferation in the developing mammalian brain.
Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury
Authors: Schwaeble Wilhelm J. , Lynch Nicholas J. , Clark James E. , Marber Michael , Samani Nilesh J. , Ali Youssif Mohammed , Dudler Thomas , Parent Brian , Lhotta Karl , Wallis Russell , Farrar Conrad A. , Sacks Steven , Lee Haekyung , Zhang Ming , Iwaki Daisuke , Takahashi Minoru , Fujita Teizo , Tedford Clark E. , Stover Cordula M.
Published: April 2011

Complement research experienced a renaissance with the discovery of a third activation route, the lectin pathway. We developed a unique model of total lectin pathway deficiency, a mouse strain lacking mannan-binding lectin-associated serine protease-2 (MASP-2), and analyzed the role of MASP-2 in two models of postischemic reperfusion injury (IRI). In a model of transient myocardial IRI, MASP-2–deficient mice had significantly smaller infarct volumes than their wild-type littermates. Mice deficient in the downstream complement component C4 were not protected, suggesting the existence of a previously undescribed lectin pathway-dependent C4-bypass. Lectin pathway-mediated activation of C3 in the absence of C4 was demonstrated in vitro and shown to require MASP-2, C2, and MASP-1/3. MASP-2 deficiency also protects mice from gastrointestinal IRI, as do mAb-based inhibitors of MASP-2. The therapeutic effects of MASP-2 inhibition in this experimental model suggest the utility of anti–MASP-2 antibody therapy in reperfusion injury and other lectin pathway-mediated disorders.
Flowers ofCypripedium fargesii(Orchidaceae) fool flat-footed flies (Platypezidae) by faking fungus-infected foliage
Authors: Ren Zong-Xin , Li De-Zhu , Bernhardt Peter , Wang Hong
Published: April 2011

Charles Darwin was fascinated by the orchid–pollinator interactions, but he did not realize that many orchid species are pollinated by deceit.Cypripedium, a model lineage of nonrewarding orchid flowers, is pollinated primarily by bees. Here we present both an example of floral mimesis of fungus-infected foliage in orchids and an example of flat-footed flies (Agathomyiasp.; Platypezidae) as pollen vectors for angiosperms.Cypripedium fargesiiis a nectarless, terrestrial, endangered orchid from southwestern China that requires cross-pollination to produce the maximum number of viable embryos. All insects caught entering or leaving the labellum sac wereAgathomyiasp. carrying conidia ofCladosporiumsp. on their mouthparts and legs, suggesting mycophagy. Blackish hairy spots on the upper surface of foliage may imitate black mold spots, serving as short-term visual lures. Some odor molecules also associated withCladosporiumcultures were isolated in the floral scent. Mimesis of fungus-infected foliage probably represents an overlooked but important option in angiosperm diversification, because there are three to five moreCypripediumspp. in southwestern China with the same mode of floral presentation and black-spotted hairy leaves.
Household expansion linked to agricultural intensification during emergence of Hawaiian archaic states
Authors: Field Julie S. , Ladefoged Thegn N. , Kirch Patrick V.
Published: April 2011

The Leeward Kohala Field System (LKFS) covering ∼60 km2on Hawai‘i Island is one of the world's best-studied archaeological examples of preindustrial agricultural intensification. Archaeological correlates for households over a 400-y period of intensification of the LKFS (A.D. 1400–1800) indicate that household age, number, and distribution closely match the expansion of agricultural features at both macro- and microscales. We excavated and dated residential complexes within portions of five traditional Hawaiian land units (ahupua‘a), two in the central core of the field system and three in the southern margins. Forty-eight radiocarbon dates from 43 residential features indicate an overall pattern of exponential increase in the numbers of households over time. Spatial distribution of these dates suggests that the core of the LKFS may have reached a population saturation point earlier than in the southern margins. Bayesian statistical analysis of radiocarbon dates from residential features in the core region, combined with spatial analysis of agricultural and residential construction sequences, demonstrates that the progressive subdivision of territories into smaller socioeconomic units was matched by addition of new residences, probably through a process of household fissioning. These results provide insights into the economic processes underlying the sociopolitical transformation from chiefdom to archaic state in precontact Hawai‘i.
Muc5ac: a critical component mediating the rejection of enteric nematodes
Authors: Hasnain Sumaira Z. , Evans Christopher M. , Roy Michelle , Gallagher Amanda L. , Kindrachuk Kristen N. , Barron Luke , Dickey Burton F. , Wilson Mark S. , Wynn Thomas A. , Grencis Richard K. , Thornton David J.
Published: April 2011

De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced in the cecum of mice resistant to Trichuris muris infection. In this study, we investigated the role of Muc5ac, which is detected shortly before worm expulsion and is associated with the production of interleukin-13 (IL-13), in resistance to this nematode. Muc5ac-deficient mice were incapable of expelling T. muris from the intestine and harbored long-term chronic infections, despite developing strong TH2 responses. Muc5ac-deficient mice had elevated levels of IL-13 and, surprisingly, an increase in the TH1 cytokine IFN-γ. Because TH1 inflammation is thought to favor chronic nematode infection, IFN-γ was neutralized in vivo, resulting in an even stronger TH2-type immune response. Nevertheless, despite a more robust TH2 effector response, the Muc5ac-deficient mice remained highly susceptible to chronic T. muris infection. Importantly, human MUC5AC had a direct detrimental effect on nematode vitality. Moreover, the absence of Muc5ac caused a significant delay in the expulsion of two other gut-dwelling nematodes (Trichinella spiralis and Nippostrongylus brasiliensis). Thus, for the first time, we identify a single mucin, Muc5ac, as a direct and critical mediator of resistance during intestinal nematode infection.
Nash equilibria in quantum games
Authors: Landsburg Steven
Published: April 2011

For any two-by-two game

G

\mathbf {G}

, we define a new two-player game

G

Q

\mathbf {G}^Q

. The definition is motivated by a vision of players in game

G

\mathbf {G}

communicating via quantum technology according to the protocol introduced by J. Eisert and M. Wilkins.

In the game

G

Q

\mathbf {G}^Q

, each player’s (mixed) strategy set consists of the set of all probability distributions on the 3-sphere

S

3

\mathbf {S}^3

. Nash equilibria in the game can be difficult to compute.

Our main theorems classify all possible mixed-strategy equilibria. First, we show that up to a suitable definition of equivalence, any strategy that arises in equilibrium is supported on at most four points; then we show that those four points must lie in one of a small number of allowable geometric configurations.
Importance of age structure in models of the response of upper trophic levels to fishing and climate change
Authors: Botsford Louis W. , Holland Matthew D. , Samhouri Jameal F. , White J. Wilson , Hastings Alan
Published: April 2011

Botsford, L. W., Holland, M. D., Samhouri, J. F., White, J. W., and Hastings, A. 2011. Importance of age structure in models of the response of upper trophic levels to fishing and climate change. – ICES Journal of Marine Science, 68: 1270–1283. There is a growing effort to use predictions of the physical state of the ocean under climate change to forecast the response of marine ecosystems. Many of these forecasts use ecosystem models rather than age-structured population models to describe upper trophic level (UTL) species. We illustrate the potential effects of climate on age-structured populations, then illustrate the ways in which ecosystem models might not depict adequately: (i) long-term changes in abundance, and (ii) variability attributable to cohort resonance. We simulated two generic species with different life histories, a short-lived semelparous species (e.g. salmon), and a long-lived iteroparous species (e.g. cod). For both species, juvenile survival was varied, first with white noise, then with the Pacific Decadal Oscillation as environmental signals. Variability in recruitment increased with fishing and became particularly sensitive to forcing at time-scales near the mean age of reproduction, consistent with the cohort resonance effect. Ecosystem models without age structure do not predict this behaviour, particularly when the ecosystem model incorrectly predicts the effective steepness of the stock–recruitment relationship, or the age structure is approximated by a stage-structured model. We suggest that ecosystem models of UTLs include full representations of age structure, fitted to available population data.
The Quaternary Lidocaine Derivative, QX-314, Exerts Biphasic Effects on Transient Receptor Potential Vanilloid Subtype 1 Channels In Vitro
Authors: Rivera-Acevedo Ricardo E. , Pless Stephan A. , Ahern Christopher A. , Schwarz Stephan K. W.
Published: April 2011

Background

Transient receptor potential vanilloid subfamily member 1 (TRPV1) channels are important integrators of noxious stimuli with pronounced expression in nociceptive neurons. The experimental local anesthetic, QX-314, a quaternary (i.e., permanently charged) lidocaine derivative, recently has been shown to interact with and permeate these channels to produce nociceptive and sensory blockade in animals in vivo. However, little is known about the specific interactions between QX-314 and TRPV1 channels. Thus, the authors examined the mechanistic basis by which QX-314 acts on TRPV1 channels.

Methods

The authors conducted an in vitro laboratory study in which they expressed TRPV1 and TRPV4 channels in Xenopus laevis oocytes and recorded cation currents with the two-electrode voltage clamp method. They used confocal microscopy for Ca²⁺ imaging in TRPV1 transient transfected tsA201 cells. Drugs were bath-applied by gravity perfusion. Statistical analyses were performed using Student t test, ANOVA, and post tests as appropriate (P < 0.05).

Results

QX-314 activated TRPV1 channels at 10, 30, and 60 mM (0.4 ± 0.1%, 3.5 ± 1.3%, and 21.5 ± 6.9% of normalized peak activation, respectively; mean ± SEM; n = 12) but not TRPV4 channels (P < 0.001). Activation by QX-314 was blocked by the TRPV1 antagonist, capsazepine (100 μM). QX-314 (60 mM) activation and blockade by capsazepine was also demonstrated in Ca²⁺ imaging studies on TRPV1-expressing tsA201 cells. At subactivating concentrations (less than 1 mM), QX-314 potently inhibited capsaicin-evoked TRPV1 currents with an IC₅₀ of 8.0 ± 0.6 μM.

Conclusions

The results of this study show that the quaternary lidocaine derivative QX-314 exerts biphasic effects on TRPV1 channels, inhibiting capsaicin-evoked TRPV1 currents at lower (micromolar) concentrations and activating TRPV1 channels at higher (millimolar) concentrations. These findings provide novel insights into the interactions between QX-314 and TRPV1 and may provide an explanation for the irritant properties of intrathecal QX-314 in mice in vivo.
Bilateral Internal Thoracic Artery Grafting Current State of the Art
Authors: Kinoshita Takeshi , Asai Tohru
Published: April 2011

The purpose of this article is to review the key literature and assess the current status of bilateral internal thoracic artery grafting. Numerous retrospective studies have demonstrated a benefit of bilateral internal thoracic artery grafting over single internal thoracic artery grafting in terms of the long-term risk of all-cause death, cardiac-related death, and cardiac events. The survival benefit of bilateral internal thoracic artery grafting manifests relatively early after operation for high-risk patients. The skeletonization technique reduces the risk of sternal wound complications in all patients and particularly in those with diabetes. Both the left and right internal thoracic arteries have better patency when grated to the left coronary territory than saphenous vein. However, the right internal thoracic artery does not always have good patency when grafted to the right coronary artery. Bilateral internal thoracic artery grafting using the skeletonization technique is recommended for revascularization of the left coronary territory.
Chylopericardial Tamponade Masquerading as Hemopericardium An Uncommon Complication of Cardiac Surgery
Authors: Tabry Imad F. , Zacharoudis Aristide , Constantini Eugene M.
Published: April 2011

Chylopericardial tamponade occurs very rarely after heart surgery. It may be the result of lymphatic duct interruption during mammary artery harvest, division of a large thymic remnant, or thrombosis of the subclavian or internal jugular vein by an indwelling central line. Although relatively straightforward when the pericardial aspirate has the usual milky appearance, the correct diagnosis can easily be overlooked particularly early after surgery when the patient is still fasting. We present a case report that illustrates the importance of sending all aspirates for chemical analysis irrespective of their color to arrive at the correct diagnosis and institute the appropriate medical management of this rare condition.
Minimally Invasive versus Open Mitral Valve Surgery a Consensus Statement of the International Society of Minimally Invasive Coronary Surgery (ISMICS) 2010
Authors: Falk Volkmar , Cheng Davy C. H. , Martin Janet , Diegeler Anno , Folliguet Thierry A. , Nifong L. Wiley , Perier Patrick , Raanani Ehud , Smith J. Michael , Seeburger Joerg
Published: April 2011

Objective

The purpose of this consensus conference was to deliberate the evidence regarding whether minimally invasive mitral valve surgery via thoracotomy improves clinical and resource outcomes compared with conventional open mitral valve surgery via median sternotomy in adults who require surgical intervention for mitral valve disease.

Methods

Before the consensus conference, the consensus panel reviewed the best available evidence up to March 2010, whereby systematic reviews, randomized trials, and nonrandomized trials were considered in descending order of validity and importance. The accompanying meta-analysis article in this issue of the Journal provides the systematic review of the evidence. Based on this systematic review, evidence-based statements were created for pre-specified clinical questions, and consensus processes were used to derive recommendations. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of each recommendation.

Results and Conclusions

Considering the underlying level of evidence, and notwithstanding the limitations of the evidence base (retrospective studies with important differences in baseline patient characteristics, which may produce bias in results of the evidence syntheses), the consensus panel provided the following evidence-based statements and overall recommendation: In patients with mitral valve disease, minimally invasive surgery may be an alternative to conventional mitral valve surgery (Class IIb), given that there was comparable short-term and long-term mortality (level B), comparable in-hospital morbidity (renal, pulmonary, cardiac complications, pain perception, and readmissions) (level B), reduced sternal complications, transfusions, postoperative atrial fibrillation, duration of ventilation, and intensive care unit and hospital length of stay (level B). However, this should be considered against the increased risk of stroke (2.1% vs 1.2%) (level B), aortic dissection (0.2% vs 0%) (level B), phrenic nerve palsy (3% vs 0%) (level B), groin infections/complications (2% vs 0%) (level B), and, prolonged cross-clamp time, cardiopulmonary bypass time, and procedure time (level B). The available evidence consists almost entirely of observational studies and must not be considered definitive until future adequately controlled randomized trials further address the risk of stroke, aortic complications, phrenic nerve complications, pain, long-term survival, need for reintervention, quality of life, and cost-effectiveness.
Robotic-Assisted Cryosurgical Treatment of Atrioventricular Node Reentrant Tachycardia
Authors: Lehr Eric J. , Rodriguez Evelio , Stevens Louis-Mathieu , Nifong L. Wiley , Chitwood W. Randolph
Published: April 2011

Atrioventricular nodal reentrant tachycardias typically arise from the existence of variable refractoriness in fast and slow conduction pathways within the triangle of Koch, which provide input to the atrioventricular node. Standard therapy includes medical management and catheter-based ablation procedures. Robotic-assisted, minimally invasive cryosurgical modification of the atrioventricular node can provide definitive therapy for patients who fail traditional therapy. A 65-year-old man presented with a several-year history of recurrent atrioventricular nodal reentrant tachycardia. Despite medical management and attempted percutaneous ablation, the patient remained symptomatic with weekly episodes. Access was via a 4-cm right anterolateral thoracotomy and peripheral perfusion. The da Vinci S robotic system was used to manipulate the cryoprobe (CryoMaze Probe; ATS Medical, Plymouth, MN USA). A series of spot freezes (tip 60°C) were made along the boundaries of the triangle of Koch until transient complete heart block was achieved and nodal rhythm was recovered. At follow-up 3 weeks postoperatively, the patient was asymptomatic in first-degree heart block. Robotic-assisted cryosurgical atrioventricular node ablation is an effective, minimally invasive treatment for patients with atrioventricular nodal reentrant tachycardia.
Effects of Community‐based Follow‐up Care in Managing Severely Underweight Children
Authors: Hossain Md Iqbal , Nahar Baitun , Hamadani Jena D. , Ahmed Tahmeed , Brown Kenneth H.
Published: April 2011

Objective:

The aim of the present study was to assess the effects of community‐based follow‐up care, food supplementation, and/or psychosocial stimulation on the recovery of severely underweight children.

Patients and Methods:

A total of 507 severely underweight children (weight‐for‐age z score <−3) ages 6 to 24 months hospitalized at the International Center for Diarrheal Disease Research, Bangladesh, were randomly assigned to 1 of the following regimens for 3 months once they recovered from diarrhea: fortnightly follow‐up care at the International Center for Diarrheal Disease Research, Bangladesh Hospital, including growth monitoring, health education, and micronutrient supplementation (group H‐C, n = 102); fortnightly follow‐up at community clinics, using the same treatment regimen as group H‐C (group C‐C, n = 99); community‐based follow‐up as per group C‐C plus cereal‐based supplementary food (SF) (group C‐SF, n = 101); follow‐up as per group C‐C plus psychosocial stimulation (PS) (group C‐PS, n = 102); or follow‐up as per group C‐C plus both SF and PS (group C‐SF + PS, n = 103).

Results:

There were no significant differences in baseline characteristics by treatment group. Attendance at scheduled follow‐up visits was greater in groups C‐SF, C‐SF + PS, and C‐PS than in C‐C and H‐C; P < 0.05. Rates of weight gain were greater in groups C‐SF + PS, C‐SF, and C‐PS (0.88–1.01 kg) compared with groups C‐C and H‐C (0.63–0.76 kg), P < 0.05. Three‐factor analysis of covariance of the effects of treatment components indicated that weight gain and change in weight‐for‐age z score and weight‐for‐length z score were greater in groups that received SF (P < 0.05) and linear growth was greater among children managed in the community (P = 0.002).

Conclusions:

Positioning follow‐up services in the community increases follow‐up visits and promotes greater linear growth; providing SF, with or without PS, increases clinic attendance and enhances nutritional recovery. Community‐based service delivery, especially including SF, permits better rehabilitation of greater numbers of severely underweight children.
Amerindian mtDNA Haplogroups and Celiac Disease Risk HLA Haplotypes in Mixed‐blood Latin American Patients
Authors: Parada Alejandra , Araya Magdalena , Pérez‐Bravo Francisco , Méndez Marco , Mimbacas Adriana , Motta Patricia , Martín Gabriela , Botero Jorge , Espinosa Nelly , Alarcon Teresa , Canales Paulina
Published: April 2011

Background and Objective:

Risk haplotypes have been described in celiac disease (CD), but the influence of native genes on CD in Hispanic Americans is unknown. The aim of the study was to measure the frequency of Amerindian mitochondrial DNA (mtDNA) haplogroups (inherited by the maternal line) in mixed‐blood patients with CD from Chile, Argentina, and Uruguay, and to assess the relation between these and human leukocyte antigen (HLA) alleles and haplotypes and clinical presentations.

Patients and Methods:

Clinical history, histological data, and genetic studies were conducted following 2 protocols: a case‐control study of 72 Chilean patients with CD and controls, and an assessment of 43 (additional) samples of celiac patients from Chile, 96 from Argentina, and 57 from Uruguay, compared with the mtDNA frequency in the corresponding country. HLA typing was performed by a commercial kit, and mtDNA was determined by means of polymerase chain reaction and restriction fragment length polymorphisms analysis.

Results:

A total of 73.6% of cases had typical presentations. The most frequent HLA alleles were HLA‐DQB*201 and 202. No‐DQ2/DQ8 HLA haplotypes were found in 7% of cases. mtDNA frequencies for typical Amerindian haplogroups were found in 71% of cases and 64% of controls (P χ2 = 0.016); in the comparative analysis, mtDNA distribution was not different from the figures reported for the respective general country population. No relation was found between haplotypes or haplogroups and clinical presentations.

Conclusions:

mtDNA haplogroups A/B/C/D were frequently found in celiac patients and controls, but no relations appeared between haplogroups, haplotypes, and clinical presentations.
Varicella Immunity in Inflammatory Bowel Disease
Authors: Ansari Faazia , Baker Robert D. , Patel Raza , Baker Susan S.
Published: April 2011

Objectives:

Varicella zoster is a childhood disease that can cause devastating illness and death in immunocompromised individuals, including those who are taking steroids. Inflammatory bowel disease (IBD) is managed by decreasing or controlling the inflammation using immunosuppression. Our objective was to show that at least 90% of patients newly diagnosed as having IBD had antibodies against varicella zoster and were protected by vaccination or natural disease.

Materials and Methods:

Retrospective review of all of the charts of the patients diagnosed with IBD at the University of Buffalo's Digestive Diseases and Nutrition Center for 5 years from January 1, 2005 to December 31, 2009.

Results:

There were 163 new diagnoses of IBD during this time; 57% were boys. Mean age was 12 years (range 1–19 years); 62% had Crohn disease, 33% ulcerative colitis, and 5% indeterminate colitis. A total of 66% of all of the patients had a history of disease or vaccination. Measurable titers against varicella were found in only 77% of all of the patients.

Conclusions:

Lack of varicella immunity is common in children and adolescents at the time of diagnosis of IBD. Routine screening for varicella immune status may be warranted. Offering immunization to susceptible patients should confer protection, but this may be difficult to achieve once immune suppression has begun.
Economic value of improved quantification in global sources and sinks of carbon dioxide
Authors: Durant A. J. , Le Quéré C. , Hope C. , Friend A. D.
Published: April 2011

On average, about 45 per cent of global annual anthropogenic carbon dioxide (CO
2
) emissions remain in the atmosphere, while the remainder are taken up by carbon reservoirs on land and in the oceans—the CO
2
‘sinks’. As sink size and dynamics are highly variable in space and time, cross-verification of reported anthropogenic CO
2
emissions with atmospheric CO
2
measurements is challenging. Highly variable CO
2
sinks also limit the capability to detect anomolous changes in natural carbon reservoirs. This paper argues that significant uncertainty reduction in annual estimates of the global carbon balance could be achieved rapidly through coordinated up-scaling of existing methods, and that this uncertainty reduction would provide incentive for accurate reporting of CO
2
emissions at the country level. We estimate that if 5 per cent of global CO
2
emissions go unreported and undetected, the associated marginal economic impacts could reach approximately US$20 billion each year by 2050. The net present day value of these impacts aggregated until 2200, and discounted back to the present would have a mean value exceeding US$10 trillion. The costs of potential impacts of unreported emissions far outweigh the costs of enhancement of measurement infrastructure to reduce uncertainty in the global carbon balance.