bluuebunny/crossref_metadata_2025 huggingface dataset:
COI barcoding of Hydroides: a road from impossible to difficult
Authors: Sun Y. , Kupriyanova E. K. , Qiu J. W.
Published: December 2012

A fragment of the cytochromec oxidase subunitI (COI) gene has been used increasingly for species identification and discovery in eukaryotes. However, amplifying COI has proven difficult, or even impossible, in some taxa due to non-homology between the universal primers and the target DNA region. Among the most problematic animal groups is Serpulidae (Annelida). These sedentary marine animals live in self-secreted calcareous tubes and many of them, especially of the genus Hydroides, are economically important reef-builders, foulers, and biological invaders. We developed novel taxon-specific primers for amplifying COI from Hydroides, and for the first time generated 460-bp COI sequences from 11 of 14 species attempted. Average Kimura-2-parameter interspecific sequence distance (26.2%) was >60 times greater than the average intraspecific distance (0.43%), indicating that the COI gene is effective for species delimitation in Hydroides. Although applicability of the new primers for a wide range of serpulids needs to be tested, barcoding of Hydroides is now on its way from impossible to difficult. We anticipate that COI barcoding will provide a modern species identification tool and, combined with other molecular markers, yield important insights in phylogeny and evolutionary ecology of this large and important genus.
DNA barcoding and morphological identification of Argentine species of Apanteles (Hymenoptera : Braconidae), parasitoids of cactus-feeding moths (Lepidoptera : Pyralidae : Phycitinae), with description of a new species
Authors: Martínez Juan José , Berta Carolina , Varone Laura , Logarzo Guillermo , Zamudio Paula , Zaldívar-Riverón Alejandro , Aguilar-Velasco R. Gabriela
Published: December 2012

The gregarious species of Apanteles that attack cactus-feeding phycitine moths (Lepidoptera : Pyralidae) from Argentina are identified using DNA barcodes and morphological data. Sequences of specimens from 10 different populations were generated. Corrected genetic divergences showed two clusters of specimens separated by COI divergences higher than 6%. Our morphological examinations were congruent with the molecular evidence and therefore two species were confidently identified: Apanteles alexanderi Brèthes and a new species, Apanteles opuntiarum Martínez & Berta, sp. nov., which we describe and illustrate. Despite these two taxa being considered to represent a single polyphagous species for at least 50 years, they can be easily distinguished by the length of their ovipositor sheaths. A key to the species of microgastrine parasitoids of cactus-feeding Lepidoptera in South America is provided. The recognition of the new species reveals a narrower host range for the species involved in this system, making it necessary to re-evaluate their potential as biocontrol agents of the prickly pear moth.
Fine-scale spatial structuring as an inbreeding avoidance mechanism in the social skink Egernia stokesii
Authors: Gardner M. G. , Godfrey S. S. , Fenner A. L. , Donnellan S. C. , Bull C. M.
Published: December 2012

Egernia stokesii is a monogamous and group-living species of Australian scincid lizard. We used genotype data from 10 microsatellite loci to examine evidence for sex-biased dispersal and kin-based discrimination as mechanisms for inbreeding avoidance of E. stokesii within seven rocky outcrops in the southern Flinders Ranges of South Australia. We also examined the relatedness of individuals observed using the same crevice within groups. We found no evidence for sex-biased dispersal at these sites, but found that adult lizards of the opposite sex observed using the same crevice were less related to each other than expected by chance. Our results suggest a behavioural mechanism for minimising inbreeding in large related aggregations of this species.
Response of vegetation to drought time-scales across global land biomes
Authors: Vicente-Serrano Sergio M. , Gouveia Célia , Camarero Jesús Julio , Beguería Santiago , Trigo Ricardo , López-Moreno Juan I. , Azorín-Molina César , Pasho Edmond , Lorenzo-Lacruz Jorge , Revuelto Jesús , Morán-Tejeda Enrique , Sanchez-Lorenzo Arturo
Published: December 2012

We evaluated the response of the Earth land biomes to drought by correlating a drought index with three global indicators of vegetation activity and growth: vegetation indices from satellite imagery, tree-ring growth series, and Aboveground Net Primary Production (ANPP) records. Arid and humid biomes are both affected by drought, and we suggest that the persistence of the water deficit (i.e., the drought time-scale) could be playing a key role in determining the sensitivity of land biomes to drought. We found that arid biomes respond to drought at short time-scales; that is, there is a rapid vegetation reaction as soon as water deficits below normal conditions occur. This may be due to the fact that plant species of arid regions have mechanisms allowing them to rapidly adapt to changing water availability. Humid biomes also respond to drought at short time-scales, but in this case the physiological mechanisms likely differ from those operating in arid biomes, as plants usually have a poor adaptability to water shortage. On the contrary, semiarid and subhumid biomes respond to drought at long time-scales, probably because plants are able to withstand water deficits, but they lack the rapid response of arid biomes to drought. These results are consistent among three vegetation parameters analyzed and across different land biomes, showing that the response of vegetation to drought depends on characteristic drought time-scales for each biome. Understanding the dominant time-scales at which drought most influences vegetation might help assessing the resistance and resilience of vegetation and improving our knowledge of vegetation vulnerability to climate change.
Viral antigen density and confinement time regulate the reactivity pattern of CD4 T-cell responses to vaccinia virus infection
Authors: Vanguri Vijay , Govern Christopher C. , Smith Rebecca , Huseby Eric S.
Published: December 2012

T-cell recognition of ligands is polyspecific. This translates into antiviral T-cell responses having a range of potency and specificity for viral ligands. How these ligand recognition patterns are established is not fully understood. Here, we show that an activation threshold regulates whether robust CD4 T-cell activation occurs following viral infection. The activation threshold was variable because of its dependence on the density of the viral peptide (p)MHC displayed on infected cells. Furthermore, the activation threshold was not observed to be a specific equilibrium affinity (KD) or half-life (t1/2) of the TCR–viral pMHC interaction, rather it correlated with the confinement time of TCR–pMHC interactions, i.e., the half-life (t1/2) of the interaction accounting for the effects of TCR–pMHC rebinding. One effect of a variable activation threshold is to allow high-density viral pMHC ligands to expand CD4 T cells with a variety of potency and peptide cross-reactivity patterns for the viral pMHC ligand, some of which are only poorly activated by infections that produce a lower density of the viral pMHC ligand. These results argue that antigen concentration is a key component in determining the pattern ofKD,t1/2and peptide cross-reactivity of the TCRs expressed on CD4 T cells responding to infection.
Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family
Authors: Porrello Enzo R. , Mahmoud Ahmed I. , Simpson Emma , Johnson Brett A. , Grinsfelder David , Canseco Diana , Mammen Pradeep P. , Rothermel Beverly A. , Olson Eric N. , Sadek Hesham A.
Published: December 2012

We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the most common antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-old mice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heart mounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. Moreover, we show that the miR-15 family of microRNAs modulates neonatal heart regeneration through inhibition of postnatal cardiomyocyte proliferation. Finally, we demonstrate that inhibition of the miR-15 family from an early postnatal age until adulthood increases myocyte proliferation in the adult heart and improves left ventricular systolic function after adult MI. We conclude that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity.
Cell-type–specific roles of Na
+
/K
+
ATPase subunits in
Drosophila
auditory mechanosensation
Authors: Roy Madhuparna , Sivan-Loukianova Elena , Eberl Daniel F.
Published: December 2012

Ion homeostasis is a fundamental cellular process particularly important in excitable cell activities such as hearing. It relies on the Na
+
/K
+
ATPase (also referred to as the Na pump), which is composed of a catalytic α subunit and a β subunit required for its transport to the plasma membrane and for regulating its activity. We show that α and β subunits are expressed in Johnston's organ (JO), the
Drosophila
auditory organ. We knocked down expression of α subunits (
ATPα
and
α-like
)
and β subunits
(nrv1, nrv2
, and
nrv3)
individually in JO with UAS/Gal4-mediated RNAi. ATPα shows elevated expression in the ablumenal membrane of scolopale cells, which enwrap JO neuronal dendrites in endolymph-like compartments. Knocking down
ATPα
, but not
α-like
, in the entire JO or only in scolopale cells using specific drivers, resulted in complete deafness. Among β subunits,
nrv2
is expressed in scolopale cells and
nrv3
in JO neurons. Knocking down
nrv2
in scolopale cells blocked Nrv2 expression, reduced ATPα expression in the scolopale cells, and caused almost complete deafness. Furthermore, knockdown of either
nrv2
or
ATPα
specifically in scolopale cells causes abnormal, electron-dense material accumulation in the scolopale space. Similarly,
nrv3
functions in JO but not in scolopale cells, suggesting neuron specificity that parallels
nrv2
scolopale cell–specific support of the catalytic ATPα. Our studies provide an amenable model to investigate generation of endolymph-like extracellular compartments.
Endothelial glucocorticoid receptor is required for protection against sepsis
Authors: Goodwin Julie E. , Feng Yan , Velazquez Heino , Sessa William C.
Published: December 2012

The glucocorticoid receptor (GR) is ubiquitously expressed on nearly all cell types, but tissue-specific deletion of this receptor can produce dramatic whole organism phenotypes. In this study we investigated the role of the endothelial GR in sepsis in vivo and in vitro. Mice with an endothelial-specific GR deletion and controls were treated with 12.5 mg/kg LPS and phenotyped. Mice lacking GR showed significantly increased mortality, more hemodynamic instability, higher nitric oxide levels, and higher levels of the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) compared with controls. There were no differences in rates of apoptosis or macrophage recruitment between the two groups. Both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression were increased after LPS challenge in mice with endothelial GR deficiency, and aminoguanidine, a specific iNOS inhibitor in mice was able to rescue hemodynamic collapse in these animals. In vitro, human umbilical vein cells (HUVECs) subjected to GR knockdown by siRNA showed increased expression of eNOS at baseline that persisted after treatment with LPS. Both eNOS and iNOS mRNA was increased by qPCR. In HUVECs lacking GR, NF-κB levels and NF-κB–dependent genes
tissue factor
and
IL-6
were increased compared with controls. Thus, endothelial GR is a critical regulator of NF-κB activation and nitric oxide synthesis in sepsis.
Disassembly of synthetic
Agrobacterium
T-DNA–protein complexes via the host SCF
VBF
ubiquitin–ligase complex pathway
Authors: Zaltsman Adi , Lacroix Benoît , Gafni Yedidya , Citovsky Vitaly
Published: December 2012

One the most intriguing, yet least studied, aspects of the bacterium–host plant interaction is the role of the host ubiquitin/proteasome system (UPS) in the infection process. Increasing evidence indicates that pathogenic bacteria subvert the host UPS to facilitate infection. Although both mammalian and plant bacterial pathogens are known to use the host UPS, the first prokaryotic F-box protein, an essential component of UPS, was identified in
Agrobacterium
. During its infection, which culminates in genetic modification of the host cell,
Agrobacterium
transfers its T-DNA—as a complex (T-complex) with the bacterial VirE2 and host VIP1 proteins—into the host cell nucleus. There the T-DNA is uncoated from its protein components before undergoing integration into the host genome. It has been suggested that the host UPS mediates this uncoating process, but there is no evidence indicating that this activity can unmask the T-DNA molecule. Here we provide support for the idea that the plant UPS uncoats synthetic T-complexes via the Skp1/Cullin/F-box protein VBF pathway and exposes the T-DNA molecule to external enzymatic activity.
Prosocial preferences do not explain human cooperation in public-goods games
Authors: Burton-Chellew Maxwell N. , West Stuart A.
Published: December 2012

It has become an accepted paradigm that humans have “prosocial preferences” that lead to higher levels of cooperation than those that would maximize their personal financial gain. However, the existence of prosocial preferences has been inferred post hoc from the results of economic games, rather than with direct experimental tests. Here, we test how behavior in a public-goods game is influenced by knowledge of the consequences of actions for other players. We found that (
i
) individuals cooperate at similar levels, even when they are not informed that their behavior benefits others; (
ii
) an increased awareness of how cooperation benefits others leads to a reduction, rather than an increase, in the level of cooperation; and (
iii
) cooperation can be either lower or higher than expected, depending on experimental design. Overall, these results contradict the suggested role of the prosocial preferences hypothesis and show how the complexity of human behavior can lead to misleading conclusions from controlled laboratory experiments.
Marked global reduction in mGluR5 receptor binding in smokers and ex-smokers determined by [
11
C]ABP688 positron emission tomography
Authors: Akkus Funda , Ametamey Simon M. , Treyer Valerie , Burger Cyrill , Johayem Anass , Umbricht Daniel , Gomez Mancilla Baltazar , Sovago Judit , Buck Alfred , Hasler Gregor
Published: December 2012

Nicotine addiction is a major public health problem, resulting in primary glutamatergic dysfunction. We measured the glutamate receptor binding in the human brain and provided direct evidence for the abnormal glutamate system in smokers. Because antagonism of the metabotropic glutamate receptor 5 (mGluR5) reduced nicotine self-administration in rats and mice, mGluR5 is suggested to be involved in nicotine addiction. mGluR5 receptor binding specifically to an allosteric site was observed by using positron emission tomography with [
11
C]ABP688. We found a marked global reduction (20.6%;
P
< 0.0001) in the mGluR5 distribution volume ratio (DVR) in the gray matter of 14 smokers. The most prominent reductions were found in the bilateral medial orbitofrontal cortex. Compared with 14 nonsmokers, 14 ex-smokers had global reductions in the average gray matter mGluR5 DVR (11.5%;
P
< 0.005), and there was a significant difference in average gray matter mGluR5 DVR between smokers and ex-smokers (9.2%;
P
< 0.01). Clinical variables reflecting current nicotine consumption, dependence and abstinence were not correlated with mGluR5 DVR. This decrease in mGluR5 receptor binding may be an adaptation to chronic increases in glutamate induced by chronic nicotine administration, and the decreased down-regulation seen in the ex-smokers could be due to incomplete recovery of the receptors, especially because the ex-smokers were abstinent for only 25 wk on average. These results encourage the development and testing of drugs against addiction that directly target the glutamatergic system.
Dynamic modulation of ANO1/TMEM16A HCO
3
−
permeability by Ca
2+
/calmodulin
Authors: Jung Jinsei , Nam Joo Hyun , Park Hyun Woo , Oh Uhtaek , Yoon Joo-Heon , Lee Min Goo
Published: December 2012

Anoctamin 1 (ANO1)/transmembrane protein 16A (TMEM16A) is a calcium-activated anion channel that may play a role in HCO
3
−
secretion in epithelial cells. Here, we report that the anion selectivity of ANO1 is dynamically regulated by the Ca
2+
/calmodulin complex. Whole-cell current measurements in HEK 293T cells indicated that ANO1 becomes highly permeable to HCO
3
−
at high [Ca
2+
]
i
. Interestingly, this result was not observed in excised patches, indicating the involvement of cytosolic factors in this process. Further studies revealed that the direct association between ANO1 and calmodulin at high [Ca
2+
]
i
is responsible for changes in anion permeability. Calmodulin physically interacted with ANO1 in a [Ca
2+
]
i
-dependent manner, and addition of recombinant calmodulin to the cytosolic side of excised patches reversibly increased P
HCO3
/P
Cl
. In addition, the high [Ca
2+
]
i
-induced increase in HCO
3
−
permeability was reproduced in mouse submandibular gland acinar cells, in which ANO1 plays a critical role in fluid secretion. These results indicate that the HCO
3
−
permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO
3
−
transport, especially in transepithelial HCO
3
−
secretion.
Repair of the degenerate retina by photoreceptor transplantation
Authors: Barber Amanda C. , Hippert Claire , Duran Yanai , West Emma L. , Bainbridge James W. B. , Warre-Cornish Katherine , Luhmann Ulrich F. O. , Lakowski Jorn , Sowden Jane C. , Ali Robin R. , Pearson Rachael A.
Published: December 2012

Despite different aetiologies, age-related macular degeneration and most inherited retinal disorders culminate in the same final common pathway, the loss of photoreceptors. There are few treatments and none reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. Recently, we demonstrated restoration of vision following rod-photoreceptor transplantation into a mouse model of stationary night-blindness, raising the critical question of whether photoreceptor replacement is equally effective in different types and stages of degeneration. We present a comprehensive assessment of rod-photoreceptor transplantation across six murine models of inherited photoreceptor degeneration. Transplantation is feasible in all models examined but disease type has a major impact on outcome, as assessed both by the morphology and number of integrated rod-photoreceptors. Integration can increase (
Prph2

+/Δ307

), decrease (
Crb1

rd8/rd8

,
Gnat1

−/−

,
Rho

−/−

), or remain constant (
PDE6β

rd1/rd1

,
Prph2

rd2/rd2

) with disease progression, depending upon the gene defect, with no correlation with severity. Robust integration is possible even in late-stage disease. Glial scarring and outer limiting membrane integrity, features that change with degeneration, significantly affect transplanted photoreceptor integration. Combined breakdown of these barriers markedly increases integration in a model with an intact outer limiting membrane, strong gliotic response, and otherwise poor transplantation outcome (
Rho

−/−

), leading to an eightfold increase in integration and restoration of visual function. Thus, it is possible to achieve robust integration across a broad range of inherited retinopathies. Moreover, transplantation outcome can be improved by administering appropriate, tailored manipulations of the recipient environment.
How a holoenzyme for DNA replication is formed
Authors: Perumal Senthil K. , Ren Wenhui , Lee Tae-Hee , Benkovic Stephen J.
Published: December 2012

Loading of the phage T4 sliding clamp gp45 by the gp44/62 clamp loader onto DNA to form the holoenzyme and their disassembly pathways were investigated using FRET-based single-molecule and ensemble kinetic studies. gp44/62-mediated assembly of gp45 onto the DNA involves a rate-limiting conformational rearrangement of the gp45−gp44/62−DNA complex. Single-molecule measurements revealed the intermediates in gp45 loading and their interconversion, suggesting that the assembly is not concerted but is broken down into many small kinetic steps. Two populations of the gp45−gp44/62−DNA complex are formed on the end-blocked DNA that are poised to form the holoenzyme with the polymerase. In the absence of a polymerase, the two clamp populations dissociated from the DNA along with gp44/62 with distinct rates. In the presence of polymerase, holoenzyme assembly involved the recruitment of the polymerase to the gp45−gp44/62−DNA complex mediated by the chaperoning activity of gp44/62. This transient multiprotein complex then decomposed through an ATP hydrolysis−dependent exit of gp44/62 leaving the holoenzyme on DNA. The rate of dissociation of the holoenzyme from the DNA is sensitive to whether the DNA ends are blocked, underscoring its mobility on the DNA.
Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2
Authors: Bos Rémi , Sadlaoud Karina , Boulenguez Pascale , Buttigieg Dorothée , Liabeuf Sylvie , Brocard Cécile , Haase Georg , Bras Hélène , Vinay Laurent
Published: December 2012

In healthy adults, activation of γ-aminobutyric acid (GABA)
A
and glycine receptors inhibits neurons as a result of low intracellular chloride concentration ([Cl
–
]
i
), which is maintained by the potassium-chloride cotransporter KCC2. A reduction of KCC2 expression or function is implicated in the pathogenesis of several neurological disorders, including spasticity and chronic pain following spinal cord injury (SCI). Given the critical role of KCC2 in regulating the strength and robustness of inhibition, identifying tools that may increase KCC2 function and, hence, restore endogenous inhibition in pathological conditions is of particular importance. We show that activation of 5-hydroxytryptamine (5-HT) type 2A receptors to serotonin hyperpolarizes the reversal potential of inhibitory postsynaptic potentials (IPSPs), E
IPSP
, in spinal motoneurons, increases the cell membrane expression of KCC2 and both restores endogenous inhibition and reduces spasticity after SCI in rats. Up-regulation of KCC2 function by targeting 5-HT
2A
receptors, therefore, has therapeutic potential in the treatment of neurological disorders involving altered chloride homeostasis. However, these receptors have been implicated in several psychiatric disorders, and their effects on pain processing are controversial, highlighting the need to further investigate the potential systemic effects of specific 5-HT
2A
R agonists, such as (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2).
Imaging a functional tumorigenic biomarker in the transformed epithelium
Authors: LeBeau Aaron M. , Lee Minhee , Murphy Stephanie T. , Hann Byron C. , Warren Robert S. , Delos Santos Romelyn , Kurhanewicz John , Hanash Samir M. , VanBrocklin Henry F. , Craik Charles S.
Published: December 2012

Proteases responsible for the increased peritumoral proteolysis associated with cancer represent functional biomarkers for monitoring tumorigenesis. One attractive extracellular biomarker is the transmembrane serine protease matriptase. Found on the surface of epithelial cells, the activity of matriptase is regulated by its cognate inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1). Quantitative mass spectrometry allowed us to show that, in selected cancers, HAI-1 expression decreases, leading to active matriptase. A preclinical probe specific for the measurement of emergent active matriptase was developed. Using an active-site–specific, recombinant human antibody for matriptase, we found that the selective targeting of active matriptase can be used to visualize the tumorigenic epithelium. Live-cell fluorescence imaging validated the selectivity of the antibody in vitro by showing that the probe localized only to cancer cell lines with active matriptase on the surface. Immunofluorescence with the antibody documented significant levels of active matriptase in 68% of primary and metastatic colon cancer sections from tissue microarrays. Labeling of the active form of matriptase in vivo was measured in human colon cancer xenografts and in a patient-derived xenograft model using near-infrared and single-photon emission computed tomography imaging. Tumor uptake of the radiolabeled antibody,
111
In-A11, by active matriptase was high in xenografts (28% injected dose per gram) and was blocked in vivo by the addition of a matriptase-specific variant of ecotin. These findings suggest, through a HAI-1–dependent mechanism, that emergent active matriptase is a functional biomarker of the transformed epithelium and that its proteolytic activity can be exploited to noninvasively evaluate tumorigenesis in vivo.
Mutation rate dynamics in a bacterial population reflect tension between adaptation and genetic load
Authors: Wielgoss Sébastien , Barrick Jeffrey E. , Tenaillon Olivier , Wiser Michael J. , Dittmar W. James , Cruveiller Stéphane , Chane-Woon-Ming Béatrice , Médigue Claudine , Lenski Richard E. , Schneider Dominique
Published: December 2012

Mutations are the ultimate source of heritable variation for evolution. Understanding how mutation rates themselves evolve is thus essential for quantitatively understanding many evolutionary processes. According to theory, mutation rates should be minimized for well-adapted populations living in stable environments, whereas hypermutators may evolve if conditions change. However, the long-term fate of hypermutators is unknown. Using a phylogenomic approach, we found that an adapting
Escherichia coli
population that first evolved a
mutT
hypermutator phenotype was later invaded by two independent lineages with
mutY
mutations that reduced genome-wide mutation rates. Applying neutral theory to synonymous substitutions, we dated the emergence of these mutations and inferred that the
mutT
mutation increased the point-mutation rate by
∼
150-fold, whereas the
mutY
mutations reduced the rate by
∼
40–60%, with a corresponding decrease in the genetic load. Thus, the long-term fate of the hypermutators was governed by the selective advantage arising from a reduced mutation rate as the potential for further adaptation declined.
MDGAs interact selectively with neuroligin-2 but not other neuroligins to regulate inhibitory synapse development
Authors: Lee Kangduk , Kim Yoonji , Lee Sung-Jin , Qiang Yuan , Lee Dongmin , Lee Hyun Woo , Kim Hyun , Je H. Shawn , Südhof Thomas C. , Ko Jaewon
Published: December 2012

The MAM domain-containing GPI anchor proteins MDGA1 and MDGA2 are Ig superfamily adhesion molecules composed of six IG domains, a fibronectin III domain, a MAM domain, and a GPI anchor. MDGAs contribute to the radial migration and positioning of a subset of cortical neurons during early neural development. However, MDGAs continue to be expressed in postnatal brain, and their functions during postnatal neural development remain unknown. Here, we demonstrate that MDGAs specifically and with a nanomolar affinity bind to neuroligin-2, a cell-adhesion molecule of inhibitory synapses, but do not bind detectably to neuroligin-1 or neuroligin-3. We observed no cell adhesion between cells expressing neuroligin-2 and MDGA1, suggesting a
cis
interaction. Importantly, RNAi-mediated knockdown of MDGAs increased the abundance of inhibitory but not excitatory synapses in a neuroligin-2–dependent manner. Conversely, overexpression of MDGA1 decreased the numbers of functional inhibitory synapses. Likewise, coexpression of both MDGA1 and neuroligin-2 reduced the synaptogenic capacity of neuroligin-2 in an artificial synapse-formation assay by abolishing the ability of neuroligin-2 to form an adhesion complex with neurexins. Taken together, our data suggest that MDGAs inhibit the activity of neuroligin-2 in controlling the function of inhibitory synapses and that MDGAs do so by binding to neuroligin-2.
pH (low) insertion peptide (pHLIP) targets ischemic myocardium
Authors: Sosunov Eugene A. , Anyukhovsky Evgeny P. , Sosunov Alexander A. , Moshnikova Anna , Wijesinghe Dayanjali , Engelman Donald M. , Reshetnyak Yana K. , Andreev Oleg A.
Published: December 2012

The pH (low) insertion peptide (pHLIP) family enables targeting of cells in tissues with low extracellular pH. Here, we show that ischemic myocardium is targeted, potentially opening a new route to diagnosis and therapy. The experiments were performed using two murine ischemia models: regional ischemia induced by coronary artery occlusion and global low-flow ischemia in isolated hearts. In both models, pH-sensitive pHLIPs [wild type (WT) and Var7] or WT-pHLIP–coated liposomes bind ischemic but not normal regions of myocardium, whereas pH-insensitive, kVar7, and liposomes coated with PEG showed no preference. pHLIP did not influence either the mechanical or the electrical activity of ischemic myocardium. In contrast to other known targeting strategies, the pHLIP-based binding does not require severe myocardial damage. Thus, pHLIP could be used for delivery of pharmaceutical agents or imaging probes to the myocardial regions undergoing brief restrictions of blood supply that do not induce irreversible changes in myocytes.
Interferon-γ mediates chemokine-dependent recruitment of natural killer cells during viral infection
Authors: Pak-Wittel Melissa A. , Yang Liping , Sojka Dorothy K. , Rivenbark Joshua G. , Yokoyama Wayne M.
Published: December 2012

Significance

The innate immune system, including natural killer (NK) cells, is responsible for limiting virus spread during the initial phases of an infection. Here, we show in mice that NK cells are recruited to lymph nodes that drain the site of infection with cowpox virus, which is endemic in wild rodents. Full NK-cell recruitment was dependent on their expression of a specific receptor for soluble attractants termed chemokines, a hormone-like substance called IFN-γ, and subcapsular sinus macrophages. Therefore, this study provides a framework for how NK cells are recruited to a site of infection.
Epistolarity
Authors: Seara Isabel Roboredo
Published: December 2012

The epistolary genre is considered to be an all-encompassing one insofar as it includes various epistemological approaches, thanks to the hybrid, nomadic, intricate and oxymoronic nature of the letter. This paper seeks to examine the relationship between letters and dialogue, a relationship based on the complicity and reciprocity that characterize dialogism in general. The topos of conversation is undoubtedly one of the most frequent and fruitful in epistolary writing. Letter writing has long been considered a reflection and prolongation or anticipation of face-to-face interaction. This study will try to show how conversation, as an underlying paradigm and a sort of presence-in-absence, represents a form of compensation, a consolation against the suffering stemming from distance in space and time.
Advice-giving and disputant empowerment in divorce mediation sessions
Authors: Garcia Angela Cora
Published: December 2012

While mediation programs vary greatly in their procedures and philosophies, most programs expect the mediator to act as a neutral facilitator who empowers disputants to resolve the dispute themselves. Advice-giving by mediators is therefore typically not recommended. However, mediators often find ways to give advice, if only indirectly. In this paper I use conversation analytic techniques to examine how mediators give advice to disputants in videotaped mediation sessions between divorcing couples. I found that while mediators display an orientation to a norm of no advice-giving, they do often give advice. Advice is often formulated indirectly, for example as a suggestion rather than as prescriptive advice, or as general information rather than advice targeted to a specific individual. Mediators also often gave procedural rather than substantive advice. These findings are discussed in terms of how advice-giving can support or detract from the ability of mediators to empower mediation clients to resolve their own disputes.
Texts-in-dialogues
Authors: Caronia Letizia
Published: December 2012

This paper discusses the process through which cultural ideas, knowledge and beliefs mediating the encounter between an audience and a text are fabricated in and enacted by everyday naturally occurring dialogues. We contend that the cultural knowledge framing any hermeneutic dialogue is communicatively constituted in daily discourses, dialogues and interactions that often concern the texts and text-related practices. By taking a developmental perspective on the role of everyday talk in the making of media ideologies, this paper empirically illustrates how human beings become cultural beings inasmuch as they are inherently dialogic beings. Examples of adult-child interactions collected during ethnographic fieldwork are discussed to illustrate how dialogues occasioned by media use are organized by the worldviews of a given community. Yet, at one and the same time, they (re)produce the value system, moral order and the canonical versions of the world for those who engage in these talking activities.
Recent developments in HCI
Authors: Feller Sebastian
Published: December 2012

In this article I critically discuss four studies in the area of Human–Computer Interaction (HCI) research. The focus is on distinct dimensions of culture including both verbal and para-verbal behavior in communication. My discussion is grounded in Weigand’s (2010) theory of dialogic action games (DAG), a pragma-linguistic theory which is based on a view of language as language action. The main question is whether or not the presented research leads in a direction towards making computers believable dialog partners.
The story of the tallat
Authors: Marshall Steve
Published: December 2012

Many Latin Americans who emigrate to Spain arrive in Barcelona, where they encounter Catalan for the first time. Many find jobs in bars shortly after arriving, where they have to deal with not understanding Catalan-speaking customers. In this article, I present selected data from interviews from a four-year qualitative, ethnographic study of the languages, migration, and identities of Latin American immigrants in Barcelona, in which participants describe their first and early encounters with Catalan. One theme that recurred in interviews was that of bar workers not understanding orders for a tallat, an espresso coffee with a shot of warm milk, known as a ‘cortado’ in Spanish. I also bring in data from a government media campaign promoting Catalan use with immigrants and a comedic sketch that parodies the same campaign using the ordering of a tallat as an example. Together, the data illustrate the multilayered, discursive construction of the story of the tallat.
English language teaching curriculum in Iran: planning and practice
Authors: Atai Mahmood Reza , Mazlum Farhad
Published: December 2012

The present study investigates English language teaching (ELT) curriculum planning in Iran%s Ministry of Education and its implementation by teachers. We studied programme evaluation; needs analysis; the ELT‐specific documents; communication channels between planning and practice levels; teacher evaluation and student assessment; interpretation and re‐examination of national policies within the Ministry; and the criteria set for ELT material development. Instrumentation included: curriculum documents; interviews with Ministry officials, material developers and headteachers; and teacher questionnaires. Results attested to the lack of any ELT‐specific document for material development and absence of research‐based needs assessment as the foundation of the programmes. Also, there are no pre‐defined linguistic and professional criteria for evaluating teachers, and planning for students' assessment is limited to a set of general guidelines. Moreover, there is neither a programme evaluation nor an ELT evaluation model and national‐level policies are not re‐examined at planning level. Results also indicate that politico‐ideological beliefs of material developers are as important as their expertise and communication channels between planning and practice levels are of a top‐down nature. It is argued that the gap between planning and practice results from a highly centralised policymaking process in which local policymakers (i.e. teachers) are not involved.
A review of curriculum in the UK: internationalising in a changing context
Authors: Hayden Mary
Published: December 2012

The present article focuses on the growing emphasis on international dimensions of the curriculum in the UK. Educators and policymakers increasingly grapple with the thorny issue of how best to prepare future generations for life in a world changing so rapidly that no‐one is able to predict precisely what knowledge and skills will be relevant for the adult of tomorrow. Overlapping with debate relating to the national context is that pertaining to the global environment, which manifests itself in current educational discourse relating to a growing number of concepts such as global citizenship education, international education, development education, world studies, and education for international understanding. Beginning with consideration of the curriculum context, this article highlights the growing number of international curriculum programmes being developed and offered worldwide, and in the UK in particular, before considering some of the reasons behind this growth and the implications of increased interest in programmes with an international focus.
Skills for innovation: envisioning an education that prepares for the changing world
Authors: Cobo Cristobal
Published: December 2012

This article explores and discusses key conditions needed to develop skills for innovation. This article analyses five trends that can contribute to fostering the development of skills for innovation within and outside formal educational institutions. These key trends, identified through a literature review, are elements that foster learning and human capital development necessary for an innovative society. These five key elements are: (1) the mismatch between formal education and the challenges of an innovative society; (2) the shift from what we learn to how we learn; (3) the fluctuating relationship between digital technologies and contents; (4) the changing conceptions of space‐time and the emphasis on lifelong learning; and (5) the development of soft skills. Finally, this article ends highlighting that the expanded learning and the development of skills for innovation are critical aspects for the future of education.
Cep164 mediates vesicular docking to the mother centriole during early steps of ciliogenesis
Authors: Schmidt Kerstin N. , Kuhns Stefanie , Neuner Annett , Hub Birgit , Zentgraf Hanswalter , Pereira Gislene
Published: December 2012

Cilia formation is a multi-step process that starts with the docking of a vesicle at the distal part of the mother centriole. This step marks the conversion of the mother centriole into the basal body, from which axonemal microtubules extend to form the ciliary compartment. How vesicles are stably attached to the mother centriole to initiate ciliary membrane biogenesis is unknown. Here, we investigate the molecular role of the mother centriolar component Cep164 in ciliogenesis. We show that Cep164 was indispensable for the docking of vesicles at the mother centriole. Using biochemical and functional assays, we identified the components of the vesicular transport machinery, the GEF Rabin8 and the GTPase Rab8, as interacting partners of Cep164. We propose that Cep164 is targeted to the apical domain of the mother centriole to provide the molecular link between the mother centriole and the membrane biogenesis machinery that initiates cilia formation.
Clostridium difficileInfection and Limitations of Markers for Severity in Patients with Hematologic Malignancy
Authors: Wang Michael S. , Evans Charlesnika T. , Rodriguez Tulio , Gerding Dale N. , Johnson Stuart
Published: December 2012

Objective.

To describe characteristics ofClostridium difficileinfection (CDI) and markers of severe CDI among patients with hematologic malignancies.

Design.

Case-control study.

Setting.

Tertiary care teaching hospital.

Patients and Methods.

Inpatients with hematologic malignancies and CDI were age and time matched with 2 control inpatients without hematologic malignancies. Chart reviews were performed, andC. difficileisolates were strain typed.

Results.

Case patients (n= 41) and control patients (n= 82) patients were different in respect to receipt of immunosuppressive agents within 2 months (92.7% vs 25.6%;P< .0001); neutropenia within 2 months (75.6% vs 3.7%;P< .0001) and mean (± standard deviation) white blood cell (WBC) count at diagnosis (4.9 ± 14.1 vs 11.8 ± 6.8 × 103cells/mL;P= .0002); baseline mean creatinine level (0.89 ± 0.1 vs 1.6 ± 2.4 mg/dL;P= .003), mean creatinine level at diagnosis (0.83 ± 0.4 vs 1.85 ± 1.9 mg/dL;P= .004), and creatinine increases of 1.5 times over baseline (2.4% vs 15.1%;P= .02). Immunosuppressive agents and creatinine level remained significant in multivariable analysis (P= .03 for both variables). Severity correlated with mortality when measured by alternate severity criteria but not when measured by the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America criteria, which are based solely on WBC count and creatinine elevation. The prevalence of the epidemic BI/NAP1/027 strain was similar in both groups.

Conclusions.

Patients with hematologic malignancies had lower creatinine levels at the time of CDI diagnosis compared with control patients. WBC counts also tended to be lower in case patients. CDI severity criteria based on WBC count and creatinine level may not be applicable to patients with hematologic malignancies.
Limited Attention to Search Costs in the Gasoline Retail Market: Evidence from a Choice Experiment on Consumer Willingness to Search
Authors: Castilla Carolina , Haab Timothy
Published: December 2012

We conduct a choice experiment to investigate whether U.S. gasoline consumers exhibit limited attention to the costs of searching for lower prices. When consumers search for prices as they drive, the search cost is a function of the amount of gasoline consumed while driving and the time spent searching for prices. We randomize the amount of information we provide the respondents to a survey about search costs in one of 3 ways: time, gasoline, or both. Results indicate that cognitive costs cause inattention to time costs. We also find that respondents overestimate the cost of the gasoline used while driving, thus forgoing consumer surplus.
Primary cardiac lymphoma mimicking infiltrative cardiomyopathy
Authors: Lee Ga Yeon , Kim Won Seog , Ko Young‐Hyeh , Choi Jin‐Oh , Jeon Eun‐Seok
Published: December 2012

Primary cardiac lymphoma is a rare malignancy which has been described as thickened myocardium due to the infiltration of atypical lymphocytes and accompanying intracardiac masses. Here, we report a case of a primary cardiac lymphoma without demonstrable intracardiac masses, mimicking infiltrative cardiomyopathy. A 40‐year‐old male presented with exertional dyspnoea and was diagnosed as having restrictive cardiomyopathy with severely decreased LV systolic function. Endomyocardial biopsy was performed and the diagnosis of primary cardiac lymphoma was confirmed. After appropriate chemotherapy, he recovered his systolic function fully.
Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study
Authors: Nanchen David , Stott David J. , Gussekloo Jacobijn , Mooijaart Simon P. , Westendorp Rudi G.J. , Jukema J. Wouter , Macfarlane Peter W. , Cornuz Jacques , Rodondi Nicolas , Buckley Brendan M. , Ford Ian , Sattar Naveed , de Craen Anton J.M. ,   on behalf of the PROSPER Group
Published: December 2012

Aims

Resting heart rate is a promising modifiable cardiovascular risk marker in older adults, but the mechanisms linking heart rate to cardiovascular disease are not fully understood. We aimed to assess the association between resting heart rate and incident heart failure (HF) and cardiovascular mortality, and to examine whether these associations might be attributable to systemic inflammation and endothelial dysfunction.

Methods and results

We studied 4084 older adults aged 70–82 years with known cardiovascular risk factors or previous cardiovascular disease, without pre‐existing HF or beta‐blockers in the PROSPER study. Over a 3.2‐year follow‐up period, we examined incident HF hospitalization and cardiovascular mortality according to resting heart rate, along with C‐reactive protein (CRP), interleukin‐6 (IL‐6), tissue plasminogen activator (tPA), and von Willebrand factor (vWf). Mean heart rate was 67 b.p.m. for men and 70 b.p.m. for women. CRP, IL‐6, tPA, and vWf levels were all positively correlated with heart rate. After multivariate adjustment, heart rate was associated with HF hospitalization [hazard ratio (HR) 1.78 for highest vs. lowest distribution third, 95% confidence interval (CI) 1.21–2.63, P= 0.003] and cardiovascular mortality (HR 1.74, 95% CI 1.23–2.47, P= 0.002). Further adjustment for both IL‐6 and vWf levels decreased HR to 1.60 (95% CI 1.08–2.38, P= 0.020) for HF and to 1.50 (95% CI 1.04–2.15, P= 0.028) for cardiovascular mortality.

Conclusion

Increased heart rate is associated with increased systemic inflammation and endothelial dysfunction. These factors are likely to contribute to, but do not fully explain, the risk of HF and cardiovascular death associated with increased heart rate in older age.
Real-time Two-dimensional Ultrasound Guidance for Central Venous Cannulation
Authors: Wu Shao-yong , Ling Quan , Cao Long-hui , Wang Jian , Xu Mei-xi , Zeng Wei-an
Published: December 2012

Background:

Use of ultrasound-guided techniques to facilitate central venous cannulation (CVC) may reduce the risk of misplacement and complications. A meta-analysis was conducted to compare real-time two-dimensional ultrasound (RTUS) guidance technique with anatomical landmark technique for CVC to determine whether RTUS has any advantages.

Methods:

Randomized studies comparing outcomes in patients undergoing CVC with either RTUS or landmark technique were retrieved from PubMed, ISI Web of Knowledge, EMBASE, and OVID EBM Reviews from their inception to March 2012.

Results:

Twenty-six studies involving 4,185 CVC procedures met the inclusion criteria. Compared with landmark technique, patients with RTUS had a pooled relative risk (RR) of 0.18 (95% CI: 0.10–0.32) for cannulation failure, 0.25 (95% CI: 0.15–0.42) for arterial puncture, 0.30 (95% CI: 0.19–0.46) for hematoma, 0.21 (95% CI: 0.06–0.73) for pneumothorax, and 0.10 (95% CI: 0.02–0.54) for hemothorax from random-effects models. However, RTUS did not show a reduction in the risk of cannulation failure (RR = 0.26, 95% CI: 0.03–2.55), arterial puncture (RR = 0.34, 95% CI: 0.05–2.60), hematoma (RR = 0.13, 95% CI: 0.01–2.42), pneumothorax (RR = 0.40, 95% CI: 0.02–9.61), and hemothorax (RR = 0.40, 95% CI: 0.02–9.61) in children or infants when the limited data were analyzed.

Conclusions:

Among adults receiving CVC, RTUS was associated with decreased risks of cannulation failure, arterial puncture, hematoma, and hemothorax. Additional data of randomized studies are necessary to evaluate these outcomes in pediatric patients.