bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of large-insert, small-insert and pyrosequencing libraries for metagenomic analysis
Authors: Danhorn Thomas , Young Curtis R , DeLong Edward F
Published: October 2012

Correction to: The ISME Journal (2012) doi: 10.1038/ismej.2012.35; published online 26 April 2012 Since the publication of this article, the authors have noticed a reference omission (Ghai et al., 2010) that should have been cited in the article. By adding the citation, the following sentence has been deleted from page 2:
CFTR mutations altering CFTR fragmentation
Authors: Tosoni Kendra , Stobbart Michelle , Cassidy Diane M. , Venerando Andrea , Pagano Mario A. , Luz Simão , Amaral Margarida D. , Kunzelmann Karl , Pinna Lorenzo A. , Farinha Carlos M. , Mehta Anil
Published: October 2012

Most CF (cystic fibrosis) results from deletion of a phenylalanine (F508) in the CFTR {CF transmembrane-conductance regulator; ABCC7 [ABC (ATP-binding cassette) sub-family C member 7]} which causes ER (endoplasmic reticulum) degradation of the mutant. Using stably CFTR-expressing BHK (baby-hamster kidney) cell lines we demonstrated that wild-type CTFR and the F508delCFTR mutant are cleaved into differently sized N- and C-terminal-bearing fragments, with each hemi-CFTR carrying its nearest NBD (nucleotide-binding domain), reflecting differential cleavage through the central CFTR R-domain. Similar NBD1-bearing fragments are present in the natively expressing HBE (human bronchial epithelial) cell line. We also observe multiple smaller fragments of different sizes in BHK cells, particularly after F508del mutation (ladder pattern). Trapping wild-type CFTR in the ER did not generate a F508del fragmentation fingerprint. Fragments change their size/pattern again post-mutation at sites involved in CFTR's in vitro interaction with the pleiotropic protein kinase CK2 (S511A in NBD1). The F508del and S511A mutations generate different fragmentation fingerprints that are each unlike the wild-type; yet, both mutants generate new N-terminal-bearing CFTR fragments that are not observed with other CK2-related mutations (S511D, S422A/D and T1471A/D). We conclude that the F508delCFTR mutant is not degraded completely and there exists a relationship between CFTR's fragmentation fingerprint and the CFTR sequence through putative CK2-interactive sites that lie near F508.
Who moved my shared service centre?
Authors: Oshri Ilan
Published: October 2012

In a search for an optimized global business service operation, firms set up and relocate shared service centres around the globe. This teaching case examines the migration process of IBM procurement shared service centre from Budapest to Sofia. The teaching case describes the challenges that the teams in Budapest and Sofia faced and the migration methodology applied and later on adapted in order to meet the transition objectives. The teaching case concludes by challenging IBM's migration approach.
Ferrite film growth on semiconductor substrates towards microwave and millimeter wave integrated circuits
Authors: Chen Z. , Harris V. G.
Published: October 2012

It is widely recognized that as electronic systems’ operating frequency shifts to microwave and millimeter wave bands, the integration of ferrite passive devices with semiconductor solid state active devices holds significant advantages in improved miniaturization, bandwidth, speed, power and production costs, among others. Traditionally, ferrites have been employed in discrete bulk form, despite attempts to integrate ferrite as films within microwave integrated circuits. Technical barriers remain centric to the incompatibility between ferrite and semiconductor materials and their processing protocols. In this review, we present past and present efforts at ferrite integration with semiconductor platforms with the aim to identify the most promising paths to realizing the complete integration of on-chip ferrite and semiconductor devices, assemblies and systems.
Infrared detectors based on semiconductor p-n junction of PbSe
Authors: Kasiyan Vladimir , Dashevsky Zinovi , Minna Schwarz Casey , Shatkhin M. , Flitsiyan Elena , Chernyak Leonid , Khokhlov Dmitry
Published: October 2012

P-n junctions based on physical vapor deposition of thin PbSe films and conductivity type inversion from n- to p-type are developed and characterized over a wide range of temperatures and bias voltages. Photosensitivity and diode characteristics in the thin film PbSe diode structures were found at temperatures up to 300 K. The values of the measured and estimated parameters of these structures demonstrate their high photodetector performance and the potential for development of IR detectors with optimal sensitivity at the highest possible operating temperature.
Piezoelectric superlattice: From piezoelectric to Huang-Kun-like equations
Authors: Huang Cheng-ping , Zhu Yong-yuan
Published: October 2012

The piezoelectric superlattice (PSL) consisting of periodically inverted ferro- electric domains is a special kind of artificially microstructured material. Similar to the ionic crystals, the strong coupling between the electromagnetic wave and superlattice vibration of PSL may generate the phonon polariton. In this paper, by starting with the piezoelectric equations and classic motion equation, the gap between the artificial and classic lattices has been bridged, where a set of Huang-Kun (HK)-like equations were established and can be shared by both systems. Our results also show that the coupling between the photon and longitudinal “optical” phonon, which is not present in a real crystal, is dominated by the HK-like equations. The connection between the two seemingly different systems suggests that they are governed by a common physics.
A Dynamic Route to Structure and Function: Recent Advances in Imine-Based Organic Nanostructured Materials
Authors: Liu Yi , Li Zhan-Ting
Published: October 2012

The chemistry of imine bond formation from simple aldehyde and amine precursors is among the most powerful dynamic covalent chemistries employed for the construction of discrete molecular objects and extended molecular frameworks. The reversible nature of the C=N bond confers error-checking and proof-reading capabilities in the self-assembly process within a multi-component reaction system. This review highlights recent progress in the self-assembly of complex organic molecular architectures that are enabled by dynamic imine chemistry, including molecular containers with defined geometry and size, mechanically interlocked molecules, and extended frameworks and polymers, from building blocks with preprogrammed steric and electronic information. The functional aspects associated with the nanometer-scale features not only place these dynamically constructed nanostructures at the frontier of materials sciences, but also bring unprecedented opportunities for the discovery of new functional materials.
Atmospheric interactions with wildland fire behaviour - II. Plume and vortex dynamics
Authors: Potter Brian E.
Published: October 2012

This paper is the second of two reviewing scientific literature from 100 years of research addressing interactions between the atmosphere and fire behaviour. These papers consider research on the interactions between the fuels burning at any instant and the atmosphere, and the interactions between the atmosphere and those fuels that will eventually burn in a given fire. The first paper reviews the progression from the surface atmospheric properties of temperature, humidity and wind to horizontal and vertical synoptic structures and ends with vertical atmospheric profiles. This second paper addresses plume dynamics and vortices. The review presents several questions and concludes with suggestions for areas of future research.
Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking
Authors: George Olivier , Sanders Chelsea , Freiling John , Grigoryan Edward , Vu Shayla , Allen Camryn D. , Crawford Elena , Mandyam Chitra D. , Koob George F.
Published: October 2012

Chronic intermittent access to alcohol leads to the escalation of alcohol intake, similar to binge drinking in humans. Converging lines of evidence suggest that impairment of medial prefrontal cortex (mPFC) cognitive function and overactivation of the central nucleus of the amygdala (CeA) are key factors that lead to excessive drinking in dependence. However, the role of the mPFC and CeA in the escalation of alcohol intake in rats with a history of binge drinking without dependence is currently unknown. To address this issue, we examined FBJ murine osteosarcoma viral oncogene homolog (Fos) expression in the mPFC, CeA, hippocampus, and nucleus accumbens and evaluated working memory and anxiety-like behavior in rats given continuous (24 h/d for 7 d/wk) or intermittent (3 d/wk) access to alcohol (20% vol/vol) using a two-bottle choice paradigm. The results showed that abstinence from alcohol in rats with a history of escalation of alcohol intake specifically recruited GABA and corticotropin-releasing factor (CRF) neurons in the mPFC and produced working memory impairments associated with excessive alcohol drinking during acute (24–72 h) but not protracted (16 –68 d) abstinence. Moreover, abstinence from alcohol was associated with a functional disconnection of the mPFC and CeA but not mPFC and nucleus accumbens. These results show that recruitment of a subset of GABA and CRF neurons in the mPFC during withdrawal and disconnection of the PFC–CeA pathway may be critical for impaired executive control over motivated behavior, suggesting that dysregulation of mPFC interneurons may be an early index of neuroadaptation in alcohol dependence.
Decoupling of rotational and translational diffusion in supercooled colloidal fluids
Authors: Edmond Kazem V. , Elsesser Mark T. , Hunter Gary L. , Pine David J. , Weeks Eric R.
Published: October 2012

We use confocal microscopy to directly observe 3D translational and rotational diffusion of tetrahedral clusters, which serve as tracers in colloidal supercooled fluids. We find that as the colloidal glass transition is approached, translational and rotational diffusion decouple from each other: Rotational diffusion remains inversely proportional to the growing viscosity whereas translational diffusion does not, decreasing by a much lesser extent. We quantify the rotational motion with two distinct methods, finding agreement between these methods, in contrast with recent simulation results. The decoupling coincides with the emergence of non-Gaussian displacement distributions for translation whereas rotational displacement distributions remain Gaussian. Ultimately, our work demonstrates that as the glass transition is approached, the sample can no longer be approximated as a continuum fluid when considering diffusion.
Newborn’s brain activity signals the origin of word memories
Authors: Benavides-Varela Silvia , Hochmann Jean-Rémy , Macagno Francesco , Nespor Marina , Mehler Jacques
Published: October 2012

Recent research has shown that specific areas of the human brain are activated by speech from the time of birth. However, it is currently unknown whether newborns' brains also encode and remember the sounds of words when processing speech. The present study investigates the type of information that newborns retain when they hear words and the brain structures that support word-sound recognition. Forty-four healthy newborns were tested with the functional near-infrared spectroscopy method to establish their ability to memorize the sound of a word and distinguish it from a phonetically similar one, 2 min after encoding. Right frontal regions—comparable to those activated in adults during retrieval of verbal material—showed a characteristic neural signature of recognition when newborns listened to a test word that had the same vowel of a previously heard word. In contrast, a characteristic novelty response was found when a test word had different vowels than the familiar word, despite having the same consonants. These results indicate that the information carried by vowels is better recognized by newborns than the information carried by consonants. Moreover, these data suggest that right frontal areas may support the recognition of speech sequences from the very first stages of language acquisition.
Link between intraphagosomal biotin and rapid phagosomal escape in
Francisella
Authors: Napier Brooke A. , Meyer Lena , Bina James E. , Miller Mark A. , Sjöstedt Anders , Weiss David S.
Published: October 2012

Cytosolic bacterial pathogens require extensive metabolic adaptations within the host to replicate intracellularly and cause disease. In phagocytic cells such as macrophages, these pathogens must respond rapidly to nutrient limitation within the harsh environment of the phagosome. Many cytosolic pathogens escape the phagosome quickly (15–60 min) and thereby subvert this host defense, reaching the cytosol where they can replicate. Although a great deal of research has focused on strategies used by bacteria to resist antimicrobial phagosomal defenses and transiently pass through this compartment, the metabolic requirements of bacteria in the phagosome are largely uncharacterized. We previously identified a
Francisella
protein, FTN_0818, as being essential for intracellular replication and involved in virulence in vivo. We now show that FTN_0818 is involved in biotin biosynthesis and required for rapid escape from the
Francisella
-containing phagosome (FCP). Addition of biotin complemented the phagosomal escape defect of the
FTN
_0818
mutant, demonstrating that biotin is critical for promoting rapid escape during the short time that the bacteria are in the phagosome. Biotin also rescued the attenuation of the
FTN_0818
mutant during infection in vitro and in vivo, highlighting the importance of this process. The key role of biotin in phagosomal escape implies biotin may be a limiting factor during infection. We demonstrate that a bacterial metabolite is required for phagosomal escape of an intracellular pathogen, providing insight into the link between bacterial metabolism and virulence, likely serving as a paradigm for other cytosolic pathogens.
Mapping multisensory parietal face and body areas in humans
Authors: Huang Ruey-Song , Chen Ching-fu , Tran Alyssa T. , Holstein Katie L. , Sereno Martin I.
Published: October 2012

Detection and avoidance of impending obstacles is crucial to preventing head and body injuries in daily life. To safely avoid obstacles, locations of objects approaching the body surface are usually detected via the visual system and then used by the motor system to guide defensive movements. Mediating between visual input and motor output, the posterior parietal cortex plays an important role in integrating multisensory information in peripersonal space. We used functional MRI to map parietal areas that see and feel multisensory stimuli near or on the face and body. Tactile experiments using full-body air-puff stimulation suits revealed somatotopic areas of the face and multiple body parts forming a higher-level homunculus in the superior posterior parietal cortex. Visual experiments using wide-field looming stimuli revealed retinotopic maps that overlap with the parietal face and body areas in the postcentral sulcus at the most anterior border of the dorsal visual pathway. Starting at the parietal face area and moving medially and posteriorly into the lower-body areas, the median of visual polar-angle representations in these somatotopic areas gradually shifts from near the horizontal meridian into the lower visual field. These results suggest the parietal face and body areas fuse multisensory information in peripersonal space to guard an individual from head to toe.
Inhibition of oncogenic Wnt signaling through direct targeting of β-catenin
Authors: Grossmann Tom N. , Yeh Johannes T.-H. , Bowman Brian R. , Chu Qian , Moellering Raymond E. , Verdine Gregory L.
Published: October 2012

Aberrant activation of signaling by the Wnt pathway is strongly implicated in the onset and progression of numerous types of cancer. Owing to the persistent dependence of these tumors on Wnt signaling for growth and survival, inhibition of this pathway is considered an attractive mechanism-based therapeutic approach. Oncogenic activation of Wnt signaling can ensue from a variety of distinct aberrations in the signaling pathway, but most share the common feature of causing increased cellular levels of β-catenin by interfering with its constitutive degradation. β-Catenin serves as a central hub in Wnt signaling by engaging in crucial protein–protein interactions with both negative and positive effectors of the pathway. Direct interference with these protein–protein interactions is a biologically compelling approach toward suppression of β-catenin hyperactivity, but such interactions have proven intransigent with respect to small-molecule targeting. Hence β-catenin remains an elusive target for translational cancer therapy. Here we report the discovery of a hydrocarbon-stapled peptide that directly targets β-catenin and interferes with its ability to serve as a transcriptional coactivator for T-cell factor (TCF) proteins, the downstream transcriptional regulators of the Wnt pathway.
Thin
, a
Trim32
ortholog, is essential for myofibril stability and is required for the integrity of the costamere in
Drosophila
Authors: LaBeau-DiMenna Elisa M. , Clark Kathleen A. , Bauman Kenneth D. , Parker Daniel S. , Cripps Richard M. , Geisbrecht Erika R.
Published: October 2012

Myofibril stability is required for normal muscle function and maintenance. Mutations that disrupt myofibril stability result in individuals who develop progressive muscle wasting, or muscular dystrophy, and premature mortality. Here we present our investigations of the
Drosophila l(2)thin
[
l(2)tn
] mutant. The “thin” phenotype exhibits features of the human muscular disease phenotype in that
tn
mutant larvae show progressive muscular degeneration. Loss-of-function and rescue experiments determined that
l(2)tn
is allelic to the
tn
locus [previously annotated as both
CG15105
and
another b-box affiliate
(
abba
)].
tn
encodes a TRIM (tripartite motif) containing protein highly expressed in skeletal muscle and is orthologous to the human limb-girdle muscular dystrophy type 2H disease gene
Trim32.
Thin protein is localized at the Z-disk in muscle, but
l(2)tn
mutants showed no genetic interaction with mutants affecting the Z-line–associated protein muscle LIM protein 84B.
l(2)tn
, along with loss-of-function mutants generated for
tn
, showed no relative mislocalization of the Z-disk proteins α-Actinin and muscle LIM protein 84B. In contrast,
tn
mutants had significant disorganization of the costameric orthologs β-integrin, Spectrin, Talin, and Vinculin, and we present the initial description for the costamere, a key muscle stability complex, in
Drosophila.
Our studies demonstrate that myofibrils progressively unbundle in flies that lack Thin function through progressive costamere breakdown. Due to the high conservation of these structures in animals, we demonstrate a previously unknown role for TRIM32 proteins in myofibril stability.
Engineering robust control of two-component system phosphotransfer using modular scaffolds
Authors: Whitaker Weston R. , Davis Stephanie A. , Arkin Adam P. , Dueber John E.
Published: October 2012

Synthetic biology applies engineering principles to facilitate the predictable design of biological systems. Biological systems composed of modular parts with clearly defined interactions are generally easier to manipulate than complex systems exhibiting a large number of subtle interactions. However, recreating the function of a naturally complex system with simple modular parts can increase fragility. Here, inspired by scaffold-directed signaling in higher organisms, we modularize prokaryotic signal transduction to allow programmable redirection of phosphate flux from a histidine kinase to response regulators based on targeting by eukaryotic protein–protein interaction domains. Although scaffold-directed colocalization alone was sufficient to direct signaling between components, this minimal system suffered from high sensitivity to changing expression levels of each component. To address this fragility, we demonstrate how to engineer autoinhibition into the kinase so that phosphotransfer is possible only upon binding to the scaffold. This system, in which scaffold performs the dual functions of activating this autoinhibited kinase and directing flux to the cotargeted response regulator, was significantly more robust to varying component concentrations. Thus, we demonstrate that design principles inspired by the complex signal-transduction pathways of eukaryotes may be generalized, abstracted, and applied to prokaryotes using well-characterized parts.
Local synaptic integration of mitogen-activated protein kinase and protein kinase A signaling mediates intermediate-term synaptic facilitation in
Aplysia
Authors: Ye Xiaojing , Marina Andreea , Carew Thomas J.
Published: October 2012

It is widely appreciated that memory processing engages a wide range of molecular signaling cascades in neurons, but how these cascades are temporally and spatially integrated is not well understood. To explore this important question, we used
Aplysia californica
as a model system. We simultaneously examined the timing and subcellular location of two signaling molecules, MAPK (ERK1/2) and protein kinase A (PKA), both of which are critical for the formation of enduring memory for sensitization. We also explored their interaction during the formation of enduring synaptic facilitation, a cellular correlate of memory, at tail sensory-to-motor neuron synapses. We find that repeated tail nerve shock (TNS, an analog of sensitizing training) immediately and persistently activates MAPK in both sensory neuron somata and synaptic neuropil. In contrast, we observe immediate PKA activation only in the synaptic neuropil. It is followed by PKA activation in both compartments 1 h after TNS. Interestingly, blocking MAPK activation during, but not after, TNS impairs PKA activation in synaptic neuropil without affecting the delayed PKA activation in sensory neuron somata. Finally, by applying inhibitors restricted to the synaptic compartment, we show that synaptic MAPK activation during TNS is required for the induction of intermediate-term synaptic facilitation, which leads to the persistent synaptic PKA activation required to maintain this facilitation. Collectively, our results elucidate how MAPK and PKA signaling cascades are spatiotemporally integrated in a single neuron to support synaptic plasticity underlying memory formation.
Structural basis for multifunctional roles of mammalian aminopeptidase N
Authors: Chen Lang , Lin Yi-Lun , Peng Guiqing , Li Fang
Published: October 2012

Mammalian aminopeptidase N (APN) plays multifunctional roles in many physiological processes, including peptide metabolism, cell motility and adhesion, and coronavirus entry. Here we determined crystal structures of porcine APN at 1.85 Å resolution and its complexes with a peptide substrate and a variety of inhibitors. APN is a cell surface-anchored and seahorse-shaped zinc-aminopeptidase that forms head-to-head dimers. Captured in a catalytically active state, these structures of APN illustrate a detailed catalytic mechanism for its aminopeptidase activity. The active site and peptide-binding channel of APN reside in cavities with wide openings, allowing easy access to peptides. The cavities can potentially open up further to bind the exposed N terminus of proteins. The active site anchors the N-terminal neutral residue of peptides/proteins, and the peptide-binding channel binds the remainder of the peptides/proteins in a sequence-independent fashion. APN also provides an exposed outer surface for coronavirus binding, without its physiological functions being affected. These structural features enable APN to function ubiquitously in peptide metabolism, interact with other proteins to mediate cell motility and adhesion, and serve as a coronavirus receptor. This study elucidates multifunctional roles of APN and can guide therapeutic efforts to treat APN-related diseases.
Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells
Authors: Varvel Nicholas H. , Grathwohl Stefan A. , Baumann Frank , Liebig Christian , Bosch Andrea , Brawek Bianca , Thal Dietmar R. , Charo Israel F. , Heppner Frank L. , Aguzzi Adriano , Garaschuk Olga , Ransohoff Richard M. , Jucker Mathias
Published: October 2012

Under most physiological circumstances, monocytes are excluded from parenchymal CNS tissues. When widespread monocyte entry occurs, their numbers decrease shortly after engraftment in the presence of microglia. However, some disease processes lead to focal and selective loss, or dysfunction, of microglia, and microglial senescence typifies the aged brain. In this regard, the long-term engraftment of monocytes in the microglia-depleted brain remains unknown. Here, we report a model in which a niche for myeloid cells was created through microglia depletion. We show that microglia-depleted brain regions of
CD11b-HSVTK
transgenic mice are repopulated with new Iba-1-positive cells within 2 wk. The engrafted cells expressed high levels of CD45 and CCR2 and appeared in a wave-like pattern frequently associated with blood vessels, suggesting the engrafted cells were peripheral monocytes. Although two times more numerous and morphologically distinct from resident microglia up to 27 wk after initial engraftment, the overall distribution of the engrafted cells was remarkably similar to that of microglia. Two-photon in vivo imaging revealed that the engrafted myeloid cells extended their processes toward an ATP source and displayed intracellular calcium transients. Moreover, the engrafted cells migrated toward areas of kainic acid-induced neuronal death. These data provide evidence that circulating monocytes have the potential to occupy the adult CNS myeloid niche normally inhabited by microglia and identify a strong homeostatic drive to maintain the myeloid component in the mature brain.
Evolution of lanthipeptide synthetases
Authors: Zhang Qi , Yu Yi , Vélasquez Juan E. , van der Donk Wilfred A.
Published: October 2012

Lanthionine-containing peptides (lanthipeptides) are a family of ribosomally synthesized and posttranslationally modified peptides containing (methyl)lanthionine residues. Here we present a phylogenomic study of the four currently known classes of lanthipeptide synthetases (LanB and LanC for class I, LanM for class II, LanKC for class III, and LanL for class IV). Although they possess very similar cyclase domains, class II–IV synthetases have evolved independently, and LanB and LanC enzymes appear to not always have coevolved. LanM enzymes from various phyla that have three cysteines ligated to a zinc ion (as opposed to the more common Cys-Cys-His ligand set) cluster together. Most importantly, the phylogenomic data suggest that for some scaffolds, the ring topology of the final lanthipeptides may be determined in part by the sequence of the precursor peptides and not just by the biosynthetic enzymes. This notion was supported by studies with two chimeric peptides, suggesting that the nisin and prochlorosin biosynthetic enzymes can produce the correct ring topologies of epilancin 15X and lacticin 481, respectively. These results highlight the potential of lanthipeptide synthetases for bioengineering and combinatorial biosynthesis. Our study also demonstrates unexplored areas of sequence space that may be fruitful for genome mining.
Quantification of lymph node transit times reveals differences in antigen surveillance strategies of naïve CD4
+
and CD8
+
T cells
Authors: Mandl Judith N. , Liou Rachel , Klauschen Frederick , Vrisekoop Nienke , Monteiro João P. , Yates Andrew J. , Huang Alex Y. , Germain Ronald N.
Published: October 2012

Naïve T cells continually recirculate between blood and secondary lymphoid organs, scanning dendritic cells (DC) for foreign antigen. Despite its importance for understanding how adaptive immune responses are efficiently initiated from rare precursors, a detailed quantitative analysis of this fundamental process has not been reported. Here we measure lymph node (LN) entry, transit, and exit rates for naïve CD4
+
and CD8
+
T cells, then use intravital imaging and mathematical modeling to relate cell–cell interaction dynamics to population behavior. Our studies reveal marked differences between CD4
+
vs. CD8
+
T cells. CD4
+
T cells recirculate more rapidly, homing to LNs more efficiently, traversing LNs twice as quickly, and spending ∼1/3 of their transit time interacting with MHCII on DC. In contrast, adoptively transferred CD8
+
T cells enter and leave the LN more slowly, with a transit time unaffected by the absence of MHCI molecules on host cells. Together, these data reveal an unexpectedly asymmetric role for MHC interactions in controlling CD4
+
vs. CD8
+
T lymphocyte recirculation, as well as distinct contributions of T cell receptor (TCR)-independent factors to the LN transit time, exposing the divergent surveillance strategies used by the two lymphocyte populations in scanning for foreign antigen.
Comparative analyses of evolutionary rates reveal different pathways to encephalization in bats, carnivorans, and primates
Authors: Smaers Jeroen B. , Dechmann Dina K. N. , Goswami Anjali , Soligo Christophe , Safi Kamran
Published: October 2012

Variation in relative brain size is commonly interpreted as the result of selection on neuronal capacity. However, this approach ignores that relative brain size is also linked to another highly adaptive variable: body size. Considering that one-way tradeoff mechanisms are unlikely to provide satisfactory evolutionary explanations, we introduce an analytical framework that describes and quantifies all possible evolutionary scenarios between two traits. To investigate the effects of body mass changes on the interpretation of relative brain size evolution, we analyze three mammalian orders that are expected to be subject to different selective pressures on body size due to differences in locomotor adaptation: bats (powered flight), primates (primarily arboreal), and carnivorans (primarily terrestrial). We quantify rates of brain and body mass changes along individual branches of phylogenetic trees using an adaptive peak model of evolution. We find that the magnitude and variance of the level of integration of brain and body mass rates, and the subsequent relative influence of either brain or body size evolution on the brain–body relationship, differ significantly between orders and subgroups within orders. Importantly, we find that variation in brain–body relationships was driven primarily by variability in body mass. Our approach allows a more detailed interpretation of correlated trait evolution and variation in the underlying evolutionary pathways. Results demonstrate that a principal focus on interpreting relative brain size evolution as selection on neuronal capacity confounds the effects of body mass changes, thereby hiding important aspects that may contribute to explaining animal diversity.
An original mode of symbiosis in open ocean plankton
Authors: Decelle Johan , Probert Ian , Bittner Lucie , Desdevises Yves , Colin Sébastien , de Vargas Colomban , Galí Martí , Simó Rafel , Not Fabrice
Published: October 2012

Symbiotic relationships are widespread in nature and are fundamental for ecosystem functioning and the evolution of biodiversity. In marine environments, photosymbiosis with microalgae is best known for sustaining benthic coral reef ecosystems. Despite the importance of oceanic microbiota in global ecology and biogeochemical cycles, symbioses are poorly characterized in open ocean plankton. Here, we describe a widespread symbiotic association between Acantharia biomineralizing microorganisms that are abundant grazers in plankton communities, and members of the haptophyte genus
Phaeocystis
that are cosmopolitan bloom-forming microalgae. Cophylogenetic analyses demonstrate that symbiont biogeography, rather than host taxonomy, is the main determinant of the association. Molecular dating places the origin of this photosymbiosis in the Jurassic (ca. 175 Mya), a period of accentuated marine oligotrophy. Measurements of intracellular dimethylated sulfur indicate that the host likely profits from antioxidant protection provided by the symbionts as an adaptation to life in transparent oligotrophic surface waters. In contrast to terrestrial and marine symbioses characterized to date, the symbiont reported in this association is extremely abundant and ecologically active in its free-living phase. In the vast and barren open ocean, partnership with photosymbionts that have extensive free-living populations is likely an advantageous strategy for hosts that rely on such interactions. Discovery of the Acantharia–
Phaeocystis
association contrasts with the widely held view that symbionts are specialized organisms that are rare and ecologically passive outside the host.
Combined targeting of HER2 and VEGFR2 for effective treatment ofHER2-amplified breast cancer brain metastases
Authors: Kodack David P. , Chung Euiheon , Yamashita Hiroshi , Incio Joao , Duyverman Annique M. M. J. , Song Youngchul , Farrar Christian T. , Huang Yuhui , Ager Eleanor , Kamoun Walid , Goel Shom , Snuderl Matija , Lussiez Alisha , Hiddingh Lotte , Mahmood Sidra , Tannous Bakhos A. , Eichler April F. , Fukumura Dai , Engelman Jeffrey A. , Jain Rakesh K.
Published: October 2012

Brain metastases are a serious obstacle in the treatment of patients withhuman epidermal growth factor receptor-2(HER2)–amplified breast cancer. Although extracranial disease is controlled with HER2 inhibitors in the majority of patients, brain metastases often develop. Because these brain metastases do not respond to therapy, they are frequently the reason for treatment failure. We developed a mouse model ofHER2-amplified breast cancer brain metastasis using an orthotopic xenograft of BT474 cells. As seen in patients, the HER2 inhibitors trastuzumab and lapatinib controlled tumor progression in the breast but failed to contain tumor growth in the brain. We observed that the combination of a HER2 inhibitor with an anti–VEGF receptor-2 (VEGFR2) antibody significantly slows tumor growth in the brain, resulting in a striking survival benefit. This benefit appears largely due to an enhanced antiangiogenic effect: Combination therapy reduced both the total and functional microvascular density in the brain xenografts. In addition, the combination therapy led to a marked increase in necrosis of the brain lesions. Moreover, we observed even better antitumor activity after combining both trastuzumab and lapatinib with the anti-VEGFR2 antibody. This triple-drug combination prolonged the median overall survival fivefold compared with the control-treated group and twofold compared with either two-drug regimen. These findings support the clinical development of this three-drug regimen for the treatment ofHER2-amplified breast cancer brain metastases.
Arabidopsis
proline-rich protein important for development and abiotic stress tolerance is involved in microRNA biogenesis
Authors: Zhan Xiangqiang , Wang Bangshing , Li Hongjiang , Liu Renyi , Kalia Rajwant K. , Zhu Jian-Kang , Chinnusamy Viswanathan
Published: October 2012

MicroRNAs (miRNAs) are important for plant development and stress responses. However, factors regulating miRNA metabolism are not completely understood. SICKLE (SIC), a proline-rich protein critical for development and abiotic stress tolerance of
Arabidopsis
, was identified in this study. Loss-of-function
sic
-1
mutant plants exhibited a serrated, sickle-like leaf margin, reduced height, delayed flowering, and abnormal inflorescence phyllotaxy, which are common characteristics of mutants involved in miRNA biogenesis. The
sic-1
mutant plants accumulated lower levels of a subset of miRNAs and transacting siRNAs but higher levels of corresponding primary miRNAs than the WT. The SIC protein colocalizes with the miRNA biogenesis component HYL1 in distinct subnuclear bodies.
sic-1
mutant plants also accumulated higher levels of introns from hundreds of loci. In addition,
sic-1
mutant plants are hypersensitive to chilling and salt stresses. These results suggest that SIC is a unique factor required for the biogenesis of some miRNAs and degradation of some spliced introns and important for plant development and abiotic stress responses.
N-terminal domain of vacuolar SNARE Vam7p promotes
trans
-SNARE complex assembly
Authors: Xu Hao , Wickner William T.
Published: October 2012

SNARE-dependent membrane fusion in eukaryotic cells requires that the heptad-repeat SNARE domains from R- and Q-SNAREs, anchored to apposed membranes, assemble into four-helix coiled-coil bundles. In addition to their SNARE and transmembrane domains, most SNAREs have N-terminal domains (N-domains), although their functions are unclear. The N-domain of the yeast vacuolar Qc-SNARE Vam7p is a binding partner for the homotypic fusion and vacuole protein sorting complex (a master regulator of vacuole fusion) and has Phox homology, providing a phosphatidylinositol 3-phosphate (PI3P)-specific membrane anchor. We now report that this Vam7p N-domain has yet another role, one that does not depend on its physical connection to the Vam7p SNARE domain. By attaching a transmembrane anchor to the C terminus of Vam7p to create Vam7tm, we bypass the requirement for the N-domain to anchor Vam7tm to reconstituted proteoliposomes. The N-domain of Vam7tm is indispensible for
trans
-SNARE complex assembly in SNARE-only reactions. Introducing Vam7(1-125)p as a separate recombinant protein suppresses the defect caused by N-domain deletion from Vam7tm, demonstrating that the function of this N-domain is not constrained to covalent attachment to Vam7p. The Vam7p N-domain catalyzes the docking of apposed membranes by promoting transinteractions between R- and Q-SNAREs. This function of the Vam7p N-domain depends on the presence of PI3P and its affinity for PI3P. Added N-domain can even promote SNARE complex assembly when Vam7 still bears its own N-domain.
Enhancing national solidarity through the deployment of verbal categories
Authors: Friedman Victor A.
Published: October 2012

The deployment of the Albanian admirative as well as the evidential particles kinse ‘allegedly’ and gjoja ‘supposedly’ in Kosovar electronic news sources to render either dubitative or neutral reports — depending on both the source and the timing — contributed to the project of an independent Kosovo. The usages can be divided into three periods: 1994–1997, 1998–1999, and post-1999. During the first period, usage was exclusively dubitative and deployed for Serbian news sources. During the second period, which corresponded to the intensification of the armed uprising, usage shifted to neutrality, and during the third period, after the NATO bombing campaign, it returned somewhat to dubitativity, this time aimed at UN and NATO sources. The discussion demonstrates how pragmatics and grammatical categories contribute to the construction of political narratives and argues that a socially informed linguistic analysis is crucial to understanding how politics is performed in the world.
From quotative other to quotative self
Authors: Nuckolls Janis
Published: October 2012

Evidentials in Pastaza Quichua, an Amazonian dialect of Ecuadorian Quechua, are examined and their uses in narratives compared. The novel contribution of this paper is to show, by comparing data from personal experience narratives, that evidentials are used to convey speaker subjectivity, rather than source of information, and that switches between different speaker subjectivities, which may be encoded as ‘selves’ or ‘others’, are particularly evident in passages where momentous, life-changing statuses or interpersonal upheavals are being articulated.
“Watching for witness”
Authors: Mushin Ilana
Published: October 2012

Linguistic forms with dedicated evidential meanings have been described for a number of Australian languages (eg. Donaldson 1980, Laughren 1982, Wilkins 1989) but there has been little written on how these are used in social interaction. This paper examines evidential strategies in ordinary Garrwa conversations, by taking into account what we know more generally about the status of knowledge and epistemic authority in Aboriginal societies, and applying this understanding to account for the ways knowledge is managed in ‘ordinary’ interactions.
Nanti self-quotation
Authors: Michael Lev
Published: October 2012

This paper describes two quotation strategies employed by speakers of Nanti, one involving grammaticalized quotatives and another involving complement-taking verbs of saying, and examines the consequences of the pragmatic differences between these strategies for two key questions in the study of evidentiality: first, the importance of degree of grammaticalization in delimiting ‘evidentials’; and second, the importance of the analytical distinction between epistemic modal and ‘source of information’ evidential meanings. Nanti use of the two quotation strategies is specifically analyzed in the context of self-quotation practices in order to isolate specific aspects of their pragmatics. This analysis shows that the lexical quotative strategy expresses that the quoted party is not only the source of the content of the utterance, but is also an ‘illocutionary source’, who is committed to the interactional force of the utterance, while the grammaticalized quotative strategy does not indicate such a commitment. The functional difference between lexical and grammatical quotative strategies in Nanti is compared with differences between lexical and grammaticalized quotative and reportive strategies found in other languages, and the Nanti results are found to be consistent with cross-linguistic tendencies towards functional differentiation of lexical quotative and reportives, on the one hand, and their grammaticalized counterparts, on the other. These facts, it is argued, motivate a distinction on functional grounds between grammaticalized reportives and quotatives and their lexical counterparts, supporting the use of grammaticalization as a criterion for distinguishing evidentials proper from evidential strategies. The commitment-augmenting function of the lexical quotative construction in Nanti self-quotation is then examined in light of the commitment-diminishing function commonly attributed to quotatives and reportives (and also found in Nanti). It is argued that both types of commitment-modulating effects emerge as implicatures from the basic information and illocutionary source semantics of Nanti lexical quotatives, and from pragmatic reasoning based on whether the quoted party is first person or third person. The fact that both commitment-modulating functions of Nanti lexical quotatives are derived from semantics of lexical quotatives elements is argued to show that the distinction between information source and epistemic modal meanings, often taken to be a pivotal notional distinction in defining evidentiality as a grammatical category, is also essential to the proper analysis of the pragmatics of evidential strategies in discourse.
Migration Strategies of Adult Chinook Salmon Runs in Response to Diverse Environmental Conditions in the Klamath River Basin
Authors: Strange Joshua S.
Published: October 2012

Biotelemetry and body temperature records of 130 adult Chinook salmon Oncorhynchus tshawytscha tagged over multiple years were used to investigate migration behaviors in response to diverse riverine conditions within the context of run timing strategies in a single river system. Four distinct runs were identified: Klamath–Trinity spring run, Trinity summer run, Klamath fall run, and Trinity fall run. Only the timing of Klamath–Trinity spring‐run and Trinity fall‐run Chinook salmon tended to prevent fish exposure to adversely high river temperatures. Faster migration rates reduced the accumulation of thermal units regardless of river temperature, especially at migration rates ≥10 km/d. Behavioral thermoregulation was minimal for all run groups (8% of all migrants), typically brief (<12 h) during summer months at nonnatal tributary confluences. Spring‐run fish migrating on the descending limb of the snowmelt peak experienced increased accumulated thermal units due to slow migration rates, resulting in more elevated relative disease risk with lower apparent migration success than rapidly migrating summer‐run fish. Klamath fall‐run fish held extensively in the lower Klamath River regardless of date or river condition, resulting in the highest cumulative thermal experience of all run groups with moderate thermal stress. Trinity fall‐run fish experienced minimal thermal stress due to their later run timing. Results demonstrate the need to comprehensively investigate fish migrations in order to detect potentially subtle but important context‐sensitive dynamics between migration behaviors and environmental conditions that can impact the viability of salmon populations. This study's findings highlight concerns regarding global warming and vulnerability runs of salmon that migrate in the late spring and early fall in the absence of adaptive shifts in run timing or appropriate human intervention. Conversely, these results also demonstrate the unexpected ability of adult Chinook salmon to migrate successfully through surprisingly warm temperatures and endure acute thermal stress if sufficiently large volumes of cold water await them at their destination.
Largemouth Bass Predation Effect on Stocked Walleye Survival in Illinois Impoundments
Authors: Freedman Jonathan A. , Hoxmeier R. John H. , Einfalt Lisa M. , Brooks Ronald C. , Wahl David H.
Published: October 2012

Survival of stocked fish can be mediated by biotic factors such as size and species, predators, and prey, and abiotic influences such as temperature and habitat. Walleyes Sander vitreus are numerically among the most stocked fish in the USA, yet stocking success of this species is highly variable. We examined the effects of predation by largemouth bass Micropterus salmoides on walleyes across 77 stocking events in 10 Illinois impoundments. Predation mortality was assessed by examining diets of largemouth bass for up to 21 d post walleye stocking. Of 8,591 largemouth bass diets examined, 2.0% contained walleye, corresponding to 4.3% walleye mortality attributable to largemouth bass predation. Largemouth bass predation was greatest within 24 h of stocking, and no predation was observed after 14 d. Predation mortality and fall CPUE of walleyes were related to largemouth bass density; however, we found no relationship between predation mortality and fall CPUE of walleyes. Our results suggest that predation by largemouth bass, a widespread and abundant predator, has a negligible effect on walleye stocking success in Illinois impoundments.

Received September 12, 2011; accepted July 18, 2012
Spring Viremia of Carp Virus in Minnehaha Creek, Minnesota
Authors: Phelps Nicholas B. D. , Armién Aníbal G. , Mor Sunil K. , Goyal Sagar M. , Warg Janet V. , Bhagyam Ranjit , Monahan Tim
Published: October 2012

Spring viremia of carp virus (SVCV) causes a highly contagious and serious disease of freshwater cyprinid fishes, generating significant economic and ecological impacts throughout the world. The SVCV is therefore listed as a notifiable pathogen by the International Organization for Animal Health. In June 2011, a significant mortality event of wild common carp Cyprinus carpio occurred in Minnehaha Creek near its confluence with Mississippi River Pool 2 in Minneapolis, Minnesota. Clinical signs of moribund fish included hemorrhagic lesions in the skin, eyes, and internal adipose tissue. The SVCV was isolated from pooled kidney and spleen of the fish. Rhabdovirus particles were seen upon examination of infected cell culture fluid by electron microscopy. The virus was confirmed to be SVCV subtype Ia by reverse transcription PCR and sequencing. This is the first report of SVCV within the state of Minnesota and the ninth documented case in North America.

Received March 27, 2012; accepted July 2, 2012