bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral suppressors of the RIG-I-mediated interferon response are pre-packaged in influenza virions
Authors: Liedmann Swantje , Hrincius Eike R. , Guy Cliff , Anhlan Darisuren , Dierkes Rüdiger , Carter Robert , Wu Gang , Staeheli Peter , Green Douglas R. , Wolff Thorsten , McCullers Jonathan A. , Ludwig Stephan , Ehrhardt Christina 
Published: December 2014

AbstractThe type I interferon (IFN) response represents the first line of defence to invading pathogens. Internalized viral ribonucleoproteins (vRNPs) of negative-strand RNA viruses induce an early IFN response by interacting with retinoic acid inducible gene I (RIG-I) and its recruitment to mitochondria. Here we employ three-dimensional stochastic optical reconstruction microscopy (STORM) to visualize incoming influenza A virus (IAV) vRNPs as helical-like structures associated with mitochondria. Unexpectedly, an early IFN induction in response to vRNPs is not detected. A distinct amino-acid motif in the viral polymerases, PB1/PA, suppresses early IFN induction. Mutation of this motif leads to reduced pathogenicity in vivo, whereas restoration increases it. Evolutionary dynamics in these sequences suggest that completion of the motif, combined with viral reassortment can contribute to pandemic risks. In summary, inhibition of the immediate anti-viral response is ‘pre-packaged’ in IAV in the sequences of vRNP-associated polymerase proteins.
OM14 is a mitochondrial receptor for cytosolic ribosomes that supports co-translational import into mitochondria
Authors: Lesnik Chen , Cohen Yifat , Atir-Lande Avigail , Schuldiner Maya , Arava Yoav 
Published: December 2014

AbstractIt is well established that import of proteins into mitochondria can occur after their complete synthesis by cytosolic ribosomes. Recently, an additional model was revived, proposing that some proteins are imported co-translationally. This model entails association of ribosomes with the mitochondrial outer membrane, shown to be mediated through the ribosome-associated chaperone nascent chain-associated complex (NAC). However, the mitochondrial receptor of this complex is unknown. Here, we identify the Saccharomyces cerevisiae outer membrane protein OM14 as a receptor for NAC. OM14Δ mitochondria have significantly lower amounts of associated NAC and ribosomes, and ribosomes from NAC[Δ] cells have reduced levels of associated OM14. Importantly, mitochondrial import assays reveal a significant decrease in import efficiency into OM14Δ mitochondria, and OM14-dependent import necessitates NAC. Our results identify OM14 as the first mitochondrial receptor for ribosome-associated NAC and reveal its importance for import. These results provide a strong support for an additional, co-translational mode of import into mitochondria.
High-energy chemistry of formamide: A unified mechanism of nucleobase formation
Authors: Ferus Martin , Nesvorný David , Šponer Jiří , Kubelík Petr , Michalčíková Regina , Shestivská Violetta , Šponer Judit E. , Civiš Svatopluk 
Published: December 2014

Significance
This paper addresses one of the central problems of the origin of life research, i.e., the scenario suggesting extraterrestrial impact as the source of biogenic molecules. Likewise, the results might be relevant in the search of biogenic molecules in the universe. The work is therefore highly actual and interdisciplinary. It could be interesting for a very broad readership, from physical and organic chemists to synthetic biologists and specialists in astrobiology.
Single-chain protein mimetics of the N-terminal heptad-repeat region of gp41 with potential as anti–HIV-1 drugs
Authors: Crespillo Sara , Cámara-Artigas Ana , Casares Salvador , Morel Bertrand , Cobos Eva S. , Mateo Pedro L. , Mouz Nicolas , Martin Christophe E. , Roger Marie G. , El Habib Raphaelle , Su Bin , Moog Christiane , Conejero-Lara Francisco 
Published: December 2014

Significance
The envelope subunit gp41 is an attractive target for therapeutic intervention against HIV-1. Interfering with the interaction between the heptad-repeat regions of gp41 is a promising approach to inhibit HIV-1 fusion to the host cell membrane. Here, we present an alternative rational design and protein-engineering approach to produce highly stable single-chain proteins that accurately mimic the trimeric coiled-coil surface of the gp41 N-terminal heptad repeat. This approach has a strong potential for development to HIV-1 drugs, vaccines, or microbicides and could be extendable to the design of proteins interfering with other types of coiled-coil interactions.
Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells
Authors: Gaub Benjamin M. , Berry Michael H. , Holt Amy E. , Reiner Andreas , Kienzler Michael A. , Dolgova Natalia , Nikonov Sergei , Aguirre Gustavo D. , Beltran William A. , Flannery John G. , Isacoff Ehud Y. 
Published: December 2014

Significance
We restored visual function to animal models of human blindness using a chemical compound that photosensitizes a mammalian ion channel. Virus-mediated expression of this light sensor in surviving retinal cells of blind mice restored light responses in vitro, reanimated innate light avoidance, and enabled learned visually guided behavior. The treatment also restored light responses to the retina of blind dogs. Patients that might benefit from this treatment would need to have intact ganglion cell and nerve fiber layers. In general, these are patients diagnosed with retinitis pigmentosa and some forms of Leber congenital amaurosis. Patients diagnosed with other types of blindness, for example, age-related macular degeneration or diabetic retinopathy, would not be candidates for this treatment.
Automated analysis of immunohistochemistry images identifies candidate location biomarkers for cancers
Authors: Kumar Aparna , Rao Arvind , Bhavani Santosh , Newberg Justin Y. , Murphy Robert F. 
Published: December 2014

SignificanceChanges in the expression of proteins are often associated with oncogenesis, and are frequently used as cancer biomarkers. Changes in the subcellular location of proteins have been less frequently investigated. In this paper, we describe a robust pipeline for identifying those proteins whose subcellular location undergoes statistically significant changes in cancers of four tissues, and also for identifying biochemical pathways that are enriched for proteins that translocate. Future investigation of these proteins and pathways may provide new insight into oncogenesis. Further, the analysis pipeline is expected to be useful for assessing disease type and severity in a clinical setting.
Optogenetic activation of GnRH neurons reveals minimal requirements for pulsatile luteinizing hormone secretion
Authors: Campos Pauline , Herbison Allan E. 
Published: December 2014

Significance
The mammalian reproductive system is critically dependent upon pulsatile hormone release patterned and driven by a small population of gonadotropin-releasing hormone (GnRH) neurons. The scattered distribution of GnRH neurons within the brain has made it extremely difficult to investigate the nature and properties of these cells in any selective manner in vivo. We report here a procedure that enables selective, high-fidelity activation of the GnRH neurons that control gonadotropin secretion in ovariectomized mice. Using this approach, we have been able to define minimal parameters of activation required to generate pulsatile gonadotropin secretion in the blood. This provides critical information for understanding and manipulating the genesis of gonadotropin pulsatility in reproductive biology.
Dopamine-associated cached values are not sufficient as the basis for action selection
Authors: Hollon Nick G. , Arnold Monica M. , Gan Jerylin O. , Walton Mark E. , Phillips Paul E. M. 
Published: December 2014

Significance
Real-world decisions frequently involve tradeoffs between multiple economic dimensions, and integration of benefits and costs into a common currency of subjective value is fundamental to action selection. Phasic dopamine is widely regarded as a critical teaching signal for learning the values assigned to actions, and these stored (“cached”) values can be read out from cue-evoked dopamine responses. Here, we observed a significant inversion between animals’ behavioral preferences and the rank ordering of dopamine-reported cached values, indicating that these cached values cannot be the sole determinant of choices in simple economic decision making. These data challenge the fundamental tenet of contemporary theories of decision making which posit that dopamine-associated cached values are sufficient to serve as the basis for action selection.
Dual-specificity phosphatase 5 regulates nuclear ERK activity and suppresses skin cancer by inhibiting mutant Harvey-Ras (HRas
Q61L
)-driven SerpinB2 expression
Authors: Rushworth Linda K. , Kidger Andrew M. , Delavaine Laurent , Stewart Graeme , van Schelven Susanne , Davidson Jane , Bryant Christopher J. , Caddye Edward , East Philip , Caunt Christopher J. , Keyse Stephen M. 
Published: December 2014

Significance
Ras/extracellular signal-regulated kinase (ERK) signaling is implicated in human cancer development and progression. ERK activation also results in the expression of MAP kinase phosphatases (MKPs) that inactivate ERK. However, it is currently unclear how MKPs regulate the oncogenic potential of the Ras/ERK pathway. Using knockout mice, we identify the MKP encoded by dual-specificity phosphatase 5 (DUSP5) as both a key regulator of nuclear ERK activity and a tumor suppressor in the DMBA/TPA model of Harvey Ras (HRas)-induced skin carcinogenesis. DUSP5 loss results in increased HRas/ERK-inducible SerpinB2 expression, which causes increased skin cancer sensitivity. Our results establish a key role for DUSP5 in the regulation of oncogenic ERK signaling and suggest that this enzyme may play a wider role in tumors containing activated Ras.
A partial hominoid innominate from the Miocene of Pakistan: Description and preliminary analyses
Authors: Morgan Michèle E. , Lewton Kristi L. , Kelley Jay , Otárola-Castillo Erik , Barry John C. , Flynn Lawrence J. , Pilbeam David 
Published: December 2014

SignificanceThe living apes share a number of important morphological similarities of torso and limbs; torsos are broad and shallow, lumbar regions short, and forelimbs adapted to mobility. For more than a century it was assumed that most of these similarities are homologous, reflecting descent from a common ancestor with these features. As the ape fossil record slowly expands, the story becomes more complicated, particularly in the case of the south Asian Miocene apeSivapithecus.Sivapithecushas facial features resembling specifically the living orangutan, but no postcranial features resembling orangutans. This newly described hipbone differs from that of all living apes. Either postcranial similarities of apes are not fully homologous or the facial similarities ofSivapithecusand orangutans cannot be homologous.
Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training
Authors: Morena Maria , Roozendaal Benno , Trezza Viviana , Ratano Patrizia , Peloso Andrea , Hauer Daniela , Atsak Piray , Trabace Luigia , Cuomo Vincenzo , McGaugh James L. , Schelling Gustav , Campolongo Patrizia 
Published: December 2014

Significance
An involvement of exogenous cannabinoids in the regulation of memory for emotional events has emerged over the past decade. The present findings demonstrate that after an aversive training experience the endogenous cannabinoid anandamide is released into the amygdala, hippocampus, and medial prefrontal cortex (mPFC) and normally plays a role in the formation of a strong memory trace. Furthermore, an intact basolateral amygdala is required to coordinate both hippocampal and mPFC endocannabinoid activity during aversive memory consolidation. Thus, our findings provide the first evidence, to our knowledge, that a dynamic network involving anandamide signaling within this prefrontal-limbic circuit modulates the consolidation of memory for emotionally arousing training.
Place cells in the hippocampus: Eleven maps for eleven rooms
Authors: Alme Charlotte B. , Miao Chenglin , Jezek Karel , Treves Alessandro , Moser Edvard I. , Moser May-Britt 
Published: December 2014

Significance
The hippocampus is thought to store a large number of experiences that, despite their similarity, can be individually retrieved with minimal interference. Studies have shown that place cells in hippocampal area CA3 form statistically independent representations of pairs of environments. It has remained unclear, however, whether CA3 place cells maintain this independence when the number of environments is increased. We recorded activity from CA3 in 11 environments with nearly identical geometric features. Spatial firing patterns remained uncorrelated across all 55 pairs of environments, with minimal overlap in the populations of active cells. The data suggest that the capacity of the CA3 network is large and speak against extensive recurrence of spatial motifs across experiences.
HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models
Authors: Whitesell Luke , Santagata Sandro , Mendillo Marc L. , Lin Nancy U. , Proia David A. , Lindquist Susan 
Published: December 2014

Significance
Although hormonal therapies for estrogen receptor-positive (ER+) breast cancer make up the earliest, and arguably most effective, “molecularly targeted” anticancer drugs, continued progress in controlling metastatic disease has been slow. Heterogeneity and the complexity of signaling in advanced cancers have frustrated efforts to prevent the rapid evolution of resistance to hormonal therapies, as well as kinase inhibitors and other agents. On the basis of earlier work defining the role of heat shock protein 90 (HSP90) in other evolutionary processes, we tested whether low-level HSP90 inhibition would limit the evolution of hormone resistance in breast cancer models. Results in culture and in mice provide support for a readily implemented strategy by which the heterogeneity and evolvability of metastatic ER+ breast tumors, and perhaps other advanced cancers, might be controlled.
Cortical plasticity induced by transplantation of embryonic somatostatin or parvalbumin interneurons
Authors: Tang Yunshuo , Stryker Michael P. , Alvarez-Buylla Arturo , Espinosa Juan Sebastian 
Published: December 2014

Significance
The cerebral cortex contains two major types of interneurons that are implicated in epilepsy and neurodegenerative diseases. Here we determined their role in the induction of critical period plasticity, a form of circuit modification essential for brain maturation and repair. Surprisingly, transplantation of either cell type was sufficient to induce critical period plasticity. The work provides insight into the cellular mechanisms that shape brain circuits during key periods of development and defines populations of inhibitory nerve cells sufficient to induce plastic changes that could help in the treatment of brain diseases.
DensiTree 2: Seeing Trees Through the Forest
Authors: Bouckaert Remco R. , Heled Joseph 
Published: December 2014

AbstractMotivationPhylogenetic analysis like Bayesian MCMC or bootstrapping result in a collection of trees. Trees are discrete objects and it is generally difficult to get a mental grip on a distributions over trees. Visualisation tools like DensiTree can give good intuition on tree distributions. It works by drawing all trees in the set transparently thus highlighting areas where the tree in the set agrees. In this way, both uncertainty in clade heights and uncertainty in topology can be visualised. In our experience, a vanilla DensiTree can turn out to be misleading in that it shows too much uncertainty due to wrongly ordering taxa or due to unlucky placement of internal nodes.ResultsDensiTree is extended to allow visualisation of meta-data associated with branches such as population size and evolutionary rates. Furthermore, geographic locations of taxa can be shown on a map, making it easy to visually check there is some geographic pattern in a phylogeny. Taxa orderings have a large impact on the layout of the tree set, and advances have been made in finding better orderings resulting in significantly more informative visualisations. We also explored various methods for positioning internal nodes, which can improve the quality of the image. Together, these advances make it easier to comprehend distributions over trees.AvailabilityDensiTree is freely available fromhttp://compevol.auckland.ac.nz/software/.
The Regulation of Photosynthetic Structure and Function during Nitrogen Deprivation in Chlamydomonas reinhardtii
Authors: Juergens Matthew T. , Deshpande Rahul R. , Lucker Ben F. , Park Jeong-Jin , Wang Hongxia , Gargouri Mahmoud , Holguin F. Omar , Disbrow Bradley , Schaub Tanner , Skepper Jeremy N. , Kramer David M. , Gang David R. , Hicks Leslie M. , Shachar-Hill Yair 
Published: December 2014

Abstract
The accumulation of carbon storage compounds by many unicellular algae after nutrient deprivation occurs despite declines in their photosynthetic apparatus. To understand the regulation and roles of photosynthesis during this potentially bioenergetically valuable process, we analyzed photosynthetic structure and function after nitrogen deprivation in the model alga Chlamydomonas reinhardtii. Transcriptomic, proteomic, metabolite, and lipid profiling and microscopic time course data were combined with multiple measures of photosynthetic function. Levels of transcripts and proteins of photosystems I and II and most antenna genes fell with differing trajectories; thylakoid membrane lipid levels decreased, while their proportions remained similar and thylakoid membrane organization appeared to be preserved. Cellular chlorophyll (Chl) content decreased more than 2-fold within 24 h, and we conclude from transcript protein and 13C labeling rates that Chl synthesis was down-regulated both pre- and posttranslationally and that Chl levels fell because of a rapid cessation in synthesis and dilution by cellular growth rather than because of degradation. Photosynthetically driven oxygen production and the efficiency of photosystem II as well as P700+ reduction and electrochromic shift kinetics all decreased over the time course, without evidence of substantial energy overflow. The results also indicate that linear electron flow fell approximately 15% more than cyclic flow over the first 24 h. Comparing Calvin-Benson cycle transcript and enzyme levels with changes in photosynthetic 13CO2 incorporation rates also pointed to a coordinated multilevel down-regulation of photosynthetic fluxes during starch synthesis before the induction of high triacylglycerol accumulation rates.
Protein Phosphatase 2A Holoenzyme Is Targeted to Peroxisomes by Piggybacking and Positively Affects Peroxisomal β-Oxidation
Authors: Kataya Amr R.A. , Heidari Behzad , Hagen Lars , Kommedal Roald , Slupphaug Geir , Lillo Cathrine 
Published: December 2014

Abstract
The eukaryotic, highly conserved serine (Ser)/threonine-specific protein phosphatase 2A (PP2A) functions as a heterotrimeric complex composed of a catalytic (C), scaffolding (A), and regulatory (B) subunit. In Arabidopsis (Arabidopsis thaliana), five, three, and 17 genes encode different C, A, and B subunits, respectively. We previously found that a B subunit, B′θ, localized to peroxisomes due to its C-terminal targeting signal Ser-Ser-leucine. This work shows that PP2A C2, C5, andA2 subunits interact and colocalize with B′θ in peroxisomes. C and A subunits lack peroxisomal targeting signals, and their peroxisomal import depends on B′θ and appears to occur by piggybacking transport. B′θ knockout mutants were impaired in peroxisomal β-oxidation as shown by developmental arrest of seedlings germinated without sucrose, accumulation of eicosenoic acid, and resistance to protoauxins indole-butyric acid and 2,4-dichlorophenoxybutyric acid. All of these observations strongly substantiate that a full PP2A complex is present in peroxisomes and positively affects β-oxidation of fatty acids and protoauxins.
Sexual signals for the colour‐blind: cryptic female mantids signal quality through brightness
Authors: Barry Katherine L. , White Thomas E. , Rathnayake Darshana N. , Fabricant Scott A. , Herberstein Marie E. 
Published: December 2014

Summary

Cryptic coloration may evolve in response to selective pressure imposed by predators, yet effective intraspecific communication may require some level of detectability. This creates a tension between the benefits of sexually selected visual traits and the predatory costs imposed by greater conspicuousness, and little is known about how this tension may be ameliorated in highly cryptic species.

We explore these competing demands in the false garden mantid Pseudomantis albofimbriata, a colour‐blind and seemingly cryptic insect. We use reflectance spectrometry and receptor‐noise modelling to characterize the conspicuousness of mantid body regions in the visual systems of mates (mantids), as well as potential predators (birds) and prey (bees). We then use condition manipulation and conspecific choice tests to further explore the colour traits of interest.

Based on visual modelling, we find that male mantids are inconspicuous to conspecifics, prey and predators – that is, they are chromatically and achromatically cryptic. In contrast, female mantids are chromatically cryptic to all potential receivers, but their abdomens are achromatically conspicuous. Our food manipulation experiment shows that females in good condition (and therefore with more eggs) have brighter abdomens than females in poor condition. Choice assays show male mantids are consistently attracted to females bearing brighter abdomens.

Our results reveal brightness‐mediated sexual signalling in a colour‐blind and classically cryptic insect. By communicating in the only visual channel available to them, female mantids are conspicuously signalling their quality to mates, while potentially minimizing their conspicuousness to predators and prey. Furthermore, by signalling with only a single body region, female mantids are apparently using coincident disruptive coloration to further decrease detectability to potential eavesdroppers.

Our data reveal a novel example of the way in which the trade‐off between sexual selection for conspicuousness and natural selection for crypsis may be mediated in a visual signalling system. Such signals may be common in apparently cryptic species, and this study once again demonstrates the importance of analysing visual signals beyond the capacity of human vision.