bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of heterogeneity and socioeconomic factors on individual behavior in decentralized sharing ecosystems
Authors: Gavaldà-Miralles Arnau , Choffnes David R. , Otto John S. , Sánchez Mario A. , Bustamante Fabián E. , Amaral Luís A. N. , Duch Jordi , Guimerà Roger
Published: October 2014

Significance

The emergence of the Internet as the primary medium for information exchange has led to the development of many decentralized sharing systems. The most popular among them, BitTorrent, is used by tens of millions of people monthly and is responsible for more than one-third of the total Internet traffic. Despite its growing social, economic, and technological importance, there is little understanding of how users behave in this ecosystem. Because of the decentralized structure of peer-to-peer services, it is very difficult to gather data on users behaviors, and it is in this sense that peer-to-peer file-sharing has been called the “dark matter” of the Internet. Here, we investigate users activity patterns and uncover socioeconomic factors that could explain their behavior.
Reputation and impact in academic careers
Authors: Petersen Alexander Michael , Fortunato Santo , Pan Raj K. , Kaski Kimmo , Penner Orion , Rungi Armando , Riccaboni Massimo , Stanley H. Eugene , Pammolli Fabio
Published: October 2014

Significance

Over a scientist’s career, a reputation is developed, a standing within a research community, based largely upon the quantity and quality of his/her publications. Here, we develop a framework for quantifying the influence author reputation has on a publication’s future impact. We find author reputation plays a key role in driving a paper’s citation count early in its citation life cycle, before a tipping point, after which reputation has much less influence relative to the paper’s citation count. In science, perceived quality, and decisions made based on those perceptions, is increasingly linked to citation counts. Shedding light on the complex mechanisms driving these quantitative measures facilitates not only better evaluation of scientific outputs but also a more transparent evaluation of the scientists producing them.
Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration
Authors: Sailland Juliette , Tribollet Violaine , Forcet Christelle , Billon Cyrielle , Barenton Bruno , Carnesecchi Julie , Bachmann Alice , Gauthier Karine Cécile , Yu Shan , Giguère Vincent , Chan Franky L. , Vanacker Jean-Marc
Published: October 2014

Significance

Several developmental and physiological processes require that cells display a controlled ability to migrate in an orientated manner. This capacity is also reacquired by certain cancer cells during their progression toward aggressiveness that allows them to establish distant metastases. The Rho GTPases are instrumental in the control of orientated migration. Here, we demonstrate that the estrogen-related receptor α (ERRα), whose high expression correlates with tumor aggressiveness and poor prognosis, decreases the stability and activity of the RHOA protein and induces orientated cell migration. Together with other published data, our results show that inactivation of ERRα may reduce tumor aggressiveness.
Netrin-4 regulates thalamocortical axon branching in an activity-dependent fashion
Authors: Hayano Yasufumi , Sasaki Kensuke , Ohmura Nami , Takemoto Makoto , Maeda Yurie , Yamashita Toshihide , Hata Yoshio , Kitada Kazuhiro , Yamamoto Nobuhiko
Published: October 2014

Significance

The environmental control of neuronal wiring is one of the most intriguing issues in neuroscience. However, the molecular mechanisms are largely unknown. Here, we demonstrate that the expression of the netrin family member netrin-4 (NTN4) is activity-dependent in the developing cortex and promotes terminal branching of thalamocortical axons. Evidence further shows that unc-5 homolog B (Unc5B), a putative receptor of NTN4, is expressed in the developing thalamus and mediates NTN4 signaling. These results suggest that NTN4 is the key molecule that underlies activity-dependent axon branch formation in neocortical circuits.
LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity
Authors: Tajan Mylène , Batut Aurélie , Cadoudal Thomas , Deleruyelle Simon , Le Gonidec Sophie , Saint Laurent Céline , Vomscheid Maëlle , Wanecq Estelle , Tréguer Karine , De Rocca Serra-Nédélec Audrey , Vinel Claire , Marques Marie-Adeline , Pozzo Joffrey , Kunduzova Oksana , Salles Jean-Pierre , Tauber Maithé , Raynal Patrick , Cavé Hélène , Edouard Thomas , Valet Philippe , Yart Armelle
Published: October 2014

Significance

LEOPARD syndrome (multiple
L
entigines,
E
lectrocardiographic conduction abnormalities,
O
cular hypertelorism,
P
ulmonary stenosis,
A
bnormal genitalia,
R
etardation of growth, sensorineural
D
eafness; LS) is a rare genetic disease associating various developmental defects mainly caused by inactivating mutations of the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). SHP2 is a key regulator of essential signaling pathways (MAPK, PI3K), which confer on SHP2 major roles in development and metabolism control. However, nothing is known about the metabolic status of LS. We thus performed an extensive metabolic exploration of an original LS mouse model. These mice display a lean phenotype (reduced adiposity, improved carbohydrate metabolism), translating into resistance to obesity and associated disorders upon obesogenic diet. This phenotype correlated with defective adipogenesis, better insulin signaling, and enhanced energy expenditure and was partially corrected by MAPK inhibition. Preliminary data in LS patients are in agreement with these findings.
Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein
Authors: Millet Jean Kaoru , Whittaker Gary R.
Published: October 2014

Significance

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV), a deadly human coronavirus, has triggered considerable interest in the biomedical community. Similar to other enveloped viruses, coronaviruses access host cells by membrane fusion, a process mediated by specific fusion or “spike” proteins on the virion, often activated by cellular proteases. We have identified unique features of the MERS-CoV spike (S) protein cleavage activation. Our findings suggest that S can be activated by furin, a broadly expressed protease, by a two-step cleavage mechanism, occurring at distinct sites, with cleavage events temporally separated. Such furin-mediated activation is unusual in that it occurs in part during virus entry. Our findings may explain the polytropic nature, pathogenicity, and life cycle of this zoonotic coronavirus.
Role of Erbin in ErbB2-dependent breast tumor growth
Authors: Tao Yanmei , Shen Chengyong , Luo Shiwen , Traoré Wilfried , Marchetto Sylvie , Santoni Marie-Josée , Xu Linlin , Wu Biao , Shi Chao , Mei Jinghong , Bates Ryan , Liu Xihui , Zhao Kai , Xiong Wen-Cheng , Borg Jean-Paul , Mei Lin
Published: October 2014

Significance

ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2) is overexpressed in around 25% of breast cancers. The present study reveals that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in
MMTV-neu
transgenic mice. Disruption of the interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in
MMTV-neu
mice. Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. ErbB2 and Erbin expression correlates in human breast tumor tissues. Thus, this study identifies the interaction of Erbin and ErbB2 as a novel drug target linking another clinical molecular target, HSP90, in ErbB2-positive breast cancer.
Structural basis of the regulatory mechanism of the plant CIPK family of protein kinases controlling ion homeostasis and abiotic stress
Authors: Chaves-Sanjuan Antonio , Sanchez-Barrena Maria Jose , Gonzalez-Rubio Juana Maria , Moreno Maria , Ragel Paula , Jimenez Marta , Pardo Jose M. , Martinez-Ripoll Martin , Quintero Francisco J. , Albert Armando
Published: October 2014

Significance

The transport of ions through the plant cell membrane establishes the key physicochemical parameters for cell function. Stress situations such as those created by soil salinity or low potassium conditions alter the ion transport across the membrane producing dramatic changes in the cell turgor, the membrane potential, and the intracellular pH and concentrations of toxic cations such as sodium and lithium. As a consequence, fundamental metabolic routes are inhibited. The CIPK family of 26 protein kinases regulates the function of several ion transporters at the cell membrane to restore ion homeostasis under stress situations. Our analyses provide an explanation on how the CIPKs are differentially activated to coordinate the adequate cell response to a particular stress.
The negligible chondritic contribution in the lunar soils water
Authors: Stephant Alice , Robert François
Published: October 2014

Significance

The hydrogen isotopic ratio of water is commonly used to identify water sources. However, because the Moon is an airless body, the external fluxes of particles and solids that reach its surface should represent an important contribution to its hydrogen budget and thus alter its pristine D/H ratio. To estimate the relative proportions of the solar wind and of the cosmogenic deuterium in the hydrogen budget, the lithium and the hydrogen isotope ratios were measured simultaneously with the Cameca NanoSIMS 50. Analyses demonstrate that all D comes from spallation reactions. On the surface of the soil grains, their D/H ratios indicate that this source of “water” can be ascribed to solar wind implantation and that the chondritic contribution is negligible.
Fluid-induced organic synthesis in the solar nebula recorded in extraterrestrial dust from meteorites
Authors: Vollmer Christian , Kepaptsoglou Demie , Leitner Jan , Busemann Henner , Spring Nicole H. , Ramasse Quentin M. , Hoppe Peter , Nittler Larry R.
Published: October 2014

Significance

Organic matter from the parent molecular cloud of our solar system can be located in primitive extraterrestrial samples like meteorites and cometary grains. This pristine matter contains among the most primitive organic molecules that were delivered to the early Earth 4.5 billion years ago. We have analyzed these organics by a high-resolution electron microscope that is exceptionally suited to study these beam-sensitive materials. Different carbon and nitrogen functional groups were identified on a submicron scale and can be attributed to early cometary and meteoritic organic reservoirs. Our results demonstrate for the first time to our knowledge that certain highly aromatic and nitrogen-containing ubiquitous organics were transformed from an oxygen-rich organic reservoir by parent body fluid synthesis in the early solar system.
Structure of the ArgRS–GlnRS–AIMP1 complex and its implications for mammalian translation
Authors: Fu Yaoyao , Kim Youngran , Jin Kyeong Sik , Kim Hyun Sook , Kim Jong Hyun , Wang DongMing , Park Minyoung , Jo Chang Hwa , Kwon Nam Hoon , Kim Doyeun , Kim Myung Hee , Jeon Young Ho , Hwang Kwang Yeon , Kim Sunghoon , Cho Yunje
Published: October 2014

Significance

In higher eukaryotes, aminoacyl-tRNA synthetases (ARSs) are assembled to form a multisynthetase complex (MSC), which plays critical roles in translation and nontranslation functions essential for cell growth and survival of organisms. The MSC complex is comprised of nine different ARSs and three accessary proteins. The crystal structure of the arginyl-tRNA synthetase (ArgRS)–glutaminyl-tRNA synthase–aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1) subcomplex reveals that the N-terminal domains of ArgRS and AIMP1 form an extended coiled-coil structure, which provides a central depot for the assembly of a ternary complex. The stability of the N-terminal helix of ArgRS is critical for its ARS activity and noncanonical function of the subcomplex, explaining the significance of the MSC structure in translation and cellular functions.
Cross-modal effects of value on perceptual acuity and stimulus encoding
Authors: Pooresmaeili Arezoo , FitzGerald Thomas H. B. , Bach Dominik R. , Toelch Ulf , Ostendorf Florian , Dolan Raymond J.
Published: October 2014

Significance

Reward-predicting signals could be acquired through any of our different sensory modalities, but should be used by other senses to achieve fast and accurate behavior. How reward information is communicated across different sensory modalities is unknown. We demonstrate that sounds associated with high rewards increase the sensitivity of vision, even when sounds and their reward associations are task-irrelevant. Multivariate analysis of the simultaneously acquired functional MRI data revealed that high-reward sounds increased the accuracy of stimulus representation in the visual cortex. Multisensory regions of the temporal cortex were modulated by sound values, and the strength of this modulation was correlated with the change in visual acuity. Our results demonstrate a value-driven cross-modal interaction that affects early stages of sensory processing and involves multisensory areas.
Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death
Authors: Hildebrand Joanne M. , Tanzer Maria C. , Lucet Isabelle S. , Young Samuel N. , Spall Sukhdeep K. , Sharma Pooja , Pierotti Catia , Garnier Jean-Marc , Dobson Renwick C. J. , Webb Andrew I. , Tripaydonis Anne , Babon Jeffrey J. , Mulcair Mark D. , Scanlon Martin J. , Alexander Warren S. , Wilks Andrew F. , Czabotar Peter E. , Lessene Guillaume , Murphy James M. , Silke John
Published: October 2014

Significance

The four-helix bundle (4HB) domain of Mixed Lineage Kinase Domain-Like (MLKL) bears two clusters of residues that are required for cell death by necroptosis. Mutations within a cluster centered on the α4 helix of the 4HB domain of MLKL prevented its membrane translocation, oligomerization, and ability to induce necroptosis. This cluster is composed principally of acidic residues and therefore challenges the idea that the 4HB domain engages negatively charged phospholipid membranes via a conventional positively charged interaction surface. The importance of membrane translocation to MLKL-mediated death is supported by our identification of a small molecule that binds the MLKL pseudokinase domain and retards membrane translocation to inhibit necroptotic signaling.
Human TLR10 is an anti-inflammatory pattern-recognition receptor
Authors: Oosting Marije , Cheng Shih-Chin , Bolscher Judith M. , Vestering-Stenger Rachel , Plantinga Theo S. , Verschueren Ineke C. , Arts Peer , Garritsen Anja , van Eenennaam Hans , Sturm Patrick , Kullberg Bart-Jan , Hoischen Alexander , Adema Gosse J. , van der Meer Jos W. M. , Netea Mihai G. , Joosten Leo A. B.
Published: October 2014

Significance

We demonstrate the biological role of TLR10, the only member of the Toll-like receptor (TLR)-family so far without a known function. We show that TLR10 acts as an inhibitory receptor, with suppressive effects. Blocking TLR10 by specific antibodies significantly upregulated TLR2-mediated cytokine production. Additionally, we show that individuals carrying loss-of-function SNPs in TLR10 display upregulation of TLR2-mediated cytokine production. After challenging human TLR10 transgenic mice with TLR2 ligand pam3CSK4 (Pam3Cys), less inflammation could be observed when compared with wild-type mice. Taking these data together, we show that TLR10 is the only pattern-recognition receptor within the TLR family that is able to dampen TLR2 responses, thereby suppressing immune responses through production of IL-1Ra.
Quantitation of interactions between two DNA loops demonstrates loop domain insulation in
E. coli
cells
Authors: Priest David G. , Kumar Sandip , Yan Yan , Dunlap David D. , Dodd Ian B. , Shearwin Keith E.
Published: October 2014

Significance

Genes are frequently regulated by interactions between proteins that bind to the DNA near the gene and proteins that bind to DNA sites located far away, with the intervening DNA looped out. In eukaryotic genomes, genes and their distant sites are intermingled in complex ways and it is not understood how the correct connections are formed. Using two pairs of DNA-looping sites in bacterial cells, we tested the idea that one DNA loop can either assist or interfere with the formation of another DNA loop. By measuring the strength of these interactions between loops, we showed that this mechanism is capable of directing a distant site to the correct gene and preventing it contacting the wrong gene.
Enhancement of anammox by the excretion of diel vertical migrators
Authors: Bianchi Daniele , Babbin Andrew R. , Galbraith Eric D.
Published: October 2014

Significance

Nitrogen, the limiting nutrient for primary production across much of the ocean, is converted to biologically inactive N
2
by denitrification and anaerobic ammonium oxidation (anammox) in anoxic waters. Anammox requires an active source of ammonium, which can be provided by concurrent denitrification. However, anammox has been observed at high rates in the absence of denitrification, and the source of ammonium has remained cryptic. Using a combination of observations and models, we suggest that zooplankton and micronekton provide a missing source of ammonium to anoxic waters through diel vertical migrations, fueling anammox and decoupling it from denitrification. This previously overlooked mechanism can help to reconcile observations with theory and highlights the role of animals on ocean biogeochemistry.
Intrinsic disorder as a generalizable strategy for the rational design of highly responsive, allosterically cooperative receptors
Authors: Simon Anna J. , Vallée-Bélisle Alexis , Ricci Francesco , Plaxco Kevin W.
Published: October 2014

Significance

Control over the sensitivity with which biomolecular receptors respond to small changes in the concentration of their target ligand is crucial to many cellular processes and likely could be of value in many biotechnologies. In nature, this control is often achieved using “Hill-type” allosteric cooperativity, an elegant mechanism that has, unfortunately, hitherto proven difficult to achieve via generalizable design strategies. In response, we demonstrate here a quantitative and apparently versatile means of rationally introducing this useful mechanism into a range of normally noncooperative receptors. We achieve in the best of our examples cooperativity, and thus sensitivity, experimentally indistinguishable from the theoretically expected maximum.
Computational design of a self-assembling symmetrical β-propeller protein
Authors: Voet Arnout R. D. , Noguchi Hiroki , Addy Christine , Simoncini David , Terada Daiki , Unzai Satoru , Park Sam-Yong , Zhang Kam Y. J. , Tame Jeremy R. H.
Published: October 2014

Significance

In this study, we have designed and experimentally validated, to our knowledge, the first perfectly symmetrical β-propeller protein. Our results provide insight not only into protein evolution through duplication events, but also into methods for creating designer proteins that self-assemble according to simple arithmetical rules. Such proteins may have very wide uses in bionanotechnology. Furthermore our design approach is both rapid and applicable to many different protein templates. Our novel propeller protein consists of six identical domains known as “blades.” Using a variety of biophysical techniques, we show it to be highly stable and report several high-resolution crystal structures of different forms of the protein. Domain swapping allows us to generate related oligomeric forms with fixed numbers of blades per complex.
Structural studies on the authentic mumps virus nucleocapsid showing uncoiling by the phosphoprotein
Authors: Cox Robert , Pickar Adrian , Qiu Shihong , Tsao Jun , Rodenburg Cynthia , Dokland Terje , Elson Andrew , He Biao , Luo Ming
Published: October 2014

Significance

In this paper, we reveal several insights into how mumps virus (MuV) replicates its RNA genome. The MuV genomic RNA is packaged by the nucleocapsid protein (N), forming a helical structure called the nucleocapsid. The nucleocapsid is the template for RNA synthesis. MuV genomes cannot be copied unless the viral polymerase (vRdRp) can read the sequestered RNA. The MuV phosphoprotein (P) appears to play a central role in this process. In this paper, we provide the first evidence, to our knowledge, of P inducing the nucleocapsid to uncoil. MuV P uses two separate domains to promote viral RNA synthesis. One domain attaches to the nucleocapsid while the other domain relaxes the helical structure to allow vRdRp to easily read the viral genome.
PGC-1β promotes enterocyte lifespan and tumorigenesis in the intestine
Authors: Bellafante Elena , Morgano Annalisa , Salvatore Lorena , Murzilli Stefania , Di Tullio Giuseppe , D’Orazio Andria , Latorre Dominga , Villani Gaetano , Moschetta Antonio
Published: October 2014

Significance

The mucosa of the small intestine is renewed completely every 3–5 d during the entire lifetime through the continuous steps of proliferation, migration, and differentiation of the cells of the mucosa from the crypt site on the bottom to the villus site on the top of the mucosa. The factors that regulate enterocyte lifespan and aging are of special interest as related to colon cancer susceptibility. Here, using genetically modified gain- and loss-of-function models, we present the importance of the mitochondrial respiration chain and reactive oxygen species homeostasis in the gut and identify the protein peroxisome proliferator-activated receptor-γ coactivator-1β as a gene-expression modulator of enterocyte lifespan in both normal and tumoral conditions.
The signaling phospholipid PIP
3
creates a new interaction surface on the nuclear receptor SF-1
Authors: Blind Raymond D. , Sablin Elena P. , Kuchenbecker Kristopher M. , Chiu Hsiu-Ju , Deacon Ashley M. , Das Debanu , Fletterick Robert J. , Ingraham Holly A.
Published: October 2014

Significance

We previously reported that lipids PI(4,5)P
2
(PIP
2
) and PI(3,4,5)P
3
(PIP
3
) bind NR5A nuclear receptors to regulate their activity. Here, the crystal structures of PIP
2
and PIP
3
bound to NR5A1 (SF-1) define a new interaction surface that is organized by the solvent-exposed PIP
n
headgroups. We find that stabilization by the PIP
3
ligand propagates a signal that increases coactivator recruitment to SF-1, consistent with our earlier work showing that PIP
3
increases SF-1 activity. This newly created surface harbors a cluster of human mutations that lead to endocrine disorders, thus explaining how these puzzling mutations cripple SF-1 activity. We propose that this new surface acts as a PIP
3
-regulated interface between SF-1 and coregulatory proteins, analogous to the function of membrane-bound phosphoinositides.
Hopping and the Stokes–Einstein relation breakdown in simple glass formers
Authors: Charbonneau Patrick , Jin Yuliang , Parisi Giorgio , Zamponi Francesco
Published: October 2014

Significance

Like crystals, glasses are rigid because of the self-caging of their constituent particles. The key difference is that crystal formation is a sharp first-order phase transition at which cages form abruptly and remain stable, whereas glass formation entails the progressive emergence of cages. This loose caging complicates the description of the glass transition. In particular, an important transport mechanism in this regime, hopping, has thus far been difficult to characterize. Here we develop a completely microscopic description of hopping, which allows us to clearly assess its impact on transport anomalies, such as the breakdown of the Stokes–Einstein relation.
Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway
Authors: Drosten Matthias , Sum Eleanor Y. M. , Lechuga Carmen G. , Simón-Carrasco Lucía , Jacob Harrys K. C. , García-Medina Raquel , Huang Sidong , Beijersbergen Roderick L. , Bernards Rene , Barbacid Mariano
Published: October 2014

Significance

In spite of the large number of biochemical studies contributing to the analysis of Ras-mediated cell cycle regulation, we do not know how Ras signaling controls the cell cycle. Here, we used an unbiased genetic approach to unveil essential components of Ras-mediated proliferation. Our results reveal that Ras signaling induces cell proliferation by a mechanism that requires inactivation of the p53/p21 Cdk-interacting protein 1 (Cip1) axis by preventing acetylation of specific p53 lysine residues. More importantly, loss of p53 or p21Cip1 can sustain cell proliferation in the absence of Ras proteins via Ras-independent activation of the Raf/Mek/Erk cascade. These results may have important implications for tumor growth and treatment, because activation of Ras oncogenes and inactivation of p53 are frequent events in human cancer.
Visual Discrimination Learning in Rats with Lesions of Superior Colliculus: Door-Push and Approach Errors in Modified Jumping Stand
Authors: Dean Paul , Pope Sian G.
Published: October 2014

It has been suggested that, for some species, lesions of the superior colliculus affect visual discrimination learning, but only in certain conditions: (a) when problems are first learnt only after operation, or (b) when discriminanda require detailed scanning, or (c) when “approach” responses to the discriminanda are measured, rather than the response of actually touching them. These suggestions were examined in rats learning visual discriminations in a modified jumping-stand apparatus, after sustaining large lesions of the superior colliculus (and in some cases also of the pretectum). The lesions produced open-field hyperactivity and reduced exploration, indicating effective tectal damage, but the rats learnt a series of difficult discriminations in a door-push task as fast as normal rats, and they did not make more approach errors. Their main abnormality in the discrimination apparatus was that they looked less often between the stimulus doors before stepping across to one of them from the central platform. It is suggested that in rats, as in other animals, lesions of the superior colliculus disrupt the control of scanning head and eye movements; in rats, however, such disruption need not affect discrimination learning (at least in some kinds of apparatus), possibly because the retina of the rat has a relatively poorly developed area centralis.
The Effects of a Flavour - Toxicosis Pairing upon Long-Delay, Flavour aVersion Learning
Authors: Westbrook R. F. , Homewood Judith
Published: October 2014

Mackintosh (1973) has suggested that rats readily associate flavours with illnesses in cue-to-consequence studies because they have already learned that changes in internal states are unrelated to changes in external stimuli. An implication of this suggestion is that learned predispositions may also subserve the ability of rats to form long-delay, flavour-illness associations. Six experiments tested this idea by examining the strengths of aversions in a delayed flavour-toxicosis paradigm after exposure to a paired or unpaired relation between another flavour and toxicosis. Exposure to a paired relation enhanced the strengths of subsequently established flavour aversions (Experiment I). The enhanced aversions were associative in origin (Experiment II), observed with delays of 3 h and 1·5 h in, respectively, a forward (Experiment III) and backward (Experiment IV) delayed conditioning paradigm and with a 10-day interval between the flavour-toxin pairing and the delayed paradigm (Experiment V). The enhanced aversions, however, were removed by the extinction of the original flavour aversion prior to the delayed flavour-toxin pairing (Experiment VI). The results supported the idea that the ability of the rat to form long-delay, flavour–illness associations reflects an associative history involving flavours and internal changes and were discussed in terms of Mackintosh's (1975) theory of the mechanism underlying stimulus selection. The effects of a flavour-toxicosis pairing upon long-delay, flavour aversion learning.
Counterconditioning of Appetitive and Defensive CRs in Rabbits
Authors: Lovibond Peter F. , Dickinson Anthony
Published: October 2014

Two experiments examined interactions between conditioned appetitive and defensive responses in the rabbit. In Experiment I, a conditioned jaw-movement response was established by following presentations of a clicker CS with intra-oral sucrose delivery on 50% of trials. The jaw-movement response was then maintained on this partial reinforcement schedule during a counterconditioning phase. A group which received para-orbital shock paired with the CS on non-sucrose trials showed acquisition of eyeblink responding and suppression of jaw-movement responding to the CS, in comparison to control groups which received either no shock or unpaired presentations of the CS and shock. Experiment II was identical in design to Experiment I except that the roles of the sucrose and shock reinforcers were reversed. The paired group acquired a conditioned jaw-movement response when sucrose was added in the counterconditioning phase, but in contrast to Experiment I showed a slight enhancement of the previously established eyeblink response. The asymmetry of appetitive and defensive counterconditioning was discussed in relation to opponent-process theories of motivation and reinforcement.
Stimulus Exposure and Discrimination in Rats: A Test of a Theory for the Role of Contextual Factors
Authors: Hall Geoffrey , Channell Stephen
Published: October 2014

In two experiments rats were trained on a simultaneous discrimination in a jumping stand. On each trial choice always lay between one stimulus (an obliquely striped object in Experiment I, and a plain grey object in Experiment II) and a second that varied from trial to trial. On half the trials this variable stimulus bore horizontal stripes (H) and on the remaining trials it bore vertical stripes (V). It was argued that the solution of this discrimination would be hindered if the animals tended to classify H and V apart (Bateson and Chantrey, 1972). It was found, however, that prior exposure to H and V in the home cage (which has been supposed to promote classifying apart) facilitated learning and that prior exposure to H and V in the apparatus itself (which might be thought to promote classifying together) hindered later learning. Possible alternative accounts for these exposure learning effects are discussed.
A Model of Dynamic Output under Fixed-Interval Schedules of Reinforcement
Authors: Wearden J. H.
Published: October 2014

A model of the dynamics of output under fixed-interval schedules of reinforcement is presented. This model primarily involves two processes: a reflex reserve-type mechanism (leading to output in successive intervals being inversely related), and a repeat output mechanism (in which the output level of the previous interval is simply repeated). On a particular interval, one or other process is followed; thus, the model has one parameter, the probability of a repeat ouput. In addition, a random factor (a value selected from a uniform distribution about zero output) is added to the output to simulate real data. Within the model, previously discrepant results from studies employing autocorrelation analyses of behaviour dynamics are seen to require small variations in the repeat output parameter. Output of the model also exhibits the more complex directional and clustering dynamics recently discovered. In general, the model is able accurately to simulate all the known characteristics of dynamic output under fixed-interval schedules.
Hyperstriatal Lesions in Pigeons Disrupt Recognition Memory at Long, but not at Short, Inter-Trial Intervals
Authors: Macphail Euan M.
Published: October 2014

Two series of experiments investigated short-term visual recognition memory in pigeons following lesions of the hyperstriatal complex; the first series used a choice technique, the second, a single-key go/no go technique. The results of the two series agreed, first, in finding impaired performance in hyperstriatal birds at long but not at short inter-trial intervals, and, second, in obtaining no evidence of differential rates of decay of traces in hyperstriatal and control subjects. A final experiment confirmed that the hyperstriatal birds were, as expected from previous work, impaired on reversals of colour and position discriminations. It is tentatively suggested that deficits following hyperstriatal damage in both recognition and reversal performance may be understood as being the consequence of an increased susceptibility to frustrating events in hyperstriatal subjects.
Long-Delay and Selective Association in Food Aversion Learning: The Role of Cue Location
Authors: Sullivan L. G.
Published: October 2014

Cue location has been an uncontrolled variable in food-aversion studies. While tastes are always attributes of the ingested object, visual, auditory and olfactory cues are often attributes of the food container or are located elsewhere in the conditioning chamber. A review of experimental studies indicates that cues which are attributes of the ingested object are almost invariably associated with both immediate and delayed illness, regardless of the sense modality of the cue and of the animal species involved. Cues which are attributes of the food container or conditioning chamber are associated with immediate but not delayed illness, again regardless of the sense modality and animal subject. Within the limits of present evidence, the same effects of cue location appear to occur when shock is the reinforcer. It is suggested that the association of attribute cues across delays is mediated by the conditioned behaviour, which is directed at the object of which they are attributes and which is biologically related to the subsequent reinforcement.
A Search for Context-Stimulus Associations in Latent Inhibition
Authors: Hall Geoffrey , Minor Hugh
Published: October 2014

Six experiments investigated the effects of pre-exposure to a tone on the subsequent acquisition of conditioned suppression by rats. In Experiments 1–3 the response suppressed was drinking; in Experiments 4–6 it was food-rewarded lever pressing. Repeated exposure to the tone resulted in latent inhibition, i.e., a retardation in the acquisition of suppression. The size of the latent inhibition effect was reduced when a different context was used for conditioning from that used for pre-exposure (Experiment 2). When the context remained the same throughout, a phase of exposure to the context alone, interposed between pre-exposure and conditioning, had no influence on the size of the latent inhibition effect ultimately observed. This last result casts doubt upon Wagner's (1976, 1979) theory of the role of contextual factors in latent inhibition, and alternative accounts are considered.
Effects of Fornix Transection upon Associative Memory in Monkeys: Role of the Hippocampus in Learned Action
Authors: Gaffan David , Saunders Richard C. , Gaffan E. A. , Harrison Susan , Shields Claude , Owen M. J.
Published: October 2014

Thirty-three monkeys took part in seven experiments designed to elucidate further the effect of fornix transection on learning and memory. In the first experiment the monkeys had to remember whether stimulus objects had previously been paired with reward or no reward, and they had to use this memory to guide choice between stimulus objects at retention tests according to an arbitrary rule which they had learned: to choose objects previously paired with no reward in preference to objects previously paired with reward. Fornix transection produced a severe and permanent impairment in this task. In the second experiment the monkeys also had to remember object-reward associations but the performance rule was more natural: to choose objects previously paired with reward. Here fornix transection had no effect. The third experiment required the monkeys to remember, given a stimulus object, which of two events of equal valence had previously been the outcome of displacing that object. The two events were either a peanut and a sultana or a black penny and a white penny of equal secondary reinforcing value. Performance was unimpaired by fornix transection. The fourth experiment also demonstrated, in a different paradigm, unimpaired recall of sensory events. The fifth experiment demonstrated an impairment following fornix transection in acquisition of simultaneous spatial-visual conditional discriminations; the sixth demonstrated normal learning by fornix-transected monkeys of a successive spatial-visual conditional discrimination and the seventh demonstrated unimpaired acquisition of a simultaneous auditory-visual conditional discrimination. These results, when considered in detail and together, are incompatible with existing hypotheses of hippocampal function. A new hypothesis is discussed.
Learning Due to the Response-Shock Contingency in Signalled Punishment
Authors: Goodall Glyn
Published: October 2014

Three experiments examined some of the parameters that affect the degree of response-specific learning in signalled punishment. Each of the experiments used a within-subject procedure in which the shocks received in the presence of a stimulus signalling response-independent shocks (CER) were yoked to the number and distribution of shocks received in a stimulus signalling punishment. Experiments 1 and 2 used different values of variable-interval (VI) or fixed-ratio (FR) schedules of shock priming, respectively, during the punishment stimulus, and Experiment 3 varied the delay of punishment. The results of all three experiments supported the conclusion that the degree of additional suppression produced by the response contingency during the punishment stimulus compared to the CER stimulus was a function of the strength of contingency between the response and the shock.
Extinguishing Conditioned Inhibition in Flavour-Aversion Learning: Effects of Repeated Testing and Extinction of the Excitatory Element
Authors: Best Michael R. , Dunn Dorothy P. , Batson John D. , Meachum Cynthia L. , Nash Susan M.
Published: October 2014

Three conditioned inhibition experiments using an A+/AX- design are reported in which lithium-mediated excitatory conditioning occurred to distinctive environmental stimuli and inhibitory conditioning to a vinegar flavour. Increased vinegar preferences were observed (i.e., conditioned inhibition) in each experiment, and these preferences extinguished with repeated testing as well as following extinction of the excitatory element. Vinegar preferences could be reinstated through reconditioning of the extinguished excitatory stimulus. These experiments speak to the status of inhibitory responding as a “slave” process to conditioned excitation.
Contingency Effects with Maintained Instrumental Reinforcement
Authors: Dickinson Anthony , Charnock Deborah J.
Published: October 2014

In three experiments we investigated the effect on the performance of thirsty rats of varying the instrumental contingency between lever pressing and the delivery of a saccharin reinforcer. In Experiment 1, the subjects performed more slowly in a non-contingent condition, in which the momentary probability of reinforcement was unaffected by whether or not the animals pressed, than in a contingent condition in which the reinforcer was never presented except following a lever press. This was true of performance under both random ratio and interval schedules in which the function determining the probability of reinforcement following a lever press remained the same across the contingent and non-contingent conditions. Experiment 2 demonstrated that instrumental performance was less affected when the contingency was degraded by the introduction of free reinforcers if these reinforcers were signalled. In Experiment 3, lever pressing was reinstated to some degree after non-contingent training by giving non-reinforced exposure to the operant chamber in the absence of the lever. These results suggest that free reinforcers depress instrumental behaviour through a performance mechanism engaged by their ability to support conditioning of the contextual cues.
The Effect of Informative Events on Response Rate
Authors: Pearce John M. , Collins L.
Published: October 2014

A single group of pigeons received two different training conditions presented on different response keys. Responding during the first component of each condition was reinforced, according to a fixed interval schedule, by gaining access to the second component. In the uninformative condition the second component consisted on every trial of the illumination of the response key for 10 sec, the key was then darkened and food presented with a probability of 0.5. In the informative condition half of the trials at the conclusion of the first component resulted in the key being darkened and no additional events were presented. On the remaining trials the second component was similar to that for the uninformative condition. The results from the first two stages revealed that responding during the first component was faster in the informative than uninformative condition when trials were presented separately. In the final stage, when the trials were presented simultaneously, the rate of responding during the first component was eventually similar in the two conditions, but subjects preferred the second component of the informative condition. These results suggest that events which are informative, or perhaps unpredictable, can support a higher response rate than those which are uninformative, or predictable.
Running Recognition of Configural Stimuli by Fornix-Transected Monkeys
Authors: Gaffan David , Saunders Richard C.
Published: October 2014

Six Rhesus monkeys were trained in a running recognition task with visual-spatial configurations as the stimuli to be remembered. Following pre-operative training half the monkeys were subjected to fornix transection and half to a control operation. Fornix transection produced a severe and apparently permanent impairment. These results add to the evidence that fornix transection produces defects in memory which cannot be explained as secondary consequences of impairments of perception.
Emergent Simple Discrimination in Children: Transfer of Stimulus Control under Non-Reinforced Conditions
Authors: Smeets Paul M.
Published: October 2014

Previous research on humans suggests that simple discriminations may emerge if both stimuli, B1 and B2, are compounded with the stimuli of a previously trained discrimination, A1 (S+) and A2 (S-), and responding to the compounds, B1A1 and B2A2, is reinforced. Two questions were addressed. First, do simple discriminations also emerge if (a) only one stimulus, B1, is compounded with a training stimulus, A1 (S+) or A2 (S-); or with both training stimuli, A1 (S+) and A2 (S-); and (b) neither B1 nor B2 is compounded with the training stimuli? Second, do simple discriminations emerge if reinforcement in the presence of the AB compounds is withheld? Normal preschool children served as subjects. The study consisted of six experiments. Transfer occurred in all experiments regardless of whether both test stimuli, one test stimulus, or none of the test stimuli were compounded with the training stimuli under non-reinforced conditions. The results can be described by the following rules: Respond to any stimulus that includes a component of a “correct” stimulus of a previous discrimination. Otherwise, respond away from the stimulus that incorporates a component from an “incorrect” stimulus of a previous discrimination. The implications of data for sensory pre-conditioning and language-based accounts are discussed.
Perceptual Learning in Maze Discriminations
Authors: Trobalon J.B. , Sansa J. , Chamizo V. D. , Mackintos N.J.
Published: October 2014

In Experiment 1, rats were trained on a discrimination between rubber- and sandpaper-covered arms of a maze after one group had been pre-exposed to these intra-maze cues. Pre-exposure facilitated subsequent discrimination learning, unless the discrimination was made easier by adding further discriminative stimuli, when it now significantly retarded learning. In Experiment 2, rats were trained on an extra-maze spatial discrimination, again after one group, but not another, had been pre-exposed to the extra-maze landmarks. Here too, pre-exposure facilitated subsequent discrimination learning, unless the discrimination was made substantially easier by arranging that the two arms between which rats had to choose were always separated by 135°. The results of both experiments can be explained by supposing that perceptual learning depends on the presence of features common to S+ and S-.
Blocking of Occasion Setting in Feature-Positive Discriminations
Authors: Bonardi Charlotte
Published: October 2014

In two experiments rats received feature-positive discrimination training in which brief conditioned stimuli (CSs) were paired with food during presentations of an extended feature stimulus, and non-reinforced in its absence. In Experiment 1 a novel feature was trained in compound with a second, pretrained feature. Acquisition of control over responding to the CS by the novel feature was blocked if the pretrained feature had also been trained in a feature-positive discrimination, compared to a group for whom the pretrained feature had been accompanied by uncorrelated presentations of CSs and food. Experiment 2 employed a within-subjects design. It demonstrated that the feature from a feature-positive discrimination with a particular CS, x, blocked acquisition of control by an added, novel feature over responding to x, compared to the control acquired by the same novel feature over a novel, CS y.
Effects of an Infusion of Morphine into the Accumbens Nucleus upon Acquisition of Hypoalgesic and Fear Responses in Rats Exposed to a Heat Stressor
Authors: Westbrook R. F. , Harris J. A. , Good A. J. , Paxinos G.
Published: October 2014

Four experiments examined the effects of an infusion of morphine into the accumbens nucleus upon the aversive conditioning that can occur in rats exposed to the heated floor of a hot-plate apparatus. An infusion of morphine into the accumbens nucleus but not into the caudoputamen or into the prefrontal cortex impaired the acquisition of a conditioned hypoalgesic (Experiment 1) and fear (Experiment 4) response. This impairment was dose-dependent (Experiment 2) and mediated by opioid receptors in the accumbens nucleus, because it was removed by a systemic (Experiment 3a) or by an accumbal (Experiment 3b) infusion of naloxone. The results were attributed to an antagonism between the reinforcement process for aversive conditioning and the appetitive properties of an accumbal infusion of morphine.
Perceptual Learning during Filial Imprinting: Evidence from Transfer of Training Studies
Authors: Honey R. C. , Horn Gabriel , Bateson Patrick
Published: October 2014

Chicks were first imprinted by exposing them to a moving training stimulus, B or C, that was projected onto a screen at one end of an experimental cabinet. Subsequently, subjects selectively approached the stimulus to which they had been exposed. On the following day, the chicks were placed into a chilled experimental cabinet (15°C) and received trials on which two stimuli (A and B) were projected onto screens located at opposite ends of the cabinet. If the subject approached Stimulus A, a stream of warm air was delivered; if it approached B, the trial terminated, and no heat was presented. For subjects that had been imprinted with Stimulus B, those in Group B, Stimulus A was novel, and Stimulus B was familiar. For chicks that had been imprinted with Stimulus C, Group C, both A and B were novel. In two experiments, Group B acquired the discrimination more rapidly than did Group C. This observation, made using a novel training procedure, was taken to support the suggestion that imprinting results in a form of perceptual learning in which the familiar imprinting object has become more discriminable from other novel objects.