The priming of priming : Evidence that the N400 reflects context-dependent post-retrieval word integration in working memory

Which cognitive processes are reflected by the N400 in ERPs is still controversial. Various recent articles(Lau et al., 2008; Brouwer et al., 2012) have revived the idea that only lexical pre-activation processes(such as automatic spreading activation, ASA) are strongly supported, while post-lexical integrative pro-cesses are not. Challenging this view, the present ERP study replicates a behavioral study by McKoon andRatcliff (1995) who demonstrated that a prime-target pair such as finger − hand shows stronger primingwhen a majority of other pairs in the list share the analogous semantic relationship (here: part-whole),even at short stimulus onset asynchronies (250 ms). We created lists with four different types of semanticrelationship (synonyms, part-whole, category-member, and opposites) and compared priming for pairsin a consistent list with those in an inconsistent list as well as unrelated items. Highly significant N400reductions were found for both relatedness priming (unrelated vs. inconsistent) and relational priming(inconsistent vs. consistent). These data are taken as strong evidence that N400 priming effects are notexclusively carried by ASA-like mechanisms during lexical retrieval but also include post-lexical inte-gration in working memory. We link the present findings to a neurocomputational model for relationalreasoning (Knowlton et al., 2012) and to recent discussions of context-dependent conceptual activations(Yee and Thompson-Schill, 2016)

Gauge-theoretic invariants for topological insulators: A bridge between Berry, Wess-Zumino, and Fu-Kane-Mele

We establish a connection between two recently-proposed approaches to the understanding of the geometric origin of the Fu-Kane-Mele invariant $\mathrm{FKM} \in \mathbb{Z}_2$, arising in the context of 2-dimensional time-reversal symmetric topological insulators. On the one hand, the $\mathbb{Z}_2$ invariant can be formulated in terms of the Berry connection and the Berry curvature of the Bloch bundle of occupied states over the Brillouin torus. On the other, using techniques from the theory of bundle gerbes it is possible to provide an expression for $\mathrm{FKM}$ containing the square root of the Wess-Zumino amplitude for a certain $U(N)$-valued field over the Brillouin torus. We link the two formulas by showing directly the equality between the above mentioned Wess-Zumino amplitude and the Berry phase, as well as between their square roots. An essential tool of independent interest is an equivariant version of the adjoint Polyakov-Wiegmann formula for fields $\mathbb{T}^2 \to U(N)$, of which we provide a proof employing only basic homotopy theory and circumventing the language of bundle gerbes.Comment: 23 pages, 1 figure. To appear in Letters in Mathematical Physic

Toxoplasma seroprevalence in a rural population in France: detection of a household effect

<p>Abstract</p> <p>Background</p> <p><it>Toxoplasma gondii</it>, the agent of toxoplasmosis, has a complex life cycle. In humans, the parasite may be acquired either through ingestion of contaminated meat or through oocysts present in the environment. The importance of each source of contamination varies locally according to the environment characteristics and to differences concerning human eating habits and the presence of cats; thus, the risk factors may be determined through fine-scale studies. Here, we searched for factors associated with seropositivity in the population of two adjacent villages in Lorraine region, France.</p> <p>Methods</p> <p>All voluntary inhabitants filled out a questionnaire and gave a blood sample. The seroprevalence was estimated globally and according to the inhabitants' ages using a cubic spline regression. A mixed logistic regression model was used to quantify the effect of individual and household factors on the probability of seropositivity.</p> <p>Results</p> <p>Based on serological results from 273 persons, we estimated seroprevalence to be 47% (95% confidence interval: 41 to 53%). That seroprevalence increased with age: the slope was the steepest up to the age of 40 years (OR = 2.48 per 10-year increment, 95% credibility interval: [1.29 to 5.09]), but that increase was not significant afterwards. The probability of seropositivity tended to be higher in men than in women (OR = 2.01, 95% credibility interval: [0.92 to 4.72]) and in subjects eating raw vegetables at least once a week than in the others (OR = 8.4, 95% credibility interval: [0.93 to 72.1]). These effects were close to statistical significance. The multivariable analysis highlighted a significant seroprevalence heterogeneity among households. That seroprevalence varied between 6 and 91% (5^thand 95^thpercentile of the household seropositivity distribution).</p> <p>Conclusion</p> <p>The major finding is the household effect, with a strong heterogeneity of seroprevalence among households. This effect may be explained by common exposures of household members to local risk factors. Future work will quantify the link between the presence of oocysts in the soil and the seroprevalence of exposed households using a spatial analysis.</p

Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks

The idea of 'date' and 'party' hubs has been influential in the study of protein-protein interaction networks. Date hubs display low co-expression with their partners, whilst party hubs have high co-expression. It was proposed that party hubs are local coordinators whereas date hubs are global connectors. Here we show that the reported importance of date hubs to network connectivity can in fact be attributed to a tiny subset of them. Crucially, these few, extremely central, hubs do not display particularly low expression correlation, undermining the idea of a link between this quantity and hub function. The date/party distinction was originally motivated by an approximately bimodal distribution of hub co-expression; we show that this feature is not always robust to methodological changes. Additionally, topological properties of hubs do not in general correlate with co-expression. Thus, we suggest that a date/party dichotomy is not meaningful and it might be more useful to conceive of roles for protein-protein interactions rather than individual proteins. We find significant correlations between interaction centrality and the functional similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure

Interaction of eukaryotic translation initiation factor 4G with the nuclear cap-binding complex provides a link between nuclear and cytoplasmic functions of the m7 guanosine cap

In eukaryotes the majority of mRNAs have an m7G cap that is added cotranscriptionally and that plays an important role in many aspects of mRNA metabolism. The nuclear cap-binding complex (CBC; consisting of CBP20 and CBP80) mediates the stimulatory functions of the cap in pre-mRNA splicing, 3' end formation, and U snRNA export. As little is known about how nuclear CBC mediates the effects of the cap in higher eukaryotes, we have characterized proteins that interact with CBC in HeLa cell nuclear extracts as potential mediators of its function. Using cross-linking and coimmunoprecipitation, we show that eukaryotic translation initiation factor 4G (eIF4G), in addition to its function in the cytoplasm, is a nuclear CBC-interacting protein. We demonstrate that eIF4G interacts with CBC in vitro and that, in addition to its cytoplasmic localization, there is a significant nuclear pool of eIF4G in mammalian cells in vivo. Immunoprecipitation experiments suggest that, in contrast to the cytoplasmic pool, much of the nuclear eIF4G is not associated with eIF4E (translation cap binding protein of eIF4F) but is associated with CBC. While eIF4G stably associates with spliceosomes in vitro and shows close association with spliceosomal snRNPs and splicing factors in vivo, depletion studies show that it does not participate directly in the splicing reaction. Taken together the data indicate that nuclear eIF4G may be recruited to pre-mRNAs via its interaction with CBC and accompanies the mRNA to the cytoplasm, facilitating the switching of CBC for eIF4F. This may provide a mechanism to couple nuclear and cytoplasmic functions of the mRNA cap structure

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Fatty acid profile in peri-prostatic adipose tissue and prostate cancer aggressiveness in African-Caribbean and Caucasian patients

BACKGROUND: Genetic and nutritional factors have been linked to the risk of aggressive prostate cancer (PCa). The fatty acid (FA) composition of peri-prostatic adipose tissue (PPAT), which reflects the past FA intake, is potentially involved in PCa progression. We analysed the FA composition of PPAT, in correlation with the ethno-geographical origin of the patients and markers of tumour aggressiveness. METHODS: From a cohort of 1000 men treated for PCa by radical prostatectomy, FA composition of PPAT was analysed in 156 patients (106 Caucasians and 50 African-Caribbeans), 78 with an indolent tumour (ISUP group 1 + pT2 + PSA &lt;10 ng/mL) and 78 with an aggressive tumour (ISUP group 4-5 + pT3). The effect of FA extracted from PPAT on in-vitro migration of PCa cells DU145 was studied in 72 patients, 36 Caucasians, and 36 African-Caribbeans. RESULTS: FA composition differed according to the ethno-geographical origin. Linoleic acid, an essential n-6 FA, was 2-fold higher in African-Caribbeans compared with Caucasian patients, regardless of disease aggressiveness. In African-Caribbeans, the FA profile associated with PCa aggressiveness was characterised by low level of linoleic acid along with high levels of saturates. In Caucasians, a weak and negative association was observed between eicosapentaenoic acid level (an n-3 FA) and disease aggressiveness. In-vitro migration of PCa cells using PPAT from African-Caribbean patients was associated with lower content of linoleic acid. CONCLUSION: These results highlight an important ethno-geographical variation of PPAT, in both their FA content and association with tumour aggressiveness