Behavioral and Brain Responses Highlight the Role of Usage in the Preparation of Multiword Utterances for Production

Usage-based theories assume that all aspects of language processing are shaped by the distributional properties of the language. The frequency not only of words but also of larger chunks plays a major role in language processing. These theories predict that the frequency of phrases influences the time needed to prepare these phrases for production and their acoustic duration. By contrast, dominant psycholinguistic models of utterance production predict no such effects. In these models, the system keeps track of the frequency of individual words but not of co-occurrences. This study investigates the extent to which the frequency of phrases impacts naming latencies and acoustic duration with a balanced design, where the same words are recombined to build high- and low-frequency phrases. The brain signal of participants is recorded so as to obtain information on the electrophysiological bases and functional locus of frequency effects. Forty-seven participants named pictures using high- and low-frequency adjective–noun phrases. Naming latencies were shorter for high-frequency than low-frequency phrases. There was no evidence that phrase frequency impacted acoustic duration. The electrophysiological signal differed between high- and low-frequency phrases in time windows that do not overlap with conceptualization or articulation processes. These findings suggest that phrase frequency influences the preparation of phrases for production, irrespective of the lexical properties of the constituents, and that this effect originates at least partly when speakers access and encode linguistic representations. Moreover, this study provides information on how the brain signal recorded during the preparation of utterances changes with the frequency of word combinations.

The Genetic Basis of Addictive Disorders

Addictive disorders are moderately to highly heritable, indicating that alleles transmitted from parents are protective, or enhance risk by whatever mechanisms. However, the inheritance of addictive disorders is complex, involving hundreds of genes and variants that are both common and rare, and that vary in effect size and context of action. Genes altering risk for addictions have been identified by pathway and candidate gene studies in humans and model organisms, and genomic approaches including genome-wide association, meiotic linkage, and sequencing. Genes responsible for shared liability to different addictive disorders have been identified, as well as genes that are relatively specific in altering risk of addiction to one agent. An impediment to overarching conclusions is that most of the heritability of addictions is unexplained at the level of gene or functional locus. However, new analytic approaches and tools have created new potentials for resolution of the “missing heritability.”

Comparison of Cytomegalovirus Terminase Gene Mutations Selected after Exposure to Three Distinct Inhibitor Compounds

ABSTRACT Letermovir, GW275175X (a benzimidazole), and tomeglovir (Bay38-4766) are chemically unrelated human cytomegalovirus (CMV) terminase complex inhibitors that have been tested in human subjects. UL56 gene mutations are the dominant pathway of letermovir resistance, while UL89 and UL56 mutations are known to confer benzimidazole resistance. This study compares the mutations elicited by the three inhibitors during in vitro CMV propagation. GW275175X consistently selected for UL89 D344E and sometimes selected for UL89 C347S, UL89 R351H, or UL56 Q204R. Tomeglovir consistently selected for UL89 V362M and sometimes selected for UL89 N329S, T350M, H389N, or N405D or UL56 L208M, E407D, H637Q, or V639M. Adding to known and novel UL56 mutations, letermovir occasionally selected for UL89 N320H, D344E, or M359I. Recombinant phenotyping confirmed that UL89 D344E conferred 9-fold resistance (an increased 50% effective concentration [EC50]) for GW275175X and increased the letermovir and tomeglovir EC50s by 1.7- to 2.1-fold for the baseline virus and the UL56 Q204R, E237D, F261L, and M329T mutants. UL89 N320H and M359I conferred <2-fold letermovir resistance but 7-fold tomeglovir resistance; the N320H mutant was also 4-fold resistant to GW275175X. UL89 N329S conferred tomeglovir and letermovir cross-resistance. UL89 T350M conferred resistance to all three inhibitors. UL89 C347S conferred 27-fold GW275175X resistance. UL89 V362M and H389N conferred 98-fold and 29-fold tomeglovir resistance, respectively, without conferring cross-resistance. Thus, characteristic UL89 mutations confer substantial resistance to GW275175X and tomeglovir and are an uncommon accessory pathway of letermovir resistance. Instances of moderate cross-resistance and the proximity of the selected UL89 and UL56 mutations suggest targeting of a similar terminase functional locus involving UL56 and UL89 interaction.

Identification of Susceptibility Genes of Adult Asthma in French Canadian Women

Susceptibility genes of asthma may be more successfully identified by studying subgroups of phenotypically similar asthma patients. This study aims to identify single nucleotide polymorphisms (SNPs) associated with asthma in French Canadian adult women. A pooling-based genome-wide association study was performed in 240 allergic asthmatic and 120 allergic nonasthmatic women. The top associated SNPs were selected for individual genotyping in an extended cohort of 349 asthmatic and 261 nonasthmatic women. The functional impact of asthma-associated SNPs was investigated in a lung expression quantitative trait loci (eQTL) mapping study (n=1035). Twenty-one of the 38 SNPs tested by individual genotyping showedPvalues lower than 0.05 for association with asthma.Cis-eQTL analyses supported the functional contribution of rs17801353 associated withC3AR1(P=7.90E-10). The asthma risk allele for rs17801353 is associated with higher mRNA expression levels ofC3AR1in lung tissue.In silicofunctional characterization of the asthma-associated SNPs also supported the contribution ofC3AR1and additional genes includingSYNE1,LINGO2, andIFNG-AS1. This pooling-based GWAS in French Canadian adult women followed by lung eQTL mapping suggestedC3AR1as a functional locus associated with asthma. Additional susceptibility genes were suggested in this homogenous subgroup of asthma patients.

The Neural Correlates of Object Familiarity and Domain Specificity in the Human Visual Cortex: An fMRI Study

Ventral occipito-temporal cortex is known to play a major role in visual object recognition. Still unknown is whether object familiarity and semantic domain are critical factors in its functional organization. Most models assume a functional locus where exemplars of familiar categories are represented: the structural description system. On the assumption that familiarity should modulate the effect of visual noise on form recognition, we attempted to individualize the structural description system by scanning healthy subjects while they looked at familiar (living and nonliving things) and novel 3-D objects, either with increasing or decreasing visual noise. Familiarity modulated the visual noise effect (particularly when familiar items were living things), revealing a substrate for the structural description system in right occipito-temporal cortex. These regions also responded preferentially to living as compared to nonliving items. Overall, these results suggest that living items are particularly reliant on the structural description system.