A pre-registered, multi-lab non-replication of the action-sentence compatibility effect (ACE).

The Action-sentence Compatibility Effect (ACE) is a well-known demonstration of the role of motor activity in the comprehension of language. Participants are asked to make sensibility judgments on sentences by producing movements toward the body or away from the body. The ACE is the finding that movements are faster when the direction of the movement (e.g., toward) matches the direction of the action in the to-be-judged sentence (e.g., Art gave you the pen describes action toward you). We report on a pre-registered, multi-lab replication of one version of the ACE. The results show that none of the 18 labs involved in the study observed a reliable ACE, and that the meta-analytic estimate of the size of the ACE was essentially zero.

Western Diet-Fed, Aortic-Banded Ossabaw Swine: A Preclinical Model of Cardio-Metabolic Heart Failure.

The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet-fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF.

TRPV4 increases cardiomyocyte calcium cycling and contractility yet contributes to damage in the aged heart following hypoosmotic stress.

Aims: Cardiomyocyte Ca2+ homeostasis is altered with aging via poorly-understood mechanisms. The Transient Receptor Potential Vanilloid 4 (TRPV4) ion channel is an osmotically-activated Ca2+ channel, and there is limited information on the role of TRPV4 in cardiomyocytes. Our data show that TRPV4 protein expression increases in cardiomyocytes of the aged heart. The objective of this study was to examine the role of TRPV4 in cardiomyocyte Ca2+ homeostasis following hypoosmotic stress and to assess the contribution of TRPV4 to cardiac contractility and tissue damage following ischaemia-reperfusion (I/R), a pathological condition associated with cardiomyocyte osmotic stress. Methods and results: TRPV4 protein expression increased in cardiomyocytes of Aged (24-27 months) mice compared with Young (3-6 months) mice. Immunohistochemistry revealed TRPV4 localization to microtubules and the t-tubule network of cardiomyocytes of Aged mice, as well as in left ventricular myocardium of elderly patients undergoing surgical aortic valve replacement for aortic stenosis. Following hypoosmotic stress, cardiomyocytes of Aged, but not Young exhibited an increase in action-potential induced Ca2+ transients. This effect was mediated via increased sarcoplasmic reticulum Ca2+ content and facilitation of Ryanodine Receptor Ca2+ release and was prevented by TRPV4 antagonism (1 µmol/L HC067047). A similar hypoosmotic stress-induced facilitation of Ca2+ transients was observed in Young transgenic mice with inducible TRPV4 expression in cardiomyocytes. Following I/R, isolated hearts of Young mice with transgenic TRPV4 expression exhibited enhanced contractility vs. hearts of Young control mice. Similarly, hearts of Aged mice exhibited enhanced contractility vs. hearts of Aged TRPV4 knock-out (TRPV4-/-) mice. In Aged, pharmacological inhibition of TRPV4 (1 µmol/L, HC067047) prevented hypoosmotic stress-induced cardiomyocyte death and I/R-induced cardiac damage. Conclusions: Our findings provide a new mechanism for hypoosmotic stress-induced cardiomyocyte Ca2+ entry and cell damage in the aged heart. These finding have potential implications in treatment of elderly populations at increased risk of myocardial infarction and I/R injury.

T Cells Exacerbate Lyme Borreliosis in TLR2-Deficient Mice.

Infection of humans with the spirochete, Borrelia burgdorferi, causes Lyme borreliosis and can lead to clinical manifestations such as arthritis, carditis, and neurological conditions. Experimental infection of mice recapitulates many of these symptoms and serves as a model system for the investigation of disease pathogenesis and immunity. Innate immunity is known to drive the development of Lyme arthritis and carditis, but the mechanisms driving this response remain unclear. Innate immune cells recognize B. burgdorferi surface lipoproteins primarily via toll-like receptor (TLR)2; however, previous work has demonstrated TLR2-/- mice had exacerbated disease and increased bacterial burden. We demonstrate increased CD4 and CD8 T cell infiltrates in B. burgdorferi-infected joints and hearts of C3H TLR2-/- mice. In vivo depletion of either CD4 or CD8 T cells reduced Borrelia-induced joint swelling and lowered tissue spirochete burden, whereas depletion of CD8 T cells alone reduced disease severity scores. Exacerbation of Lyme arthritis correlated with increased production of CXCL9 by synoviocytes, and this was reduced with CD8 T cell depletion. These results demonstrate T cells can exacerbate Lyme disease pathogenesis and prolong disease resolution possibly through dysregulation of inflammatory responses and inhibition of bacterial clearance.

Statistical Learning is Related to Early Literacy-Related Skills.

It has been demonstrated that statistical learning, or the ability to use statistical information to learn the structure of one's environment, plays a role in young children's acquisition of linguistic knowledge. Although most research on statistical learning has focused on language acquisition processes, such as the segmentation of words from fluent speech and the learning of syntactic structure, some recent studies have explored the extent to which individual differences in statistical learning are related to literacy-relevant knowledge and skills. The present study extends on this literature by investigating the relations between two measures of statistical learning and multiple measures of skills that are critical to the development of literacy-oral language, vocabulary knowledge, and phonological processing-within a single model. Our sample included a total of 553 typically developing children from prekindergarten through second grade. Structural equation modeling revealed that statistical learning accounted for a unique portion of the variance in these literacy-related skills. Practical implications for instruction and assessment are discussed.

Exploring the breadth of the top-down representations that control attentional disengagement.

Recent studies attribute top-down control as the primary determinant of the speed with which attention can be disengaged from an object, and disengagement has received increased interest as a means to distinguish between top-down and bottom-up accounts of attention capture. We present the results of three experiments exploring the breadth of the representations that delay attentional disengagement based on top-down goals. Experiments 1 and 2 examined whether objects similar to an observers' search target, but differing in luminance and hue, delayed the reallocation of attention in a search paradigm designed to isolate disengagement time. Experiment 3 explored whether the representations that delay disengagement are based on absolute similarity with the search target, or are tuned based on target/nontarget relationships. These three studies confirmed the role of top-down goals in automatically contributing to dwell times and revealed that the representations that underlie disengagement effects are broad (automatically delaying disengagement for items similar, but not identical to, the search target). In some cases, attention sets appeared to be graded in nature, but in others target-distractor relationships influenced the degree to which an irrelevant item held attention. Implications for theories of attention capture and potential functional significance of these automatic effects are discussed.

Global statistical learning in a visual search task.

Locating a target in a visual search task is facilitated when the target location is repeated on successive trials. Global statistical properties also influence visual search, but have often been confounded with local regularities (i.e., target location repetition). In two experiments, target locations were not repeated for four successive trials, but with a target location bias (i.e., the target appeared on one half of the display twice as often as the other). Participants quickly learned to make more first saccades to the side more likely to contain the target. With item-by-item search first saccades to the target were at chance. With a distributed search strategy first saccades to a target located on the biased side increased above chance. The results confirm that visual search behavior is sensitive to simple global statistics in the absence of trial-to-trial target location repetitions.

Structural priming as implicit learning: cumulative priming effects and individual differences.

We explored the claim that structural priming is a case of implicit learning within the language production system. The experiment began with a baseline phase, in which we assessed participants' rates of production for double object and prepositional object constructions. Then participants were biased toward the production of either the double object or prepositional object construction. Finally, we again assessed participants' rates of production for the target constructions. Consistent with claims that structural priming is a case of implicit learning, we found that biasing participants toward the prepositional object construction produced stronger cumulative priming effects than did biasing participants toward the double object construction. We also found that individual differences in implicit learning were marginally correlated with overall rates of production for the double object construction. Participants who scored better on the learning task tended to produce fewer double object constructions.

Sequence elements in cis influence heterochromatic silencing in trans.

The brown(Dominant) (bw(D)) allele contains a large insertion of heterochromatin, which causes the locus to aberrantly associate with heterochromatin in interphase nuclei and silences the wild-type allele in heterozygotes. Transgenes placed near the bw(+) locus, in trans to bw(D), can also be silenced. The strength of silencing (called trans inactivation) varies with the regulatory sequences of the transgene and its distance away from the bw(D) insertion site in trans. In this study, we examine endogenous sequences in cis that influence susceptibility of a reporter gene to trans inactivation. Flanking deletions were induced in two parental lines containing P-element transgenes showing trans inactivation of the mini-white reporter. These new lines, which have mini-white under the influence of different endogenous sequence elements, now show varied ability to be silenced by bw(D). Determination of the deleted regions and the levels of mini-white expression and trans inactivation has allowed us to explore the correlation between cis sequence elements and susceptibility to trans inactivation and to identify a 301-bp sequence that acts as an enhancer of trans inactivation. Intriguingly, this region encompasses the upstream regions of two divergently transcribed genes and contains a sequence motif that may bind BEAF, a protein involved in delimiting chromatin boundaries.