3). Disease development in IPF is thought to result selleck kinase inhibitor from repetitive injury to epithelial cells and an abnormal fibrotic response. Proinflammatory mediators, such as IL-1β, are known to promote fibrosis, but can be regulated by the receptor antagonist IL-1Ra. In the present study, we found that the ratio between IL-1Ra and IL-1β was decreased in both serum and BALF of IPF patients compared to healthy controls. Furthermore, we showed that one SNP in IL1RN, rs2637988, associated with susceptibility

to IPF and with the IL-1Ra/IL-1β ratio in BALF. A predisposing effect of genetic variation in IL1RN was described previously by Whyte et al., who found an increased risk of fibrosing alveolitis in an Italian and a British population [6]. They investigated the IL1RN + 2018 SNP, which in the Caucasian Hapmap panel is in complete linkage Cell Cycle inhibitor disequilibrium with our tag rs408392 (r2 = 1). In our study, rs408392 was not the most significantly associated SNP, although carriership of allele 2 of rs408392 was more common in patients with IPF (P = 0·07). In other studies the variable number of tandem repeats (VNTR) in intron 2 of IL1RN was investigated and found to be in linkage disequilibrium with the IL1RN + 2018 SNP. However, both a small Australian [7] and an independent Czech cohort [12] did not reveal any association between the VNTR and

IPF susceptibility [13]. Functional effects of IL1RN + 2018 alleles have been demonstrated by Carter et al. They showed that IL1RN + 2018 allele 2 not only correlated with Racecadotril the susceptibility to ulcerative colitis, but also to a significantly decreased ratio between the protein and mRNA content of IL-1Ra and total IL-1 in the colonic mucosa [14]. Although we found the same trend as reported in the Italian and British cohorts, our data suggest that carriership

of the G allele of IL1RN rs2637988 is associated more strongly with IPF. Carriership of the G-allele is higher in IPF patients (75%) compared to controls (61%), P = 0·02. In addition, we showed that IPF patients carrying the rs2637988 G-allele had a significantly lower IL-1Ra/IL-1β ratio in BALF, suggesting a relative shortage of IL-1Ra compared to IL-1β. This implies that presence of the G allele has a pathogenic role in IPF. The balance between IL-1 and IL-1Ra seems crucial in inflammatory diseases [15–18]. Although IPF is not primarily an inflammatory disease, IPF is characterized by high levels of inflammatory parameters. The balance between IL-1 and IL-1Ra has rarely been studied in IPF, but extensively in inflammatory diseases. In inflammatory bowel disease, changes in the IL-1Ra/IL-1β ratio have also been studied. Protein levels in the colonic mucosa of IL-1Ra, IL-1α and IL-1β were higher than in controls, but the ratio between IL-1Ra and total IL-1 was decreased significantly [14,19].

Splenic tissue sections (8 μm) were mounted on precooled slides, stored unfixed at −70°C and in situ hybridization

performed as described previously 46. Hybridized digoxigenin-labeled anti-sense RNA probes (SP6/T7 labeling kit, Roche) were detected with alkaline phosphatase-conjugated anti-digoxigenin Fab (Roche), and developed with BCIP/NBT (Promega). In situ hybridization for each RNA probe was performed in two independent experiments. Specificity of hybridization was controlled by using sense RNA probes. The MI-503 authors thank H. Schliemann (DRFZ) for technical support and R. S. Jack for critical discussion. This work was supported by the BMBF (Verbundprojekt 0312106). The DRFZ is supported by the Berlin Senate of Research and Education. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”.

Such documents are peer-reviewed, PF-01367338 supplier but not copy-edited or typeset. They are made available as submitted by the authors. “
“This issue of Infancy marks the transition to a new editorial team. The previous team, led by editor Martha Ann Bell at Virginia Tech University, will be a hard act to follow; at last report, manuscript turnaround was 57 days and Infancy’s impact factor had been raised to over 1.9. Many of the papers in this issue were accepted by the previous team (which included Celia Brownell, Thierry Nazzi, Lisa Oakes, and Douglas Teti), and the next few issues will feature a mix of papers from the teams as the transition continues.

I am honored to have been chosen to serve as Infancy’s new editor, and I am pleased to announce a team featuring three new associate editors, Suzanne Curtin (University of Calgary), Ronny Geva (Bar Ilan University), and Catherine Tamis-LeMonda (New York University). Megan Blossom here at the University of Kansas will serve as our Editorial Assistant. In this term, we will look to maintain the accomplishments and capitalize on the momentum of the previous team. However, we will look to initiate some changes to the journal as well. First, we hope to publish more papers in a more timely fashion by setting length limits for submissions; look for word count limits on submissions in author instructions on the Tacrolimus (FK506) Wiley website by the start of the calendar year 2014. Second, we will look to encourage and promote more translational science in Infancy over our term; while maintaining its traditional emphases (i.e., early normative cognitive, language, social, and affective development) and we hope to extend the scope and impact of Infancy by opening it up to rigorous work in (for example) early intervention and neurodevelopmental disorders in infancy. We are grateful to the Martha Ann’s team for their service to the Society, and we look forward to the opportunity to serve and help shape the field of infant studies for the next 5 years.

Most of these can be attributed to the impaired metabolism of brain biogenic amines. To gain new insights into the dithiocarbamates and their effects on neurotransmitter systems, an in vivo experimental model based on daily injections of DEDTC in adult mice for 7 days was established. To this end, the concentrations of the three major brain monoamines, dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were

measured in whole brain extracts with high-performance liquid chromatography (HPLC). The levels of D2 dopamine receptor (D2R) were evaluated by Western blot and by immunohistochemical techniques the cell pattern of tyrosine hydroxylase (TH), dopa beta hydroxylase (DBH) and choline acetyltransferase ChAT) were analysed. selleck compound A significant reduction in DA and 5-HT levels was observed, whereas NA was not affected. Moreover, decreases in D2R levels, as well as

in enzymes such as TH, DBH and ChAT, were found. Our data suggest that DEDTC provokes alterations in biogenic amines and in different substrates of neurotransmitter systems, which could explain some of the neurobehavioural effects observed in patients treated with disulphiram. “
“T. N. Phoenix, D. S. Currle, G. Robinson and R. J. Gilbertson (2012) Neuropathology and Applied Neurobiology38, 222–227 Developmental origins of neural tumours: old idea, new approaches The recent convergence of pathology, cancer research and basic neurobiology disciplines is providing unprecedented

insights to the origins of brain tumours. This new knowledge holds buy GS-1101 great promise for patients, transforming the way we view and develop new treatments for these devastating diseases. “
“Filaments made Benzatropine of hyperphosphorylated tau protein are encountered in a number of neurodegenerative diseases referred to as “tauopathies”. In the most prevalent tauopathy, Alzheimer’s disease, tau pathology progresses in a stereotypical manner with the first lesions appearing in the locus coeruleus and the entorhinal cortex from where they appear to spread to the hippocampus and neocortex. Propagation of tau pathology is also characteristic of argyrophilic grain disease, where the tau lesions appear to spread throughout distinct regions of the limbic system. These findings strongly implicate neuron-to-neuron propagation of tau aggregates. Isoform composition and morphology of tau filaments can differ between tauopathies suggesting the existence of conformationally diverse tau strains. Altogether, this points to prion-like mechanisms in the pathogenesis of tauopathies. “
“Pilomyxoid astrocytoma (PMA) is a newly identified variant of pilocytic astrocytoma (PA). We report three cases of PMA with comparison to seven cases of PA in terms of their clinicopathological features.

However, tumor progression and eventual invasion of the host is also dependent on the host response in terms of inflammation and antitumor immunity.

This host response provides both a tumor-promoting environment and an immune barrier to tumor progression that the tumor needs to neutralize or overcome in order to progress (reviewed in [80-82]). Indeed for colorectal carcinoma and other types of cancer, the presence of adaptive immune cells within the tumor has been shown to be a better predictor of tumor progression and prognosis than traditional or molecular tumor staging [83]. Tumors have been shown GSK1120212 mw not only to originate in inflamed JAK inhibitor tissues due to infections, but some human tumors develop in sterile chronic inflammation, due to mechanical, chemical, radiation, or other types of injury, or due to genetic pathology. For example, chronic indwelling of urinary catheters has been shown to be associated with bladder carcinoma [84], chronic exposure to asbestosis is associated with lung cancer and mesothelioma (chemical) [85], and secondary pancreatitis resulting from a mutation in the trypsinogen gene has been associated with pancreatic carcinoma

[86]. Inflammation has been proposed to be involved in the promotion of cancer, in part through the production of reactive oxygen and nitrogen species; both species induce the formation of DNA cross-links, single- or double-strand breaks that can drive genomic instability and mutations within oncogenes and tumor suppressor genes [80, 87-89]. In addition, clear experimental evidence indicates

that inflammation provides a tumor-promoting environment in which stromal cells and infiltrating inflammatory hematopoietic cells, such as macrophages, produce growth and angiogenic factors as well as tissue remodeling enzymes [80, 90-94] (Fig. 1). Activation of certain oncogenes, such as RET, Hras and Kras, has been shown to NADPH-cytochrome-c2 reductase induce, both in the transformed cells as well as in surrounding tissue, an intrinsic inflammation with a secretory pattern; this pattern is reminiscent of that observed in senescent cells, of inflammatory mediators and chemokines that attract inflammatory hematopoietic cells, thus initiating and amplifying the inflammatory response [95-99]. Inflammation also causes infiltration by bone-marrow-derived tumor-associated macrophages and monocyte-derived myeloid cell subsets [100], which perform a critical protumorigenic function in creating the tumor environment by remodeling healthy tissue to accommodate the expanding tumor, increasing angiogenesis and suppressing antitumor T-cell responses [101, 102].

1% sodium azide, and then stained with the amine-reactive LIVE/DEAD fixable violet dead cell

stain kit (Molecular Probes, Invitrogen) 47 and with allophycocyanin (APC)-conjugated anti-CD4+ mAb (BD Pharmingen, San Josè, CA, USA) in incubation buffer (PBS-1% FCS-0.1% Na azide) for 30 min at 4°C. Subsequently, PBMC were washed, permeabilized (Cytofix/Cytoperm Kit, BD Pharmingen) according to the manufacturer’s instructions and stained for intracellular cytokines with anti-IFN-γ-PE, anti-IL-2-FITC Y27632 and TNF-α-PECy7, or isotype-matched control mAb. All mAb were from BD Pharmingen. Cells were washed, fixed in 1% paraformaldehyde and at least 250 000 lymphocytes were acquired using a modified FACS Aria (BD Biosciences), following gating according to forward and side scatter plots. FACS plots were analysed using FlowJo software (version 6.1.1; Tree Star, Ashland, OR, USA). Nonviable cells were excluded using a dump channel versus CD4+. Percent frequencies of the different combinations of IFN-γ, IL-2 and TNF-α-positive cells following antigenic stimulation were calculated within the total population of CD4+ T cells and background values subtracted (as determined from the medium alone control). Nonspecific background was extremely low when more GSK2126458 than one cytokine was examined. A cutoff of 0.01% was used as described previously

48; values below this were set to zero. PBMC were stimulated in IMDM (Invitrogen, Breda, The Netherlands) containing 10% pooled human serum and ESAT-6+CFP-10 peptides, tested in pools containing 1 μg/mL per peptide. Cells were cultured in a humidified incubator at 37°C with 5% CO2 for 6 days, the last 18 h in the presence of 5 μg/mL Brefeldin A (Sigma, Zwijndrecht, The Netherlands). Intracellular staining was performed using intrastain reagents (Dako cytomation, Heverlee,

Belgium). Ab used were CD3−APC-Cy7, CD4+-PE-Cy7, CD8+-Am Cyan, IFN-γ-Alexa 700, IL-2-PE and TNF-α-APC (all from BD Biosciences, Alphen aan den Rijn, The Netherlands). Data were acquired on a BD LSRII flow cytometer using FACSDiva software (BD Biosciences) and analysed using FlowJo software (Tree Star). Graphical representations were made using Pestle and Spice software, software provided free of charge by the National Institute of stiripentol Allergy & Infectious Disease (Bethesda, MD, USA), written in collaboration with Dr. Mario Roederer, Senior Investigator of the ImmunoTechnology section of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases. Median and interquartile range of data were calculated and Mann–Whitney U-test was used to compare medians. Chi-square testing was used for dichotomous (positive/negative) measures. Values of p<0.05 were considered significant. Data were analyzed using statistical software SYSTAT 11 (Systat Software) or Graph Pad Prism (4.02) (Graph Pad Software). The authors acknowledge Dr.

None of the authors has any conflicts of interest associated with this study. “
“Bone morphogenetic proteins (BMPs) are multifunctional growth factors regulating differentiation and proliferation in numerous systems including the immune system. Previously, we described that the BMP signaling pathway is functional in human monocyte-derived dendritic cells (MoDCs), which were found to express both the specific receptors and the Smad proteins required for signal transduction. In this study, Autophagy inhibitor we provide evidence that human MoDCs

produce BMP-4 and that this production is increased over the maturation process as is BMP signal transduction. When DCs are matured in the presence of an inhibitor of the BMP pathway, the expression of the maturation https://www.selleckchem.com/products/PD-0332991.html markers PD-L1 and PD-L2 is reduced, while cytokine production is not affected. As a result, these mature DCs present an augmented ability to stimulate both T cells and NK cells. Eventually, the inhibition of BMP signaling during maturation causes a reduced expression

of IRF-1, a transcription factor that positively regulates the expression of PD-L1 and PD-L2. The present study indicates that the BMP signaling pathway regulates PD-L1 and PD-L2 expression in human MoDCs during the maturation process, probably through the IRF-1 transcription factor, and also points out that the manipulation of BMP signaling might considerably improve the immunogenicity of MoDCs used in immunotherapy. “
“Recent years have witnessed an explosion in the amount of genomic information available for Toxoplasma gondii and other closely related pathogens. These data, many of which have been made publicly available prior to publication, have facilitated a wide variety of functional genomics studies. In this review, we provide a brief overview of existing

database tools for querying the Toxoplasma genome and associated genome-wide data and review recent publications that have been facilitated by these data. Topics covered include strain L-NAME HCl comparisons and quantitative trait loci mapping, gene expression analyses during the cell cycle as well as during parasite differentiation, and proteomics. The primary repository for functional genomics data for Toxoplasma can be found at EupathDB.org (1,2). This site provides access to data from 22 species of apicomplexans and kinetoplastids and provides a variety of search tools to mine data, as well as genome browsers for each species. The site has complex query building software built in to allow users to customize searches and filter the results based on a number of relevant criteria. These include polymorphism and orthology profiles, gene expression across strains and developmental stages, and genomic location. From a comparative genomics perspective, the current version of EupathDB allows for searches to be conducted both within and between species. This is an incredibly powerful tool for comparative genomics.

To isolate such cells, BM cells excluded of lineage positive cells, were sorted for the CD117intermediateCD135+CD16/32lo surface expression [22]. These committed precursor cells STA-9090 in vitro were cultured in the presence

of Flt3L or Flt3L+GM-CSF for 8 days before loosely adherent cells were harvested for phenotypic analysis. The pro-DCs proliferated 5.1-fold under dual cytokines compared with 2.3-fold under Flt3L alone (Fig. 5). The DCs produced under dual cytokines compared with those under Flt3L alone were larger. They contained very few pDCs (CD45RA+) and CD8eDCs (Sirpα−), but were mostly CD8− equivalents (Sirpα+) (Fig. 5). Furthermore, the intracellular ROS level of the Sirpα+ subset of the DC progeny cultured Lenvatinib datasheet under dual cytokine conditions was higher than those cultured under Flt3L alone (Fig. 5). Taken together, these findings suggest that GM-CSF can divert FL-DC committed precursor cells to develop into GM-DCs. Since GM-CSF is also present in the steady state, albeit at lower levels [17], we investigated whether steady-state GM-CSF could exert any negative influence on CD8+ DC development in vivo. We firstly compared

the spleen DC composition between wild-type (WT) and GM-CSF deficient (GMKO) mice. Interestingly, we observed that spleen DCs of GMKO mice contained significantly higher numbers and percentages of CD8+ DCs, compared with WT mice (Fig. 6A). To confirm the above findings, we made mixed BM irradiation chimeras with equal numbers

of WT (Ly5.1) and βcKO (defective for GM-CSF signaling; Ly5.2) mice so that both types of DC developed in the same environment. In the reconstituted mice (4–6 weeks after BM transfer), both types of BM cells reconstituted approximately equally for CD11c+ cells and the total number of DCs of each origin was not significantly different (data not shown). However, the percentage and absolute number of CD8+ DCs of βcKO origin was higher compared with that of WT origin (Fig. 6B). Overall, these data indicate that disruption to GM-CSF signaling, whether by ligand or receptor deficiency, enhances the differentiation of CD8+ DCs. We hypothesized Terminal deoxynucleotidyl transferase that the fate of the DC subsets in vivo under elevated GM-CSF levels should mirror what we found in vitro. Indeed, a reduction in the proportion of pDCs and CD8+ DCs was observed in GM-CSF transgenic (GMtg) mice. GM-CSF transgenesis led to a great expansion of total splenocyte numbers (splenomegaly). We therefore enriched DC lineage by density centrifugation. Different DC subsets were sequentially gated, and the proportion of the total number of DCs per spleen was examined (Fig. 7A). Compared with WT controls, constitutive overexpression of GM-CSF reduced the proportion of pDCs by 5.7-fold, and CD8+ DCs by twofold. In contrast, a threefold increase in the proportions of mDCs, and a 1.2-fold increase in Ly6C−CD11b+ DCs were noted.

We should point out that TSLP can also activate mast cells find more [63]. Enterocytes also produce high amounts of TGF-β[64]. This cytokine functions by inhibiting the activity of NF-κB on the promoters of proinflammatory genes in macrophages and DCs [65]. Together with TSLP, TGF-β induces a tolerogenic phenotype in myeloid-derived

DCs in vitro[66]. TGF-β produced by DCs promotes a Th3 regulatory phenotype in some naive T cells in MLN [67]. TGF-β is also present in human milk [68], and rodent enterocytes have TGF-β receptors [69]. TGF-β is involved in suppressing inflammatory responses in the neonatal gut and in consolidating the barrier function of the intestinal mucosa [70,71]. Enterocytes also influence antibody production in the intestinal mucosa; through TSLP secretion, enterocytes promote B cell activating factor (BAFF) and APRIL (a proliferation inducing

ligand) production by adjacent DCs and class-switching of B cells towards the production of sIgA [72,73]. APRIL synthesis is initiated after bacterial stimulation of TLR-4 [74] and results in IgA2 production, an isoform of IgA which is more resistant to proteolysis [75]. After synthesis, sIgA translocates to the intestinal lumen via pIgR; once in the gut lumen, sIgA acts in favour of decreasing the antigenic pressure generated by food and microbes on the mucosa. Among intraepithelial cells, M cells and enterocytes are capable of mediating the encounter between antigens within the gut lumen and DCs. M cells are dedicated to this function, selleck kinase inhibitor differing from normal

enterocytes which are only secondarily involved in antigen presentation. M cells are located above Peyer’s patches (PP) in the small intestine and in close contact with luminal antigens, due to reduced glycocalyx and mucin secretion. They have a particular morphology that allows them to promote uptake and Endonuclease transport of luminal content to professional antigen-presenting cells present in Peyer’s patches and lymphoid follicles. M cells possess fewer lysosomes [76], probably indicating a low intracellular antigen degradation, and are present mainly in the small bowel, but also in the colon, rectum or respiratory tract [77]. They are very low in number, counting for only one cell for every 10 million normal enterocytes. Human and mouse M cells express important PRRs, such as TLR-4, platelet-activating factor receptor (PAFR) and α5b1 integrin [78]. These molecules, belonging to the innate immune system, recognize PAMPs and mediate translocation of bacteria across the epithelium. Jejunal M cells express major histocompatiblity complex (MHC)-II and contain acidic endosomal and prelysosomal structures, indicating that they are able of presenting endocytosed antigens to lymphocytes [79]. It is noteworthy that colonic M cells do not express MHC-II antigens, suggesting that they may not present antigen [80].

The involvement of DJ-1 and β-catenin in glioma cell lines was evaluated by immunohistochemistry and Western blotting. High DJ-1 expression (37.5%) and high β-catenin expression (34.1%) in glioma specimens were significantly associated with high grade and poor prognosis in glioma patients. However, only high levels of DJ-1 (P = 0.014) was a strong

independent prognostic factor, correlated with a reduced overall survival time. In vitro DJ-1 expression was positively correlated with the expression levels of β-catenin and p-Akt, and negatively correlated with PTEN expression in U87, U251 MG, SWO-38 and SHG44 human glioma cell lines. After the knockdown of DJ-1, Akt, p-Akt or β-catenin expression levels were not affected in the

PTEN-null cell lines (U87 and U251 MG). However, in the SWO-38 cell line, which has wild-type PTEN protein, the level of PTEN increased while Akt/p-Akt and β-catenin Aloxistatin solubility dmso levels were reduced. Furthermore, β-catenin staining weakened in SWO-38 cells after DJ-1 levels decreased according to immunocytochemical analysis. In conclusion, DJ-1 and β-catenin may contribute to the development and recurrence of glioma and are valuable prognostic factors for glioma patients. DJ-1 may regulate β-catenin expression via PTEN and p-Akt. “
“Two Japanese families with benign hereditary chorea (BHC) 2 have recently been reported. Astemizole BHC 2 is characterized by adult-onset non-progressive chorea, and by Ceritinib in vitro genetic abnormality in the locus of chromosome 8q21.3-q23.3. This differs from the genetic abnormality previously reported in BHC. Here we report the first autopsied case of a member of one of two known families with BHC 2. A normally developed woman

recognized choreiform movements of her bilateral upper extremities beginning approximately at age 40. The movements had slowly spread to her trunk and lower extremities by approximately age 60. Generalized muscular hypotonia was also observed. The symptoms persisted until her death at the age 83, but had not worsened. Neuropathological examination revealed mild to moderate neuronal loss and astrocytosis in the striatum and decreased volume of cerebral white matter with astrocytosis bilaterally. Additionally, sparse but widely distributed neurofibrillary tangles and argyrophilic threads as well as scattered tufted astrocytes immunoreactive for 4-repeat isoform of tau were observed in the cerebrum, brainstem and cerebellum, showing 4-repeat tauopathy similar to that of progressive supranuclear palsy (PSP). Unique neuronal cytoplasmic inclusions were observed in the oculomotor nuclei; however, any specific immunoreactivities (e.g. ubiquitin and p62) were not detected, suggesting the presence of previously undescribed protein intracellular inclusions.

Dialect variation may also be problematic for infant learners, who have less language experience. However, less is known about how such phonetic variation may impact infant speech perception, particularly word recognition (although, see Best, Tyler, Gooding, Orlando,

& Quann, 2009 for its impact on budding semantic representations). As infants gain experience with their ambient language, they attune to phonetic information that is linguistically relevant. Language experience may also help infants ignore information irrelevant to word identity, such as variation attributable to gender, affect, and accent (foreign and dialectal). From an early age, infants exhibit some ability to deal with irrelevant speaker check details variability. Two-month-olds detect a syllable

change when produced by multiple speakers (Jusczyk, Pisoni, & Mullenix, 1992) and 6-month-olds discriminate a phonetic contrast between vowels, despite variability across speaker age and gender (Kuhl, 1979, 1983). Although infants can cope with linguistically irrelevant variability in sound discrimination, this ability does not translate to word recognition. Indeed, 7.5-month-olds fail to recognize a word when spoken by two speakers with dissimilar voices (e.g., male versus female; Houston & Jusczyk, 2000) and the same word spoken in different affective states (e.g., happy versus neutral; Singh, Morgan, & White, 2004). It is not until learn more 10.5 months that infants ignore irrelevant gender and affect variability MK-8669 cost in word recognition (Houston & Jusczyk, 2000; Singh et al., 2004).

Surprisingly little is known, however, about whether infants can accommodate the linguistically irrelevant variation introduced by dialectal accent when recognizing words in fluent speech. Although infants as young as 5–7 months of age can discriminate different dialectal accents (Kitamura, Panneton, Deihl, & Notley, 2006; Nazzi, Jusczyk, & Johnson, 2000), it is unknown how the aspects that differ across accents impact word recognition. One exception is Schmale and Seidl (2009), where 9- and 13-month-olds were tested on their ability to generalize words from a native speaker of infants’ ambient dialectal accent (North Midland-American English) to a foreign-accented speaker (Spanish-accented English). Results showed that, although the 13-month-olds recognized words across these accents, 9-month-olds failed. The authors suggest that one explanation for this developmental pattern may relate to an increase in the flexibility of infants’ word representations, with older infants being better able to ignore linguistically irrelevant variation introduced by different accents.