Many genetic [3,26] and virological factors [27] have been thought to predispose to severe disease along with the host immune response

[27]. However, the correlates of a protective immune response have not been defined due to the inability to define DENV-serotype specific T cell responses. The lack of data regarding the constituents of a DENV-specific protective immune response has hampered the development of a safe and effective dengue vaccine. As we have identified serotype-specific and highly conserved peptides from all four DENV serotypes, these tools can be used to dissect DENV-specific immune responses in greater detail. As the peptides identified by us are serotype-specific and conserved, they can be used to determine past infecting DENV serotypes and would help us to understand the CB-839 cell line dynamics of the silent DIs in the community. This will be of value to address a number of questions, such as whether the sequence of infections with DENV serotypes

and/or the timing of DIs determine severity. Such data would help us to define the correlates of a protective DV-specific immune response and help us to develop safe and effective vaccines. In summary, we have shown that DENV-4 infection is www.selleckchem.com/products/CAL-101.html likely to be more common than thought previously in Sri Lanka. We have identified T cell responses to 19 regions of the four DENV serotypes, which are serotype-specific and highly conserved from dengue immune donors who have had asymptomatic/mild DI. The use of conserved serotype-specific T cell epitopes to determine past infecting DENV serotypes will be of value to determine the silent and symptomatic transmission of the DENV in the community and to identify the correlates of a DENV-specific protective immune response. Funding was

provided by the Medical Research Council (UK). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. An application has been made for protection of the intellectual property herein. Table S1. Degree of conservation of the identified peptides in the published dengue virus sequences. Degree of conservation was assessed by Urocanase the use of the virus variation resource on the dengue virus sequence database available at: http://www.ncbi.nlm.nih.gov/genomes/VirusVariation/Database/nph-select.cgi “
“Successful mammalian pregnancy relies upon acceptance of a semi-allogeneic fetus by the maternal immune system. Lessons learned from studies on protective immunity to microbial infections and tumours, prevention of autoimmunity, and allograft rejection have contributed to delineate the mechanisms leading to T-cell tolerance at the fetomaternal interface.

Similar studies are likely to identify other such endogenous molecules that can act in a complex synergy to protect the FRT from harmful pathogens. The authors thank Richard Rossoll, MS (Dartmouth Medical School), Deena Ratner, BS (University of Pittsburgh), Irma Rodriguez (Brown University) and Jessica Ingersoll, MS (Emory University), BGB324 in vivo for excellent technical assistance in the preparation of samples, cells and virus stocks. The authors also thank Dr Phalguni Gupta (University of Pittsburgh) for generous sharing of reagents and information.

Additionally, the authors thank Vincent Memoli, MD, Section Chief of Anatomical Pathology, for procuring tissues; other members of the Department of Pathology for inspecting and dissecting tissue specimens: Jorge Gonzalez, MD, Alan Schned, MD, Peter Seery, Shannon Schutz, Elizabeth Rizzo, Richard Merrill, Charles-Robert Moultry, Patricia Larkin, Aimee Larson, Jennifer Simonton and Dawn Maddaline; for PF-562271 molecular weight clinical support and scheduling: Laura Wolfe, Linda Hallock, Kathleen Pilchman, Karen Carter, Kris Ramsey, Tamara Krivit and Joanne Lavin; surgeons: Barry

Smith, Joan Barthold, Jackson Beecham, John Currie, Leslie Demars, Paul Hanissian, John Ketterer, Benjamin Mahlab, Paul Manganiello, Misty Porter, Karen George, William Young, Kris Strohbehn, Roger Young, Stephen Andrews and Eric Sailer; and OR nurses: Jeanette Sawyer, Tracy Stokes, Fran Reinfrank and Jaclyn Logan. This work was supported by AI51877 awarded Dichloromethane dehalogenase to Dr Charles Wira from National Institute of Health; by AI40350 and AI066884 awarded to Dr Susan Cu-Uvin

from National Institute of Health; and by Lifespan/Tufts/Brown CFAR P30AI42853 and CDC CCU106795 awarded to Dr Susan Cu-Uvin and Dr Kenneth Mayer. The authors have no conflicts of interest to declare. “
“IRAK4, a serine/threonine kinase is a central adaptor protein in TLR signaling. To better understand the clinical significance of IRAK4 deficiency we examined the impact of IRAK4 on bacterial recognition in human monocytes. We show that IRAK4 knockdown modulates monocyte-derived cytokine secretion in response to Staphylococcus aureus and Streptococcus pneumoniae, resulting in decreased IL-12 and elevated IL-10 production, a finding also reproducible with ligands for TLR2 and TLR4. In contrast, silencing of MyD88 leads to a complete loss of cytokine secretion, indicating that IRAK4 acts as a differential regulator of bacteria/TLR-induced cytokine secretion downstream of MyD88. Further analysis revealed that this modulatory function results from IRAK4-mediated suppression of protein kinase B (PKB/Akt).

0 mutations. This broad similarity in the extent of mutations between IgG sequences from PNG villagers and sequences from urban residents of developed nations is surprising. It might be expected that mutation numbers would reflect an individual’s history of antigen exposure. Individuals from developed nations could therefore be expected to have substantially fewer mutations than individuals who have lived in the less hygienic circumstances of the developing world. Our observation may be explained by recent studies of Selleck LY2157299 the memory response. It has been shown that in a recall response, IgG+ memory cells rapidly give rise to plasma cells, but IgM+ memory cells re-enter the germinal centre reaction [33].

As CD27+ IgM+ memory cells carry few mutations in their immunoglobulin

genes [34, 35], the extent of mutations generated in the germinal centre reaction of a recall response is likely to be little different from that seen as a result of the earlier exposure to the antigen. Repeated exposure to common microbial antigens, which is a likely feature of village life in developing countries, would therefore be likely to lead to a relatively slow rise in mean mutation levels with age. As expected, many IgG sequences displayed a significantly higher proportion of replacement mutations within the CDRs than is seen in a model of random mutation. This can be taken as evidence that antigen selection guided the evolution of these sequences. The percentage of such sequences ranged between 22% (IgG3) and 39% (IgG2). The majority of sequences do not show evidence of antigen selection. This is not because most find more IgG sequences develop in the absence of antigen selection, but rather it likely reflects the underlying random nature of the mutational process, which makes it impossible

to see clear evidence of antigen selection in more than a fraction of all selected sequences. In contrast to the IgG sequences, only 12% of IgE sequences showed evidence of antigen selection. This is in line with previous observations of allergic IgE sequences. We and others have reported an absence of antigen selection, and therefore presumably the absence of affinity maturation in allergic IgE sequences [13, 36, 37]. Kerzel et al. [14] recently used the same kind of comparison with a random model of mutation in a study of antigen selection and mutations in allergic IgE sequences. In their study, a different probability of mutation GABA Receptor was used, as different definitions of the CDRs were also used. The use of these different definitions and probabilities do not alter the conclusions of the present analysis. The relative lack of antigen selection in the evolution of IgE sequences in parasitized individuals could be the result of early departure of IgE-committed cells from the germinal centre reaction and the continuing accumulating of mutations at other sites where follicular dendritic cells and follicular helper T cells, that are essential to the antigen selection process, are absent [6, 38].

In this review, we summarize recent research examining the modifiable lifestyle and environmental determinants affecting the retinal microvasculature (Table 1) and potential clinical implications of these findings. Dietary fiber intake, regular fish consumption, and low

GI diets, such as those high in sugars and simple carbohydrates, are all associated with reduced risk of vascular disease [8,24,31]. Emerging data suggests that the relationship between diet and macrovascular disease may partly be mediated by associated changes in the microcirculation [20–22]. Recent work has shown that diet may have effects on retinal vascular caliber in the general population. For example, data from the ARIC study showed NVP-BKM120 chemical structure that higher intake of dietary fiber was independently Dorsomorphin supplier associated with wider retinal arteriolar caliber and narrower venular caliber, indicating a lower risk of cardiovascular

diseases [20]. Similarly, findings from the BMES also demonstrated beneficial effects of increasing frequency of fish consumption on retinal microvasculature independent of other cardiovascular risk factors [21]. On the contrary, high-GI diets have been linked to deleterious anatomic changes in the retinal microvasculature [21,22]. Kaushik et al. [22] suggest that high-GI diets were associated with wider retinal venules and greater stroke mortality in persons 50 years and older. This suggests that postprandial glucose may have deleterious effects on the cerebral microcirculation and may play a significant role in the relationship between diet and stroke mortality. More recent data from 823 schoolchildren

aged 12.8 (±0.8) years [42] demonstrated that there was no association between a high-GI diet and retinal arteriolar or venular caliber. This evidence suggests a possible dose-dependent, cumulative effect of diet on the microvasculature over time. The physiologic influence of diet on the retinal Vasopressin Receptor microcirculation is probably complex. Kan et al. [20] found that the effect of fiber intake on retinal microvascular caliber might be confounded by current hypertension and dyslipidemia. This suggests that the beneficial retinal microvascular changes seen with increased fiber intake may not be directly affected by fiber intake itself, but by associated decreases in adverse systemic conditions like hypertension and dyslipidemia. For example, fish consumption is associated with increases in HDL [5]. Increased concentration of HDL has a well-established vaso-protective and anti-atherogenic effect [44] and may alone explain the beneficial retinal microvascular changes associated with higher fish consumption. Findings demonstrating that the microvascular effects of diet were not evident in children free of systemic disease [42] support this theory.

We studied the behaviour of the receptors

(CCR2, CXCR1 and CXCR2) for the CCL2 and CXCL8 in human myometrium, because both have been shown to be important in labour. We found that there was a significant decline in the mRNA expression of all three receptors in the upper segment and a similar trend in the lower segment with the onset of term labour (TL). Chemokine receptor mRNA expression was increased by stretch, reduced by oxytocin and PGF2α acting via phospholipase CT99021 mouse C (PLC). CXCR2 declined with exposure to CXCL8, consistent with the negative relationship observed in labouring myometrial tissue. The mRNA changes were confirmed by western analysis and flow cytometry. These data show that myometrial chemokine receptor expression is reduced with the onset of term

labour probably in response to the increased activity of chemokines, oxytocin and PGF2α. “
“Cytokine and chemokine levels were studied in infants (<5 years) with uncomplicated (MM) and severe malaria tropica (SM), and in Plasmodium falciparum infection-free controls (NEG). Cytokine plasma levels of interleukin (IL)-10, IL-13, IL-31 and IL-33 were strongly elevated in MM and SM compared to NEG (P < 0·0001). Inversely, plasma concentrations of IL-27 were highest in NEG infants, lower in MM cases and lowest in those with SM (P < 0·0001, NEG compared to MM and SM). The levels of the chemokines macrophage inflammatory protein (MIP3)-α/C–C ligand 20 (CCL20), monokine induced by gamma interferon (MIG)/CXCL9 and CXCL16 were enhanced in those FXR agonist with MM and SM (P < 0·0001 compared to NEG), and MIP3-α/CCL20 and MIG/CXCL9 were correlated positively with parasite density, while that of IL-27 were correlated negatively. The levels of 6Ckine/CCL21 were similar in NEG, MM and SM. At 48–60 h post-anti-malaria treatment, the plasma concentrations of IL-10, IL-13, MIG/CXCL9, CXCL16 and MIP3-α/CCL20 were clearly diminished compared to before treatment, while

IL-17F, IL-27, IL-31 and IL-33 remained unchanged. In summary, elevated levels of proinflammatory and regulatory cytokines and chemokines were generated in infants during and after acute malaria tropica. The proinflammatory Digestive enzyme type cytokines IL-31 and IL-33 were enhanced strongly while regulatory IL-27 was diminished in those with severe malaria. Similarly, MIP3-α/CCL20 and CXCL16, which may promote leucocyte migration into brain parenchyma, displayed increased levels, while CCL21, which mediates immune surveillance in central nervous system tissues, remained unchanged. The observed cytokine and chemokine production profiles and their dynamics may prove useful in evaluating either the progression or the regression of malarial disease.

All animal experiments were carried out within institutional guidelines (permission numbers: 1887 and 1888). FITC-, PE-, allophycocyanin-Cy7-, PE-Cy7- or biotin-conjugated mAbs specific for mouse CD4 (GK1.5), CD5 (53-7.3), CD8α (53-6.7), CD11b (M1/70), CD19 (1D3), CD21 (CR2/CR1), CD23 (B3B4), CD45R (B220; RA3-6B2) and λ1+2-LC were purchased from

BD Biosciences. Human CD10-PE (HI10a) and CD19-alloophycocyanin (HIB19) were purchased from Biolegends. Anti-human IgM-FITC (SA-DA4) was purchased from Southern Biotech. Antibodies specific for IgM (M41), κ-LC (187.1), CD93 (PB493, C1qRp), anti-mouse BAFF-R (9B9) 20 and anti-human BAFF-R (HuBR9.1) were purified from hybridoma supernatant and labeled with FITC or biotin using ITF2357 mouse standard procedures. (Biotin-labeled antibodies were revealed by PE-Cy7-streptavidin; BD Biosciences.) Staining of cells was performed as described previously 39. Apoptotic cells were determined by using an Annexin V

apoptosis detection kit (eBioscience). Flow cytometry was performed using a FACS Calibur (BD Biosciences), and data were analyzed using the Cell Quest Pro Software (BD Biosciences). For flow cytometry with five colors or for cell sorting, the FACS Aria (BD Biosciences) was used. For cell sorting, erythrocyte-depleted BM cells were stained in IMDM supplemented with 2% FBS with saturating concentrations of the appropriate antibodies. After a 30-min incubation at 4°C, cells were washed in PBS https://www.selleckchem.com/screening/anti-infection-compound-library.html with 2% FBS, resuspended in filtered PBS with 2% FBS and then filtered through a 20-μm diameter nylon mesh prior to sorting. Re-analyses of sorted cells indicated that in all instances they were >98% pure. BM samples were from routine clinical specimens taken from patients at Ospedale San Gerardo (Monza, Italy). Fully informed written

parental consent was obtained in accordance with national guidelines. Total mononuclear cells (MNCs) were isolated by Ficoll gradient centrifugation. MNCs were stained for CD19, CD10, IgM and BAFF-R (mAb Hu-Br 9.1 generated in our laboratory) Carnitine palmitoyltransferase II and sorted as previously described 39. Sorted BM B cells were maintained in IMDM medium supplemented with 2% FBS, 100 U/mL penicillin and 100 μg/mL streptomycin and grown at 37°C in 10% CO2. Twenty-five micrograms per milliliter anti-κ-LC (clone 187.1) or 25 μg/mL anti-IgM (clone M41) antibody was added as indicated. Total RNA was extracted from cells using TRI Reagent® (MRC, Cincinnati, USA), and first-strand synthesis was performed with Superscript® RT kit (Roche) according to manufacturer’s guidelines. PCR for Rag-2 and β-actin was carried out with Taq polymerase (Sigma-Aldrich). For amplification of mouse Rag-2, the following primers were used: 5′-CAC ATC CAC AAG CAG GAA GTA CAC-3′ and 5′-GGT TCA GGG ACA TCT CCT ACTA AG-3′. Semi-quantitative RT-PCR was performed by serial dilutions of cDNA. The reaction conditions were 30 s at 94°C initially, 30 s at 94°C, 30 s at 64°C and 90 s at 72°C for 40 cycles, and 10 min at 72°C.

We conclude that inducible complex formation between Syk and 14-3-3γ signals feedback inhibition to limit Syk-mediated B-cell activation. The family of 14-3-3 proteins comprises seven mammalian members of acidic 30 kDa polypeptides that participate as homo- or heterodimers in diverse cellular processes by modulating enzymatic activities, altering the subcellular localization of proteins, and inhibiting or promoting protein–protein interactions 39. Although

non-phosphorylated targets have been reported, the most common mode of 14-3-3 action is by binding to phosphoserine- AZD1152-HQPA solubility dmso or phosphothreonine-containing motifs. Canonical 14-3-3-binding sites harbor a central phosphoserine residue flanked by a positively charged arginine (or lysine) and proline on their N- and C-terminus, respectively. Two consensus 14-3-3 recognition motifs are RSXpSXP (mode 1) and RXF/YpSXP (mode 2) 41, 42. Human Syk accommodates seven putative docking sites for 14-3-3 proteins but our mutational analysis established that phospho-S297 within a classical mode 1 motif provides the critical anchor residue for 14-3-3γ. It is however likely that other 14-3-3 family members can also recognize phospho-S297.

Moreover, we cannot formally rule out the possibility of hierarchical 14-3-3 binding in that only upon initial binding of 14-3-3 to phospho-S297 selleck one or more of the additional docking sites become accessible for further recruitment of 14-3-3 family members. Nonetheless, our reconstitution experiments unambiguously established that BCR-induced phosphorylation of S297 of human Syk and concomitant binding of 14-3-3γ attenuates Syk action. As to the multi-functionality of 14-3-3 proteins several mechanisms are conceivable. For example, 14-3-3 binding may directly inhibit the catalytic activity of Syk, which is consistent with the reduced phosphorylation of Syk substrates such as SLP65 Temsirolimus and PLC-γ2. However, we favor the possibility that 14-3-3 lowers the efficiency with which Syk is recruited from the cytosol to the activated BCR where Syk

becomes allosterically activated by SH2/phospho-ITAM interactions. Our reverse interactome analysis and direct microscopic imaging support this sequestration model, which in fact represents a common theme of 14-3-3 action as binding of these adaptors retains many client proteins in the cytosol. Interestingly, the short Syk isoform that is predominantly expressed in breast cancer cells 46 lacks the linker insert encompassing serine 297. It is thus tempting to speculate that the absence of the inhibitory 14-3-3 module is involved in Syk-related pathogenicity. While this manuscript was in preparation, Paris et al. reported that protein kinase C phosphorylates murine Syk at serine 291, which corresponds to S297 in human Syk 47.

We thank Kim Barrymore for editing the manuscript. This project was supported by the Japan Science and Technology Agency within the framework of the Science and Technology Research Partnership for Sustainable Development and the Japan Initiative for Global Research Network on Infectious Diseases. Katendi Changula was also sponsored by the Southern African Center for Infectious Diseases Surveillance with Wellcome Trust Grant WT087546MA. The authors declare no conflict of interest. “
“It is known that NB-UVB therapy can suppress a broad range of immune cells, but the additional effect of bathing in geothermal

seawater still remains unclear. To study the influence of treatment on the expression of circulating immune cells contributing to the pathogenesis of psoriasis, six patients with psoriasis were treated with bathing find more in geothermal seawater two times daily combined with NB-UVB five times/week for 2 weeks and six patients were treated with NB-UVB therapy three times/week for 8 weeks. Disease severity (Psoriasis Area and Severity Index, PASI), chemokines, inflammatory cytokines,

T cells and Toll-like receptors in the blood and skin samples were evaluated on enrolment (W0) and at BAY 73-4506 in vivo 1 (W1), 3 (W3) and 8 (W8) weeks. Compared with healthy controls, psoriasis patients with active disease had significantly higher proportion of peripheral

CLA+ T cells expressing CCR10 and CD103 and T cells with both Th1/Tc1 (CD4+/CD8+ IFN-γ+ or TNF-α+ cells) and Th17/Tc17 (CD4+CD45R0+IL-23R+, CD4+/CD8+ IL-17A+ or IL-22+ cells) phenotypes. Both treatments gave a significant clinical effect; however, bathing in geothermal seawater combined with NB-UVB therapy was more effective than NB-UVB therapy alone. This clinical improvement was reflected by a reduction in circulating CLA+ peripheral blood T cells and by a decreased Th1/Th17 and Tc1/Tc17 inflammatory response. These Fluorouracil findings suggest that the inflammatory response in psoriasis is predominantly driven by both CD4+ and CD8+ skin-homing tissue retaining T cells of the Th17/Tc17 lineages. Bathing in geothermal seawater from the Blue Lagoon (BL) in Iceland has been reported to have a beneficial effect on psoriasis [1, 2]. Additional treatment with narrow-band ultraviolet (NB-UVB) phototherapy further increases the efficacy of the treatment [3-5]. The BL contains geothermal seawater originating from underground reservoirs filled with a mixture of fresh water and seawater. Sampling from the lagoon shows that no pathogenic bacteria thrive in this ecosystem [6]. The fluid in the lagoon has a high level of silica but is moderate in temperature (37 °C) and salinity (2.7%) [7].

Recently, a defect in the NCF4 gene that encodes the p40phox has been shown to produce a disease phenotype

limited check details to a chronic inflammatory feature of CGD, at least in this single patient. Matute et al. [45] reported the autosomal recessive mutations in NCF4 in a boy who presented with granulomatous colitis. His neutrophils showed a substantial defect in intracellular, but not extracellular, superoxide production during phagocytosis, which is distinct from other forms of CGD where both intracellular and extracellular oxidant production is affected. Genetic analysis of NCF4 showed compound heterozygosity for a frameshift mutation (K52RfsX79) with premature stop codon and a missense mutation predicting a R105Q substitution in the PX domain. The importance of the small G protein Rac2 (OMIM # 608203) was underlined when a severe immunodeficiency different from classical CGD was described in male child and related to a dominant negative

mutation in the RAC2 gene (D57N). A male infant of non-consanguineous parents presented with a perirectal abscess and delayed umbilical cord fall at MAPK Inhibitor Library clinical trial 5 weeks of age. In the subsequent 4 months, he had recurrent perirectal abscesses, infected urachal cyst, failure to heal surgical wounds and the absence of pus in infected areas. His older sibling was healthy, and there was no family history of an increased incidence of infections or poor wound healing. A second, recently reported patient also had omphalitis, as well as a paratracheal abscess that grew

Stenotrophomonas and Prevotella but showed dramatically decreased pus formation [46, 66]. Rac2 is a member of the Rho family of GTPases that regulates both actin cytoskeleton and superoxide anion production; this isoform constitutes more than 96% of RAC expression in neutrophils [67]. During NADPH activation, Rac2 binds Progesterone GTP and migrates to the membrane independently of the p67phox/p47phox complex [68, 69]. The transcription factor nuclear factor-κB (NF-κB) is a heterodimer formed from members of the mammalian rel gene family, which includes p105/p50, 100/p52, p65 (RelA), RelB and c-Rel [70, 71]. The general mechanism of activation of the conventional and most common NF-κB complex (p50/RelA) starts with its sequestration in the cytoplasm by interaction with a family of inhibitory proteins, termed inhibitors of κB (IκBs), and the proto-oncogene Bcl-3. Activation by extracellular signals induces phosphorylation of IκB by specific IκB kinases (IκKα and IκKβ) on critical serine residues, Ser32 and Ser36, within the N-terminal signal response domain [72]. IκB phosphorylation leads rapidly to its ubiquitinization and rapid proteolytic degradation, thus releasing the NF-κB heterodimer to move into the cell nucleus.

“
“We investigated the development

of the other-race effect “ORE” in a longitudinal selleck chemicals sample of 3-, 6-, and 9-month-old Caucasian infants. Previous research using cross-sectional samples has shown an unstable ORE at 3 months, an increase at 6 months and full development at 9 months. In Experiment 1, we tested whether 9-month-olds showed the ORE with Caucasian and African faces. As expected, the 9-month-olds discriminated faces within their own ethnicity (Caucasian) but not within the unfamiliar ethnicity (African). In months. In Experiment 2, we longitudinally tested infants at 3, 6, and 9 months by presenting either the Caucasian or the African faces used in Experiment 1. In contrast to previous cross-sectional studies and Experiment 1, we found that infants discriminated between all stimuli. Hence, we did not find the ORE in this longitudinal study even at 9 months. We assume that the infants in our longitudinal study showed no ORE because of previous repetitive exposure to African faces at 3 and

6 months. We argue that only a few presentations of faces from other ethnic categories sufficiently slow the development of the ORE. Selleckchem PF 2341066 “
“Reduced responsiveness to joint attention (RJA), as assessed by the Early Social Communication Scales (ESCS), is predictive of both subsequent language difficulties and autism diagnosis. Eye-tracking measurement of RJA is a promising prognostic tool because it

is highly precise and standardized. However, the construct validity of eye-tracking assessments of RJA has not been established. By comparing RJA an eye-tracking paradigm to responsiveness to joint attention during the ESCS, the current study evaluated the construct validity of an eye-tracking assessment of RJA for 18-month-old infant siblings of children with autism. Relations between measures of RJA and concurrent language skills and autistic symptomatology were assessed. Correlations between measures of ESCS RJA and eye-tracking RJA were statistically significant, but few relations between either ESCS or eye-tracking assessments of RJA and language or symptoms were observed. This study establishes the construct validity of eye-tracking assessments of RJA. “
“We used eye tracking to examine 4.5- to 12.5-month-old infants’ (N = 92) Isoconazole eye movements during 3-s presentations of upright and inverted faces. Scanning of inverted faces was statistically indistinguishable at 4.5, 6.5, 8, and 12.5 months of age; at each of these ages, infants disproportionately scanned the region containing the eyes. Scanning of upright faces changed over this age range. When viewing upright faces, 4.5-month-old and 6.5-month-old infants focused disproportionately on the region containing the eyes, whereas 12.5-month-old and 8-month-old infants distributed looking more broadly, scanning more of the internal area of the faces.