NOD proteins also recognize certain damage-associated molecular patterns (DAMP) of the host cell [39]. Regarding NOD proteins, only NOD1 was found in enterocytes, NOD2 being specific for Paneth cells [40]. Almost all TLRs are present at the mRNA level in enterocytes, but there are differences concerning their distribution along the intestinal tract. By immunohistochemistry and laser capture microdissection of the intestinal epithelium, it was shown that TLR-2 and TLR-4 are expressed at low levels by intestinal epithelial cells (IECs) in normal human colon tissues [41]. TLR-3 is expressed highly in Bortezomib chemical structure normal human

small intestine and colon, whereas TLR-5 predominates in the colon [42]. mRNA coding for all TLR types has been identified in colonic epithelium; the expression Silmitasertib datasheet of TLR-1, TLR-2, TLR-3, TLR-4, TLR-5 and TLR-9 has also been detected in IECs of the human small intestine [43]. Concerning microbial recognition, TLR-2, -4, -5 and -9 detect bacterial and fungal structures, while TLR-3, -7 and -8 respond to viral products. Signal transmission from TLR to NF-κB is achieved through several adapter proteins, such as MyD88, MyD88 adapter-like (MAL), TNF receptor

(TNFR)-associated factor (TRIF) and TRIF-related adaptor molecule (TRAM), which form a complex with the Dolichyl-phosphate-mannose-protein mannosyltransferase C-terminal domains of different TLRs [44]. NOD1 induces NF-κB activation through receptor

interacting protein 2 (RIP2) and a serin/threonin kinase. In enterocytes, TLR and NOD-mediated signalling display specific features which allow the maintenance of minimal proinflammatory cytokine levels, despite increased antigenic pressure from the gut content [31]. Thus, TLR-9 stimulation induces different patterns of protein synthesis. Activation of TLR-9 on the apical pole of enterocytes leads to intracellular accumulation of IκB-α, therefore preventing NF-κB activation, while stimulation of TLR-9 located on the basolateral membrane results in IκB-α degradation. In a similar fashion, enterocytes express TLR-4 only in the Golgi apparatus, unlike macrophages, which express TLR-4 on the plasma membrane. As a result, bacterial lipopolysaccharide present in the gut lumen activates enterocytes only if it penetrates into them [45]. This polarization of enterocytes restrictively enables the initiation of an inflammatory response against microbes that have surpassed the tight junctions between enterocytes and have reached the basolateral membrane; conversely, in contact with the apical region of enterocytes, gut microbes have a limited inflammatory effect [46]. In the same respect of maintaining tolerance to the intestinal content, enterocytes express a limited number of TLRs in the apical region.

Renal hyperfiltration was associated with prehypertension and prediabetes, while hypofiltration was associated with dyslipidemia, abdominal obesity, overt hypertension, and overt diabetes. Conclusion: The number of MetS components is a good risk indicator of early- and late-stage kidney

damage. Therefore, kidney function should be monitored in subjects with MetS components. MetS components should be treated as early as possible to prevent the development of kidney damage and cardiovascular diseases in people with hyperfiltration, regardless of their body weight. YATABE JUNICHI1, learn more MATSUNAGA SHIGERU3, OGAWA ATSUSHI4, YATABE MIDORI2, TAKANO KOZUE2, ASAHI KOICHI1, TERAWAKI HIROYUKI1, NAKAYAMA MASAAKI1, WATANABE TSUYOSHI1 1Department of Chronic Kidney Disease Initiatives, Fukushima Medical University; 2Department of Pharmacology, Fukushima Medical University School of Medicine; 3Department of Biological Production, Akita Prefectural University; 4Aizufujikako Co., LTD Introduction: Advanced-stage renal disease patients have potassium restriction on their diet. In a survey on 38 hemodialysis patients, a majority (52.6%) of patients answered they are not eating

as much vegetable as they like and many (73.7%) answered that they would like to try low-potassium vegetables. Therefore, Aizufujikako, Co. Ltd. has developed low-potassium vegetables and fruits to meet this Apoptosis inhibitor need. Methods: Low-potassium lettuce is grown hydroponically in clean rooms of what used to be semiconductor factories using the cultivation method patented by Akita Prefectural University. The lettuce seeds are planted one by one in plastic pots for germination then the seedlings were transferred to water culture system. After 14–21 days, control solution in the growth chamber

was substituted with a “no potassium” solution, and the seedlings were cultivated for another 10–21 days with controlled Leukotriene-A4 hydrolase light cycles. Testing for potassium content, microbes and metals were performed for quality control. One hundred and eighty healthy volunteers tasted the low-potassium lettuce and answered the questionnaire. Results: The newly developed low-potassium lettuce contained 44.7 ± 20.0 mg potassium per 100 g, close to 90% less potassium compared to regular lettuce (approximately 400 mg potassium per 100 g). There was no significant difference in dietary fiber and vitamin contents between the low-potassium lettuce and regular lettuce. However, low-potassium lettuce contained significantly greater amount of sodium compared to regular lettuce. In the taste testing by healthy volunteers, 73.6% answered that the low-potassium lettuce tasted good, 63.9% wished to purchase the lettuce for themselves to eat, and 84.9% would suggest to buy the low-potassium lettuce if people close to them were on potassium restriction.

This is in agreement with previous observations, that 5–10% of the Caucasian population is MBL-deficient [7]. It is well known that mannan besides activating the MBL pathway also has the potential to trigger activation of the CP and the AP [22]. In assays that are not able to block the influence of the AP when measuring the MBL activity, it

is necessary to dilute the serum up to a level where the contribution from the AP is minimal. This may result in false negative MBL measurements in samples where the MBL activity is only reduced. The results obtained by Seelen et al. [21] showed that 28% of the 120 sera from healthy donors had functional MBL activities below a normal threshold set at 10%, which is an unrealistically

high proportion Crizotinib mouse of MBL-deficient individuals in a normal population. This may be due to the fact BMN673 that the serum samples were diluted 1:101 prior to analysis, and thus samples with low MBL activity will read out as negative. This present ELISA set-up using SPS for assessment of the MBL activity completely blocks the interference from the AP and the CP, allowing valid analysis of samples in high serum concentration. By analysing serum samples in twofold serial dilutions starting at a high serum concentration (10%), a more precise determination of MBL activity is obtained, which removes the risk of generating false negative measurements. Data were analysed using regression analysis on logistically transformed values taking the dilution factor into account. To illustrate the influence of the AP when measuring MBL pathway activity on a mannan-coated surface, seven samples with no MBL pathway activity click here (all either homozygous

or compound heterozygous for the structural MBL-2 gene mutations) in our MBL activity assay were analysed using the commercial kit Wielisa for assessment of MBL pathway. Each sample was analysed using 1:10 dilutions. All samples, which should have no functional MBL pathway activity, showed measureable false positive MBL pathway activities. This clearly indicates interference from the AP and illustrates why it is necessary to dilute samples in order to minimize the influence of the AP using this commercial kit. The concerns regarding diluting samples at 1:101 prior to analysing MBL pathway activity, which may give false negative results, were also tested using the Wielisa kit. The results obtained from the kit showed that six of 10 samples (two XA/XA, four XA/O and four YA/O), which had measurable MBL activity in our assay, showed no MBL pathway activity using the Wielisa kit. Taken together, the data indicate a risk of both false negative and false positive results using MBL pathway assays that do not block the AP. Although the terminal complement complex (C5b-9) is used as readout in the above-mentioned commercial assay, we recommend the use of the central complement factor C3 as readout in the assays presented in this study.

Importantly, no significant side effects have been reported so far, thus corroborating the apparent safety of sTRAIL treatment in humans. In addition, a number of agonistic antibodies (HGS-ETR1, HGS-ETR2, HGS-TR2J, LBY135, CS-1008, AMG 655) that selectively target TRAIL-R1 or TRAIL-R2 have been developed. All of these antibodies have potent tumouricidal activity in vitro and in vivo and appear to have a low toxicity profile in early-phase clinical studies Ku-0059436 in vivo [33,36–39]. An obvious difference between these TRAIL receptor-selective mAbs and TRAIL is the fact that TRAIL interacts with both of its agonistic receptors. This might provide TRAIL either with a wider

therapeutic spectrum or a narrower and more unpredictable therapeutic window, especially in light of its additional interaction with decoy TRAIL receptors. It is interesting to note that several groups have pursued the design of sTRAIL variants Luminespib mouse that show selectivity for TRAIL-R1 or TRAIL-R2

[40–43]. Although the precise fine specificity of some of these variants remains a matter of debate, the use of TRAIL receptor-selective variants for the treatment of a specific tumour type may prove valuable. For instance, CLL appears to be preferentially sensitive to TRAIL-R1 apoptotic signalling, whereas certain solid tumours appear to preferentially signal via TRAIL-R2. Rational integration of TRAIL receptor-selective sTRAIL variants may in those cases help to optimize efficacy. Importantly, as will be described in more detail below, normal cells can be sensitized to sTRAIL by certain other anti-cancer drugs. These side effects are likely due to a sensitizing effect by the co-administered drug on normal cells for the ubiquitous priming of TRAIL-R1 by sTRAIL trimers, as sTRAIL trimers are fully capable of TRAIL-R1 activation. In contrast, TRAIL-R2 is not/minimally activated by homotrimeric sTRAIL. Therefore, it seems a reasonable assumption that TRAIL-R1 signalling Isotretinoin is the main

culprit behind potential side effects of sTRAIL trimers. Thus, the rational design and use of TRAIL-R2-selective sTRAIL variants may help to optimize therapeutic efficacy, while minimizing the occurrence of toxic side effects. The available preliminary data indicate that activation of apoptotic TRAIL receptor signalling using sTRAIL or agonistic TRAIL-R antibodies may indeed prove beneficial to cancer patients and certainly warrant further evaluation of this reagent in clinical trials. However, intrinsic and/or acquired resistance to TRAIL receptor signalling is likely to pose a significant hurdle to clinical efficacy. Indeed, almost half of tumour cell lines analysed have intrinsic resistance to TRAIL receptor signalling, which also holds true for GBM cell lines.

, 2008). Subsequently, activated neutrophils kill the bacteria and initiate innate and adaptive immunity by producing important pro-inflammatory cytokines, chemokines, and other granule products that can drive the recruitment of monocytes, T cells, and dendritic cells (DCs) (Scapini et al., 2000; Yamashiro et al., 2001; Alemán et al., 2007; Sawant & McMurray, 2007; Mantovani et al., 2011). The secretory products of PMN have also been shown to regulate antimicrobial activities in monocytes and macrophages (Soehnlein et al., 2007). The neutrophil cell membrane expresses a complex array of adhesion molecules and receptors for various ligands,

including mediators, cytokines, immunoglobulins, and membrane molecules

on other buy Alpelisib cells. The FCγ receptors namely CD32 and CD64, expressed on neutrophils, have been shown to promote phagocytosis and respiratory burst (Hoffmeyer et al., 1997; Rivas-Fuentes et al., 2010). Also, PMN infected with MTB undergo apoptosis, which is essential for the resolution of inflammation (Kasahara Erlotinib solubility dmso et al., 1998; Alemán et al., 2002). Neutrophils recognize microbial molecules through toll-like receptors (TLRs). In turn, TLR-stimulated neutrophils help in recruitment of innate, but not acquired, immune cells to sites of infection (Hayashi et al., 2003). Thus, beside their key function as professional phagocytes, neutrophils influence both the induction phase and the effector phase of immunity. A strong immune response enough to prime the innate immunity and in turn the adaptive immunity is sufficient to counteract subsequent infections. A vaccine administered with such vigor will thus be effective to the optimum dipyridamole level. Mycobacterium bovis bacillus Calmette–Guerin (BCG) is the only vaccine available today for the protection against tuberculosis. Many human studies have been carried out to understand effective and protective immune responses post-BCG vaccination (Burl et al., 2010; Smith et al., 2010). However,

very few studies have focused on the effect of BCG on the functions of granulocytic PMN. Mycobacterium indicus pranii (MIP), also known as Mw, is another potent immunomodulator and shares antigens with MTB. Mw enhances T-helper1 response, resulting in the release of type-1 cytokines, predominantly interferon-γ, and thereby propagates cell-mediated immune responses (Nyasulu, 2010). In experimental models, Mw has shown a protective effect against tuberculosis in mice (Singh et al., 1992). Clinical trials have shown significant benefits of Mw in leprosy (Zaheer et al., 1993). Thus, Mw can be a successful vaccine candidate for tuberculosis (TB), and further clinical studies are planned in this direction. There is an increasing support to the hypothesis that PMN are involved in early inflammatory host response during mycobacterial infections and hence might be involved in immune protection against them (Brown et al., 1987).

falciparum (72). Further analyses also confirmed the colocalization of the heterochromatin protein 1 to H3K9me3, along with their association with regions of the genome that code for Plasmodium virulence factors (73,74). Global histone mass spectrometry analysis also confirmed the prevalence of active acetylated histone marks compared with inhibitory methylated ones (75). All together, these results suggest an atypical euchromatin/heterochromatin structure in the malaria parasite; active chromatin is prevalent

genome-wide, whereas silencing marks are less frequent although they seem to play a significant role in transcriptional control of genes involved in phenotypic variation and pathogenesis. Upon transcriptional activation, eukaryotic promoter Gefitinib nucleosomes are partially removed by sliding or disassembly, allowing DNA to become directly accessible to transcription factors (76,77) and other DNA-binding proteins.

Indeed, various genome-wide analyses provided evidence that active regulatory regions and gene promoters of highly expressed genes are, at least partially, nucleosome-depleted (78,79). Nucleosome positioning is typically driven by active remodelling complexes or dictated by the sequence of the binding DNA itself (80). In particular, poly(dA:dT) tracks are harder to bend around histones, and nucleosomes have a lower affinity for such sequences (81,82). Considering the extremely high AT content of P. falciparum’s YAP-TEAD Inhibitor 1 mouse genome, this latest observation may have important consequences for the parasite’s biology. Recently, the nucleosome landscape of P. falciparum was investigated next in reference to gene regulation by using two genome-wide methods, both coupled to NGS: (i) FAIRE to isolate protein-free DNA; and (ii) micrococcal nuclease-assisted isolation of mononucleosomal elements (MAINE) to isolate DNA fragments associated with histones (13). The combined use of both methods provides a comprehensive view of the chromatin structure across P. falciparum’s genome. Complementary opposite results were obtained by both methods (nucleosome-bound regions were identified with MAINE, and interspacing nucleosome-free

regions were identified with FAIRE) as reflected by a high negative correlation coefficient. Nucleosomes were predominantly found within coding sequences, which have a higher GC content relative to noncoding regions. Similar results were obtained using an anti-histone H4 ChIP-on-chip (52) and are consistent with three recent analyses of nucleosome distribution in human, worms and flies, demonstrating a marked preference of nucleosomes for exons (83–85). Moreover, Ponts et al. demonstrated the occurrence of massive and atypical genome-wide nucleosome depletion at the early trophozoite stage (‘open’ transcriptionally active state) before a progressive repacking of chromatin, while the cycle progresses towards the schizont stage (‘closed’ transcriptionally silent stage) of the intra-erythrocytic cycle.

The antibiotic resistance cassettes were cloned into a synthetic AatII site; the plasmid was linearized with AhdI and electroporated into competent B. burgdorferi as previously described (Samuels, 1995; Gilbert et al., 2007; Lybecker & Samuels, 2007). Transformants were cloned in liquid BSK II medium in 96-well plates (Yang learn more et al., 2004) containing either 50 μg mL−1 streptomycin or 40 μg mL−1 gentamicin at 34 °C in a 1.5% CO2 atmosphere. Positive clones were screened by PCR and assayed for the presence of plasmids lp28-1, lp28-4, lp25, and lp54 (Purser & Norris, 2000; Labandeira-Rey & Skare, 2001). The malQ mutants were trans-complemented by amplifying the malQ gene, including

165 bp of upstream sequence, using primers malQ U165F + AatII and malQ 1521R + AatII (Table 1). The PCR product was cloned into pCR®2.1-TOPO and confirmed by DNA sequencing. The malQ gene and the shuttle vector pBSV2 (Stewart et al., 2001) were digested with AatII and ligated together to generate pBSmalQ. Competent malQ mutant strains were electroporated with the pBSmalQ and selected in liquid BSK II medium containing 200 μg mL−1 kanamycin. Borrelia burgdorferi cultures were grown at 35 °C to

late log phase and RNA isolated using TRIzol™ Reagent (Gibco BRL) as previously described (Lybecker & Samuels, 2007). RNA was treated with DNase I (Invitrogen). cDNA was synthesized using the Roxadustat mw RETROscript™ kit (Ambion) according to the manufacturer’s instructions. cDNA was analyzed by PCR using primers malQ 385F and malQ 630R or flaA 64F and flaA 284R (Table 1). The University of Montana Institutional Animal Care Sclareol and Use Committee approved all mouse experiments.

C3H-HeJ female mice were intraperitoneally needle-inoculated with 1 × 104 cells of wild-type, malQ mutant, or complemented 297 clones (Barthold et al., 1990, 2010). Ear biopsies were taken 3 weeks postinoculation and cultured in BSK II containing 50 μg mL−1 rifampicin, 20 μg mL−1 phosphomycin, and 2.5 μg mL−1 amphotericin B. Mice were sacrificed 5 weeks postinjection, and ear biopsies, ankles, and bladders were collected and cultured as described above. Cultures were screened for B. burgdorferi by dark-field microscopy. To examine B. burgdorferi acquisition by ticks, unfed naive Ixodes scapularis larvae (National Tick Research and Education Resource, Oklahoma State University) were allowed to feed to repletion on infected mice 5 weeks postinjection. Five to 10 days after feeding, ticks were crushed with a pestle in a 1.5-mL tube (Jewett et al., 2009) and DNA was isolated (Samuels & Garon, 1993). PCR using primers to the flaA gene (Table 1) was used to detect B. burgdorferi. To follow transmission by tick bite, five infected nymphs were placed on a naive C3H-HeJ female mouse and allowed to feed to repletion. Mouse ear biopsies, bladder tissue, and ankle joints were collected 5 weeks post-tick feeding, cultured in BSK II, and screened for B. burgdorferi as described above.

In agreement with these observations, CD169+ macrophages retained intact Ag, induced cognate activation of B cells and increased expression of co-stimulatory molecules upon activation. In addition, macrophages were required for the production of cytokines that promote B-cell responses. Our results identify CD169+ macrophages as promoters of high affinity humoral immune responses and emphasize the value of BYL719 mw CD169 as target for Ag

delivery to improve vaccine responses. This article is protected by copyright. All rights reserved “
“CD127 is the IL-7 receptor α-chain and its expression is tightly regulated during T-cell differentiation. We previously showed that the bone marrow (BM) is a key organ for proliferation and maintenance of GW-572016 nmr both antigen-specific and CD44high memory CD8+ T cells. Interestingly, BM memory CD8+ T cells express lower levels of membrane CD127 than do the corresponding spleen and lymph node cells. We investigated the requirements for CD127 downmodulation by CD44high memory-phenotype CD8+ T cells in the BM of C57BL/6

mice. By comparing genetically modified (i.e. CD127tg, IL-7 KO, IL-15 KO, IL-15Rα KO) with wild-type (WT) mice, we found that the key molecule regulating CD127 downmodulation was IL-15 but not IL-7, and that the intact CD127 gene was required, including the promoter. Indeed, CD127 mRNA transcript levels were lower in CD44high CD8+ T cells from the BM than in those from the spleen of WT mice, indicating organ-specific regulation. Although levels of the CD127 transactivator Foxo1 were low

in BM CD44high CD8+ T cells, Foxo1 was not involved in IL-15-induced CD127 downmodulation. Thus, recirculating CD44high CD8+ T cells passing through the BM transiently downregulate CD127 in response to IL-15, with implications for human therapies acting on the IL-7/CD127 axis, for example cytokine treatments Buspirone HCl in cancer patients. Interleukin 7 (IL-7) is produced by stromal cells in the thymus and bone marrow (BM) and is a master regulator of lymphopoiesis and T-cell homeostasis, with stimulatory effects on memory CD8+ T-cell activation, proliferation, and survival [[1, 2]]. The IL-7 receptor comprises an α-chain (CD127) and a γ-chain (CD132), which is shared by receptors for IL-2, IL-4, IL-9, IL-15, IL-21 [[1]]. CD127 is also a component of the thymic stromal lymphopoietin (TSLP) receptor, a dimeric molecule formed by CD127 and TSLP-R [[1]]. Although TSLP increases CD8+ T-cell survival and directly enhances activated CD8+ T-cell proliferation, its contribution to memory CD8+ T-cell homeostasis is not as critical as that of IL-7 [[1, 3]]. The current view is that the two main cyto-kines maintaining memory CD8+ T cells are IL-15 and IL-7, with IL-15 mostly augmenting proliferation and IL-7 cell survival [[1, 4]].

After centrifugation (14 500 g for 5 min) at 4°C the pellet

was resuspended in 500 µl extraction buffer containing 1 M NaCl, incubated on ice for 20 min and centrifuged (14 500 g for 5 min) at 4°C. The supernatant representing the nuclear protein fraction was collected and stored at −70°C until used. To characterize the NFR further, sera of the 11 patients in group 1 subjected to molecular study were analysed for IgA reactivity with nitrocellulose-blotted Caco2 cell proteins. Total cell protein extract, as well as its cytosolic and nuclear fractions, were boiled for 3 min and submitted to denaturing 10% preparative sodium dodecyl sulphate-polyacrylamide gel electrophoresis Lapatinib price (SDS-PAGE). Gel-separated proteins were blotted onto nitrocellulose membranes (Protran nitrocellulose transfer membrane; Schleicher & Schuell Whatman Gefitinib cell line group, Dassel, Germany). Nitrocellulose strips (width 2 cm) were cut from the membranes and were then blocked twice for 5 min and once for 30 min in buffer A [50 mM sodium phosphate buffer at pH 7·4, containing 0·5% Tween 20 and 0·5% bovine serum albumin (BSA)]. Blocked strips were probed overnight at 4°C with sera diluted 1:500 in the same buffer. Thereafter, strips were washed twice for 5 min and once for 15 min with buffer B (50 mM sodium phosphate buffer at pH 7·4, containing 0·5% Tween 20) and incubated overnight at room temperature with a peroxidase-conjugated anti-human IgA polyclonal antibody (Chemicon, Temecula, CA, USA)

diluted 1:8000 in buffer A. Strips were finally washed and dried before exposition to Hyperfilms ECL (Amersham

Pharmacia Biotech, Uppsala, Sweden) for approximately 3–5 s. The purity of nuclear and cytosolic protein fractions Urease was assessed by exposing the nitrocellulose-blotted total cell protein extract and its fractions to anti-human histone H2B anti-serum (Chemicon). Significant statistical differences between EMA and NFR antibodies, detected as total IgA, IgA1 and IgA2 in sera of the 11 patients in group 1 subjected to NFR characterization, were calculated by χ2 test for qualitative and independent data. The P-values ≤0·05 were considered significant. At baseline, all 20 untreated CD patients in group 1 showed serum IgA EMA-positive and NFR-negative results. Serum EMA disappeared after 76 ± 34 days from starting the GFD while, at the same time, serum NFR antibodies became apparent. The NFR antibodies cleared completely from sera in the following 75 ± 41 days for a total of 151 ± 37 days from starting the GFD (Fig. 2). At the time of monitoring, 24 of 87 treated CD patients in group 2 showed serum IgA EMA-negative and NFR-positive results, while the remaining 63 patients displayed negative results for both circulating antibodies. The combination of three GFD control levels (self-reported, dietetic assessment and serum EMA determination) highlighted that, during the previous months, the 24 patients presenting serum NFR-positive results were introducing small amounts of gluten.

In most behavioral experiments, eye gaze and head orientation have been used simultaneously to indicate a person’s focus of visual attention (Hoehl et al., 2009). However, it has been a matter of debate to what extent, if at all, young infants rely on information from the eyes instead of head orientation alone. For instance, Corkum and Moore (1995) reported that 12-month-olds follow someone’s head turn to the side even if the person maintains eye contact with them. In a later experiment, the authors found that only 18-month-olds, but not younger infants, followed an experimenter’s isolated

eye movements (Moore & Corkum, 1998). A more recent study showed that eye gaze influences 12-month-olds’ attention allocation to the ceiling more than head orientation (Tomasello, Hare, Lehmann, & Call, 2007). Correspondingly, Meltzoff and Brooks (2007) reported Crizotinib that 10-

to 11-month-olds follow someone’s head turn to the side when the person’s eyes are open, but refrain from doing so when her eyes are closed, indicating an understanding of “looking” as involving open eyes. However, younger infants in these experiments followed head turns even when the experimenter’s eyes were closed (Meltzoff & Brooks, Selleck beta-catenin inhibitor 2007). Thus, although the age at which the status of the eyes becomes relevant for infants’ following of others’ attention focus varies in different studies between 10 and 18 months, it is quite unequivocal that younger infants are more

affected by head direction and hardly seem to take into account the eyes at all. In contrast to these studies on overt gaze following, research using attention cueing paradigms showed that 3-month-olds (Hood, Willen, & Driver, click here 1998) and even newborns (Farroni, Massaccesi, Pividori, & Johnson, 2004) allocate attention in the direction of eye gaze cues. These studies differ from the aforementioned gaze following studies in that they involve computer presentations instead of live actors and shorter distances between face and target. It has been suggested that gaze cueing effects in very young infants rely on rather automatic processes to be distinguished from more deliberate gaze following and joint attention in live studies with older infants (Moore & Corkum, 1998). However, eye gaze seems to serve a function in directing young infants’ attention and thereby affecting their processing of objects (Hoehl et al., 2009). Using event-related potentials (ERPs), Reid, Striano, Kaufman, and Johnson (2004) presented 4-month-olds with full frontal view faces directing gaze toward or away from peripheral objects. When objects were subsequently presented again, those objects that were not cued by the person’s eye gaze elicited a more pronounced brain response. On the behavioral level, uncued objects also received more of 4-month-olds’ attention than cued objects in a visual preference task (Reid & Striano, 2005).