glabrata (24%), C tropicalis (15%), C krusei (13%) and C parap

glabrata (24%), C. tropicalis (15%), C. krusei (13%) and C. parapsilosis (3%). Multiple Candida infections ranged between 3% and 15% of all autopsy cases with documented yeast infection whereas non-Candida yeast and yeast-like selleck products species (i.e. Trichosporon,

Rhodoturula, Saccharomyces cerevesiae) occurred in 4–10% of cases during the 20 year period. Interestingly, infections caused by Candida species with variable (C. glabrata) or non-susceptibility (C. krusei) to fluconazole decreased in the final 5 years of the study, whereas C. albicans and C. tropicalis infections increased. The pattern of organ involvement by IFIs differed depending on the fungal pathogen and type of underlying immunosuppression. Candida spp. were frequently detected by both culture and histopathology in the lung (79%), blood (37%), gastrointestinal tract (35%), kidney (34%),

liver (20%) and spleen (19%). Patterns of organ involvement did not differ significantly, BIBW2992 research buy however, among the isolated species. Patients with persistent neutropenia were more likely to have invasion of the kidney (P = 0.02) and heart (P = 0.02) compared with non-neutropenic patients. High-dose corticosteroid therapy did not appear to predispose to a specific pattern of organ involvement. The lungs were the most common site of infection for moulds, occurring in more than 90% of all infections. Aspergillus infections most frequently affected the lung (92%), central nervous system Mirabegron (25%), heart (24%), kidney (15%) and gastrointestinal tract (15%). Aspergillus spp. were rarely (4%) isolated from blood cultures, and nearly all of the positive cultures were caused by A. terreus (60%) or A. flavus (40%). Compared with Aspergillus spp., Mucorales were more likely to be associated with invasion of the sinuses (23% vs. 5%, P = 0.007). Fusarium spp. were isolated frequently from the heart (63%), kidney (50%), spleen (50%) and bloodstream (40%). We also compared patterns of organ dissemination over the study period for the four most common monomicrobial infections detected at autopsy among patients with haematological malignancies. Significant reductions in

Candida dissemination to the spleen, kidney, heart, gastrointestinal tract and liver were observed over the 20 year study period, although Candida spp. dissemination to the liver rebounded back to a percentage observed in earlier periods of the study by 2004–2008 (Fig. 2). After 2003, moulds accounted for the majority of infections identified at autopsy in four of these five organs including the spleen, kidney, heart and gastrointestinal tract. To our knowledge, this is the largest single-institution study of autopsy proven IFI in patients with haematological malignancies spanning two decades. Collectively, these autopsy data support the findings of recent epidemiological surveys that have documented a declining prevalence of IFIs and associated mortality in this high-risk population.

Monocyte subsets are also critical in complications of atheroscle

Monocyte subsets are also critical in complications of atherosclerosis such as myocardial infarction. In this case of acute inflammation, inflammatory and proteolytic Ly6Chigh CCR2high and reparative Ly6Clow CCR2− monocytes accumulate in the infarcted myocardium sequentially 24. Monocyte subsets contribute in specific ways to myocardial ischemic injury: the Ly6Chigh cells, which dominate early, degrade released macromolecules and scavenge dead cardiomyocytes, whereas the Ly6Clow cells accumulate later and mediate

aspects of granulation tissue formation and remodeling. Many of the recruited monocytes accumulate from a recently recognized splenic monocyte reservoir 25. Regardless of subset, lipid Selleck Lorlatinib encounter in the vascular wall may be a decisive experience in the life of a lesion-infiltrating monocyte. We have known for years that monocyte-derived macrophages recognize and ingest

oxidized lipoproteins via scavenger receptors, and that the ensuing lipid-rich foam cells contribute to the development of a necrotic core, a key feature of a vulnerable plaque 6. At the molecular level, we now understand that recognition of cholesterol crystals activates the NLRP3 inflammasome that then releases IL-1β 26, 27. This cytokine is an upstream inflammatory mediator and a contributor to atherosclerosis 28, 29. Nuclear receptors, known as peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs), represent another link between lipid metabolism and inflammation. As lipid-activated Tolmetin DMXAA research buy transcription factors, both PPARs and LXRs integrate metabolic cues and elicit a broad range of effects 30, including the expression of inflammatory genes, such as

IL-1β, IL-6 and MCP-1, and genes associated with lipid metabolism and cholesterol efflux, such as ABCA1 and ABCG1. These last two genes also control the proliferation of hematopoietic cells because their deletion leads to severe leukocytosis and monocytosis 31. Thus, monocytes and their progeny translate metabolic cues to inflammatory signals through engagement of the NLRP3 inflammasome and cholesterol-sensing pathways (Fig. 1). These findings are important because they identify inducers, sensors and mediators of inflammation that drive atherosclerosis, and thus represent molecular therapeutic targets. It is not surprising that much research in the context of atherosclerosis has focused on the intersection between metabolism and inflammation. The disease involves lipid accumulation and metabolic deregulation, and the propensity of these components to accelerate atherogenesis was appreciated long before it was recognized that inflammation plays a decisive role. In cancer, the influence of lipids is poorly understood and, indeed, high lipid content is not a defining feature of most tumors.

In agreement with these observations, CD169+ macrophages retained

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 AZD6244 in vitro 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 learn more 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 selleckchem 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]].

The rationale for such a strategy is further strengthened by evid

The rationale for such a strategy is further strengthened by evidence that existing therapies for allergic diseases, such as allergen immunotherapy and glucocorticoids, are associated with the induction of Treg cells in patients [2]. Nevertheless, considerable scope for improving the safety and efficacy of these treatments exists. Recent studies have focused on the capacity of vitamin D to modulate Treg-cell subsets. For example, culturing dendritic cells (DCs) with Sirolimus mw the active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1α25VitD3) leads to impaired DC maturation, development of

tolerogenic properties [3], and the capacity to induce CD4+Foxp3+ cells with suppressive activity [4], or IL-10 expressing Treg cells [5]. In animal models of human disease, administration of 1α25VitD3 successfully treats transplant rejection [6] and a range of autoimmune conditions, including antiretinal autoimmunity [7], acute colitis [8], diabetes [6], arthritis [9], and EAE [10], as well as allergic airway disease [11]. Bioactive Compound Library These studies demonstrate a correlation between therapeutic efficacy and increased frequency or quantities of CD4+CD25+ T cells, IL-10, TGF-β, and CTLA-4. Our earlier studies have highlighted the capacity of 1α25VitD3 to promote human CD4+ IL-10 secreting

Treg cells (IL-10-Treg) in culture both alone [12] and in concert with glucocorticoids such as dexamethasone [13, 14]. Furthermore, treatment of severe steroid refractory asthma patients with 1α25VitD3 in vivo directly increased IL-10 gene expression

in CD3+CD4+ T cells [12], and restored the impaired steroid-induced IL-10 response in CD4+ cells in vitro [14, 15]. The present study was designed to further investigate the mechanisms underlying the therapeutic potential of 1α25VitD3 in the context of asthmatic disease, and to determine effects on the induction of both IL-10+ and Foxp3+ T cells. Specifically, we have examined the effects of 1α25VitD3 on total, unfractionated CD4+ T-cell populations, representative of those likely to be encountered in vivo. The data demonstrate that 1α25VitD3 increases the frequency not only of IL-10-Treg cells, but also of Foxp3+ Treg cells, that these cells express increased levels of the inhibitory receptors CTLA-4 and PD-1, and exhibit inhibitory mafosfamide function. The data further suggest that 1α25VitD3 functions to maintain Foxp3 expression in the existing Foxp3+ Treg-cell pool. We have previously described the induction of IL-10 secreting cells following culture of human CD4+ T cells with 1α25VitD3 in vitro and directly ex vivo following administration of calcitriol to asthma patients [12, 14]. An unusual dose response was observed in vitro with 1α25VitD3 at the very highest concentration tested (10−6 M 1α25VitD3) resulting in considerably lower IL-10 secretion than the optimal concentrations of 10−7 M and 10−8 M 1α25VitD3 [12].

After embedding the brain samples in paraffin, coronal sections 5

After embedding the brain samples in paraffin, coronal sections 5 μm in thickness were mounted on γ-aminopropyl Pifithrin�� trimethoxysilane-coated glass slides (Matsunami, Osaka, Japan). All animal experiments were conducted in accordance with the Standards Relating to the Care and Management of Experimental Animals promulgated by Gifu University, Japan (Allowance No. 08119). For immunohistochemistry, deparaffined brain sections were immersed in 10 mM citrate buffer (1.9 mM citric acid, 8.3 mM trisodium

citrate, pH 6.0) for 5 min at 120°C by using an autoclave for antigen retrieval and then incubated with 3% H2O2 for 10 min to block endogenous peroxidase activity. After blocking with 3% BSA solution in PBS, the sections were incubated with MAb 13–27 specific for RC-HL N protein (19), which had been purified with a R788 solubility dmso MAb Trap kit (GE Healthcare, Little

Chalfont, UK) and then biotinylated with an EZ-Link Sulfo-NHS LC-Biotiniylation kit (Pierce, Rockford, IL, USA) in advance. After 2 hr incubation at room temperature, the sections were colorized by the ABC method using a Vecta stain ABC kit (Vector, Burlingame, CA, USA) and 3, 3′-diaminobenzide tetrahydrochloride as a substrate. Nuclei were counterstained with hematoxylin. Overview pictures were scanned in an Epson GT-X770 scanner (Epson, Suwa, Japan). Microscopic photographs were taken with an Axiovert 200 microscope (Carl Zeiss, Jena, Germany). NA cells grown on an 8-well chamber slide (BD Falcon, Franklin Lakes, NJ, USA) were infected with each virus at a MOI of 2. Mock-infected cells were inoculated with diluent (E-MEM supplemented with 5% FCS) alone. The infected cells were fixed with 3-oxoacyl-(acyl-carrier-protein) reductase 3.7% formaldehyde and permeabilized with 90% methanol

at 48 hpi. Apoptotic cells were detected by a TUNEL assay using a Neuro TACS II kit (R&D Systems, Minneapolis, MN, USA) according to the manufacturer’s protocol. The results of TUNEL assays were examined using a BZ-8000 digital microscope (Keyence, Osaka, Japan). We chose five microscope fields at random and determined the ratio of numbers of TUNEL-positive cells to total cells in the five fields (more than 800 cells in each field). Student’s t-test was applied for statistical analysis and P < 0.05 was considered to be statistically significant. Apoptotic cells in infected mouse brains were detected by TUNEL staining of paraffin-embedded sections described above, using a Neuro TACS II kit (R&D Systems) according to the manufacturer’s protocol. Photographs were taken with an Axiovert 200 microscope (Carl Zeiss). Monolayers of NA cells were inoculated with each virus at an MOI of 2. Mock-infected cells were inoculated with diluent alone. After 2 days, cells were lysed with lysis buffer consisting of 20 mM Tris (pH 8.0), 150 mM NaCl, 20 mM 3-([3-cholamidopropyl] dimethyl-ammonio) propanesulfonic acid, 2 mM EDTA and 0.04 mM p-amidinophenylmethylsulfonyl fluoride. The lysate was clarified by centrifugation at 13 000 ×g for 10 min at 4°C.

Screening the diabetes population for DKD and intervening with AC

Screening the diabetes population for DKD and intervening with ACE inhibitors and ARB as indicated, Belnacasan clinical trial together with appropriate glycaemic control and management of lifestyle-related risk factors, is a priority in responding to the health burden of diabetes

in Australia. The first priority in screening for DKD should be the detection of microalbuminuria Since the vast majority of DKD is associated with the presence of albuminuria, testing for microalbuminuria is key to screening strategies for the detection of DKD. Numerous studies have evaluated the cost-effectiveness of screening for albuminuria in the diabetes population, concluding that screening in diabetics based on dipstick urinalysis and/or measurement of urinary albumin to creatinine

ratio, followed by intervention with an ACE inhibitor or ARB, is cost-effective across all age groups.[33-35] Screening the diabetes population for DKD on the basis of eGFR has also been shown to be cost-effective,[36] although is most favourable above 50–60 years of age;[37] thus, these two markers potentially have complementary roles in screening different age groups.[38] The underlying burden of DKD will increase as long as diabetes prevalence is increasing, and this challenge must be met with lifestyle change The underlying burden of DKD in Australia is rising and will continue to do so as an inevitable Tanespimycin solubility dmso result of increasing diabetes prevalence, driven by rates of obesity isothipendyl and population aging. Therefore, averting the burden of DKD in Australia requires engagement with lifestyle change and healthy aging. A 2012 review from the American Heart Association of interventions to promote healthy lifestyles concluded

that, whereas interventions oriented around the individual were unlikely to have significant impact, population-based multicomponent interventions involving government mandated economic incentives and changes to the physical environment were able to effect change in lifestyle behaviours and health outcomes.[39] Nephrologists should consider themselves stakeholders in these types of population interventions for the primary prevention of diabetes and DKD. Health services planning requires accurate projections of the future burden of DKD and ESKD There is an urgent need to gather Australian data on longitudinal trends in the incidence and prevalence of diabetes and DKD, and more accurate information regarding attributable costs. Predicting future rates of DM-ESKD for the purposes of health services planning is complex and requires data on the current and future population at risk, longitudinal data on disease incidence trends and rates of progression, mortality data indicating trends in competing risks, and information on changing demographics of the diabetes population.

Therefore the events that govern early B-cell activation followin

Therefore the events that govern early B-cell activation following influenza virus infection are crucial for ameliorating disease outcome. The mechanisms underlying early B-cell activation, however, are incompletely understood. Rapid Ab

production originates from extrafollicular foci developing at the edges of the T- and B-cell zones in secondary lymphoid tissues following antigen exposure. These responses are thought to generate primarily short-lived plasma cells 9. Rapid Ab production at extrafollicular sites is attributed to T cell-independent as well as T-dependent responses 10, 11. AZD9291 ic50 In contrast, the slower intrafollicular germinal center reactions require cognate CD4 T-cell–B-cell interactions 12, 13. They are regarded as the birthplace of long-lived humoral immunity, providing both memory B cells and long-lived plasma cells 11, 13. Both extra and intra-follicular responses develop strongly in the regional

LN following Ku-0059436 cost influenza virus infection 14. The selection events that underlie the establishment of extrafollicular versus germinal center B-cell responses are important events in the initiation of the adaptive immune response. They coordinate the formation of crucial rapidly protective responses, while ensuring long-term protection from re-infection 11. There is evidence that rapid (antiviral) Ab production can be provided by distinct B-cell subsets 1, 11, 15–19. Marginal zone (MZ) B cells are one such subset. They can respond to blood-borne antigens through rapid production of Ab at extrafollicular sites 17, 18. In the mouse these B cells are only found in the spleen, however, and not in LN 20, 21. Thus, MZ B cells are unlikely to play a role in the response to influenza virus infections, as respiratory tract draining MedLN are the main sites of the initial influenza virus-induced B-cell response 14. Whether there are other subsets in the LN that act as functional equivalents to splenic MZ B cells is currently unknown. Recently, BCR affinity-guided selection events have been implicated as a factor that could determine the B-cell fate following protein immunization 22. Paus et al.22 used an elegant

adoptive cell transfer approach with transgenic hen egg lysozyme-specific B cells to provide evidence that BCR affinity thresholds exist that steer B cells toward Avelestat (AZD9668) a particular response. In that study high-affinity B cell–antigen interactions resulted in predominantly extrafollicular foci responses, whereas hen egg lysozyme-specific B cells binding antigen with weaker overall affinities were predominately selected into the germinal center response. These data are consistent with a study on vesicular stomatitis virus infection-induced B-cell responses, in which Roost et al. observed no improvement on the overall Ab-affinity during the course of vesicular stomatitis virus infection and showed that early induced virus-specific Ab are of relatively high affinities 23.

8 From a conceptual standpoint, these side-effects might be antic

8 From a conceptual standpoint, these side-effects might be anticipated because many cytokines function physiologically in a paracrine fashion, over short distances between cells.6 An important challenge Panobinostat is to develop methods to deliver cytokines to tumour sites where they might enhance immune responses without producing undesirable systemic effects. Experimentally this has been achieved in a variety of ways including direct local injections of cytokines,10–12 injection of tumours with viruses encoding cytokine genes,13–15 or by transplanting genetically modified viable tumours into animals.16,17

These approaches have greatly contributed to our understanding of the effects of the local production of cytokines on the number and function of immune cells within the tumour microenvironment and also illustrated the considerable potential of cytokines to enhance anti-tumour immune responses. However, because metastatic lesions are often numerous and not easily accessible, translating these advances into a clinical setting remains a challenge. Hence, there remains a critical

need to develop ways in which the cytokine milieu in the tumour microenvironment can be altered. In our current work, Kinase Inhibitor Library we set out to develop a general strategy to construct cytokines that are biologically inactive but could be activated by proteases. Ultimately this approach could be used to deliver inactive cytokines systemically but have them activated locally by tumour-site-expressed proteases. In principle, this should reduce systemic side-effects but retain the enhancement of anti-tumour immune responses. The strategy we are developing uses a fusion protein approach that takes advantage of proteases that are secreted by tumours. As an initial test of this general strategy, we have used different proteases, prostate-specific 3-oxoacyl-(acyl-carrier-protein) reductase antigen (PSA), matrix metalloproteinase 2 (MMP2) or MMP9. The expression of the protease PSA is highly restricted to prostate epithelial cells; PSA is produced by prostate tumours, and as such, is an excellent target protease

for activating the cytokine fusion protein.18 The MMPs have been known to have critical and varied roles in tumour development and progression and are preferentially expressed in a variety of tumours.19 We have used IL-2 as the test cytokine in the fusion protein because it is a potent factor for T-cell and natural killer (NK) cell development20,21 and the local production of IL-2 within tumours has demonstrated anti-tumour immunological effects in animal models.16,17 Moreover, an IL-2-containing fusion protein might be able to be more easily translated to the treatment of human cancers because IL-2 is already Food and Drug Administration approved for the treatment of certain tumours.7–9 In this report, we examine several strategies of blocking the biological activity of IL-2, yet allowing it to be functionally activated by PSA or MMP proteases.

The distal toenail bed was perfused by the dye through the FHB I

The distal toenail bed was perfused by the dye through the FHB. In clinical application, all the toenail flaps flourished and survived. We suggest that the toenail flap based on the FHB may be useful for fingernail reconstruction with minimal donor morbidity. © 2011 Wiley-Liss, Inc. Microsurgery 2011. “
“Serosanguinous drainage after breast reconstruction by deep inferior epigastric perforator

flap (DIEP) can limit patient’s discharge. We introduced fibrin sealant in immediate breast reconstruction find more by DIEP flap to reduce drainage after mastectomy with axillary dissection. We performed an open study on 30 consecutive female aged from 28 to 63 years old. All underwent immediate breast reconstructions by DIEP flaps after mastectomy and axillary dissection for cancer. Patients were divided in group 1 (N = 15) without fibrin sealant and group 2 (N = 15) where the flap, thoracic, and axillary areas were sprayed with 5 mL of liquid

fibrin sealant PLX4032 supplier before drains insertion. There was no difference in the patient’s BMI, height, weight or age between both the groups. Blake suction drains were placed under the flap and in the axillary area. No adverse effects were reported, after a 20-month median follow-up. Drainage volumes or durations were not correlated to the patient’s BMI, nor the height, weight or age. Thoracic drainage duration was longer than abdominal drainage in both the groups. Average drained volumes from the thoracic area were lower (427 vs. 552 mL; P = 0.015) and thoracic drains were removed earlier (5.47 vs. 6.33 days P = 0.022), in group 2 than in group 1. The length of stay was also reduced after the use of fibrin sealant (5.53 vs. 6.33 days; P = 0.032). This

study introduce the interest of fibrin sealant to significantly decrease the postoperative drainage volume and duration in the thoracic area after immediate Rutecarpine breast reconstruction by DIEP flap. © 2010 Wiley-Liss, Inc. Microsurgery, 2011. “
“Conventional nerve conduits lack cellular and extracellular guidance structures critical for bridging larger defects. In this study, an exogenous matrix for axonal regeneration was provided by pretreated muscle tissue. In 24 rats, 14-mm sciatic nerve segments were resected and surgically reconstructed using one of the following methods: autograft (AG); bovine type I collagen conduit; (MDM) collagen tube filled with modified denatured autologous muscle tissue. For 8 weeks, functional regeneration was evaluated by footprint and video gait analysis. Evaluation was complemented by electrophysiology, as well as qualitative and quantitative structural assessment of nerves and target muscles. Group AG was superior both structurally and functionally, showing higher axon counts, a more normal gait pattern, and less severe muscle atrophy. Fiber quality (fiber size and myelin thickness) was highest in group MDM, possibly related to the myelin-producing effect of muscular laminin.

Amplitude of the Nc is thought to reflect the

amount of a

Amplitude of the Nc is thought to reflect the

amount of attention directed at a visual stimulus and is related to autonomic arousal (Reynolds & Richards, 2005). These findings suggest that gaze and head orientation direct infants’ attention JAK inhibitor toward peripheral targets, thus facilitating processing of gaze-cued objects. Uncued objects, in contrast, seem to be encoded less effectively and require further processing when they are presented again, eliciting increased brain responses and visual examination. To sum up, even though infants’ overt “gaze” following is affected by the status of a person’s eyes only by the end of the first year, eye gaze serves as an attention-directing cue from birth on, influencing infants’ object

processing by 4 months of age. There is strong evidence that eye gaze shifts in the absence as well as in the presence of congruent changes in head orientation affect infants’ processing of novel objects (Hoehl, Wahl, Michel, & Striano, 2012; Reid & Striano, 2005; Reid et al., 2004; Theuring, Gredebäck, & Hauf, 2007; Wahl et al., 2012). However, do isolated head orientation cues also influence infants’ object processing? Selleck RAD001 Can this information even override incongruent gaze cues? These questions bear importance for our understanding of the early development of social attention cueing mechanisms. According to an influential model on the direction of attention through social cues, separate but interconnected neuronal populations process eye gaze, head orientation, and body orientation (Perrett & Emery, 1994; Perrett, Hietanen, Oram, & Benson, 1992). Investigating the effects of isolated eye gaze and head orientation cues will provide information on whether these cues are processed isolated from each other or in conjunction in Non-specific serine/threonine protein kinase early development and whether both are equally effective

in influencing young infants’ object processing. Thus, the aim of the current study is to disentangle the effects of eye gaze and head orientation on 4-month-olds’ processing of objects using eye tracking and ERPs. We present infants with isolated eye gaze or head orientation cues in a between-subjects design. We predict that infants will direct more visual attention and neural resources to uncued objects in the eye gaze condition when they are presented a second time, thus replicating earlier work. We tentatively predict that infants will also follow the direction of the head turn alone, which may consequently affect object processing.