These data show that 2 h exposure of S. cerevisiae to JBU interferes on the energy metabolism of the cells, with no visible changes in membrane permeability. As the exposure of C. tropicalis ( Fig. 3, panel C), P. membranisfaciens, C. parapsilosis and K. marxiannus cells to JBU for 24 h caused membrane permeabilization, monitoring of JBU-treated S. cerevisiae for a longer time is required to evaluate if progression of antifungal effect would

eventually lead to cell death. Hydrolysis of JBU with papain produced fungitoxic peptides smaller than 10 kDa. Five of these peptides were identified by mass spectrometry and none of them match putative see more antifungal domains of JBU homologous to other plant antifungal proteins. At this point, two possibilities should be considered: these peptides are not associated with antifungal(s) domain(s) of JBU, or the JBU antifungal(s) domain(s) click here are unlike any other fungitoxic proteins already known. One of these peptides contained part of the N-terminal sequence of the insecticidal peptide Jaburetox-2Ec. Becker-Ritt et al. [7], reported that Jaburetox-2Ec did not affect the micellar growth of phytopathogenic fungi, including that P. herguei. In that study, the peptide was added to the medium at a lower dose (0.57 μМ), after 16 h of culture, at a later stage of germination of the spores. Here, Jaburetox was added simultaneously with the

spores, leading to inhibition of germination and growth, and delaying development of hyphae. This result indicates that besides its Branched chain aminotransferase insecticidal activity, this internal peptide of C. ensiformis urease is also antifungal, affecting the early stages of development of the mycelium, a step also susceptible to ureases [7]. The variations in methodology used in the two studies may have influenced the different results obtained. The time

course and characteristics of the fungitoxic effects indicated similar antifungal mechanisms for JBU and Jaburetox, probably based on the ability of these polypeptides to insert in membranes, altering the cell permeability. The antifungal activity of Jaburetox on yeasts required 2–3 times larger doses as compared to the holoprotein JBU, indicating the possibility that other protein domains are involved in this activity. Becker-Ritt et al. reported the antifungal activity of the two-chained urease from H. pylori. Bacterial ureases lack part of the amino acid sequence (the N-terminal half) of Jaburetox, which in single-chained plant ureases corresponds to a linker region between bacterial subunits. This fact strongly suggests that other antifungal domain(s) besides the region corresponding to the entomotoxic domain are present in ureases. The discovery of new antifungal agents becomes increasingly important due to the increasing number of cases of invasive mycoses.

9% (m/v) saline (100 mL) followed by 4% (m/v) formaldehyde at pH 9.5 and 4 °C (800–1000 mL). The brains were removed from the skull, post-fixed for 4 h in the same fixative with the addition

of 20% sucrose and then transferred to 0.02 M potassium phosphate-buffered saline (KPBS) at learn more pH 7.4 with 20% (m/v) sucrose. The brains were sliced in four series of coronal sections (at bregma 2.70 mm, −0.30 mm, −1.80 mm, and −3.14 mm) at a thickness of 30 μm with the use of a freezing microtome and stored at −20 °C in buffered antifreeze solution (Sita et al., 2003). One series of each brain slice was stained by immunohistochemistry as follows: sections were treated in 0.3% (v/v) peroxide in KPBS + 0.3% (v/v)

Triton X-100 for 30 min and incubated in primary antiserum anti-c-Fos (PC38T IgG anti-c-Fos (Ab5) (4-17)) rabbit polyclonal antibody (Calbiochem, La Jolla, CA, USA) at 1:5000 and see more 3% (v/v) normal goat serum in KPBS + 0.3% (v/v) Triton X-100 for 18 h at room temperature. Sections were rinsed in KPBS and incubated for 1 h in biotinylated secondary antiserum made from goat anti-rabbit antibody (Jackson Labs 1:1000) for one additional hour in avidin–biotin complex (Vector, 1:500). Next, the sections were incubated in diaminobenzidine tetrahydrochloride (DAB; Sigma Chem Co.) and 0.01% (v/v) hydrogen peroxide dissolved in KPBS. The reaction was terminated after 2–3 min with repeated rinses in KPBS. Sections were mounted on slides and intensified with 0.005% (m/v) osmium tetroxide solution. To aid in the identification of brain regions presenting little or no c-Fos-immunoreactive neurons (mainly in the sections of control brain slices), Nissl method of counterstaining with thionin was used (Windle et al., 1943). Photomicrographs were acquired through a Spot RT digital camera (Diagnostics Instruments) adapted to a Leica DMR microscope

and an Apple Macintosh Power PC computer PRKACG using the software Adobe Photoshop 5.0. Contrast, sharpness, colour balance and brightness were adjusted and images were combined in plates using Corel Draw 11 software. For the intravenous administration of nigriventrine, the rats were anaesthetised with chloral hydrate (7%, 350 mg/kg, ip) and submitted for venous catheterisation. A Silastic catheter containing heparinised saline (10 U/mL of pyrogen-free saline, Sigma, St. Louis, MO) was inserted into the femoral vein and sutured in place. The free end of the catheter was passed under the skin of the back, exteriorised between the scapulae, and plugged with a sterile wire stylet. A week later, nigriventrine (100 ng kg−1) was intravenously applied. For the quantitative analysis of c-Fos-ir and/or NMR1-ir cells, three representative slices of each brain region were chosen for each rat.

, 2002). The resulting receptor clustering will further trigger death signaling pathways (Cremesti et al., 2001 and Grassme et al., 2001a). At the mitochondrial level, a physiological role of

ceramide-induced membrane permeability has been suggested to be of importance for apoptosis signaling (Siskind and Colombini, 2000 and Siskind et al., 2006). Ceramide may form channels in mitochondria leading to increased permeability Galunisertib order of mitochondrial outer membranes to c-type cytochrome and other small pro-apoptotic proteins. Furthermore, a recent study found that anti-apoptotic proteins, Bcl-xL and Bcl-2, disassemble ceramide channels in the outer membrane of mitochondria isolated from rat liver and yeast (Siskind et al., 2008). Interestingly, another recent study reports the formation of mitochondrial ceramide-rich macrodomain which would favor Bax insertion (Lee et al., 2011). Thus, ceramide channels could play a role in the extrinsic and intrinsic apoptotic pathway (Siskind et al., 2008). Lipid rafts have been shown to be involved in the extrinsic apoptosis dependent on Fas (Gajate and Mollinedo, selleck compound 2001, Gajate and Mollinedo, 2005, Hueber et al., 2002, Lacour et al., 2004 and Muppidi and Siegel, 2004), TNF-R1 (Legler et al., 2003 and Lotocki et al., 2004) or TRAIL-R2/DR5 (Gajate and Mollinedo, 2005). The multimerisation of these receptors in lipid rafts is essential

for the transduction of the apoptotic signals. The mechanisms leading to the aggregation of the death receptors in lipid rafts have been extensively studied. Two major hypotheses are formulated. One suggests that the clustering of death receptors are due to changes in the plasma membrane; the other model suggests modifications in the structure of the death receptors leading to their redistribution inside lipid rafts. However, in both cases plasma membrane plays a determinant role

in the apoptotic signaling. The exact mechanism leading to receptors relocalization in lipid rafts remains to be fully elucidated. It has been suggested that UV may induce an ASM translocation near lipid rafts, which increases the production of ceramide; such a production then leads to see more a fusion of lipid rafts, which results in Fas aggregation and transduction of apoptotic signals (Dimanche-Boitrel et al., 2005 and Grassme et al., 2001a). Furthermore, lipid raft destabilization by cholesterol depleting agents (like methyl-β-cyclodextrin) has been reported to induce Fas-dependent apoptosis following spontaneous aggregation of Fas receptors independently of Fas ligand (Gniadecki, 2004). In another hand, it has been shown that trimerisation of Fas receptor induced by Fas ligand (Chan et al., 2000 and Siegel et al., 2000), is necessary for its activation (Nagata and Golstein, 1995 and Tanaka et al., 1995).

The yield for IgM was quite similar between the different lines

(Fig. 3A); often up to 500 μg/ml as identified in wt controls and only occasionally somewhat reduced but never less than selleck chemicals half of the wt level analyzed in parallel. Thus, despite some variation, the IgM concentrations in all lines were in good agreement with the levels produced in wt rats kept under the same conditions. Near normal increase in IgM titer was also seen after immunization and in all lines specific IgM levels were similar to wt (not shown). For IgG purification on protein A, the results were split as low and normal levels were identified (Fig. 3B). For HC14, HC17 and wt this revealed 500–1000 μg IgG/ml serum; this level was established from several experiments and agrees with previous findings despite the suboptimal purification of rat IgG using protein A (Bruggemann et al., 1989 and Osborn et Selleckchem BGB324 al., 2013). A consistently lower amount, ~ 10% of normal levels was identified in HC10 and HC13 animals, where some rats had barely more than 50 μg IgG/ml serum. In these rats specific IgG was lacking

after immunization while HC14 and HC17 produced extensive immune responses frequently similar to wt rats (Fig. 3C). Immunizations were carried out using 4 different antigens, β-galactosidase (β-gal), human progranulin (hPG), ovalbumin (OVA) and hen egg lysozyme (HEL), all of which failed to work efficiently in HC10 and HC13. Previously we showed that a chimeric IgH locus with human VHs, Ds and JH segments linked to rat C-region genes and control sequences, produced highly diverse and near-normal expression levels of antibodies with human idiotypes (Osborn et al., 2013). Here we assess the performance of 4 translocus rat-lines, with silenced endogenous IgH locus (Menoret et al., 2010), carrying the same human VH-region but different rat CH-regions. The comparison was aimed at identifying minimal CH transloci, which would permit near normal expression. In these lines, the IgM expression level with a diverse repertoire of human VH-D-JH

rearrangement was very similar, with surface μ+ B-cells and secreted IgM in serum comparable to wt rats. This suggests that DNA rearrangements with developmental stages from pro to pre to immature B-cells are adequately performed as described (Almqvist and Martensson, IKBKE 2012). In previous transgenic IgH lines carrying only human CH-genes reduced levels of serum IgM and IgM+ B-cells have been identified (Green and Jakobovits, 1998, Nicholson et al., 1999 and Brüggemann et al., 2007), even with Eμ, Cμ and downstream regions analogous to our transgenic constructs (Lonberg et al., 1994, Mendez et al., 1997 and Nicholson et al., 1999). The suboptimal performance of fully human IgH constructs is likely to reflect imperfect interaction of the human C-genes with the rodent cellular signaling machinery.

1H=0.1 m. Initially, dense cold water, with temperature perturbation T-T0=-0.5T-T0=-0.5 °C, fills one half of the domain, xclick here other half, x⩾L/2x⩾L/2. At t=0t=0 s, u=0u=0 m s−1 everywhere. At the end walls, x=0x=0, LL, a free-slip, no normal flow condition, u=0u=0 m s−1, is applied. At the bottom boundary, z=0z=0, a no-slip condition, u=0u=0 m s−1, is applied.

At the top boundary, z=Hz=H, a free-slip, no normal flow condition, w=0w=0 m s−1, is applied. Gravity currents at both no-slip and free-slip boundaries can therefore be considered in one simulation which is particularly useful for the comparison of the Froude numbers, Section 5.3. The velocity and pressure fields are discretised using a continuous Galerkin finite-element formulation (Piggott et al., 2008 and Piggott et al., 2009). Linear basis functions

are used for both fields and the loss of LBB stability is overcome through the use of a pressure filter (Piggott et al., 2009). A node-centred control-volume advection scheme with a Sweby limiter is used for discretisation of the temperature field (LeVeque, 2002, Sweby, 1984 and Wilson, 2009). A semi-implicit, Crank–Nicolson scheme is used to advance the equations in time, with a time step of Δt=0.025Δt=0.025 s and two non-linear Picard iterations. BMN 673 price For further details of these methods see the cited references and references therein. The simulations are run for 500 s. This allows both the propagation stage and the oscillatory stage to be simulated, Section 5.1. By the end of the time period, the system is expected to reach a less active state, IMP dehydrogenase with a significantly reduced or near zero mixing rate, Section 5.2 (Özgökmen et al., 2007). Time will be scaled by the buoyancy period Tb=2πN∞-1, where N∞=g′/H is the buoyancy frequency, Table 1 (Özgökmen et al., 2007); 500 s corresponds to a scaled time of t/Tb=25.2t/Tb=25.2.

The lock-exchange configuration is run using four different fixed meshes. The meshes are generated with Gmsh (Geuzaine and Remacle, 2009). The meshes produced have triangular elements and are structured in both the horizontal and vertical, Fig. 1. The fixed meshes are distinguished by the length of an element edge, |v||v|, in the horizontal and vertical with |v|=0.002|v|=0.002, 0.0005, 0.00025 and 0.000125 m. The simulations that use each of these meshes are labelled F-coarse, F-mid, F-high1 and F-high2, respectively. The number of vertices in each mesh is given in Table 2. The adaptive mesh capabilities in Fluidity-ICOM are for use with unstructured meshes, Fig. 1 (Applied Modelling and Computation Group, 2011). The process used to adapt the mesh can be divided into three main steps: metric formation, which determines how to adapt the mesh; mesh optimisation, the process of altering the mesh based upon the metric; and interpolation of the fields from the pre- to post-adapt mesh.

137.0 mequiv./L; P = 0.001); P = no. No differences were observed with respect to age, race, aetiology of cirrhosis, diabetes, hypertension, hepatocellular carcinoma, prior upper gastrointestinal bleeding, spontaneous Z-VAD-FMK datasheet bacterial peritonitis, current use of diuretics, urea, haemoglobin, platelets, serum sodium, serum potassium, spot urine potassium, ALT, ALP, GGT, albumin, and INR when individual with poor urinary sodium excretion were compared to those with Nau24h ≥ 78 mequiv. There was a strong positive correlation between the

Na/Ku and Nau24h (r = 0. 857, P < 0.001) ( Fig. 1). A negative correlation between MELD score (r = −0.498; P = 0.025) and serum creatinine (r = −0.498; P = 0.025) was evidenced. There were no significant correlations between the Na/Ku ratio and age, platelet count, serum sodium, AST, ALT, direct bilirubin, Roxadustat research buy albumin and INR. The AUROC for Na/Ku in the prediction of

Nau24h < 78 mequiv. was 0.948 ± 0.046, P = 0.001 ( Fig. 2). Table 3 shows in details the diagnostic performance of the Na/Ku ratio in predicting Nau24h < 78 mequiv. For the Na/Ku ratio, the classical cut-off (≤1.0) showed 70% positive predictive value (PPV) to diagnose Nau24h dosage < 78 mequiv. with negative predictive value (NPV) of 90%, accuracy of 80%, 88% sensitivity and specificity of 75%. Cirrhosis is the twelfth leading cause of death in the United States of America.17 Several authors evaluated patients with decompensated liver cirrhosis ascites. Usually, the studied population is predominantly composed by men, 59–74%, age ranging from 53.6 to 60 years.18, 19 and 20 In this study it has been observed that 70% of subjects were male; mean age was 56.1 years, which coincides with that described in literature. With regard to the aetiology of cirrhosis, it varies according to the prevalence of the diseases on the studied area,

with a higher prevalence of HBV (64.8%) in China, higher incidence of alcoholic cirrhosis (76.4%) in Germany (19) and Barcelona (44.7%).18 The present study demonstrated a higher prevalence of HCV as compared to Europe and Asia, the latter Leukotriene-A4 hydrolase being an area of high prevalence of HBV21 and exhibits high prevalence of alcoholism as a cause of chronic liver disease. In cirrhosis, the development of ascites and diuretic response are determined by the renin–angiotensin–aldosterone and renal sodium handling.22 This study observed that patients presenting with more severe liver disease (MELD, creatinine, bilirubin, AST) are those who have lowest urinary sodium excretion. Likewise, Cholongitas et al. recently demonstrated that the factors independently associated with poor urinary sodium excretion in cirrhosis are albumin, creatinine and Na/Ku.11 The Na/Ku ratio emerged as an option to Nau24h in evaluating the ability of cirrhotic patients with ascites to excrete salt. During ascites treatment, absence of weight loss may be secondary to poor response to diuretics or a consequence of non-adherence to low sodium diet.

0001) and an interaction of disease and poly I:C (F = 23.98, df 1, 14, p < 0.0005). Similarly OAS1a showed much higher induction in ME7 + poly I:C animals than in NBH + poly I:C animals. There were main effects of disease (F = 43.96, df 1, 14, p < 0.0001) and of poly I:C (F = 79.41, df 1, 14, p < 0.0001) and an interaction of these two factors (F = 21.32, df 1, 14, p < 0.0005). Likewise, Mx1, assessed at the exon 2–exon

3 junction, showed an exaggerated induction in ME7 animals treated with poly I:C. There were main effects of disease (F = 7.70, df 1, 14, p < 0.05) and of poly I:C (F = 45.29, df 1, 14, p < 0.0001) and an interaction of these two factors (F = 5.87, df 1, 14, p < 0.05). Finally, PKR was more robustly induced by poly I:C in ME7 animals than in NBH animals. There were main effects of disease (F = 9.51, this website df 1, 14, p < 0.01) and of poly I:C (F = 55.12, df 1, 14, p < 0.0001), but

no significant interaction (F = 0.89, df 1, 14, p = 0.36) in this case. Thus, there is exaggerated type I IFN action in the CNS of ME7 animals challenged with poly I:C with respect to NBH animals similarly challenged. IL-10 was modestly induced by both poly I:C in normal animals (F = 34.97, df 1, 12, p < 0.0001) and by disease (main effect of disease: F = 28.32, df 1, 12, p = 0.0002) ( Fig. 6a). There was also an interaction of disease and poly I:C, ME7 + poly selleck products I:C showing considerably more marked induction than all other groups (F = 22.23, df 1, 12, p = 0.0005). TREM2 (Fig. 6b) was markedly induced by disease (two-way ANOVA main effect of disease (F = 34.13, df 1, 12, p = 0.0001), and was slightly, but not significantly, affected by poly I:C (F = 4.49, df 1, 12, p = 0.0576). However there was a significant interaction between disease and poly I:C. TREM2 was Amino acid markedly more elevated in ME7 + poly I:C than in any other group (F = 5.32, df 1, 12, p = 0.0415). The expression of iNOS was

increased by poly I:C in NBH animals but was not increased by poly I:C in ME7 animals (Fig. 6c). As such, there were no main effects of disease or poly I:C but an interaction between these (F = 5.22, df 1, 14, p = 0.0385). The expression of MMP9 was very low and was not altered by any treatment (Fig. 6d). There were no statistically significant changes. IFNγ (Fig. 6e) was modestly increased in ME7 animals (main effect of disease, F = 21.34, df 1, 14, p = 0.0004) and decreased by poly I:C (main effect of poly I:C: F = 6.3, df 1, 14, p = 0.025). There was no interaction between these factors. Thus, in addition to reduced TNF-α expression (Fig. 3), there are further anti-inflammatory changes that appear to be selectively apparent in ME7 animals upon poly I:C treatment. Heightened expression of the signalling type I interferon receptor, IFNAR2 in ME7 animals (Fig.

We performed CCDS of the SSS and the adjacent venous structures (lacunae, bridging veins) within the craniotomy window both before and after removal of PSM. It is important to apply on the SSS as little pressure as possible (up to the

appearance of artifact due to air between the SSS and the probe) since the SSS is very easy to compress and blood flow velocity significantly increases. MR venography showed absence of blood flow in the SSS in 16 out of 30 cases, which was confirmed by intraoperative CCDS in 9 cases only (complete invasion in 7 cases, thrombosis in 2 cases). In the remaining 7 cases the SSS was patent (blood flow velocity in the SSS was 5–29 cm/s and flow index reached 40 ml/min). In 14 out of 30 patients ITF2357 mw MR venography revealed flow in

the SSS and it was confirmed by CCDS. Thus, false-positive results of complete occlusion of the SSS according to MR venography in our series were obtained in 7 out of 16 cases (for the anterior third of the SSS – 5 out of 6; middle third – 1 out of 8; posterior third – 1 out of 2). CCDS additionally evaluated the degree of SSS invasion/compression with its hemodynamics selleck products and differentiated invasion from compression of the SSS. Examples of different types of SSS invasion by PSM obtained intraoperatively by CCDS, where consistency (Fig. 1) and discrepancy (Fig. S1 – to view the figure, please visit the online supplementary file in ScienceDirect) between CCDS and preoperative MR venography are presented. B-mode in the frontal (transverse) plane allows verification of compression, partial invasion and complete invasion of the SSS. It helps to determine

the limits of completely invaded SSS in order to resect it en bloc (Fig. S2 – to view the figure, please visit the online supplementary file in ScienceDirect). This data allows to classify PSM according to degree of SSS invasion according to classification by Sindou and Alvernia [3], which is the mostly widely used (Fig. 2). Nowadays CCDS seems to be the only method that allows doing this noninvasively (without excision of the SSS). However, this classification is not ideal and could not encompass all the Nintedanib (BIBF 1120) cases we had like in Fig. S3 (to view the figure, please visit the online supplementary file in ScienceDirect), where all three walls of the SSS are invaded but the latter is still patent. B-mode can also visualize intrasinal structures like septum (Fig. S4 – to view the figure, please visit the online supplementary file in ScienceDirect). It should be noted that arachnoid granulations may mimic invasion of the SSS angle. CCDS may also be used to visualize venous lacunae, bridging veins (Fig. S5 – to view the figure, please visit the online supplementary file in ScienceDirect) and inferior sagittal sinus (Fig.

Following one of these preparations, the selectively labeled protein thiols can be assessed by a range of analytical procedures based on the nature of the thiol label that has been employed (Figure 2c). Typically, the labels attached

to the cysteine residues are biotinylated, fluorescently conjugated, or isotopically modified derivatives of the thiol alkylating reagents NEM or iodoacetaminde (IAM). Such labeling procedures allow for separation of the proteins by gel electrophoresis followed by the identification of the labeled protein by peptide mass fingerprinting, or by the separation and identification of the labeled peptides by liquid chromatography–mass spectrometry (LC–MS). The details of these labeling methods are first discussed below, followed later by a comparison of the various types of thiol-reactive probe molecule that can be used and procedures

that can be employed to separate and identify the labeled SAHA HDAC chemical structure proteins and peptides. A simple but limited strategy for the identification of modified protein thiols is to label all unmodified protein thiols with detectable thiol-reactive probes (Figure 2b, Selleckchem INK128 top) [28, 29 and 30]. Then control labeled protein samples can be separated by electrophoresis, or derived peptides are separated by LC–MS, and compared with related samples prepared under stressed or oxidant-treated conditions. Probe signal loss between conditions is indicative of both reversibly and irreversibly modified protein thiols (Figure 3a). However, the reliance on measuring signal loss, instead of signal increase over baseline, is a significant limitation to the sensitivity of this approach since most intracellular protein thiols are maintained in a reduced state by the glutathione and thioredoxin systems.

Consequently, this strategy is best suited for determining changes due to high concentrations of oxidants or in simple protein samples. The signal loss method can in principle be adapted to detect only irreversible protein thiol modifications by the treatment of samples with a thiol reductant, such as tris(2-carboxyethyl)phosphine (TCEP) or dithiothreitol (DTT) before labeling. In this case any RVX-208 signal loss would be attributable to irreversibly oxidized thiols. A more widely used strategy, and one that is generally the most useful for the detection of reversibly modified protein thiols, blocks all unmodified thiols with a general thiol reagent such as NEM. This is followed by the selective reduction and labeling of all reversibly modified cysteine residues with a thiol probe. All redox-sensitive cysteine residues will be labeled and screened for by this procedure, regardless of the nature of the reversible modification (Figure 3b and c). This is advantageous when the conditions being compared involve a range of reversible modifications, of which the combination and proportion are unknown.

, 1999). The

aim of this study was to compare the phenotype and morphology of microglia in various regions of young (4 months) and aged (21 months) mouse brain using a range of functional surface markers and to assess their phenotype following a systemic inflammatory challenge. We selected eight distinct regions of grey or white matter distributed along a rostral-caudal neuraxis. The regions included in our study were: striatum, corpus callosum, fimbria, dentate gyrus, substantia nigra, cerebellar nuclei, molecular layer of the cerebellar cortex and the inferior cerebellar peduncle. The striatum is a mixed white/grey matter region – we studied the most caudal segment of the putamen, CH5424802 cost an area that is mostly grey matter. The corpus callosum and fimbria are rostral white matter areas, while the dentate gyrus is a grey matter region from the hippocampus. The substantia nigra is a grey matter area caudal to the hippocampus with a particularly high microglial density (Lawson et al., 1990).

Within the cerebellum we analysed the white matter tracts of the inferior cerebellar peduncle, the deep cerebellar Ibrutinib in vivo nuclei, which represent a mixture of white and grey matter, and the molecular layer, which is grey matter neuropil of the cerebellar cortex. The functional markers used in this study were selected for their sensitivity to changes in the activation Fossariinae state of microglia and their relevance to microglial function. CD11b

and CD11c are adhesion molecules that play a role in cell migration and phagocytosis, CD68 is involved in phagocytosis and MHCII is important for antigen presentation (Kettenmann et al., 2011). FcγRs bind IgG, and play a role in antigen presentation and uptake of opsonised cell debris (Nimmerjahn and Ravetch, 2008). F4/80 contributes to peripheral tolerance induction in T regulatory cells by myeloid cells (Lin et al., 2005), Dectin-1 is a non-TLR pattern recognition receptor expressed during alternative activation of macrophages (Shah et al., 2008) and DEC-205 is a dendritic cell marker involved in antigen presentation (Jiang et al., 1995). These markers are myeloid cellspecific within the CNS and up-regulated upon cell activation (Buttini et al., 1996, Lunnon et al., 2011, Ponomarev et al., 2005, Qin et al., 2004 and Shah et al., 2008). In this study we show that microglial age-related phenotypes vary regionally, with evidence of a differential expression of myeloid antigens along the rostro-caudal neuraxis. These phenotype differences correlate with age-related behavioural deficits dependent on hippocampus and cerebellum integrity. Female C57BL/6 mice (Harlan, UK, bred in house) were used in all experiments. Mice were housed in groups of 5–10 in plastic cages with sawdust bedding and standard chow diet and water available ad libitum.