6 variants/binding site, P = NS by t-test), even though the vacci

6 variants/binding site, P = NS by t-test), even though the vaccine elicited significantly lower magnitude of V4 binding (1955 vs. 10,468 MFI, P = 0.0031 by t-test). In addition, the depth of V2 binding among vaccinated guinea pigs could not be predicted by magnitude alone. For example, while HIV-1-infected humans and HIV-1-vaccinated

guinea pigs had the same magnitude of V2-specific responses (5998 vs. 7770 MFI, P = NS by t-test), the vaccinated guinea pigs had significantly greater depth of V2-specific binding (7 vs. 20 variants/binding site, P = 0.0161 by t-test). Despite substantial differences in the human and guinea pig studies, this example demonstrates how the microarray can discriminate between magnitude and depth of selleck antibody responses. This information may be highly relevant

to HIV-1 vaccine researchers who aim to design a global HIV-1 vaccine capable of blocking acquisition of diverse HIV-1 strains. We also calculated the relative clade- or CRF-specific binding present for the three most frequent clades (A, B, and C). Fig. 7 demonstrates the percent of each clade- or CRF-specific peptide set that was positive for the four groups within the variable regions V1V2 and V3. In Fig. 7A, we can see that among vaccinated monkeys and guinea pigs, V1V2-specific responses were increased compared to the other cohorts, CAL-101 cell line and that binding to clades A and C V1V2 peptides predominated, whereas clade B-specific binding was relatively low. This finding likely reflects the fact that both monkeys and guinea Methisazone pigs received clade C Env immunogens. In contrast, in Fig. 7B, we can see that among HIV-1-infected subjects, who had increased

V3-specific responses, binding to clade B peptides predominated. This finding presumably reflects the fact that these subjects were from North America and were infected with clade B HIV-1. These data suggest that the microarray may not only be useful for measuring cross-clade immune responses following vaccination, but also may have an application in serotyping HIV-1-infected subjects. Further studies with larger numbers of HIV-1-infected subjects from different regions could test this hypothesis. Finally, we also designed the microarray to assess HIV-1-specific binding across the HIV-1 proteome. In Fig. 8A, we demonstrate the magnitude, breadth, and depth of HIV-1-specific binding to gp120, gp41, Gag, Nef, Pol, Rev, Tat, and Vif proteins among 5 HIV-1-infected human subjects. We observed that gp41 (which includes regions from the cytoplasmic tail) has the highest binding magnitude, followed by Gag. Fig. 8B shows the antibody binding pattern for Gag among 5 HIV-1-infected subjects; peak values are noted within the p17 region, with very little Gag-specific binding among naïve controls (Fig. 8C). Antibody binding to non-Env proteins may be relevant to evaluate vaccine potency and for certain non-neutralizing antibodies (Lewis, 2014).

2B, e g at 7, 12 and 18 min) Probably, these are single peaks o

2B, e.g. at 7, 12 and 18 min). Probably, these are single peaks of a flutter phase, below the temporal resolution of our measurement setup and therefore forming a graduated slope. In our opinion these graduated slopes are flutter phases merging with the consecutive open phases ( Fig. 3, large triangles; Table 2, marked data). We suppose that this represents DGC on the verge of cyclic respiration. This resembles findings of Contreras and Bradley (2009) on R. prolixus. At temperatures higher than 36 °C, open phases of wasps occurred in such close succession that the peaks merged at the base and the CO2 signal never reached baseline levels. Their metabolic Cobimetinib supplier rate was so high that the produced

and emitted CO2 could not be entirely removed from

the measurement chamber before the next pulse was generated. The respiration pattern became entirely cyclic (compare Gray and Bradley, 2003). The wasps’ RMR increases exponentially with rising Ta (see Käfer et al., 2012)). They respond to the according demand of increased gas exchange with a likewise exponential increase in respiration frequency ( Fig. 5) but not with an increasing CO2 emission per respiration cycle ( Fig. 6). This was also reported for honeybees ( Kovac selleck chemicals et al., 2007) and fire ants ( Vogt and Appel, 2000). A comparison over flying and non-flying insect species reveals a positive correlation of respiration frequency and RMR ( Fig. 7, Table 1). In spite of a high variation in level as well as in slope of the single species data, Farnesyltransferase a trend is obvious in insects to increase CO2 emission with an increase in respiration frequency rather than in “depth of breath” or other measures. In the lower to medium temperature range (Ta = 10–27 °C), resting yellow jackets’ respiration

frequency did not differ much from that of honeybees (see Fig. 5). The increasing deviation of the curves above 27.5 °C could result from the exceptional steep increase in RMR in yellow jackets compared to honeybees (see Käfer et al., 2012). Regarding CO2 emission per respiration cycle, yellow jackets show a slight decrease with Ta similar to honeybees ( Kovac et al., 2007; Fig. 6). Because of virtually identical testing arrangements in Vespula sp. and Apis mellifera, a straight comparison of these two species is possible. At similar respiration frequencies ( Fig. 5), resting yellow jackets have a much higher energetic turnover (see Käfer et al., 2012) and emit CO2 on average in much higher amounts per cycle ( Fig. 6 and Fig. 7) than honeybees at similar ambient temperatures. Wasps seem to breathe more efficiently with respect to gas exchange volume per cycle than honeybees. This might base on anatomical (compare Snelling et al., 2011 on Locusta migratoria tracheae), physiological or behavioral differences between the two species.

In Fig  3A, we found that the fraction Fv6 presented a strong and

In Fig. 3A, we found that the fraction Fv6 presented a strong and single band of 65 kDa; fractions Fv7, Fv8 and Fv9 showed similar bands of 65 and 75 kDa and fractions Fv10 Fv11 presented the same two bands with lower intensity, ABT 263 a band of 48 kDa and an intense band of 12 kDa. In Fig. 3B, the fractions of the skin mucus presented more and complex protein bands. The fraction Fm8 presented an intense band of 62 kDa that was also present on the fraction Fm9 with other compounds up to 74 kDa and under

18 kDa. The fraction Fm10 can be considered the most complex presenting bands of approximately 40 kDa and at least 7 bands under 25 kDa. Fractions Fm11, Fm12 and Fm13 showed similar profiles, an intense band of 46 kDa and 12 kDa and a weak band of 23 kDa. Together, these results show that sting venom and skin mucus have distinct constituents that distinguished them like structural proteins, chaperones, ion transport, carbohydrate metabolism, oxidoreductase, cell cycle and protein binding present in sting venom

and like tropomyosin 3 isoform 2 and energy metabolim proteins in skin mucus. But in a group of common 13 proteins we identified and isolated a WAP65 protein. Next we evaluated the inflammatory effects of peptide Ruxolitinib chemical structure and protein fractions on microcirculation in mouse cremaster muscle by intravital microscopy. The topical application of 10 μL of the sting venom, skin mucus and

each fraction induced changes in the microcirculatory environment (i.e. rolling of leukocytes, changes in blood flow and vessel diameter). learn more Peptide fractions of sting venom (4 and 5) and of skin mucus (3, 4, 5, and 7) were able to increase the number of rolling leukocytes, but in contrast, fractions 1 to 3 of the sting venom and 1, 2 and 6 of the skin mucus were unable to elicit leukocyte mobilization (Fig. 4 and Fig. 5). The peptide sting venom fraction Fv4 induced the highest increase of rolling leukocytes compared to Fv5 and to sting venom or PBS. The number of rolling leukocytes induced by Fv5 after 10 min remained similar until 30 min after application. Until 20 min, all peptide skin mucus fractions induced elevated number of rolling leukocytes, but at 30 min after application of samples, the fraction Fm3 presented the higher capacity of increase the number of rolling leukocyte (Fig. 4). In Fig. 5A we observed that all protein sting venom fractions except for Fv6, exhibited the capacity to induce moderate increase of rolling leukocyte during 30 min of observation. Interestingly, Fv6 that showed as a unique band in SDP-PAGE induced the highest increase of rolling leukocyte until 20 min after topical application that diminished thereafter, remained similar to all protein sting venom fractions.

Flavonoid-type phenolics can possibly detoxify Al inside plant ce

Flavonoid-type phenolics can possibly detoxify Al inside plant cells. Kidd et al. [77] found that phenolics including catechol and quercetin were released in maize treated with Al and Si, and the release was dependent on Al concentration. However, due to a lack of efficient methodologies, our understanding of internal mechanisms of Al tolerance in plants is still fragmentary. Genetic markers are useful tools to reveal Al tolerance mechanisms in higher plants following their detection by inheritance studies and identification

of relevant genes or loci. During the last two decades, molecular markers based on DNA sequence variations were widely used to study Al tolerance. By detecting molecular markers, the gene or trait could be easily identified and traced [78]. Based on the techniques used, molecular markers could be classified as PCR-based MK0683 mouse or hybridization-based [79]. DArT (Diversity Arrays Technology) and RFLP (restriction fragment length polymorphism) are hybridization-based markers, whereas AFLP (amplified fragment length polymorphism), RAPD (randomly amplified of polymorphic DNA), SSR (simple sequence repeat) NVP-BEZ235 purchase and SNP (single

nucleotide polymorphism) are based on polymerase chain reaction (PCR) techniques. PCR-based markers are preferred and widely used as they are highly efficient, use less DNA, are less labor intensive and amenable to automation and avoidance of autoradiography [80]. The use of molecular markers in Al-tolerance studies includes Al-tolerance gene/loci identification and molecular mapping as well as MAS. One RFLP marker bcd1230, co-segregating with a major gene for Al tolerance, on wheat chromosome 4DL, explained 85% of the phenotypic variation in Al tolerance [81]. Using an F2 population derived from barley varieties Dayton and Harlan, three RFLP markers, Xbcd1117, Xwg464 and Xcdo1395, were closely linked to Alp on chromosome 4H [82]. The authors pointed out that Al tolerance in barley was controlled by a single gene that could be an ortholog of AltBH on wheat chromosome

4D. Five AFLP markers, AMAL1, AMAL2, AMAL3, AMAL4 and AMAL5, were closely linked to, and flanked Alt3 on the long arm of chromosome 4R [83]. After screening 35 Al-tolerant wheat landrace accessions using ten AFLP primer combinations, Stodart et al. [84] found that these accessions had diverse find more genetic background and were therefore valuable germplasms for Al tolerance breeding. RAPD marker OPS14705 was linked to the Alt3 locus in rye. A SCAR marker ScOPS14705 derived from a RAPD marker, was further shown to be linked to Alt3 locus [85]. Ma et al. [86] reported SSR markers Xwmc331 and Xgdm125 flanking the ALMT locus and they indicated that these markers could be used for MAS in breeding Al-tolerant wheat cultivars. In barley, several SSR markers, Bmag353, HVM68 and Bmac310, were closely linked with an Al tolerance gene [87] and [88]. Wang et al.

In contrast, hemorrhage and edema induced by jararhagin were unaf

In contrast, hemorrhage and edema induced by jararhagin were unaffected by deletion of any of the inflammatory mediators investigated, indicating that these effects occurs independent of these pro-inflammatory mediators. Besides its relevance in snakebite, the action of jararhagin Akt inhibitor was investigated in a number of different cell systems. In fibroblasts, it presented an agonist effect leading to cellular activities similar to those induced when fibrillar collagen triggers the α2β1 integrin receptor as the expression of MMP-1, MT1-MMT and α2β1 integrin (Zigrino et al., 2002). In epithelial cells, jararhagin inhibited cellular adhesion to the substrate,

but stimulated cellular migration and phosphorylation of FAK, inducing the rearrangement of the actin cytoskeleton, increased of actin polymerization and formation of motility-associated cell processes (Costa and Santos, 2004). In neuroblastoma cells, jararhagin also stimulates spreading, actin dynamics, neurite outgrowth, and activation of Rac1 Selleckchem KU-60019 GTPase (Costa et al., 2008). In addition, studies have been carried out to investigate the ability of jararhagin to interfere on cancer cell functions. Treatment of Skmel-28 human melanoma cells altered morphology, viability and adhesion

to ECM components, resulting in a significant reduction of lung metastasis compared to controls (Corrêa et al., 2002). This toxin also up-regulated cell cycle and apoptosis-related genes in Skmel-28 cells (Klein et al., 2011) and was evoked as a putative model for an anti-cancer drug. Due to the importance of SVMPs in venom pathology, the neutralization of their biological effects is crucial for the efficacy of Isotretinoin antivenoms, the currently accepted treatment for snakebite. In this regard, commercial and experimental antivenoms are efficient in inhibiting venom-induced hemorrhagic activity (Lopes-Ferreira et al., 1992)

indicating the immunogenicity of hemorrhagic SVMPs. However, aiming the development of antibodies directed solely at specific medically-important toxins, jararhagin was used for immunization protocols to raise antibodies by hybridoma technology (Tanjoni et al., 2003a) or by DNA immunization (Harrison et al., 2000). Seven murine monoclonal antibodies raised against jararhagin have been isolated. They reacted preferentially with jararhagin-C and one monoclonal antibody (MAJar 3) inhibited jararhagin/collagen interactions and jararhagin-induced hemorrhagic activity (Tanjoni et al., 2003a). Specific antibodies were also raised by immunization of mice with the cDNA encoding for recombinant jararhagin-C using a Gene-Gun approach. The resulting antiserum partially inhibited the hemorrhage induced by whole B. jararaca venom ( Harrison et al., 2000). Jararhagin-specific antibodies showed a marked antigenic cross-reactivity with venoms from other snakes.

117 per 100 person-years (PY) The

incidence of DVT appea

117 per 100 person-years (PY). The

incidence of DVT appears Bioactive Compound Library in vitro to increase markedly with age.12 Heit et al13 found that institutionalization (current or recent hospitalization or nursing home residence) was independently associated with 21.72 odds (among those with recent surgery) and 7.98 odds (without recent surgery) of having VTE. In another study, Heit et al14 found that 59% of VTE cases in the community could be attributed to institutionalization: hospitalization for surgery accounted for 24%; hospitalization for medical illness 22%; and nursing home residence 13%. To facilitate risk assessment for the unique characteristics of nursing home residents, a literature-based long term care (LTC) risk stratification tool for VTE has recently been developed by Zarowitz et al.15 In the nursing home setting, 3 studies evaluated the incidence of VTE diagnosed during facility residence,16, 17 and 18 and 1 study evaluated prevalence of asymptomatic disease.19 Using Minnesota Case Mix Review Program (MCMRP) data for the period 1988 to 1994, Liebson et al16 found a crude incidence rate of 1.2 (95% confidence interval [CI]:

0.9–1.5) to 1.5 (95% CI: 1.1–1.9) cases per 100 PY. In the same study, analysis of a second database (Rochester Epidemiology Project of Olmstead County, MN, 1998–1994) revealed a crude incidence rate of 3.6 (95% CI: 3.0–4.2) cases per 100 PY.16 Gomes C59 wnt et al,17 compiling Minimum Data Set (MDS) and Medicare records for residents in Kansas for the period

1997 to 1998, found a crude VTE incidence rate of 1.30 events per 100 PY (95% CI: 1.10–1.51) when excluding warfarin users. Gatt et al18 evaluated VTE incidence for residents with a length of stay (LOS) of 3 months or longer in a nursing home in Jerusalem, Israel, during the period 1991 to 2001. The crude incidence rate of VTE was similar in both chronically immobilized and mobile cohorts: 1.39 and 1.58 per 100 PY, respectively (P = .77). 18 Arpaia et al19 recently concluded that “[d]ata on the frequency of VTE among nonacute patients nursed at home or in long term care residential homes are still scarce.” The FER current study updates earlier US research regarding the incidence of VTE events that occur during nursing home residence16 and 17 and introduces an analysis of the proportion of nursing home admissions that were coded for VTE. Data for this study were extracted for the data collection period January 1, 2007, to June 30, 2009, from the AnalytiCare longitudinal LTC database (www.analyticare.com). This database included MDS 2.0 assessments, pharmacy dispensing records, and resident characteristics from 181 nursing home facilities across 19 states (29% of facilities had 0–100 beds, 70% 101–200 beds, 1% >200 beds).

Keevallik & Soomere 2010) Also, the directional structure of the

Keevallik & Soomere 2010). Also, the directional structure of the winds in the Gulf of Finland differs considerably from that in the Baltic Proper (Soomere & Keevallik 2003). In contrast to the gradual increase in the mean wind speed over most of the Baltic Proper (Pryor & Barthelmie 2003, Broman et al. 2006), there is a very slow decrease (about 0.01 m s−1 year−1) in the annual mean wind speed at Kalbådagrund (Soomere et al. 2010). Therefore, drastic long-term variations in the wave properties are unlikely in this gulf. The numerical simulations indicate very minor changes in the annual mean wave height in the entire gulf, including its entrance area

(Soomere et al. 2010). Suursaar & Kullas (2009b) noted a decreasing trend in 99%-iles Target Selective Inhibitor Library near the north Estonian

Forskolin coast and a weak, opposite, gradually increasing trend in the average wave height. Simulations using the WAM model show that, unlike the average wave height, maximum wave heights have exhibited a clear pattern of changes since the 1970s (Figure 10). There has been a substantial decrease (by about 10%) in the threshold in question near the southern coast of the gulf (especially in the narrowest central part of the gulf). This is accompanied by an almost equal increase to the north of the axis of the gulf and especially in the widest sea area. The changes reach about 0.40 m, that is, up to 20% of this wave height threshold over the 38 simulated years. Therefore, although the average wave heights have remained basically the same, the wave heights in very strong storms show a clear decreasing trend near the southern coast. This feature is apparently related to the major changes in the wind direction over the Estonian mainland: the frequency of south-westerly winds has increased considerably over the last 40 years (Kull 2005). A key message from these results is that the extension of spatial patterns of wave climate changes is substantially different for phenomena at different scales. While interannual variations in wave heights are correlated well over distances

Immune system > 500 km during about a half-century, the decadal variations embrace much smaller areas and are of a different nature at distances exceeding 200–300 km. The spatial pattern of changes to the average and extreme wave heights signifies that open sea areas as small as about 100 × 200 km may host changes of a completely different nature. This feature calls for a much more detailed analysis of the patterns of climatological changes in the Baltic Sea than is usually thought to be sufficient for open sea areas (BACC 2008). Such small scales of long-term variations in wave properties may considerably change our understanding about the past, present and future of wave-driven coastal processes and the relevant spatial resolution of wind and wave information necessary for their adequate modelling.

Other toxins acting on Sodium channel site III, as Tx2-6, fail to

Other toxins acting on Sodium channel site III, as Tx2-6, fail to induce priapism possibly by pharmacokinetic reasons but this should still be investigated experimentally. The question whether selleck compound these other toxins that act on Sodium channel site III interfere with NO/NOS/cGMP system was never addressed and could eventually explain why these other toxins don’t induce priapism. The cascade of events triggered by the toxin is currently under investigation

in our laboratory. It is clear though, that more investigations are needed to identify the ultimate mechanism of action involved in the erectogenic effect as well as the local consequences of a long-term use of this toxin. We conclude that crude venom and pure Tx2-6 toxin seem to produce identical effects on the organs examined suggesting that the possible cause of death is lung intra alveolar hemorrhage; toxin and crude venom seem to exert mild to moderate effects on brain tissue as suggested by our previous results (Troncone et al., 2011). In addition, the observed edema could be alternatively

attributed to the respiratory impairment caused by the severe lung hemorrhage. We gratefully acknowledge Dr. Daniel Pimenta and Dr. Isabel F. C. Correia (Biochemistry Laboratory – I. Butantan) for mass spectrometry of fractions and amino acid sequencing and the technical support of Mr. Wilson B. D’Ávila. Supported by research grants from FAPESP No. 98/02039-0 5-FU mw to LRPT and 06/57922-3 to MS. “
“The Farnesyltransferase skin of fish constitutes a pivotal immunological protection against the external environment. The layer of mucus on the fish surface, considered the first line of defence, participates in a number of functions including disease resistance, respiration, ionic and osmotic regulation, locomotion, reproduction, communication, feeding

and nest building (Negus, 1963, Ingram, 1980, Shephard, 1994 and Zhao et al., 2008). The mucus, such as that produced by the skin of the stingrays, has a complex set of components, which may include amino acid residues, peptides, complex carbohydrates, glycopeptides, glycolipids and other chemicals (Klesius et al., 2008, Alexander and Ingram, 1992 and Birkemo et al., 2003). Fish epidermal mucus was found to display antimicrobial activity against broad range of infectious pathogens (Mozumder, 2005 and Hellio et al., 2002). We recently described the antimicrobial activity of catfish Cathorops spixii mucus ( Ramos et al., 2012). Moreover, histone H2B and two ribosomal proteins are examples of proteins with antimicrobial activity that have been isolated from epidermal mucus of Atlantic cod ( Bergsson et al., 2005). Members of some families of antimicrobial peptides (AMPs) were also found to be important innate defence components in the epidermal mucosal layer of Moses sole fish (Pardachirus marmoratus) ( Oren and Shai, 1996), winter flounder (Pleuronectes americanus) ( Cole et al.

There were 32 8% men and 66 2% women in the total study populatio

There were 32.8% men and 66.2% women in the total study population, and 83% of the subjects were non-smokers,

3% former smokers, and 14% smokers. The median age of the subjects from the control area was 7–10 years higher than the median age from the other two areas (p-value Kruskal–Wallis-test < 0.001). Median levels of B-Cd and U-Cd increased from low to high exposure groups, and the same trends were seen for all kidney markers apart from UNAG, where low and moderate exposure groups demonstrated similar median levels. Thus, the genetic association MAPK Inhibitor high throughput screening studies were based on exposure groups. However, as there was an overlap between the B-Cd values among the groups, in an alternative approach the subjects were grouped by B-Cd tertiles. The cut-off values were 1.7 μg/L and 3.2 μg/L. Thus, there were N = 174 in the lowest, N = 164 in the middle, and N = 173 in the highest tertile. The genotype and allele frequencies of MT1A rs11076161, MT2A rs10636 and MT2A rs28366003 were tabulated in Table 2.

All three SNPs demonstrated allele frequencies Bafetinib in vitro > 5%. The Chi square (χ2) test showed that the genotypic distributions of all three SNPs did not deviate from the Hardy–Weinberg equilibrium (p > 0.05). First, the impact of genotype on the B-Cd concentration was evaluated in each exposure group. For MT1A rs11076161 and MT2A rs10636, an allele-dosage effect could be observed ( Fig. 1, and Supplementary Fig. 1) where variant genotypes showed slightly higher B-Cd levels in the moderate and the high exposure groups. There were very few (≤ 10) variant Fossariinae homozygotes for MT2A rs28366003 and the variant genotypes (GG and AG) were thus combined. The variant genotypes for MT2A rs28366003 demonstrated higher B-Cd levels as well, also in the low exposure group (Supplementary

Fig. 2). The trend for higher B-Cd with increasing number of variant alleles was significant for MT1A rs11076161 in the high exposure group (p-value = 0.032 unadjusted; p-value = 0.033 adjusted for sex, age and smoking). P-values for trend in the other exposure groups were p > 0.1. A non-significant trend was also seen for MT2A rs28366003 in the low exposure group (unadjusted p-value = 0.099; adjusted p-value = 0.075). In the analysis grouped by B-Cd tertiles, the trend for increased B-Cd with increasing number of variant alleles of rs11076161 became more pronounced in the middle tertile (p-value for trend = 0.001 both, unadjusted and adjusted for age, sex, and smoking). The trends for rs10636 and rs28366003 disappeared. In the analyses grouped by B-Cd tertiles, there was very little difference between the adjusted R2 for rs11076161 only (0.06) compared to the model including age, sex and smoking as well (0.07). Secondly, the same analysis was performed for U-Cd, but no clear allele dosage effect for MT1A rs11076161 or MT2A rs10636 was found (data not shown).

The norms cover a maximum age of 12 years, 11 months; therefore,

The norms cover a maximum age of 12 years, 11 months; therefore, we used data from a larger control sample to convert raw scores to standard scores (see Barry et al., 2007). Handedness was assessed using a brief demonstration hand preference (based

upon the Edinburgh Handedness Inventory; Oldfield, 1971). Children were asked to demonstrate how they would perform each of 10 actions; write, BIBW2992 order draw, throw, use scissors, brush their teeth, cut with a knife, use a spoon, sweep with a broom (upper hand), take the lid of a box, and deal cards. Left, Right, or either (if child indicated both) hand was recorded in each case. The number of right hand preferences was taken as a measure of hand dominance. MRI data were obtained using a 1.5-T Siemens Sonata scanner with a single-channel head coil. Participants wore noise-attenuating headphones and padding was inserted around the head to restrict movement. They watched a DVD of their choice via a mirror on the head coil during acquisition of the structural data. A T1-weighted image was acquired in each participant Panobinostat clinical trial for structural analysis and image registration (3D

FLASH; TR = 12 ms; TE = 5.6 ms; 1 mm isotropic voxels; matrix = 256 × 256 × 208; elliptical sampling; orientation = coronal). One acquisition of this T1-weighted sequence took five minutes. At the end of these five minutes, the image was inspected for motion artefacts and, if necessary, children were reminded to keep still for a further five minutes. Three artefact-free images were successfully acquired in each participant. The first and third images were registered (rigid-body transformation; 6 degrees of freedom; trilinear interpolation) to the second image to correct for movement Inositol monophosphatase 1 between acquisitions and summed to create a single T1-weighted

image in each participant. Before the functional task, participants were removed from the scanner for a break if necessary. For the functional scan, whole-head T2∗-weighted echo-planar images (TR = 3s; TE = 50 ms; 120 volumes, 6 min), were acquired. Each volume comprised 35 4-mm axial slices (in-plane resolution 3 mm × 3 mm). Stimuli were presented over MRI compatible headphones (MR Confon: http://www.mr-confon.de) at a comfortable listening level (estimated ∼70 dB). Participants were asked to keep their eyes closed. The task used for functional imaging was based on the Auditory Responsive Naming task previously used with PET (Bookheimer et al., 1998). It was chosen because it was thought to be engaging for children, easy enough for them to comply with and known to produce activation in both posterior and anterior language areas (Wernicke’s and Broca’s area, respectively). In the Speech condition, participants heard simple three-word auditory definitions of a high frequency word and were required to silently generate an appropriate word; for example, ‘wear on head’ > silently generate ‘hat’.