Less self-determined forms of motivation could be internalized to be more self-determined forms of motivation by satisfying the individuals’ basic psychological needs, which are presumed to be universal aspects of human beings across developmental and cross-cultural settings. Many studies across domains have been conducted to estimate the correlates and consequences of autonomous and controlled motivation. Consistently, autonomous motivation has been correlated with greater persistence, find more a more positive affect, enhanced performance, and greater psychological well-being.5 To examine the exercise motivation within the SDT framework, a number of behavioral regulation measures have been developed e.g.,

the Behavioral Regulation in Exercise Questionnaire (BREQ),6 the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2),7 the Exercise Motivation Scale (EMS),8 and the Perceived Locus of Causality (PLOC).9 The most widely used one is the Fluorouracil supplier BREQ-2, which is a revised version of the 15-item BREQ by adding an amotivation subscale (4 items) and renamed as the BREQ-2.7 The BREQ-2 is a self-report measure assessing amotivation, plus external, introjected, identified, and intrinsic regulations. In common with some other behavioral regulation instruments for different

contexts,10 it does not attempt to distinguish between integrated regulation and intrinsic regulation because it is thought that these two forms of regulation are easy to distinguish theoretically but difficult to distinguish empirically.6 Therefore, the BREQ-2 is a five

correlated factor, 19-item measure. Previous studies have provided strong empirical evidence for the validity6, 7, 11, 12 and 13 and reliability7, 14 and 15 of the scores derived from the BREQ/BREQ-2. Furthermore, the factor loadings and factor variance and covariance of the structure of the instrument were found to be invariant across gender.6 All of these findings suggest that the instrument (BREQ/BREQ-2) is psychometrically strong and appropriate for research Vasopressin Receptor in the exercise setting. The translation of relevant instruments to other languages is thought to be a method for extending the application of theories and models across cultures and nations.11 The BREQ-2 has been translated into several languages, such as Spanish, Greek, and Chinese, and the psychometric properties of the BREQ-2 in different languages have been examined.11, 12 and 16 The factor structure hypothesized in the original scale was replicated, and the internal reliabilities of the subscales were also found to be acceptable. However, one identified regulation item (I get restless if I don’t exercise regularly) was found problematic, and was finally removed from the final translated versions of the BREQ-2 (e.g., the Spanish version BREQ-2,12 the Greek version BREQ-2,11 the Chinese version BREQ-216).

, 2012, who found significant results with prizeCM in cocaine-dependent outpatients conducted their trials in community-based clinics and compared CM to treatment as usual, and not to CBT. A prizeCM only condition might have been helpful in order to draw conclusions regarding independent

effects of the prizeCM component. However, for ethical reasons a prizeCM only condition was not feasible. Another explanation could be that the value of our prizes may have been too low to produce a rewarding effect in our participants and greater incentives might have provided more favorable outcomes. Finally, the sample size was too small as indicated by the power analysis. The overall retention rate of 63.3% at week 24 in the present trial was high. Previous studies over 12 weeks (Epstein et al., 2003 and Rawson et al., 2006) found comparable retention rates. In accordance with the findings of Epstein et al.

(2003) (CBT = 79%; combination = 69%), the two Selleck PD0332991 groups in the present study did not differ in retention, while Rawson et al. (2006) found a significant group difference (CBT = 40%; combination = 59%). Furthermore, both interventions were effective in a clinical sample of patients with high rates of poly drug use and comorbid psychiatric conditions, which supports previous findings (Magill and Ray, 2009, Petry et al., 2013 and Rash et al., 2008). One explanation for this is that the Bortezomib mouse effects of prizeCM and CBT in reducing psychiatric symptoms are mediated by reductions in drug use. Interestingly, trends in favoring prizeCM plus CBT were found at 6-month follow-up.

This found finding suggests an additive effect of the two psychosocial approaches. Furthermore, prizeCM produced a sustained effect beyond the cessation of incentives, which is in support of the findings of McKay et al. (2010) and Epstein et al. (2003). Those patients who completed the trial showed highly significant reductions in SDS, BDI, and cocaine craving scores as well as in 4 ASI composite scores (drug, alcohol, employment, psychiatric problems), indicating clinical relevance of both treatment interventions. Furthermore, participants in both intervention groups were very satisfied and reported high acceptability of CBT and prizeCM. Finally, those patients with higher frequency of cocaine use at baseline had a higher risk of dropping out of the study. Therefore, we suggest that these patients should have a detoxification treatment before beginning CBT or prizeCM plus CBT. The generalizability of the present findings is limited by the sample size. The original targeted sample size could not be achieved, due to difficulties in recruiting participants. First, the recruiting process was initially planned at two sites, but data from one center was not included due to poor adherence to the study protocol and incomplete data. Second, the recruitment had to be stopped after 3 years due to running out of funds.

2% groups, but a statistical difference (p > 0.05) was observed in these groups and the Control group after March ( Fig. 3), with an emphasis in D. flagrans that, at the end of the experiment, the animals had a 9.3 kg of weight gain. The Moxidectin 0.2% group

had 5.7 kg of weight gain, and in the Control group, the animals had a 1.1 kg weight reduction. selleck compound Comparison of mean PCV showed a statistical difference (p < 0.05) between the D. flagrans group and the other groups in April, May and August ( Fig. 4). In the leukogram was observed an increase in the average of the total leukocyte count, with a statistical difference (p < 0.05) in April, June and July ( Table 2). It was also observed that in most collections, the segmented percentage was high and the lymphocytes percentage was reduced. However, rates of eosinophils remained normal in all collections. It was observed that the tracer goats from the D. flagrans group had a significantly lower parasite load compared to the other groups (p < 0.05) since April ( Table 3). In most cases, H. contortus was the most prevalent, followed by T. axei, S. papillosus, T. colubriformis and O. columbianum. Immature larvae of H. contortus

were observed in all groups since July. This study was the first to test the efficacy of D. flagrans in the control of goat gastrointestinal helminths in a semi-arid region of northeastern Brazil. The use of these fungus pellets in a sodium alginate matrix at a dose of 3 g/10 kg l. w., twice a week, proved to be effective in controlling gastrointestinal Ivacaftor mw worms, reducing the EPG in 58.9%, even at high temperatures, which reached 33.7 °C, and low rainfall, averaging 45.5 mm3 in the second quarter. Similar results were found by Silva et al. (2009), who administered the same fungus in sheep at doses of 1 g of pellets (0.2 g of fungus/10 kg l. w.) in Southeastern Brazil, twice a week for 5 months, and obtained a 71.6% EPG reduction. In another work, Silva et al. (2010) demonstrated the effect of this fungus on gastrointestinal nematodes of sheep (June–November

2010) with average percentage of EPG decreasing in the treated group compared to the control group. These results are similar to those presented in this study, since there was an average EPG decrease confirming that the action of this fungus Bumetanide is in the faecal environment. The mycelia used in the present experiment had been proven effective in previous studies carried out in Brazil ( Assis and Araújo, 2003, Braga et al., 2009, Silva et al., 2009, Silva et al., 2010 and Tavela et al., 2011). Sagués et al. (2011) also observed an EPG reduction in sheep by D. flagrans in Argentina. Other studies have also showed the effectiveness of this fungus in controlling animal helminths ( Araújo et al., 2004, Dias et al., 2007, Paraud et al., 2007, Braga et al., 2009 and Tavela et al., 2011). Rodrigues et al.

016, uncorrected] as well as preference to objective over retinal planar motion [t(11) = 1.83, p = 0.049, uncorrected], with no response modulation by retinal planar motion. V5/MT maintained its weak preference to retinal compared to objective planar motion components [t(14) = 2.01, p = 0.033, uncorrected]. That V6 was able to segregate self-induced 2D motion components during exposure to 3D flow corroborates the suggestion that V6 in particular is specialized in high-level motion processing, involving 3D as well as object- and self-motion

estimation (Cardin and Smith, 2010, Cardin and Smith, 2011 and Pitzalis et al., 2010). The prior experiments examined conditions where www.selleckchem.com/products/Gemcitabine-Hydrochloride(Gemzar).html objective planar motion and pursuit were either matched in velocity, or where one of them was absent. We have not yet examined how V3A and V6 respond to planar objective motion when pursuit eye movements

and planar objective motion are both present but differ in velocity, inducing retinal motion that is neither fully self-induced nor fully equivalent to objective motion. To answer this question and to extend the findings of experiment 2, we performed the final experiment 4. It contained the same four conditions as experiment 2 (pursuit and objective planar motion with 0% or 100% velocity each), plus four additional conditions: objective planar motion with 50% and 150% velocity during fixation [i.e., (−/+50%) and (−/+150%), respectively], and objective planar motion with 50% and 150% velocity during 100% pursuit velocity [i.e., (+/+50%) and (+/+150%), respectively] (illustrated in Figure 7A). Note that in the latter two conditions, MycoClean Mycoplasma Removal Kit the direction of IBET151 pursuit and objective motion were the same, such that the two differed in speed by 50% at all times. These latter conditions are of primary interest in this experiment because both were matched in pursuit (100% pursuit velocity) and in retinal motion (50% retinal motion velocity), yet differed in objective motion velocity

(50% and 150%, respectively). We expected regions that respond only to retinal motion to be equally activated by (+/+50%) and (+/+150%) (both contain 50% retinal motion), but regions responsive to objective planar motion velocity to differentiate between (+/+50%) and (+/+150%) conditions. Figures 7B and 7C show that only V3A and V6 differentiated between (+/+150%) and (+/+50%), with higher responses to (+/+150%) [V3A: t(12) = 3.13, p = 0.029; V6: t(9) = 3.20, p = 0.038, both Bonferroni corrected for six comparisons]. In contrast, V5/MT (and MST) responded equally to (+/+150%) and (+/+50%), with higher responses compared to (+/+), indicating that V5+/MT+ was primarily driven by retinal motion during pursuit. In the corresponding set of conditions during fixation [i.e., (−/+50%) and (−/+150%), respectively], V5/MT (as well as V3A and V6) significantly differentiated between velocities (Figures S5A and S5B).

Binding was observed only for the Sas::Ptp10D pair. The mean signal value for Sas::Ptp10D was 30- to 43-fold higher than for any of the three controls, and these differences were highly statistically significant (p < 0.0001). These data show that Sas binds to Ptp10D and not to other RPTP-AP fusion AC220 in vivo proteins, but do not address the possibility that 10D-AP is “sticky” and can bind nonselectively to any Fc fusion protein. To evaluate this, we conducted the experiment

in Figure 3B, in which 10D-AP was mixed at an ∼1:1 molar ratio with two other Fc fusion proteins, Unc5-Fc and Fasciclin II (FasII)-Fc, with one of the controls from the Figure 3A experiment, Sas-Fc::Lar-AP, serving as the blank. Eight identical replicates of each binding reaction were assessed. As in Figure 3A, binding was observed only between Ptp10D and Sas. The mean signal value for Sas::Ptp10D was 13- to 32-fold higher than for the two Fc controls, and the differences were highly statistically significant (p < 0.0001 for both the Unc5::10D and FasII::10D controls). The AlphaScreen relies on a proximity-dependent chemical reaction to measure binding between two proteins bound to “donor” and “acceptor” beads. This assay can work well for low-affinity interactions, because the high concentrations of protein on the beads facilitate bead-bead interactions via avidity effects. Cell-cell interactions mediated by adhesion Sorafenib mw molecules are strongly influenced

by avidity. Indeed, the AlphaScreen worked extremely well for Dscam, which is a homophilic adhesion molecule. The signal due to homophilic binding of the 7.13.25 isoform was 178-fold higher than that for heterophilic binding of 7.13.25 to 7.8.25, which differs only in exon 3 (see Wojtowicz et al., 2007 for nomenclature). We were also able to detect concentration-dependent binding of Sas to Ptp10D using the AlphaScreen. However, the signal-to-background ratio else (Sas-Fc::10D-AP versus Sas-Fc::69D-AP or Sas-Fc::blank) was only ∼6-fold (Figure S3), so this assay was inferior to the ELISA for this ligand-receptor pair. These results show that Sas and Ptp10D selectively interact with each other, but do not define whether their

in vivo interactions are likely to be in cis (between proteins on the same cell surface), in trans (between proteins on different cell surfaces), or both. We used a cell aggregation assay to evaluate whether Ptp10D and Sas can interact in trans. This was done by making stable Schneider 2 (S2) cell lines expressing full-length Ptp10D and a Sas-mCD8-GFP fusion protein. Ptp10D-expressing cells formed small clusters ( Figure 3C), consistent with the observation that 10D-AP binds to ectopically expressed Ptp10D in embryos ( Figure S1). Sas-expressing cells did not aggregate ( Figure 3D). When the cell lines were mixed, we observed Ptp10D-expressing cell clusters that were associated with one to several Sas-expressing cells ( Figure 3E).

LL induced all three types of behavior in both WT and Eif4ebp1 KO animals. Most WT mice were either arrhythmic (AR) or weakly rhythmic (WR), while most KO mice were rhythmic (R) in LL ( Figure 4B). Distribution of the three types of behavior (AR, WR, and R) in both genotypes is quantified in Figure 4C. Strikingly, a smaller percentage of KO mice (6.3%, 1/16) exhibited arrhythmic behavior than did WT mice (38.5%, 5/13) (KO versus WT, p < 0.05, χ2 test). The pooled periodograms from all the mice used in the experiment are shown in Figure 4D. The main peak of the periodogram is higher in the KO mice than in the

WT mice, demonstrating stronger rhythmicity in the KO mice in LL. To verify that the rhythms of clock protein expression are disrupted in behaviorally arrhythmic mice, PER2 was immunostained in the SCN at CT0 and CT12 Rapamycin ic50 for the rhythmic mice and at two random time points 12 hr apart for the arrhythmic mice. CT12 was defined as the onset time of the active phase, and CT0 was defined as the time point 12 hr apart from CT12. As expected, PER2 was not rhythmic in the SCN of behaviorally arrhythmic mice (KO or WT), as compared to the rhythmic mice ( Figure 4E). Thus, these data show that Eif4ebp1

KO mice are more resistant to LL-induced disruption of circadian behavioral and PER2 rhythms, consistent with Ipatasertib in vivo enhanced synchrony in the SCN cells. VIP plays a critical role in mediating synchrony in SCN cells. To investigate the

mechanisms of enhanced re-entrainment and synchrony of the SCN clock in Eif4ebp1 KO mice, we first studied VIP expression in these animals. Using double immunofluorescent labeling, we first examined the expression pattern of VIP and arginine vasopressin Phosphoprotein phosphatase (AVP) in the SCN. AVP is generally used as a neuropeptide marker for the dorsolateral SCN ( Abrahamson and Moore, 2001). Confocal microscopic imaging revealed that VIP was expressed in a subset of ventromedial (core) SCN neurons, while AVP was expressed in some cells in the dorsal and lateral (shell) SCN ( Figure 5A). The spatial distribution of VIP and AVP was similar in the SCN of KO and WT animals. Immunohistochemical staining also revealed robust VIP expression in the SCN ( Figure 5B and Figure S4A). In both the WT and the KO mice, expression of VIP at ZT12 was decreased compared to ZT0 (ZT12 versus ZT0, p < 0.05, ANOVA), which is consistent with a previous report ( Takahashi et al., 1989). Interestingly, VIP level was increased by ∼1-fold in the Eif4ebp1 KO mice at both ZT0 and ZT12 (KO versus WT, p < 0.05, ANOVA) ( Figure 5B), suggesting constitutive repression of VIP expression by 4E-BP1. To investigate the mechanisms underlying VIP increase in Eif4ebp1 KO mice, we examined the expression of the VIP precursor protein, prepro-VIP, in the brain.

, 2003). The organization found by Bathellier et al. (2012)—which contained a small number of discrete, spatially separated modes—could thus be a more natural behavior for locally recurrent circuits that are not fine tuned. Like all surprising results, this study raises many questions. First, how general is this organization of neuronal activity? Evidence for attractor dynamics in other networks has been inconsistent (e.g., Wills et al., 2005; Leutgeb et al., 2005). Is a similar organization of discrete modes Selleckchem CP690550 seen in other cortical regions, other cortical layers,

and other brain structures? Second, would a similar pattern be seen in actively behaving animals, as well as the anesthetized and awake passive mice studied here? Third, what causes particular groups of cells to form an assembly? In Hebb’s original theory, the composition of cell assemblies was determined by experience. But Bathellier et al. (2012) could predict one mouse’s classification choices from the mode organization observed in different animals, suggesting that auditory cortical assemblies arise either from an innate process, or at least from commonalities in the sensory experience of these mice. Finally, why should the cortex work like this, using hundreds of neurons

do convey a single number? Although this may seem inefficient from the perspective of information coding, the brain is not just there to represent external stimuli, but to act on them. Is cortical attractor dynamics in fact a fundamental mechanism

of decision making? Characterizing cortical dynamics in behaving animals, and how it changes Ceritinib in vivo with learning, may well answer these questions. “
“Charles Darwin famously wrote that the eye caused him to doubt that random selection could create the intricacies of nature. Fortunately, Darwin did not know the structure of the L-NAME HCl retina: if he had, his slowly gestating treatise on evolution might never have been published at all. Among other wonders, the neurons of the retina are tiny (Figure 1). The ∼100 million rod photoreceptors appear to be the second most numerous neurons of the human body, after only the cerebellar granule cells. The retina’s projection neuron, the retinal ganglion cell, has less than 1% the soma-dendritic volume of a cortical or hippocampal pyramidal cell. Although the retina forms a sheet of tissue only ∼200 μm thick, its neural networks carry out feats of image processing that were unimagined even a few years ago (Gollisch and Meister, 2010). They require a rethinking not only of the retina’s function, but of the brain mechanisms that shape these signals into behaviorally useful visual perception. The retinal neurome—the census of its component cells—continues to be refined. An initial estimate of 55 cell types in the retina (Masland, 2001) appears to have been something of an underestimate.

, 2011). AVPR1a was shown to be associated with listening behavior and audio structuring ability. Highly significant epistatic interactions have also been observed between promoter region polymorphisms in the AVPR1a and SLC6A4 genes

and VX-770 molecular weight musical memory ( Ebstein et al., 2010). Future studies would be well advised to study genes that encode for oxytocin (OXTR), a neuropeptide with a pervasive role in mammalian social behaviors, including empathy, and with a known association with the AVPR1a gene. AVPR1a has been linked to anxiety and depression, and the connection between musical creativity and these traits is well known. Taken together, this suggests a role for AVPR1a as part of a putative genetic basis for both creativity and the artistic temperament. Linking genetic polymorphisms to personality variables

is an area of active research. Data from these investigations should be brought to bear on the question of identifying candidate genes for musicality to the extent that those personality variables are discovered to be linked to the musical phenotype. In summary, musicality is polymorphic. It is a complex interaction of physical, emotional, cognitive, and psychosocial traits, including some that are overtly “musical” and others that are not but that contribute to musicality in a variety of supporting ways. Musicality presents as both productive and receptive ability, SAR405838 and skill can manifest itself as primarily technical, cognitive, intuitive, or emotional, or in various

combinations. If research is to provide an adequate account Linifanib (ABT-869) of how music, genes, environment, and neural development interact, it must embrace the full variety of musical experiences and contexts (Sloboda, 2008). Studies of the genetics of music promise both practical and theoretical benefits. They can help in music education through identifying those students with high potential in specific areas of musical endeavor and can ultimately help teachers to select the most efficient instructional methods based on a student’s background and aptitudes. The important theoretical promise is in identifying and learning to measure component musical abilities more accurately so that musical behaviors can be correctly linked to genetics, to brain structures, and to other, nonmusical behaviors. In this latter case, there has been great interest in the question of cognitive transfer, that is, whether “music makes you smarter” (e.g., Kraus and Chandrasekaran, 2010). Questions such as these would benefit by a fractionating of musical ability, so that we can know which aspects of music correlate specifically with which other cognitive abilities. Finally, more accurately quantifying the musical phenotype is a necessary precursor to performing rigorous genetic studies. “
“Nociceptive pain reflects our capacity to detect the presence of potentially damaging stimuli; it is an essential early warning mechanism (Basbaum et al., 2009 and Woolf and Ma, 2007).

The primers used in the study have been described previously [17]. The amplified product was then analyzed on 2% agarose gel. Samples which did not react to any of G or P genotype specific primers were considered non-typeable. Of the VX 770 756 diarrheal specimens collected from two hospitals (AIIMS and KSCH), we found 290 (38.4%) positive for rotavirus. All 290 rotavirus positive

samples were subjected to both G and P genotyping. We observed genotype G9 most frequently circulating in Delhi with a prevalence rate of 25.2% followed by G1 and G2 at 22.4% and 17.2%, respectively (Table 1). The previously reported [17] fast emerging genotype G12 had an overall prevalence of 14.8% throughout the study period. However, this website we seldom detected the G4 genotype (2.1%). Amongst the P genotypes, P[4] (25.5%) was most prevalent while P[6], P[8] and P[11] accounted for 20%, 16.9% and 2.1%, respectively (Table 1). Among the G–P combinations, we commonly detected 16 different rotavirus strains at varying frequencies. Among the globally common G–P combinations, G9P[8] was detected among 5.2% of the samples while both G1P[8] and G2P[4] showed 7.2% detection each. We detected 13 other unusual rotavirus strains of which, G12P[6] (10%), G9P[4] (6.5%) and G2P[6] (3.4%) were more frequent (Table

1). We also observed a high percentage of mixed infections: 6.9% of G mix and 14.5% of P mix. Besides mixed infections, Libraries nearly 11% and 21% of the total RV positives could not be G and P genotyped, respectively. At AIIMS, we found 35.9% (184/513) of samples positive for rotavirus antigen compared to 43.6% (106/243) of samples

at KSCH. At both hospitals we found all G (G1/G2/G4/G9/G12) and major P (P[4]/[6]/[8]) genotypes, besides genotype P[11] which was found ADAMTS5 at AIIMS only (Fig. 1A and B). At KSCH we detected relatively high frequency of G1 (29.2%), G2 (19.8%) and G9 (32.1%) genotypes, while at AIIMS G1, G2, G9 and G12 had 19%, 15.8%, 21.2% and 21.2% detection rates, respectively. Among the G–P combinations, the common rotavirus strains at both the hospitals were G1P[8], G2P[4] and G9P[8] and in total constituted 19% and 20.7% of the total strains genotyped at AIIMS and KSCH, respectively (Fig. 1C). Among the unusual RV strains, we detected G2P[6] at KSCH only, and G9P[11] only at AIIMS. Although we found G12P[6] and G9P[4] at both hospitals, G12P[6] was more common at AIIMS (14.7%) than KSCH (1.9%) while G9P[4] was commonly found at KSCH (12.3%) than AIIMS (3.3%). We found nearly similar percentages of G and P mixes at both hospitals, however, G (15.8%) and P (25.5%) non-typeables at AIIMS were relatively more than G (4.8%) and P (13.2%) non-typeables at KSCH. The present rotavirus surveillance study (2007–2012) at AIIMS showed G12P[6], G2P[4], G9P[8] and G1P[8] to be the most prevalent strains with 14.7%, 8.7%, 5.4% and 4.9% detection rates, respectively (Fig.

The seven group X strains were isolated in Burkina Faso, Ghana and Uganda. Two strains from Burkina Faso expressed fHbp ID73, the other isolates expressed ID74. The strains from Burkina Faso were sequence type 751 and 181, respectively. The two strains from Uganda were ST5403 and expressed PorA subtype P1.19,26, while the other five group X strains were P1.5-1,10-1. The two strains from Uganda inhibitors differed

from each other by the level of fHbp expression. Strain Ug11/07 had 4% and Ug9/06 has 200% of the fHbp expression level compared to the reference strain (Table 1). GMMA with selleck kinase inhibitor or without fHbp over-expression elicited high bactericidal titres that were not significantly different from each other against the three W strains AT13387 order expressing either fHbp v.1 or v.2 (Fig. 3A). This is consistent with previous observations that bactericidal activity against strains sharing the same PorA as the GMMA-production strain is predominantly mediated by anti-PorA antibodies [26]. GMMA from the Triple KO, OE fHbp strain induced antibodies that were

able to kill six out of seven serogroup A strains (geometric mean titres [GMT] ranging from 20 to 2500) (Fig. 3B). The only isolate that was resistant to killing was readily killed by a mouse serum raised against group A polysaccharide conjugate vaccine. The antibodies induced by the GMMA from the Triple KO, OE fHbp strain were able to kill all serogroup X strains tested (GMT = 18–5500) (Fig. 3C). GMMA produced from the W strain which lacked fHbp v.1 over-expression (Triple KO), induced antibodies that were only able to kill one X strain (BF7/07), consistent with the majority of bactericidal antibodies induced by the GMMA vaccine being directed against fHbp. Antibodies made against the

recombinant fHbp ID1 were only bactericidal against serogroup X strain Ug9/06 with the highest fHbp expression. We investigated the dose-dependent bactericidal antibody response against one W (1630), A (N2602) and X (BF7/07) isolate (Fig. 4A). Sera raised against GMMA with over-expressed fHbp were bactericidal against MYO10 these strains in a dose-dependent manner (Spearman Rank P = 0.001 for group A and P < 0.0001 for group W and X) with killing occurring at all three doses (0.2, 1 and 5 μg). GMMA from the triple KO, OE fHbp mutant was prepared from a mutant with deleted capsule expression in order to attenuate virulence of the vaccine strain and reduce serogroup-specific antibody production. To test the latter, we investigated whether maintaining capsule expression in the GMMA-producing strain affects the bactericidal antibody response. Sera from mice immunised with GMMA prepared from the Triple KO, OE fHbp vaccine strain had significantly higher SBA activity against three of five A and X strains tested than GMMA from the isogenic mutant that expressed the capsule ( Fig. 4B).