, 2005; He et al.,

2006). As already noted above, RecA is selleck products not required for the stationary-phase mutagenesis in P. putida (Tegova et al., 2004). At the same time, nonhomologous end-joining (NHEJ), an essential pathway responsible for the repair of DSBs, composed of the DNA end-binding Ku protein and a multifunctional DNA ligase (LigD), has been identified recently in many prokaryotes including Pseudomonas species and mycobacteria (Pitcher et al., 2007a, b; Shuman & Glickman, 2007). DNA repair provided by the bacterial NHEJ system has been shown to be inaccurate, resulting in single nucleotide additions or deletions with various lengths at the break site (Gong et al., 2005; Malyarchuk et al., 2007; Stephanou et al., 2007). Recent studies with Mycobacterium smegmatis revealed that NHEJ mutant strains are more sensitive to ionizing radiation and desiccation during the stationary phase than the wild-type

strain (Pitcher et al., 2007b). In addition, NHEJ is required for the repair of artificially induced, I-SceI-mediated chromosomal DSBs in stationary-phase cells (Stephanou et al., 2007). In Bacillus subtilis, NHEJ is also growth phase regulated, contributing to DSBR only during the outgrowth of spores or in stationary-phase cells (Wang et al., 2006; Moeller et al., 2007; Simmons et al., 2009). Therefore, it would be important to study whether NHEJ could play a role in BIBW2992 stationary-phase mutagenesis in bacteria. These studies are currently in progress in our laboratory. There is no single mechanism for the generation of stationary-phase mutations in bacteria. Multiple factors Pyruvate dehydrogenase including oxidative damage of DNA and proteins, other kinds of DNA damage, errors occurring during DNA replication and inefficiency of DNA repair may cause mutations. Additionally, DNA repair synthesis itself may be a source of mutagenesis

under the growth-restricting conditions of bacteria. Moreover, because bacteria differ in the content of DNA polymerases and DNA repair enzymes, several mechanisms that have not discovered with the E. coli model may become apparent in other bacterial species. Bacteria belonging to the genus Pseudomonas, which represents one of the most diverse and ecologically widely distributed groups of microorganisms, carry, similar to many other bacterial species, a different set of specialized DNA polymerases compared with that characterized in enterobacteria. There are also differences in DNA repair enzymes/systems whose connection with stationary-phase mutagenesis needs further exploration. I wish to thank R. Hõrak, M. Putrinš, S. Saumaa, K. Tarassova and M. Tark for their comments on the draft version of this manuscript.

4c). These results suggested the involvement of protein phosphorylation in ATP attenuation of nucleolytic

function. When AP-treated samples were incubated with ATP in the presence of 10 mM sodium fluoride, a selleck products phosphatase inhibitor (Mishra & Parnaik, 1995), the nucleolytic activity was inhibited in all PIR fractions, but not in unirradiated control (Fig. 5a). The 1-h PIR sample was dephosphorylated with AP and subsequently treated with sodium fluoride to inactivate phosphatase enzyme. When such samples were incubated with ATP in the presence or absence of protein kinase A (PKA) inhibitor (H89) and protein kinase C inhibitor (staurosporine) separately, the ATP attenuation of nucleolytic degradation was observed only in the absence of protein kinase inhibitors (Fig. 5b and c). As both, H89 and high concentrations of staurosporine inhibit PKA activity, it appears that ATP attenuation of nucleolytic function might be regulated through PKA-type kinase(s). These results indicated that the DNA damage induces an ATP-responsive function and the nucleolytic activity was modulated by reversible protein phosphorylation. The effect of γ radiation on phosphoproteins and protein kinase activity was measured both in vivo and in vitro. In vivo phosphoprotein profiles were monitored on cells labeled with [32P]phosphoric www.selleckchem.com/products/pirfenidone.html acid and changes in phosphoprotein profile were detected by autoradiography. The protein kinase activity

in γ-irradiated cell-free extract monitored in vitro was highest in 0.5-h PIR cells, which subsequently decreased to the levels of unirradiated control in 3 h PIR Selleck 5-Fluoracil (Fig. 3). Similarly, 1-h PIR cells showed very high levels of protein phosphorylation as compared with unirradiated sample and the samples beyond 1 h PIR (Fig. 6). These results suggest that γ radiation induces protein kinase activity, possibly leading to the enhanced protein phosphorylation, which are considered strong indicators of signal transduction

mechanisms in any organism. Recently, the involvement of protein phosphorylation in bacterial radiation resistance and DSB repair has gained significant importance. It has been demonstrated that (1) D. radiodurans showing relatively low protein kinase activity also exhibits DSB repair impairment and γ radiation sensitivity (Rajpurohit et al., 2008); (2) a multiprotein complex isolated from D. radiodurans contains DNA repair proteins along with protein kinase and phosphoproteins (Kota & Misra, 2008) and (3) the deletion of deinococcal-response regulator DR_2418 from bacterial genome leads to repression of catalase, recA and pprA gene expression and decreased γ radiation resistance (Wang et al., 2008). A periplasmic protein kinase activity required for radiation resistance and DSB repair in E. coli (Khairnar et al., 2007), as well changes in the DNA substrate-binding preference of Bacillus subtilis single-stranded DNA-binding protein by phosphorylation (Mijakovic et al.

In addition to advances in fluorescent proteins derived from GFP, a new class of fluorescent proteins has recently been isolated

and proven useful in environments deprived Selleck R428 of oxygen. Drepper et al. (2007) demonstrated that FbFPs expressed in the facultative anaerobe Rhodobacter capsulatum in hypoxia was fully fluorescent. More recently, Drepper et al. (2010) have quantitatively monitored the fluorescent intensity of FpFP in vivo in E. coli under oxygen limitations by continuously measuring wavelength excitation at 460 nm and emission at 492 nm. A different study showed that FbFPs expressed in Candida albicans and Saccharomyces cerevisiae under anaerobic conditions render the cells fluorescent (Tielker et al., 2009). In this work, we demonstrate that FbFPs expressed in the obligate anaerobe B. fragilis confer fluorescence to the cells when grown under anaerobic conditions. In the absence of oxygen, B. fragilis cells were remarkably fluorescent (Fig. 2), presenting an emission in the range of 475–505 nm when excited with light at 450 nm in agreement with previous works using FbFPs as the fluorescent marker (Drepper et al., 2007; Tielker et al., 2009). Although GFP protein derivatives have been engineered to increase photostability, intensity, broad

pH range tolerance, faster maturation rates and different colors, which allow researchers to use multiple probes within the same image experimental set (Shaner et al., 2007), selleck chemicals llc they are still dependent on molecular oxygen to Fenbendazole display their fluorescence. This requirement for oxygen for proper post-translational modification of the protein fluorophore is a significant limitation to their use in anaerobic environments. Thus, our findings are important for the study of anaerobic bacteria as there is a lack of imaging tools to study molecular trafficking and gene expression in these organisms, which require anaerobic conditions during their growth and metabolism under both in vitro and in vivo conditions. This is particularly relevant with regard to B. fragilis because it will allow us to investigate this opportunistic

anaerobic human pathogen under low or limited oxygen conditions similar to the ones that occur during anaerobic infection in human tissues. In this regard, as a first step to understand gene expression in B. fragilis during infection, we demonstrate in this study that the ahpC and dps genes are expressed following incubation with a cell line macrophage. These findings indicate that B. fragilis cells were internalized by macrophages and that its intracellular environment induced B. fragilis oxidative stress response as demonstrated by the upregulation of the ahpC∷bs2 and dps∷bs2 transcription fusion. In animal models of intraperitoneal infection, the B. fragilis oxidative stress response is required for survival (Sund et al., 2008).

The mtfA and mtfB encode for an ABC-type I transporter system, and mdbA codes for a putative regulator. Microcin N has a bactericidal

activity against pathogenic strains, such as E. coli O157:H7, Salmonella enteritidis, and Salmonella enterica serovar Typhimurium, but it does not show antibacterial activity against strains of Campylobacter jejuni and Listeria monocytogenes (Wooley et al., 1999). Many properties of the microcin N system have not been characterized Tipifarnib order as yet, such as the spectrum of action against other bacteria, the identity of its receptor in the sensitive cell, its production kinetics, and the mechanism of action against the target cell. A key step in elucidating these properties is to purify microcin N to further perform biochemical and microbiological characterizations. In this work, we describe the DNA sequence of the microcin N genetic system, the purification and characterization of microcin N, and its expression pattern during bacterial growth. Escherichia coli DH5α was used as the indicator strain for the antimicrobial activity assays. The microcin N-producing strain used in all the experiments was E. coli MC4100 containing the

plasmid pGOB18. This plasmid is a pBR322 derivative that contains a fragment of 5.25 kb with microcin N genetic elements (O’Brien & Mahanty, 1994); mcnN and mcnI genes were amplified by PCR with primers IN1 (5′-CAA CAG ATT TAT CTG CTG GCC AGT-3′) and S2 (5′-TAT LDK378 nmr TCT ACC TTA ATG AAT CTT ATC CT-3′) and the PCR product was ligated to pGEM-T Easy (Promega Co., Madison, WI) to obtain pKAR. Table 1 summarizes the E. coli strains and plasmids used in this work. Plasmids pGOB18, pKAR, and pIN were purified using the EZNA Plasmid Minikit II (Omega Bio-Tek, Norcross, GA). The sequencing of the segment that encodes for the genetic elements that produce microcin N was carried out using the primer walking strategy, starting with a primer that anneals to the HindIII site of pBR322. Plasmids pIN

and pKAR were sequenced using the T7 and SP6 universal primers. The sequencing reactions Bcl-w were performed at Macrogen Co. (Seoul, South Korea). Liquid cultures of microcin N producer strains were grown in nutrient broth (Nut) (Difco, Franklin Lakes, NJ), Luria broth (LB) (MoBio, Carlsbad, CA), Müller–Hinton (MH) broth (Difco), and M63 minimal media supplemented with glucose (0.2%). For the antimicrobial-activity plate assay, the sensitive strain lawn (E. coli DH5α) was grown on nutrient agar (Difco). The antimicrobial assay was performed according to protocols described by Mayr-Harting et al. (1972). To prepare the sensitive strain lawn, 100-μL aliquots of a culture (OD600 nm∼0.6) were mixed with 4 mL of melted soft agar (0.7% w/v) and plated on nutrient agar. A culture of the strain E.

Whereas the absence of DnaE2 increases the frequency of mutations, the lack of ImuB has a negative effect on the mutation frequency (Koorits et al., 2007). There is a competition of different DNA polymerases for binding to the β-clamp to take over the DNA synthesis (Johnson & O’Donnell, 2005).

For example, in E. coli Pol II competes with Pol IV SCH727965 datasheet on stationary-phase mutagenesis and limits Pol IV’s mutagenic activity (Layton & Foster, 2003). Thus, one may speculate that ImuB (like eukaryotic Rev1) serves as a scaffold protein for the recruitment of various DNA polymerases. As already mentioned above, bacteria that carry the dnaE2-containing operon lack umuDC genes in their chromosome. This raises an interesting question of whether the coexistence of these two operons in the same bacterium would be disadvantageous under certain circumstances. Several studies indicate that this is not the case. For example, the Pol V homologue RulAB encoded by toluene catabolic plasmid (TOL plasmid) pWW0

increases the survival of P. putida under conditions of DNA damage (Tark et al., 2005). Moreover, P. putida carrying the rulAB STA-9090 genes introduced into the chromosome expresses a strong GASP phenotype. Thus, this DNA polymerase significantly increases the evolutionary fitness of bacteria during prolonged nutritional starvation of a P. putida population, which indicates that RulAB increases the probability of accumulation of

beneficial mutations, allowing genetic adaptation of bacterial populations under conditions of environmental stress. Another study by Saumaa et al. (2007) revealed that although the frequency of accumulation of stationary-phase mutations in P. putida was not significantly affected by the presence of the rulAB genes, some differences appeared in the spectra of base substitutions. Namely, the introduction of rulAB into P. putida increased the proportion of Cepharanthine A-to-C and A-to-G base substitutions among mutations, which occurred under starvation conditions, implying that RulAB may perform mutagenic TLS past damaged adenine. umuDC orthologues are widely distributed in broad-host-range catabolic and antibiotic resistance plasmids (Permina et al., 2002; Tark et al., 2005). Such plasmids have contributed significantly to virulence and ecological fitness in bacteria. For example, Pseudomonas strains harboring umuDC orthologues rulAB on plasmids have increased UV tolerance, enabling bacteria to survive on leaf surfaces that are exposed to DNA-damaging UV irradiation (Sundin & Murillo, 1999). Hence, the question arises: why do these genes locate usually on plasmids and not in the bacterial chromosome? Under the conditions of environmental stress that leads to the accumulation of DNA damage in a cell, the activation of DNA polymerase Pol V increases the survival of cells due to continuing DNA synthesis by Pol V at damaged sites.

Dilution aliquots were plated in parallel on LB agar and LB agar containing 5 μM CmC. From the 5 μM CmC plate, 24 clones were isolated and found to be tryptophane auxotroph, proving by this genetic marker their descent from strain 168. Two independently isolated resistant clones designated 8R and IR revealed no cross-resistance

against most antibiotics tested, either structurally related or different (summarized in Supporting Palbociclib Information, Table S2). However, they were more resistant, in particular, against doxorubicin, a hydrophobic polyketide cancer antibiotic (Table S2). Both mutants grew in the presence of 5 μM CmC, and this resistance was unchanged after propagation for >20 generations in the absence of the drug. In contrast, Ohki & Tatenu (2004) obtained their spontaneous multidrug-resistant mutant on the bmr3 gene in a one-step procedure. The genomes of the resistant clones 8R and IR as well as the parent strain B. subtilis 168 were

sequenced to near completion and compared with the reference GenBank: AL009126.3 database (Srivatsan et al., 2008; Barbe et al., 2009). Two of the mutations could be confirmed by PCR amplification and sequencing. Sequence comparison localized these two mutations 40 bp apart in the 5′ noncoding region of the yvcC=bmrA gene (Fig. 1). In S. tendae, the producer of the cervimycin complex, self-resistance is facilitated by a member of the MFS superfamily,

possibly extruding cervimycin (M. Unger & C. Hertweck, unpublished data). BmrA (Steinfels et al., 2002; Orelle et al., 2003) belongs to the largest gene class of Daporinad ic50 ATP-dependent ABC exporters in B. subtilis and was found to be expressed constitutively (Steinfels et al., 2004). Previously, the in vitro transport of Hoechst 33342, doxorubicin, 7-aminoactinomycin and EtBr by next BmrA was shown using membrane vesicles, whereas reserpine inhibited the EtBr-efflux (Steinfels et al., 2004). The bmrA knockout mutant (Steinfels et al., 2002) had a twofold reduced resistance to CmC compared with B. subtilis 168. This supports the conclusion that this gene is responsible for CmC resistance, but also indicates the involvement of more factors contributing to the basal resistance. A PCR fragment of bmrA obtained from mutant 8R genomic DNA with primers px yvcC-F/-R1 transformed B. subtilis 168 to 5 μg mL−1 CmC resistance. In accordance with published data (Steinfels et al., 2004), we found additionally that in the presence of 50 mg L−1 reserpine, the mutant was unable to grow in the presence of CmC. From these data, we could conclude that the ABC transporter BmrA is responsible for the CmC resistance of the mutants. So far, reports on spontaneous constitutively resistant mutants in Gram-positive bacteria revealing overexpression due to promoter mutations are rare (Piddock, 2006). One case was reported after growing B.

To induce transcallosal motor interference on the activity of the left muscle, TMS was delivered to the left M1 using a magnetic stimulator (Magstim 200; Magstim Co., UK) with a figure-of-eight-shaped coil (each diameter 70 mm). The coil was located at a hot-spot where weak stimulation elicited the largest motor response in the right abductor pollicis brevis (APB), and was held tangentially over the

scalp and rotated clockwise at 45°. The induced current in the cortex was set to run in the posterior–anterior direction. The stimulus intensity was set at 1.5 times the resting motor threshold (RMT). This intensity was quite strong because we aimed to induce an observable perturbation in the abduction force of the left thumb. However, we LDK378 nmr confirmed that TCI tested during isometric contraction was not saturated at this intensity

(Supporting Information Fig. S1). The RMT was defined as the minimum stimulus intensity that produced a > 50 μV motor evoked potential (MEP) at the right APB in at least 5 out of 10 consecutive trials. The participants sat comfortably on a reclining chair with both shoulders and elbow angles semi-flexed throughout the experiment. Their left and right hands were separately placed on wooden boards with their palms downward. Each hand was strapped at the metacarpophalangeal joints of four fingers selleck and the wrists. The thumbs were extended approximately Bay 11-7085 40° and the thumb cushion was in contact with a horizontal metal plate (Fig. 1A). The contact area was confined to 20 × 20 mm and was covered with a rubber sheet. The force regulation task was constructed on the basis of our previous experimental design (Kida et al., 2004). The participants were instructed to perform bimanual thumb abductions under visuomotor tracking. The target line moved sinusoidally up and down at 0.1 Hz on the right half of a dual-beam oscilloscope

screen (VC-9; Nihon Kohden, Japan) positioned in front of the participants at a distance of 60 cm (Fig. 1A). The range of the target line displacement on the oscilloscope was 8 cm in height, which corresponded to a force range from 1 to 11 N (with a resolution of approximately 0.02 N). Left and right abduction forces were displayed as horizontal lines on the left and right half of the oscilloscope, respectively. In the symmetric condition, bilateral forces were displayed in the same manner; when the participant pushed the plates with both thumbs, both lines moved from bottom to top (Fig. 1B). Under this condition, the participants tracked the target line with bilateral thumb abduction forces in a symmetrical manner. In contrast, in the asymmetric condition, the right force line was displayed upside down by using an inverse function switch (Fig. 1C).

Such events increase the risk of emerging multiresistant strains with transducing bacteriophages able to transfer resistance determinants into other strains. Effective transfer of resistance plasmids between strains of the USA300 clone intermediated by transduction contributes to this clone’s faster evolution. Comparative DNA analysis of the φJB phage and prophages of several clinical S. aureus strains

demonstrated substantial match in their DNA profiles. The highest similarity rate was for the prophage of recent MRSA isolate E53 (ST624/t211/SCCmec IA) related to the Iberian clone and of the φNM4 prophage of S. aureus strain Newman (Bae et al., 2006), both members of the CC8 lineage. http://www.selleckchem.com/products/Staurosporine.html This evidences that in naturally occurring S. aureus strains some prophages of serological group B are very closely related

to the φJB prophage, for which similar transduction abilities can be expected. We would like to thank P. Petráš from the National Reference Laboratory for Staphylococci, National Institute of Public click here Health, Prague for providing MRSA isolates. We gratefully acknowledge financial support of the Czech Science Foundation (310/09/0459), and Ministry of Education, Youth and Sports of the Czech Republic (MSM 0021622415). “
“This study investigates new aspects of the possible role of antioxidant defenses in the mechanisms of resistance to ciprofloxacin in Proteus

mirabilis. Four ciprofloxacin-resistant variants (CRVs), selected in vitro by repeated cultures in a sub-minimum inhibitory concentration (MIC) concentration of ciprofloxacin, attained different levels of antibiotic resistance and high Ferric reducing antioxidant power, with 10−6 frequencies. However, no mutations occurred in positions 83 or 87 of gyrA, 464 or 466 of gyrB, or 78, 80 or 84 of parC, suggesting that resistance took place without these typical mutations in DNA gyrase or topoisomerase IV. Assays with ciprofloxacin and the pump inhibitor carbonyl cyanide m-chlorophenylhydrazone showed that in addition to the antioxidant mechanisms, the influx/efflux mechanism also contributed GBA3 to the increase in the resistance to ciprofloxacin in one CRV. Moreover, lipid oxidation to malondialdehyde and protein oxidation to carbonyls and advanced oxidation protein products were higher in sensitive than in the resistant strains, as a new factor involved in the mechanisms of resistance in P. mirabilis. The oxidative stress cross-resistance to telluride in CRVs enhanced the role of the antioxidants in the ciprofloxacin resistance of P. mirabilis, which was reinforced during the assays of reduction of susceptibility to ciprofloxacin by glutathione and ascorbic acid.

The cereulide-producing B. cereus strain NVH 1257 was used for positive control. The Bacillus spp. strains were tested for their ability to produce cereulide under standard conditions, essentially as described by Andersson et al. (2004), with minor modifications. The cereulide-producing strain NVH 1257 was used as a positive control. The virulence properties of the various strains were assessed by comparing the killing effect, by injection into the haemocoel and Enzalutamide manufacturer by oral force feeding. The tests were performed with G. mellonella last-instar larvae weighing about 200 mg, reared at the

INRA laboratory by free feeding on pollen and beeswax at 25 °C. The general protocols have been described earlier (Bouillaut et al., 2005). Briefly, both oral and haemocoel infections were performed with exponential growth phase bacteria

(OD600 nm≈1–2). The needed volume (≈1–3 mL) of bacterial Luria–Bertani culture was centrifuged at 20 000 g. for 5 min, and pellets were suspended in phosphate-buffered saline (PBS), pH 7, either alone (for haemocoel) or in Cry1C toxin diluted in PBS (0.3 mg mL−1) Selleck Dorsomorphin for oral infection. A total of 300 μL suspension was prepared for each dose in order to infect 20 larvae with 10 μL of this suspension. For haemocoel infections, tested doses were from 5.0 × 103 to 1.4 × 104 bacteria per larva and oral infection was performed with 3–7 × 106 bacteria per larva. Cry1C toxin is necessary for sacrifice by oral infection because neither the toxin nor bacteria alone confer high mortality (Salamitou et al., 2000); meanwhile, the exact role of the synergistic effect of Cry1C toxin is not yet elucidated. Bacterial suspensions used for infection

experiments were quantified by plate counting for every experiment, as confirmation of estimated dose from measurements of OD600 nm before infection. Tests were repeated at least three times. Control larvae were injected with PBS, pH 7.4, or PBS and Cry1C for oral infection. Infected larvae were kept at 15 and 37 °C [five larvae per Petri-dish (5 cm diameter) without food] and mortality was recorded at 24, 48, 66, 96 and 120 h postinfection. Mortality Calpain analyses comparing temperature, time, strains and route of infection were carried out using regression analysis. The dataset consisted of 505 observations from two species and seven strains (four B. weihenstephanensis and three B. cereus strains). Linear regression was performed with mortality as the response variable and categorical factors: temperature (low=15 °C, high=37 °C), species (B. cereus, B. weihenstephanensis), hours after infection (numerical) and infection route (haemocoel=haemocoel injection, oral=oral force feeding) as predictor variables. To account for the inherent time aspect of mortality, two interaction terms were added to model interconnectivity between hours after infection and both infection route and temperature.

, 2006; Hoogendam et al., 2010; Ziemann et al., 2008 for review). The theta-burst stimulation (TBS) protocol has been proposed as a putative measure of synaptic plasticity (Huang et al., 2005). When applied over the motor cortex, and depending on the stimulation parameters, TBS can induce a transient suppression of corticospinal excitability

(following continuous TBS; cTBS), or an enhancement (following intermittent TBS; iTBS). Suppression of corticospinal excitability by cTBS and its this website enhancement by iTBS appear to be mediated by cortical processes (Di Lazzaro et al., 2011), are considered indices of long-term depression (LTD)- and long-term potentiation (LTP)-like mechanisms (Huang et al., 2005; Huerta & Volpe, 2009), and have been shown to involve GABAergic and glutamatergic NMDA receptor pathways respectively (Huang et al., 2007; Stagg et al., 2009). Here we used single-pulse TMS to assess corticospinal excitability in 20 individuals with Asperger’s syndrome (AS) and 20 age-, gender- and IQ-matched neurotypical controls before and after cTBS and iTBS. We hypothesised that in individuals with AS the effects of cTBS and iTBS upon TMS-induced motor evoked potentials (MEPs) would be significantly enhanced, possibly reflecting a human correlate of the alterations in LTD and LTP mechanisms found in animal models of ASD (Rinaldi et al., 2007; Bassell & Warren, 2008). Following the results

of our first experiment, in order to evaluate the reliability of this TMS measure and its diagnostic Thymidylate synthase potential

GW-572016 we evaluated a separate cohort of 15 individuals with AS and 15 matched controls participants with the same cTBS protocol. We studied two cohorts of participants with AS and matching neurotypical controls. Data from cohort one was collected in Boston, Massachusetts, and was composed of 20 individuals with AS [16 male (M), four female (F); age 18–64 (mean ± SD, 34.3 ± 16.4) years; mean ± SD IQ, 118.2 ± 17.3)] and 20 age-, gender- and full-scale IQ-matched typically developing (TD) individuals (16 M, four F; mean age, 34.9 ± 16.2 years; mean IQ, 112.0 ± 13.0). All participants in cohort one completed the cTBS protocol. A subset of these individuals (nine with AS and nine of their matched TD participants) also underwent the iTBS protocol (AS: seven M, two F; mean age 40.7 ± 18.02 years; mean IQ, 117.2 ± 21.8; TD: eight M, two F; mean age, 41.3 ± 17.4 years; mean IQ, 111.5 ± 12.92). For those who participated in both the cTBS and iTBS protocols, the two sessions were separated by at least 1 week. Not all participants consented to come back for the iTBS session. Data from the second cohort was collected in Barcelona, Spain, and was composed of 15 individuals with AS [(14 M, one F; mean age, 42.4 ± 7.36 years; mean IQ, 110.4 ± 18.75) and 15 age-, gender- and IQ-matched TD individuals (14 M, one F; mean age, 42.4.1 ± 7.36 years; mean IQ, 115.