Trials containing voluntary electromyographic activity were excluded from further analysis. The effect of the attention locus (baseline, attention to hand, visual attention) on MEP amplitudes (series 1) was examined using repeated-measures anova with factors of Condition and ISI. For SICI and ICF, separate anova s with Condition and ISI as a repeat factor were analysed. More detailed information is given

in the Results. If appropriate, correction for multiple comparisons was used. For all experiments significance was set at P < 0.05. The behavioural results showed similar values for the visual and the attention-to-hand tasks (correct answers: visual attention 87.77 ± 6.5%; Ipilimumab datasheet attention to hand, cutaneous stimulation above

the FDI muscle area 92.48 ± 1.7%; attention to hand, cutaneous stimulation above ADM area 93.32 ± 2.0%), indicating similar difficulty Selleck Selisistat for the two tasks and suggestive of similar levels of attentional demand. Figure 3(A) shows the MEP amplitude in the three blocks of trials (no attention, attention to hand, visual attention) as the difference between the two attention blocks and the no-attention block. An anova on the MEP amplitudes (no attention, 1.2 ± 0.1 mV; attention to hand, 0.87 ± 0.3 mV; visual attention, 1.87 ± 0.2 mV) revealed a significant effect of Condition (F2,22 = 23.67, P < 0.001). Post-hoc analysis confirmed that visual attention significantly increased the MEP size compared with baseline

(P < 0.001) and compared with attention to the hand (P < 0.005). Attention to the hand (at this location of the stimulus, i.e. the dorsum manum) did not significantly change the MEP size compared with baseline, although there was a trend (P = 0.06) towards suppression (Fig. 3). There was no difference in any condition between SICI measured at an ISI of 2 or 3 ms. Figure 3(B) shows the mean SICI in the three conditions as the difference between the two attention tasks and the baseline task, Figure 4 shows corresponding Baricitinib absolute values. Two-way anova on the amount of SICI (in % unconditioned test MEP) (no attention: 2 ms, 54.1 ± 8.6; 3 ms, 62.9 ± 13.8; attention to hand: 2 ms, 62.1 ± 15.2; 3 ms, 59.5 ± 12.4; visual attention: 2 ms, 76.5 ± 14.3; 3 ms, 78.1 ± 12.4) revealed a significant main effect of Condition (F2,22 = 4.24, P < 0.05), no significant effect of ISI (F1,11 = 0.06, P > 0.5) and no significant interaction of both (F2,22 = 0.43, P > 0.5). Post-hoc analysis showed that SICI was less effective during visual attention both when compared with the baseline task (P < 0.05) and the attention-to-hand task (P < 0.05). There was no difference in the amounts of ICF (in % unconditioned test MEP) at the two ISIs (no attention: 12 ms, 167.5 ± 23.5; 15 ms, 163.2 ± 20.8; attention to hand: 12 ms, 149.0 ± 14.1; 15 ms, 146.2 ± 18.4; visual attention: 12 ms, 159.1 ± 24.1; 15 ms, 137.5 ± 22.1).

Little variation was observed during the replicate experiments. The standard deviation for

the antirestriction results is 25% or less. Data on antirestriction activity of the recombinant plasmid pKLH53.1, containing Tn5053, are given in Table 2. The factor of restriction relief (R) is about 100. We suspected that the nucleotide sequence of the mercury-resistance transposon Tn5053 contains a fragment encoding an antirestriction protein. We used both insertion and deletion mutants of Tn5053 for all transposition genes (tni) as well as plasmid constructs containing various fragments of the Tn5053 DNA, while searching for the locus responsible for the antirestriction activity (Fig. 1). The results of searches Staurosporine for the determinant of antirestriction activity PLX3397 in vivo within Tn5053 are shown in Table 2. It is evident that neither insertion (plasmids pKLH53.1tniA, pKLH53.1tniB2) or deletion (plasmids pKLH53.1tniQ2 and pKLH53.1tniQ1) mutations of the tni genes have any effect on antirestriction activity: about 100-fold decrease in EcoKI restriction level is preserved. Deletion of the major part of the mer operon (plasmid

pTLΔHindIII) completely removed the effect of antirestriction (Table 2). We assumed that the location of the gene coding for an antirestriction protein is within the mer operon. However, the recombinant plasmids pTLHindIII-ClaI and pTL2.5 with fragments HindIII-ClaI and HindIII from the mer operon (without the merR gene) in vector pUC19 show no antirestriction effect (Table 2). No antirestriction effect was also observed for the hybrid plasmid pKLH53.2, containing all the genes tni Tn5053 under its own promoter (in vector pACYC184; Fig. 1, Table 2). A paradox appeared: the mer operon together with the transposition genes (tni) of Tn5053 produce an antirestriction effect, while the plasmids with separately cloned mer operon or tni genes show no antirestriction effect.

We considered that the nucleotide sequence coding for the ORF with antirestriction activity is located within the region of the tni genes, but orientated in reverse to the direction of transcription of the tni genes. Consequently, the coding strand for this ORF is the same as for the mer operon. If so, transcription of this DNA fragment passes 3-mercaptopyruvate sulfurtransferase from the side of the mer operon. We analysed the DNA sequence from the region of the tni genes of Tn5053 in reverse direction, and found several orfs. Of main interest was orf-5, encoding a negatively charged protein with a motif close to the antirestriction motif of the proteins Ard (Fig. 2). The protein ORF-5 contains 147 amino acid residues of summary charge −1. It is encoded by orf-5 at positions 7511–7954 on the complementary strand of the tniA gene (positions numbered according to the nucleotide sequence of Tn5053, deposited in DBJ/EMBL/GenBank under accession number L40585).

73 m2 (median per year 6; IQR 3–10) was different from that in patients with normal eGFR (median per year 6; IQR 2–10; Wilcoxon P-value=0.12). The most frequently used NRTI pairs were tenofovir/emtricitabine (24%) and zidovudine/lamivudine (22%); 48% of the person-years of follow-up Tanespimycin cell line (PYFU) was spent on an NNRTI-containing regimen, 28%

on a ritonavir-boosted PI-containing regimen (not including indinavir) and 11% on a single-PI-containing regimen (not including indinavir) (Table 3). Over 1412 person years of follow-up (PYFU) while patients were receiving at least one antiviral drug, we observed 96 events (confirmed eGFR decrease ≥20% from pre-cART levels), resulting in a crude incidence rate of 6.8 per 100 PYFU (95% CI 5.5–8.2). Factors independently associated with a ≥20% decrease in eGFR were female gender [relative risk (RR)

2.25 vs. male; 95% CI 1.32–3.84] and older age (RR 1.41 per 10 years older; 95% CI 1.11–1.79); compared with patients treated with zidovudine/lamivudine, those currently receiving tenofovir/emtricitabine (RR 4.78; 95% CI 2.19–10.43), tenofovir/lamivudine (RR 4.20; 95% CI 1.95–9.02) or didanosine/emtricitabine (RR 11.88; 95% CI 2.27–62.18) appeared to be at increased risk of a decrease in eGFR. Similarly, patients on a PI-containing cART (even after exclusion of indinavir) were at increased risk compared with those receiving NNRTI-containing ART (RR 3.18; 95% CI 1.62–6.23 if on an old, single-PI regimen and RR 2.15; 95% CI 1.25–3.70 if on a ritonavir-boosted regimen),

Fulvestrant supplier although, interestingly, patients receiving NRTIs alone were those at the highest risk (RR 9.39; 95% CI 1.79–49.42; Table 4). After controlling for the most recent CD4 cell count and viral load (as opposed to the baseline values), results were similar; in addition to the confirmed association with female gender and age, the following RR values were estimated for the comparison of NRTI pairs to zidovudine/lamivudine: tenofovir/emtricitabine, RR 4.86 (95% CI 2.28–10.34); tenofovir/lamivudine, RR 4.64 (95% CI 2.22–9.68), and didanosine/emtricitabine, GBA3 RR 7.68 (95% CI 1.52–38.66); and for the third drug class compared to NNRTIs: RR 4.33 (95% CI 2.24–8.35) for a single PI; RR 2.46 (95% CI 1.48–4.08) for PIs/r, and RR 11.9 (95% CI 2.09–67.48) for NRTIs alone. Results were similar in sensitivity analyses using the alternative cut-offs of 10% and 30% reductions from pre-cART levels (data not shown). In 437 patients who had a value of eGFR >90 mL/min/1.73 m2 at the time of starting cART (68% of the total 644 who started cART), the median eGFR value was 109 mL/min/1.73 m2 (IQR 99–121 mL/min/1.73 m2). In this subset, we observed 104 patients who experienced a decrease in eGFR to a value of <90 mL/min/1.73 m2 over a total of 846 PYFU for a crude incidence rate of 12.3 per 100 PYFU (95% CI 10.2–14.7).

In addition www.selleckchem.com/products/Adrucil(Fluorouracil).html to GlxR, two additional transcriptional regulators, RamB and RamA, are also involved in regulating the expression of aceB and aceA (Gerstmeir et al., 2004; Cramer et al., 2006). However,

in contrast to RamB, which only represses aceB and aceA genes in the presence of glucose, GlxR repressed both genes, regardless of the carbon source. RamA is an activator of aceB and aceA in the presence of acetate (Arndt & Eikmanns, 2008). The involvement of the three regulators GlxR, RamA and RamB or even more regulator(s) in the same aceB–aceA intergenic region would appear to make the regulation of both genes more complex (Cramer et al., 2006). The crp gene from S. coelicolor successfully complemented Protein Tyrosine Kinase inhibitor the glxR mutant of C. glutamicum; thus, the growth defect phenotype was restored to that of the wild type. Derouaux et al. (2004b) suggested that the CRP homologues of the actinomycetes species, including S. coelicolor, C. glutamicum and mycobacterial strains, belong to the same CRP subgroup under the large CRP–FNR superfamily. Interestingly, Derouaux et al. (2004a) also reported that the CRP of S. coelicolor does not play any role in CCR, and yet modulates complex physiological processes such as germination

and morphological development, via a Cya– cAMP–CRP system. Based on the classification of both CRPs under the same CRP subfamily and successful complementation, there is a strong possibility of functional similarities between the two CRP homologues from C. glutamicum and S. coelicolor, even though C. glutamicum does not have any developmental processes, such as morphological differentiation. As in the case of S. coelicolor, the growth defect phenotype of the glxR mutant indicates that GlxR plays an important role in cell viability. Based on physiological and molecular genetic studies, and bioinformatic analyses of the whole genome sequence of C. glutamicum, it would appear that the molecular mechanism of global carbon regulation such as CCR is quite different from that in Gram-negative or low GC Gram-positive bacteria (Moon et al., 2007; Arndt & Eikmanns, 2008; Cha et al., 2010). The first report of CCR in C. glutamicum was related

to glutamate uptake (Krämer & Lambert, 1990; Kronemeyer et al., 1995). However, there is no in vivo experimental evidence that GlxR is involved in the catabolite Thiamet G repression of glutamate uptake. The derepression of pgluA-lacZ in the glxR mutant in the glucose medium suggests that the gluABCD operon is repressed by GlxR. In C. glutamicum, the enzymes involved in gluconate catabolism (gntP and gntK), phosphoenolpyruvate carboxykinase (pck) and alcohol dehydrogenase (adhA), are also subjected to CCR by glucose (Letek et al., 2006; Han et al., 2007; Kohl et al., 2008). The presence of potential GlxR-binding sites (TGTGA-N6-TCACA) in the promoter regions of the genes encoding these enzymes indicates that GlxR is a repressor of these genes.

In addition Regorafenib to GlxR, two additional transcriptional regulators, RamB and RamA, are also involved in regulating the expression of aceB and aceA (Gerstmeir et al., 2004; Cramer et al., 2006). However,

in contrast to RamB, which only represses aceB and aceA genes in the presence of glucose, GlxR repressed both genes, regardless of the carbon source. RamA is an activator of aceB and aceA in the presence of acetate (Arndt & Eikmanns, 2008). The involvement of the three regulators GlxR, RamA and RamB or even more regulator(s) in the same aceB–aceA intergenic region would appear to make the regulation of both genes more complex (Cramer et al., 2006). The crp gene from S. coelicolor successfully complemented Apitolisib in vivo the glxR mutant of C. glutamicum; thus, the growth defect phenotype was restored to that of the wild type. Derouaux et al. (2004b) suggested that the CRP homologues of the actinomycetes species, including S. coelicolor, C. glutamicum and mycobacterial strains, belong to the same CRP subgroup under the large CRP–FNR superfamily. Interestingly, Derouaux et al. (2004a) also reported that the CRP of S. coelicolor does not play any role in CCR, and yet modulates complex physiological processes such as germination

and morphological development, via a Cya– cAMP–CRP system. Based on the classification of both CRPs under the same CRP subfamily and successful complementation, there is a strong possibility of functional similarities between the two CRP homologues from C. glutamicum and S. coelicolor, even though C. glutamicum does not have any developmental processes, such as morphological differentiation. As in the case of S. coelicolor, the growth defect phenotype of the glxR mutant indicates that GlxR plays an important role in cell viability. Based on physiological and molecular genetic studies, and bioinformatic analyses of the whole genome sequence of C. glutamicum, it would appear that the molecular mechanism of global carbon regulation such as CCR is quite different from that in Gram-negative or low GC Gram-positive bacteria (Moon et al., 2007; Arndt & Eikmanns, 2008; Cha et al., 2010). The first report of CCR in C. glutamicum was related

to glutamate uptake (Krämer & Lambert, 1990; Kronemeyer et al., 1995). However, there is no in vivo experimental evidence that GlxR is involved in the catabolite isometheptene repression of glutamate uptake. The derepression of pgluA-lacZ in the glxR mutant in the glucose medium suggests that the gluABCD operon is repressed by GlxR. In C. glutamicum, the enzymes involved in gluconate catabolism (gntP and gntK), phosphoenolpyruvate carboxykinase (pck) and alcohol dehydrogenase (adhA), are also subjected to CCR by glucose (Letek et al., 2006; Han et al., 2007; Kohl et al., 2008). The presence of potential GlxR-binding sites (TGTGA-N6-TCACA) in the promoter regions of the genes encoding these enzymes indicates that GlxR is a repressor of these genes.

Diabetes mellitus was defined by antidiabetic drug use, at least two glucose values of >126 mg/dL or an abnormal glucose tolerance test; hyperlipidaemia was defined by: 1) use of lipid lowering agents or at least two total cholesterol values >240 mg/dl, or 2) at least two low-density lipoprotein (LDL) cholesterol values >160 mg/dl, or 3)

at least two high-density lipoprotein (HDL) cholesterol values <40 mg/dl; alcohol abuse was defined as a history of admission because of alcohol-related conditions or a history of alcohol consumption that compromises daily activities; hepatitis B and C virus (HBV and HCV) infections were defined as the presence of positive confirmation buy Cabozantinib serologies or viral load. Exposure was assessed for the controls and the case at the same point in time relative to baseline (i.e. controls were assigned ‘index dates’ similar to those of the corresponding cases), and within 1 year before the index date. Different laboratory markers were analysed at the index date; for example, the latest recorded viral load and CD4 cell

count selleck chemicals values; the rate of change in CD4 cell counts, defined as the difference in the two latest recorded CD4 cell counts divided by the time elapsed between them, and the area under the CD4 cell count curve during the last year prior to the index date. Additionally, the history of AIDS events prior to the index date was captured in the following variables: having had opportunistic infections ever, years from last AIDS event to index date and incidence of AIDS events since HIV diagnosis to index date (1/person-years of follow-up). Exposure to antiretroviral treatment by the index date was summarized using different variables in order to capture the history of antiretroviral treatments: ever received antiretroviral treatment, on treatment at index date, ever received abacavir during the prior 6 months, time elapsed since treatment initiation (in months), percentage of time off treatment since starting antiretroviral treatment, and maximum period (in months) off

antiretroviral treatment. The patient’s cumulative exposure to specific antiretroviral drugs was defined as: number of months receiving nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), abacavir or stavudine. Adenosine triphosphate Both the retrospective cohort and the current project were approved by corresponding Institutional Review Boards. Four different outcomes were analysed: all SNA cases, cardiovascular events, terminal liver failure or cirrhosis and non-AIDS-defining malignancies. Conditional logistic regression models (univariate and multivariate) were fitted to investigate the relationship between the risk of an SNA event and the recorded factors (PHREG procedure, sas, version 9.1; SAS Institute, Cary, NC, USA). Under the sampling scheme used to select controls, the proportional hazards model has been shown to produce consistent estimates of the relative risks [23,24].

, 2001) in future. Besides the enhanced expression of cold adaptation genes, accumulation of point mutations that enhance the activities of proteins at low temperatures

could be an alternative strategy for adaptation PFT�� to permanently cold environments. Given that hiC6 genes were differentially expressed in the two strains at 20 and 4 °C, we wondered whether the expressed isoforms of HIC6 have different cryoprotective activities. To answer this question, we cloned the encoding regions of NJ7hiC6-3 (NJ7hiC6-4 and -5 encode the same protein) and 259hiC6-1, -3 and -4, and expressed them as fusion proteins with 6His·tag in E. coli. In the fusion proteins, the N-terminal 36-amino acid transit signal of HIC6 (Joh et al., 1995; Honjoh et al., 1995) was deleted. The cryoprotection of LDH was assayed with different concentrations of HIC6 isoforms.

Bovine serum albumin was used as the positive control as in other reports (Honjoh et al., 2000; Griffith et al., 2005). The cyanobacterial RNA-binding protein 1 (Rbp1), which has a very slight protective effect on LDH, was used as the negative control. As seen with CDK inhibitor drugs the LDH residual activities after a freeze–thaw cycle, the cryoprotective activities of all four isoforms of HIC6 showed no differences from each other (Fig. 5). This result suggested that the amino acid substitutions in HIC6 made no or only a very slight contribution to the increased freezing tolerance of the Antarctic strain. HIC6 and HIC12 are two cold-inducible

LEA proteins found in Chlorella, both possessing cryoprotective activities. HIC6 has been shown to enhance the freezing tolerance in transgenic plants (Honjoh et al., 2001). Initially identified in C-27 of C. vulgaris (Joh et al., 1995; Honjoh et al., 1995), their encoding genes were also found Tolmetin in the temperate strain UTEX259 and the Antarctic strain NJ-7 of C. vulgaris (Li et al., 2009). In this study, we identified a tandem array of five hiC6 genes in NJ-7 and a tandem array of four hiC6 genes in UTEX259 and investigated the differential expression of these genes. Unlike hiC6, hiC12 is present as a single gene in the two Chlorella strains (Y. Wang and X. Xu, unpublished). In C-27 and UTEX259, the expression of hiC6 can be detected at very low levels at 20–25 °C but was greatly induced after exposure at 3–4 °C (Joh et al., 1995; Li et al., 2009). In the Antarctic strain NJ-7, however, hiC6 genes can be expressed at a relatively high level even without cold induction, and the expression appeared to be less dependent on temperature. At the other extremity of temperature adaptation, the chilling-sensitive strain C-102 of C. vulgaris has no hiC6 (Joh et al., 1995). The induced expression of hiC6 probably reflects the seasonal changes of temperature in temperate regions. However, in the permanently cold environments of Antarctica the induction of hiC6 genes in response to cold stress might have been unnecessary and, consequently, hiC6 genes in C.

6b). Intriguingly, protected bands included the SMAG repeat labeled as c in Fig. 6b. The same result was obtained in RNA extension experiments, in which bands of elongation extended over SMAG repeat c only (Fig. 6c). We hypothesize that repeats a and

b fold into one large secondary structure, which is cleaved, and this promotes rapid 3′–5′ degradation of upstream 4478 transcripts. The number of predicted SLSs is significantly higher in prokaryotic genomes existing in nature than in random sequences of comparable GC content (Petrillo et al., 2006). This implies that the ability of a variety of sequences to fold into secondary structures is positively selected in prokaryotic genomes and may have functional significance. A fraction of SLSs is represented by REPs, selleck chemicals sequences shown or hypothesized Selleckchem DAPT to serve different functions. REPs are binding sites for the integration host factor, a protein required for site-specific recombination and DNA replication

(Engelhorn et al., 1995). REPs are targets for the DNA gyrase (Espéli & Boccard, 1997), and repeats located between convergent genes may be a privileged target for the enzyme, in order to counteract the excess of positive supercoiling induced in the chromosome by DNA transcription (Moulin et al., 2005). As RNA elements, REPs may enhance the stability of 5′ proximal mRNA segments (Khemici & Carpousis, 2004). Finally, REPs induce innate immune system stimulation via TLR9, and could play a key role in the pathogenesis of Gram-negative septic shock (Magnusson et al., 2007). Tobes & Ramos (2005) established that, for a palindromic sequence to be considered as REP, the following criteria should be met: (a) be extragenic, (b) range in size from 21 to 65 bp and (c) constitute >0.5% of the total intergenic space. SMAGs meet all these criteria, and constitute the largest set of REPs described so far. SMAGs correspond to the repeats identified by Nunvar et

al. (2010). SMAGs can be sorted into five distinct subfamilies, buy Docetaxel and come in different genomic formats. Single units make up only 1/5 of the SMAG family. The remaining elements are organized as dimers or are grouped in tandem arrays of variable lengths. Altogether, SMAGs and intermingled DNA occupy 13% of the overall intergenic space, and make up 1.4% of the total chromosome. SMAG families residing in the environmental R551-3 and SKA14 S. maltophilia strains are comparable in size to the repeat family found in K279a. Yet, the sizes of some subfamilies vary, and K279a is enriched in SMAG-3. Most SMAG-3 are organized as HH dimers that feature conserved spacers, and may thus represent a relatively young sequence family variant. Changes in the abundance and chromosomal distribution may make SMAG-3 sequences suitable for use in accurate genotyping and epidemiological studies. Also, the ∼500 REPs identified in the E. coli MG1655 strain have been sorted into subfamilies.

However, the correlation between clinical check details response and fluconazole MIC has been variable [31,32]. Although fungal susceptibilities should be requested initially, the decision to switch therapy should not be based on the antifungal MIC alone but requires supportive laboratory or clinical markers of an impaired response to therapy (category IV recommendation). Poor prognostic factors are blood culture positivity, low white blood cell in CSF (<20 cells/mL), high CSF cryptococcal antigen (>1:1024), a confused state and a raised intracranial pressure [33]. 2.4.4.1 Induction. • Standard induction therapy of cryptococcal

meningitis is with amphotericin B, usually combined with flucytosine 100 mg/kg/day (category Ib recommendation). Historically, the standard of care for the treatment of cryptococcal meningitis in HIV-seronegative individuals has been amphotericin B deoxycholate (0.7–1 mg/kg/day) combined with flucytosine (100 mg/kg/day) [34,35]. However, the advantages and disadvantages of the addition of flucytosine to amphotericin B deoxycholate Stem Cell Compound Library in the HIV setting should be carefully weighed for each individual patient [36–39]. The addition of flucytosine speeds the rate of sterilization of the CSF [36,39] and reduces the incidence of relapse [40] in patients not receiving HAART. However, flucytosine has been associated with enhanced toxicity in some (though not other) studies and has not been

shown to impact on early or late mortality [14,36]. In addition, most of the benefits of flucytosine have been observed in patients not receiving HAART. When flucytosine is given, it may be prescribed orally or intravenously. Flucytosine is associated with haematological toxicity and daily blood counts are required with monitoring of flucytosine levels. Standard amphotericin

B is associated with renal toxicity, and where possible should be L-gulonolactone oxidase replaced by liposomal amphotericin B as the first choice agent (category III recommendation). In one study (including a small number of HIV-seropositive individuals) 30% of those receiving amphotericin B deoxycholate developed acute renal failure with significant associated mortality [41]. Further research has demonstrated that liposomal amphotericin B (4 mg/kg) without concomitant flucytosine therapy sterilized the CSF faster than standard amphotericin B and was associated with lower nephrotoxicity but not with any survival advantage [42]. On the basis of the lower incidence of nephrotoxicity, many pharmacy departments have stopped stocking amphotericin B deoxycholate and, on the basis of at least equivalent efficacy and lower nephrotoxicity, liposomal amphotericin B (4 mg/kg/day intravenously) is the preferred amphotericin B preparation when available for the treatment of cryptococcal meningitis. Alternative therapies to an amphotericin-based regimen are listed in Table 2.2.

e. FgGFP1 (male) × Z3643 (female)]. Availability of individual MAT

transcript expression profiles in various fungal strains provides clues to the variation in self-fertility among the Fg complex at the level of MAT loci. The differing expression pattern of individual MAT genes in all F. asiaticum strains compared with F. graminearum strains can be attributable to the defect in self-fertility in these strains. Failure to up-regulate MAT1-1-2 and MAT1-1-3, and reduced up-regulation of MAT1-1-1, MAT1-2-1, and MAT1-2-3 during the entire sexual cycle may cause a putative set of genes under the control of these MAT genes to be abnormally or not properly expressed, leading to self-sterility in F. asiaticum. Nevertheless, similarity in expression patterns of MAT1-1-1, MAT1-2-1, ABT-199 and MAT1-2-3 in all F. graminearum and F. asiaticum strains

examined cannot exclude the possibility that the early induction pathway of sexual development controlled by these genes is I-BET-762 cell line not responsible for the self-fertility differences in these Fg complex strains. To test these postulates, a comparison of genome-wide expression profiles using combinations of wild-type F. graminearum and F. asiaticum strains and their MAT-deleted strains would be necessary. To date, several approaches have been used to identify the target genes of MAT loci in several filamentous fungi (Qi et al., 2006; Hallen et al., 2007; Keszthelyi et al., 2007; Klix et al., 2010; Bidard et al., 2011). For example, comparing transcription profiles during sexual development, or between a fertile fungal strain and its transgenic strain lacking a MAT gene (e.g. in P. anserina, F. verticillioides, Ribonuclease T1 and S. macrospora), provided several sets of genes

differentially regulated in the mutant strains. However, the genes directly regulated by individual MAT genes remain undetermined. The developmental up-regulation pattern and transcript abundance in two sets of MAT genes (a set of MAT1-1-1, MAT1-2-1, and MAT1-2-3, and the other of MAT1-1-2 and MAT1-1-3) provide new insight into functional role(s) of individual MAT genes for sexual development in F. graminearum, which are also supported by the phenotypic changes in the gene deletion strains. The former set of MAT genes can be considered key regulators of sexual development, particularly required for the early sexual stage for the following reasons. First, the gene expressions peaked at 2 dai, and the transcripts were more (at least 65-fold higher) abundant than those of the latter set of MAT genes at 2 dai. Secondly, the absence of perithecium-like structures in ΔMAT1-2-1 strain or the presence of barren perithecia in the ΔMAT1-1-1 strain, which were even smaller than those in the ΔMAT1-1-2 and ΔMAT1-2-3 strains, on carrot agar could be attributable to blockage of early events such as internuclear recognition, formation of ascogenous hyphae, and nuclear fusion.