Adult neurogenesis is a process of continually adding new neurons to specific regions of the brain throughout life of many vertebrate species, including humans.

The olfactory bulb (OB) is one of the best studied brain structures that receive daily supplies of new neurons. Specific types of interneurons, namely granule and periglomerular cells, are produced by rapidly dividing neural precursors called neuroblasts in the rostral migratory stream (RMS), a rostral extension of the subventricular zone (SVZ) of the lateral ventricle (Zhao et al., 2008). Neuroblasts in the RMS maintain their ability to proliferate, but once they reach the OB, they differentiate into interneurons. Over 30 000 neuroblasts are found to migrate tangentially this website along the mouse RMS on a daily basis (Lois & Alvarez-Buylla, 1994). Neurogenesis in the RMS is important for the structural integrity of the OB and has selleck chemicals llc been functionally implicated in odor memory formation and odor discrimination in rodents (Imayoshi et al., 2008; Gheusi et al., 2000; Rochefort et al., 2002). There is an emerging picture of the genetic regulation of neural proliferation during OB neurogenesis. For instance, using targeted gene-driven approaches, knockouts of querkopf (Qkf) (Merson et al., 2006), ventral anterior homeobox (Vax1) (Soria

et al., 2004), and the orphan nuclear receptor tailless (Tlx/Nr2e1) (Liu et al., 2008) exhibited significant reduction of neuroblasts in the RMS and resulted in substantially fewer interneurons in the OB compared to the controls. Studies have also shown that neural proliferation in the adult mouse brain is differentially influenced by the genetic background of several mouse strains (Lee et al., 2003; Kempermann & Gage, 2002), leading us to suspect that a considerable portion of this variance is modulated by polymorphisms and their associated genes. The present study aims to identify genetic loci and candidate genes that are responsible for the natural variation in proliferation within the RMS. We have taken a phenotype-driven approach whereby we identified significant

differences in the RMS proliferative capacity between two inbred mouse strains, C57BL/6J and A/J, based upon a quantitative analysis of bromodeoxyuridine (BrdU)-immunoreactive Chlormezanone cells. We also examined cell cycle parameters between the two strains and found no significant differences. We then probed for the genetic basis of variation in RMS proliferative cell number using a series of recombinant inbred (RI) mice derived from the parental A/J and C57BL/6J strains to map quantitative trait loci (QTL) responsible for adult neurogenesis. We found that chromosome 11 harbors a QTL that significantly modulates cell proliferation in the adult RMS but not proliferation in another major site of neurogenesis called the subgranular zone of the dentate gyrus.

5. Is TraB able to promote intergeneric DNA transfer? The capability of the T4SS conjugation system to transfer plasmids between distantly related bacteria, even across kingdoms, is well documented (Bates et al., 1998; Thomas & Nielsen, 2005). Although conjugative transfer of Streptomyces plasmids between different Streptomyces species has been observed (Hopwood & Kieser, 1993), conjugative transfer to other bacteria has not been reported.

Therefore, the relevance of the Streptomyces conjugative DNA transfer system in the dissemination of the Streptomyces reservoir of resistance genes Tanespimycin price is still concealed. We thank the DFG (SFB766) for financial support. “
“The capture of pathogen gene expression signatures directly from the host niche promises to fuel our understanding of the highly complex nature of microbial virulence. However, obtaining and interpreting biological information from infected tissues presents multiple Selleckchem LBH589 experimental and intellectual challenges, from difficulties in extracting pathogen RNA and appropriate choice of experimental design, to interpretation of the resulting infection transcriptome, itself a product of responses to multiple host-derived cues. The recent publication of several host-infecting fungal transcriptomes offers new opportunities to study the commonalities of animal and plant pathogeneses,

which in turn might direct the rational design of new and broader spectrum antifungal agents. Here, we examine the transcriptional basis of modelled Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Ustilago maydis and Magneporthe infections,

placing our analysis of the published findings within the context of the various modelling procedures used, and the relevant pathogen lifestyles, to facilitate the first cross-species comparison of fungal transcription during infectious growth. Significant concordance was identified among infecting transcriptomes of the inhaled fungal pathogens C. neoformans and A. fumigatus. The significance of gene clustering and subtelomeric gene repertoires is also discussed. Smoothened A fractional proportion of known fungal species is pathogenic. What distinguishes these virulent organisms from more than a million benign species is largely unknown; certainly their lifestyles and modes of pathogenesis are as varied as the range of diseases they cause. Despite this variance, commonalities at the molecular level are often found. Some regulatory pathways, for example nutrient acquisition, pH adaptation and morphogenetic reprogramming, are widely relevant to virulence in multiple species and hosts. However, neither aligned nor comparative transcriptional studies of disease-initiating fungi have been reported.

The majority of axonal mitochondria were stationary for 3 h at both developmental stages, with a small number of appearance (red arrowheads) and disappearance (white arrowheads) events. The mitochondrial population identified at t = 0 min Quizartinib supplier progressively changed their positions with time. The fraction of mitochondria that remained at their initial positions was calculated as a position survival rate

P(t) (see ‘Materials and methods’). To examine the relationship between the proximity to presynaptic sites and mitochondrial dynamics, P(t) was measured from mitochondria near presynaptic sites (synaptic) and also away from presynaptic sites (non-synaptic; Fig. 3D and E). Because mitochondria found at t = 0 min included both stationary and mobile mitochondria, Δ(P(0) − P(180)) was not

an appropriate estimate of mitochondria that started to move during the 180 min observation period. Selleck DAPT Instead, we used Δ(P(30) − P(180)) as an index of the transition from stationary to mobile state (Fig. 3G and H). Using this index, we found that synaptic mitochondria were less likely to restart translocation than non-synaptic mitochondria at both developmental stages (2 weeks, t14 = 4.32, P < 0.001; 3 weeks, t12 = 3.57, P = 0.004; unpaired t-test; Fig. 3H). Both synaptic and non-synaptic mitochondria were less likely to transit to mobile state at 3 weeks than at 2 weeks (all, t13 = 9.65, P < 0.001; synaptic, t13 = 8.05, P < 0.001; non-synaptic, t13 = 4.89, P < 0.001; unpaired t-test; Fig. 3H). The treatment of neurons at 20 DIV with the sodium channel blocker TTX increased the transition probability to mobile state (3 weeks + TTX, 3297 mitochondria from n = 7 experiments; Non-specific serine/threonine protein kinase all, t12 = 4.72, P < 0.001; unpaired t-test; Fig. 3C,E,F and H). This effect was present in both synaptic and non-synaptic mitochondria (synaptic, t12 = 3.95, P = 0.002; non-synaptic, t12 = 3.88, P = 0.002; unpaired t-test; Fig. 3H). These results suggest that neuronal maturation, proximity

to synaptic sites and neuronal activity affect the stability of stationary mitochondria in the axon. We estimated the fraction of mobile mitochondria at t = 0 min [mobile fraction; calculated from P(t) at t = 0, 30 and 60 min; see Eqn (3) in 'Materials and methods'] (Fig. 3G). The mobile fraction at 3 weeks was smaller than at 2 weeks (t13 = 4.98, P < 0.001; unpaired t-test; Fig. 3I) and at 3 weeks with TTX (t12 = 3.82, P = 0.002; unpaired t-test; Fig. 3I). These results suggest that the ratio of mobile to stationary mitochondria in the axon was dependent on neuronal maturation and activity. In time-lapse imaging over 3 h, the majority of axonal mitochondria imaged at the initial time point remained stationary throughout the experiments (Fig. 3D–F), suggesting that the duration of stationary state is usually longer than several hours.

In this study, we attempted to investigate the potency of allicin against C. albicans, the predominant fungal species isolated from human infections. Allicin alone could exhibit antifungal activity, and when used in synergy with antimicrobial agents, it increased the efficacy of the therapeutic agents (Aala et al., 2010; Khodavandi et al., 2010). For example, combination of allicin

with amphotericin B and fluconazole has been demonstrated to have a significant synergistic effect in a mouse model of systemic candidiasis (An et al., 2009; Guo et al., 2010). Garlic and some of its derivatives destroy the Candida cell membrane integrity (Low click here et al., 2008), inhibit growth (Lemar et al., 2002) and produce oxidative stress (Lemar et al., 2005) in C. albicans. Most of these abilities are related to an SH-modifying potential, because the activated disulfide bond of allicin has an effect on thiol-containing www.selleckchem.com/products/ly2157299.html compounds such as some proteins; however, the main targets of allicin on Candida are not well understood. It has been demonstrated that the antifungal activity

of allicin in vivo may be related to some secondary metabolites such as ajoene, diallyl trisulfide and diallyl disulfide, because the chemical structure of allicin is too unstable and converts to these secondary products immediately (Miron et al., 2004). Nonetheless, little is known about the potential in vivo activity of allicin against Candida. In this study, we used fluconazole as the standard anticandidal drug for comparison against allicin. The MICs of allicin Tryptophan synthase and fluconazole against C. albicans fell within the ranges 0.05–12 and 0.25–16 μg mL−1, respectively (Table 1), which is similar to findings from previous reports (Ankri & Mirelman, 1999; Khodavandi et al., 2010). All of the samples were sensitive to fluconazole and drug resistance was not seen. The time–kill study demonstrated a significant inhibition of Candida growth comparing untreated controls against those treated with allicin

and fluconazole, using inoculum sizes of 1 × 106 Candida cells mL−1 (P<0.05) and 1 × 104 Candida cells mL−1 (P<0.001) after 2- and 4-h incubation, respectively. This demonstrates that allicin decreased the growth of C. albicans almost as efficiently as fluconazole (P>0.05) for both inoculum sizes of Candida, demonstrating a comparable ability to inhibit the growth of the yeast cells (Fig. 1). The presence of pits on the cell surface and cellular collapse with high concentrations of allicin indicates that the cell membrane could be one of the targets of allicin in Candida (Lemar et al., 2002), whereas fluconazole in high concentrations can destroy the Candida cell entirely (Fig. 2).

Where more than one

codon is used for an amino acid, codons with A or T in the third position are used more than twice as often as those with G or C. There is a significant bias toward A and T, which compose 75.5% of this genome. A significant proportion of the T. cingulata genome is made up of the cox1 gene that is punctuated by large type I introns. Type I introns are usually characterized by the presence of long ORFs encoding endonucleases that are involved in intron mobility and self-splicing. The endonucleases, often referred to as homing endonucleases, have rare recognition sites and cleave the target gene, which activates the cell’s DNA repair mechanism. This leads to precise insertion of the intron www.selleckchem.com/products/Deforolimus.html into the target gene (Lang et al., 2007). All of the type I introns in the T. cingulata

mitochondrial genome have an ORF with either a LAGLIDADG or a GIY-YIG endonuclease-like sequence. These endonucleases could be responsible for intron homing, whereby introns move into previously intronless genes, a mechanism that could account for the large differences in the size of the mitochondrial genomes that are unrelated to the gene content. The variability in the size of cox1 is apparent and can be directly attributed to the number of introns in the gene (Fig. 2, Table 2). The gene structure and content of Buparlisib the T. cingulata mitochondrial genome is very similar to the genomes of the recently published genomes of P. ostreatus and M. perniciosa. The same subset of genes is also seen in the other basidiomycetes we used in this study and the ascomycete Aspergillus niger (Juhasz et al., 2008), with one or more minor changes such as the apparent absence of rps3 in A. niger (Table 2), although this gene is usually present in other ascomycetes. The DNA and RNA polymerases reported in the mitochondrial genomes of P. ostreatus and

M. perniciosa are thought to be from integrated plasmids (Formighieri et al., 2008; Wang et al., 2008), a feature absent in the T. cingulata mitochondrial Lck genome. The phylogeny of Trametes species and related genera has proven difficult using morphological characteristics (Ko & Jung, 1999) and rDNA studies (Matheny et al., 2007). The number of Trametes species is unknown and ranges from a conservative 50 in the Catalogue of Life (Bisby et al., 2009) to 335 in the Index Fungorum database (http://www.indexfungorum.org). The polypore clade includes many wood-degrading species that are ecologically and industrially important including the widely studied Phanerochaete chrysosporium (Tien & Kirk, 1983; Wariishi et al., 1991; Vanden Wymelenberg et al., 2006). The mitochondrial genome sequence of T. cingulata provides another tool for evolutionary biologists to clarify the evolutionary relationships among this group.

Some members of this family have been studied in detail, and their role as PAMPs is emerging (Wilson et al., 2002; Djonović et al., 2006, 2007; Seidl et al., 2006; Jeong et al., 2007; Vargas et al., 2008; Yang et al., 2009; Zaparoli et al., 2009), while others, instead, are allergenic in humans (Pan & Cole, 1995; Kurup et al., 2002). However, not much work has been aimed to study the regulation of the genes encoding

cerato-platanins and to highlight their primary role in fungal life. A clue to address this question can be provided by the recently published 3D structure of CP, which revealed that the protein has a double-ψβ-barrel fold similar to that occurring in endoglucanases, in the plant-defence protein barwin and in domain I of expansins (de Oliveira et al., Fulvestrant manufacturer 2011). As CP lacks lytic activity and is located in the fungal cell wall, the authors suggested that its similarity to expansins RO4929097 might indicate a role in the remodelling and enlargement of the cell wall. In the present work, we investigated the regulation of cp during the in vitro growth of C. platani exposed to many potential abiotic and biotic stresses. The promoter region of cp was also isolated and studied. Ceratocystis platani Cf AF 100, Trichoderma harzianum T22 and Trichoderma atroviride P1 were used in previous

studies (Pazzagli et al., 1999; Tucci et al., 2011). Solid or liquid cultures of C. platani were prepared with potato dextrose agar (PDA) or broth (PDB) (Difco, Detroit, MI), respectively. An autoclaved cellophane disc was placed on the surface of the solid cultures. For the establishment of fungal cultures, conidia were obtained as described

in Bernardi et al. (2011) and inoculations were performed with about 6 × 104 conidia. Ceratocystis platani was exposed to the following stresses: high and low temperature, ionic and nonionic osmotic stress, matric stress, oxidative stress, addition to the culture medium of sawdust from different sources or of the plane tree phytoalexin umbelliferone, and co-culture with mycoparasitic fungi. Still or shake liquid cultures were also prepared. Unless specified otherwise, cultures were grown on PDA or GPX6 PDB for 3 days in the dark at 25 °C. To test the effect of temperature, C. platani was grown at 15 or 32 °C for 3 days on PDA. The influence of water potential was assessed by adding to PDA the ionic solute NaCl (Lang, 1967), the nonionic solute glycerol (osmotic stress) (Dallyn & Fox, 1980) or PEG 8000 (matric stress) (Steuter et al., 1981). Theoretical water potentials of −1.5 MPa with NaCl and glycerol, or −5.5 MPa with PEG 8000 were obtained (Michel & Kaufmann, 1973). Sawdust-agar media were prepared with 15 g L−1 of agar (Sigma-Aldrich, St Louis, MO) and 100 g L−1 of sawdust from susceptible P. acerifolia, from the resistant P. acerifolia clone ‘Vallis clausa’ (Vigouroux & Olivier, 2004) and from the nonhost plant Ulmus spp. Co-cultures of C. platani with the mycoparasitic fungi T. harzianum and T.

Some members of this family have been studied in detail, and their role as PAMPs is emerging (Wilson et al., 2002; Djonović et al., 2006, 2007; Seidl et al., 2006; Jeong et al., 2007; Vargas et al., 2008; Yang et al., 2009; Zaparoli et al., 2009), while others, instead, are allergenic in humans (Pan & Cole, 1995; Kurup et al., 2002). However, not much work has been aimed to study the regulation of the genes encoding

cerato-platanins and to highlight their primary role in fungal life. A clue to address this question can be provided by the recently published 3D structure of CP, which revealed that the protein has a double-ψβ-barrel fold similar to that occurring in endoglucanases, in the plant-defence protein barwin and in domain I of expansins (de Oliveira et al., Barasertib manufacturer 2011). As CP lacks lytic activity and is located in the fungal cell wall, the authors suggested that its similarity to expansins Trichostatin A ic50 might indicate a role in the remodelling and enlargement of the cell wall. In the present work, we investigated the regulation of cp during the in vitro growth of C. platani exposed to many potential abiotic and biotic stresses. The promoter region of cp was also isolated and studied. Ceratocystis platani Cf AF 100, Trichoderma harzianum T22 and Trichoderma atroviride P1 were used in previous

studies (Pazzagli et al., 1999; Tucci et al., 2011). Solid or liquid cultures of C. platani were prepared with potato dextrose agar (PDA) or broth (PDB) (Difco, Detroit, MI), respectively. An autoclaved cellophane disc was placed on the surface of the solid cultures. For the establishment of fungal cultures, conidia were obtained as described

in Bernardi et al. (2011) and inoculations were performed with about 6 × 104 conidia. Ceratocystis platani was exposed to the following stresses: high and low temperature, ionic and nonionic osmotic stress, matric stress, oxidative stress, addition to the culture medium of sawdust from different sources or of the plane tree phytoalexin umbelliferone, and co-culture with mycoparasitic fungi. Still or shake liquid cultures were also prepared. Unless specified otherwise, cultures were grown on PDA or ifenprodil PDB for 3 days in the dark at 25 °C. To test the effect of temperature, C. platani was grown at 15 or 32 °C for 3 days on PDA. The influence of water potential was assessed by adding to PDA the ionic solute NaCl (Lang, 1967), the nonionic solute glycerol (osmotic stress) (Dallyn & Fox, 1980) or PEG 8000 (matric stress) (Steuter et al., 1981). Theoretical water potentials of −1.5 MPa with NaCl and glycerol, or −5.5 MPa with PEG 8000 were obtained (Michel & Kaufmann, 1973). Sawdust-agar media were prepared with 15 g L−1 of agar (Sigma-Aldrich, St Louis, MO) and 100 g L−1 of sawdust from susceptible P. acerifolia, from the resistant P. acerifolia clone ‘Vallis clausa’ (Vigouroux & Olivier, 2004) and from the nonhost plant Ulmus spp. Co-cultures of C. platani with the mycoparasitic fungi T. harzianum and T.

Relevant quotes supporting the framework could then be displayed. Identifiers for individual patients followed each quote and were given as the patient number, the paragraph number in the transcript, sex, age and TABS scores represented as the ABS and NABS. A framework analysis provided

a robust technique for the analysis of qualitative data as it facilitates rigorous and transparent data management.[38,39] This analysis was completed in parallel with recruitment until data saturation was determined. The rationale for choosing TABS has already been discussed. The TABS questionnaire was validated in another chronic-condition cohort, chronic obstructive pulmonary disease, and was shown to be a reliable score for measuring adherence in a population with chronic disease.[35] Twenty patients (15 male, 5 female) met the study’s inclusion/exclusion criteria and consented GSK3235025 to take part

– there were no refusals to participate in this research. This sample size achieved data saturation: this was the stage at which no new themes were generated. Eight additional interviews were conducted with no new themes emerging to define data saturation. Data was wide ranging with regard to age, height and weight of the participants. Only five patients (25%) were found to be of a healthy body mass index (20–25 kg/m2); seven (35%) were clinically obese with a body mass index of more than 30 kg/m2. Male patients comprised 75% of the cohort. The majority of selleck compound the patients were employed (60%) (Tables 2 and 3). Patients were colour-coded

according to their TABS scores (Figure 1). Six patients (30%) (patient numbers 001, 004, 005, 014, 017 Sclareol and 019) were found to have low ABS (<19/20) (Figure 2). Of those six, only two (patients 014 and 019) were also found to have high NABS (>8/20). The median ABS for this cohort was 19/20, whereas the median NABS was 7/20; both scores were suggestive of good adherence within the cohort (Table 4). The high value of the median ABS and low value of the median NABS indicated a desire in most patients to take their medication. The value of Pearson’s r exhibited no correlation between the NABS and the ABS. The clustering of patients in the box on the top left of Figure 2 indicated that 70% of patients scored high for ABS and low for NABS, which is suggestive of good adherence. The full thematic analysis can be seen in Figure 3. The main themes that relate to medication adherence can be found in Figure 4. Most of the themes were positively associated with increased medication adherence. However, the role of adverse drug reactions (ADRs) had a significant negative effect, while the community pharmacist role was considered non-significant by the majority of patients. In general, the cohort (especially those with low ABS and high NABS) had a good knowledge of commonly experienced ADRs due to medication they were prescribed.

Figure 1 shows the distribution of CHIKV and DENV imported cases by months, from 2008 to 2011 in Italy. In 2010, the number of DENV cases reached the peak (during August), and during the study period the trend increased (p < 0.0001),

while the number of CHIKV imported infections decreased (p < 0.0001). Considering that in Italy the period of activity for A albopictus is conventionally settled from June 15 to November 15 (10), according to temperature and humidity conditions, 5-Fluoracil 47.6 and 60.6% of CHIK and DENV imported cases, respectively, were reported in this period. The incidence of CHIKV and DENV per 100,000 by study year is reported in Table 1. When we attempt to estimate the number of imported infections to Italian municipalities, in order to define the GDC-0449 mouse degree of underreporting, our results show that during the study period

the number of estimated cases was higher than the number of CHIKV and DENV cases reported in Italy (Table 1). In particular, depending on the study year, an increase of 48- to 276-fold and of 10- to 87-fold was observed in CHIKV and DENV estimated exposed travelers arriving in Italy, respectively, compared to notified infections in Italy. From January 2008 to October 2011 a total of 130 cases of DENV/CHIKV cases were reported in travelers returning to Italy. During the study period the observed trend decreased for CHIKV while it increased for DENV, according with the increasing trend of DENV described worldwide.[9] In our study, 42.8% of CHIKV cases were imported from Indian Ocean islands (Mauritius, Maldives, Bali, and Sri Lanka), whereas for DENV 44.4% of imported cases reported to have visited Asia within the incubation period. The estimated number of exposed travelers to CHIKV and DENV arriving in Italy was higher compared to notified cases, suggesting a possible risk of introduction and autochthonous transmission in Italian areas where the competent vector is present.[13] Nevertheless, Arachidonate 15-lipoxygenase when considering the risk of introduction of imported cases and of the subsequent autochthonous

transmission two factors should be taken into account: the presence and the period of activity of the competent vector. Italy is an Aedes aegypti-free country while A albopictus is present is almost all Italian regions since the 1990s.[10] Aedes albopictus is one of the competent vectors for CHIKV, however, it is widely recognized also as a possible vector for DENV.[14, 15] The activity period for A albopictus in Italy conventionally starts on June 15 and ends on November 15[10] and therefore the risk of autochthonous transmission after the importation of an infected individual is higher during this period and lower during the rest of the year; in fact the risk is not only proportional to the number of imported cases.

The functionalibility of these genes has been experimentally demonstrated for pNL1, as this plasmid has been conjugatively transferred among different sphingomonads. In contrast, Selleckchem R788 no experimental evidence for a conjugative transfer of plasmid pCAR3 could be demonstrated (Romine et al., 1999; Shintani et al., 2007). Also plasmid pSWIT02 (which also belongs to the ‘Mega-RepAC-group’)

carries genes coding for conjugative functions, but these genes had been annotated as vir genes. The annotated sequence of plasmid pSWIT02 suggested that this vir-operon consisted of the genes virB1–virB11 (NCBI registry numbers ABQ71617–ABQ71626). The organization of these genes is identical to the organization of the homologous genes on the Ti plasmid from A. tumefaciens and the Tra-systems of broad-host-range plasmids belonging to the IncN and IncW incompatibility groups. In addition, also the gene encoding the ‘coupling protein’ VirD4 could be identified in direct neighbourhood to the vir genes. Thus, on plasmid pSWIT02, all genes are present which allow the conjugative

transfer of broad-host-range plasmids. The absence/presence of certain genes and also the organization of conserved genes suggested that the conjugative system of plasmid pSWIT02 is different to that of plasmids pNL1 and pCAR3. Thus, the conjugative systems from plasmids pNL1 and pCAR3 are closer related to the system present on the F-plasmid, and the transfer functions encoded by plasmid

pSWIT02 are closer related to the Ti plasmid or the IncN/IncW plasmids. The plasmids belonging to the ‘Mega-Rep3-group’ (pCHQ1, pSLCP, pSPHCH01, pISP0, pLA1) all seem to carry a find more full set of conjugative genes. The respective gene clusters had been annotated for plasmids pISP0, pSLPG, pSPHCH01 as vir genes, and all required genes (virB1–virB11, virD2 and virD4 with some exceptions regarding virB7) have been annotated. In contrast, on plasmids pCHQ1 and pLA1, the isofunctional genes had been annotated as trb or tra genes. Furthermore, the respective gene clusters from pCHQ1 and pLA1 also included traW, traU/trbC, traN, traF, traH, traG, which are specifically found in plasmids related to the F-plasmid and which do not have homologous genes in the vir-operon Methane monooxygenase (Lawley et al., 2004). Significant differences in the conjugative systems are also observed for the plasmids belonging to the ‘Mega-RPA-group’. Thus, plasmid pISP1 carries a large cluster of tra genes (traL, traE, traK, traB, traC, traW, traU, traN, traF, traH, traG, traI, traH; NCBI registry numbers YP_007618159–YP_0076181751617). These tra genes show the same organization as those found on plasmids pNL1 and pCAR3 (and also the F-plasmid). In contrast, the two other plasmids from this group (pNL2 and Mpl) do not code for ‘conjugative genes’. It is conspicuous that these plasmids are the largest sequenced plasmids from sphingomonads (pNL2 = 487 kb; Mpl = 1160 kb).