| 1. |
- Guy, Lionel, et al.
(författare)
-
A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen Bartonella
- 2013
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:3, s. e1003393-
-
Tidskriftsartikel (refereegranskat)abstract
- Gene transfer agents (GTAs) randomly transfer short fragments of a bacterial genome. A novel putative GTA was recently discovered in the mouse-infecting bacterium Bartonella grahamii. Although GTAs are widespread in phylogenetically diverse bacteria, their role in evolution is largely unknown. Here, we present a comparative analysis of 16 Bartonella genomes ranging from 1.4 to 2.6 Mb in size, including six novel genomes from Bartonella isolated from a cow, two moose, two dogs, and a kangaroo. A phylogenetic tree inferred from 428 orthologous core genes indicates that the deadly human pathogen B. bacilliformis is related to the ruminant-adapted clade, rather than being the earliest diverging species in the genus as previously thought. A gene flux analysis identified 12 genes for a GTA and a phage-derived origin of replication as the most conserved innovations. These are located in a region of a few hundred kb that also contains 8 insertions of gene clusters for type III, IV, and V secretion systems, and genes for putatively secreted molecules such as cholera-like toxins. The phylogenies indicate a recent transfer of seven genes in the virB gene cluster for a type IV secretion system from a catadapted B. henselae to a dog-adapted B. vinsonii strain. We show that the B. henselae GTA is functional and can transfer genes in vitro. We suggest that the maintenance of the GTA is driven by selection to increase the likelihood of horizontal gene transfer and argue that this process is beneficial at the population level, by facilitating adaptive evolution of the host-adaptation systems and thereby expansion of the host range size. The process counters gene loss and forces all cells to contribute to the production of the GTA and the secreted molecules. The results advance our understanding of the role that GTAs play for the evolution of bacterial genomes.
|
|
| 2. |
- Bakke, Kristin A, et al.
(författare)
-
Levetiracetam reduces the frequency of interictal epileptiform discharges during NREM sleep in children with ADHD
- 2011
-
Ingår i: European journal of paediatric neurology. - : Elsevier BV. - 1090-3798 .- 1532-2130. ; 15:6, s. 532-538
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Symptoms of attention deficit hyperactivity disorder (ADHD) are more common in children with epilepsy than in the general paediatric population. Epileptiform discharges in EEG may be seen in children with ADHD also in those without seizure disorders. Sleep enhances these discharges which may be suppressed by levetiracetam. AIM: To assess the effect of levetiracetam on focal epileptiform discharges during sleep in children with ADHD. METHOD: In this retrospective study a new semi-automatic quantitative method based on the calculation of spike index in 24-h ambulatory EEG recordings was applied. Thirty-five ADHD children, 17 with focal epilepsy, one with generalised epilepsy, and 17 with no seizure disorder were evaluated. Follow-up 24-h EEG recordings were performed after a median time of four months. RESULTS: Mean spike index was 50 prior to levetiracetam treatment and 21 during treatment. Seventeen children had no focal interictal epileptiform discharges in EEG at follow-up. Five children had a more than 50% reduction in spike index. Thus, a more than 50% reduction in spike index was found in 22/35 children (63%). Out of these an improved behaviour was noticed in 13 children (59%). CONCLUSION: This study shows that treatment with levetiracetam reduces interictal epileptiform discharges in children with ADHD. There is a complex relationship between epilepsy, ADHD and epileptiform activity, why it is a need for prospective studies in larger sample sizes, also to ascertain clinical benefits.
|
|
| 3. |
- Berglund, Eva C., et al.
(författare)
-
Run-off replication of host-adaptability genes is associated with gene transfer agents in the genome of mouse-infecting Bartonella grahamii
- 2009
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:7, s. e1000546-
-
Tidskriftsartikel (refereegranskat)abstract
- The genus Bartonella comprises facultative intracellular bacteria adapted to mammals, including previously recognized and emerging human pathogens. We report the 2,341,328 bp genome sequence of Bartonella grahamii, one of the most prevalent Bartonella species in wild rodents. Comparative genomics revealed that rodent-associated Bartonella species have higher copy numbers of genes for putative host-adaptability factors than the related human-specific pathogens. Many of these gene clusters are located in a highly dynamic region of 461 kb. Using hybridization to a microarray designed for the B. grahamii genome, we observed a massive, putatively phage-derived run-off replication of this region. We also identified a novel gene transfer agent, which packages the bacterial genome, with an over-representation of the amplified DNA, in 14 kb pieces. This is the first observation associating the products of run-off replication with a gene transfer agent. Because of the high concentration of gene clusters for host-adaptation proteins in the amplified region, and since the genes encoding the gene transfer agent and the phage origin are well conserved in Bartonella, we hypothesize that these systems are driven by selection. We propose that the coupling of run-off replication with gene transfer agents promotes diversification and rapid spread of host-adaptability factors, facilitating host shifts in Bartonella.
|
|
| 4. |
- Alsmark, Cecilia M., et al.
(författare)
-
The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae
- 2004
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 101:26, s. 9716-9721
-
Tidskriftsartikel (refereegranskat)abstract
- We present the complete genomes of two human pathogens, Bartonella quintana (1,581,384 bp) and Bartonella henselae (1,931,047 bp). The two pathogens maintain several similarities in being transmitted by insect vectors, using mammalian reservoirs, infecting similar cell types (endothelial cells and erythrocytes) and causing vasculoproliferative changes in immunocompromised hosts. A primary difference between the two pathogens is their reservoir ecology. Whereas B. quintana is a specialist, using only the human as a reservoir, B. henselae is more promiscuous and is frequently isolated from both cats and humans. Genome comparison elucidated a high degree of overall similarity with major differences being B. henselae specific genomic islands coding for filamentous hemagglutinin, and evidence of extensive genome reduction in B. quintana, reminiscent of that found in Rickettsia prowazekii. Both genomes are reduced versions of chromosome I from the highly related pathogen Brucella melitensis. Flanked by two rRNA operons is a segment with similarity to genes located on chromosome II of B. melitensis, suggesting that it was acquired by integration of megareplicon DNA in a common ancestor of the two Bartonella species. Comparisons of the vector-host ecology of these organisms suggest that the utilization of host-restricted vectors is associated with accelerated rates of genome degradation and may explain why human pathogens transmitted by specialist vectors are outnumbered by zoonotic agents, which use vectors of broad host ranges.
|
|
| 5. |
- Backe, Cecilia, et al.
(författare)
-
Kadmiumsituationen i Skåne : Delrapport 2 Kadmium inom Höjeåns avrinningsområde – en substansflödesanalys
- 2003
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- är stort. En analys av flödesschemat visar att det sker en utfasning av kadmium via produktoch avfallsflödet. Kadmium ingår i allt färre nyproducerade varor, och därför blir inflödet avkadmium också allt mindre, medan förbrukningen av äldre produkter som innehållerkadmium leder till att flödet via avfallsflödet fortfarande är relativt stort.Inom jordbrukssektorn tillförs den Skånska åkermarken kadmium bl.a. via handelsgödsel,kalk och rötslam. Atmosfärsdepositionen bidrar också med en betydande mängd kadmium.Tillförseln av kadmium balanseras av bortförseln av kadmium via grödor och markläckage.Vad gäller jordbrukssektorns tillförsel bör det dock påpekas att tack vare minskadekadmiumhalter i handelsgödsel och i rötslam så är skillnaden mellan tillförsel och bortförselnästan ± 0 inom Höjeåns avrinningsområde. Tillskottet av kadmium viaatmosfärsdepositionen gör dock att en upplagring av kadmium i avrinningsområdetfortfarande sker.Det regionala miljömålet om att det inte ska ske någon nettotillförsel av kadmium tilljordbruksmarken i Skåne, utöver tillförsel via luften, ser enligt flödesanalysen ut att kunnauppfyllas.SAMMANFATTNINGMiljöproblemens karaktär ändras över tiden. Från att under 60- och 70-talet dominerats avpunktutsläpp från industrin så utgörs idag en stor del av miljöproblemen om föroreningar ochskadliga ämnen av diffusa emissioner. Myndigheternas miljöövervakning av föroreningarmåste i samma takt ändras för att kunna verka effektivt. Substansflödesanalys ellermaterialflödesanalys är exempel på effektiva verktyg som kan användas för att få en ökadkunskap om och en helhetsbild av föroreningars spridningsvägar och upplagring i samhället.Denna studie är ett försök att via en flödesanalys kartlägga omsättningen av kadmium inomHöjeåns avrinningsområde i sydvästra Skåne. Flödesanalysen har genomförts på uppdrag avLänsstyrelsen i Skåne. Syftet med flödesanalysen är att tjäna som vägledning för framtidamiljöövervakning av kadmium och i det fortsatta miljömålsarbetet inom Skåne län.Kadmium är ett exempel på ett ämne som kan ge betydande konsekvenser för människor ochdjur om halterna i vår omgivning är för höga. Kadmium kan orsaka njurskador och benskörhethos människor och ämnet misstänks också vara cancerframkallande. Kadmium finns naturligti vissa typer av berggrund. Det har använts i stora mängder inom plastindustrin somstabilisator och pigment. Det har använts i industrin till ytbehandling och i legeringar. Idag ärden största användningen förknippad med tillverkning av NiCd- batteri. I Sverige och EUarbetar man för att fasa ut användningen av kadmium för produktionsändamål. Kadmiumförekommer även som förorening i zink och andra mineral. Via handelsgödsel spridskadmium till åkermark eftersom kadmium, i varierande halt, finns som förorening i råfosfatsom är råvara till fosforgödsel.Det största inflödet av kadmium till Höjeåns avrinningsområde sker via produkter, och utgörstill ca 70% av kadmium i NiCd-batterier. De flesta flödena är ett resultat av att kadmium ingåri produkter i låga koncentrationer eller som förorening i råmaterial, som t.ex. ijordbrukssektorns handelsgödsel. Det sker ingen aktiv import av kadmium som råvara tillavrinningsområdet. Kadmiumflödet via atmosfärsdeposition är förhållandevis stort i Skåneoch ca 90% av depositionen kommer från utländska källor. Ytterligare ett betydelsefulltkadmiuminflöde till avrinningsområdet är via bränsle för energi och värmeproduktion.Återvinningen av NiCd-batteri är det klart dominerande utflödet av kadmium från systemet.Allt annat avfall som genereras innanför systemgränserna transporteras också ut frånavrinningsområdet, det finns ingen aktiv avfallsdeponering eller avfallsförbränning inomavrinningsområdet.Utsläppen av kadmium i samband med industriella aktiviteter och via trafiken inomavrinningsområdet är mycket små. Utsläppen av kadmium till Höjeå domineras av flöden fråndagvatten och utgående vatten från avloppsreningsverken (och troligen även en del frånenskilda avlopp som dock inte har kvantifierats i denna studie). Kadmium i slam somuppkommer vid reningsverken används både som jordförbättringsmedel inom jordbruket, ochi olika kommunala planteringar i avrinningsområdet. En del slam exporteras ut frånavrinningsområdet för att deponeras på avfallsupplag eller användas.De stora förråden av kadmium i avrinningsområdet är i nedlagda avfallsupplag och iprodukter. Kadmiumförrådet i avfallsupplagen kommer troligen att bestå under mycket långtid. Utlakningen av kadmium, liksom emissionen till luft, är mycket långsam. Idag ärkadmiumemissionen via lakvatten och biogas försumbar. Det är dock osäkert hur rörlighetenav kadmium i deponier förändras i takt med nedbrytningen. Förrådet av kadmium i produkter
|
|
| 6. |
- Tamas, Ivica, et al.
(författare)
-
50 million years of genomic stasis in endosymbiotic bacteria.
- 2002
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 296:5577, s. 2376-9
-
Tidskriftsartikel (refereegranskat)abstract
- Comparison of two fully sequenced genomes of Buchnera aphidicola, the obligate endosymbionts of aphids, reveals the most extreme genome stability to date: no chromosome rearrangements or gene acquisitions have occurred in the past 50 to 70 million years, despite substantial sequence evolution and the inactivation and loss of individual genes. In contrast, the genomes of their closest free-living relatives, Escherichia coli and Salmonella spp., are more than 2000-fold more labile in content and gene order. The genomic stasis of B. aphidicola, likely attributable to the loss of phages, repeated sequences, and recA, indicates that B. aphidicola is no longer a source of ecological innovation for its hosts.
|
|
| 7. |
- Eriksson, Ann-Sofie
(författare)
-
A pharmacokinetic and pharmacodynamic study of an antiepileptic drug (lamotrigine) in young patients with drug-resistant generalized epilepsy
- 2000
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of the present study was to investigate the safety and efficacy of lamotrigine in young patients with drug-resistant generalised epilepsy. This group of patients is difficult to study due to a high seizure frequency, comorbidity and the frequent use of polytherapy. "Drug-resistant" was defined as not being seizure-free despite consecutive treatment attempts of adequate duration and with adequate therapeutic doses of at least three conventional AEDs. "Generalised" was defined according to the definition of the International League Against Epilepsy requiring a scalp EEG showing generalised or multifocal epileptiform activity. Thirty consecutive patients, 15 boys and 15 girls, satisfied the inclusion criteria and took part in the study. The mean age at entry was 9.9 years (range 2.5-22 years) and the median duration of epilepsy at entry was 8.3 years (range 1.4-19.1 years). The mean number of seizures per month at entry was 102 (range 4-315), and the patients (n=30) were treated with 19 different AED combinations. Four patients had normal IQs, 9 patients showed mild mental retardation (MR) and 17 showed severe MR with IQs lower than 50. Twenty-one patients could be said to have epileptic syndromes: one child with juvenile myoclonic epilepsy and 20 children with Lennox-Gastaut syndrome. Our patients had one to five types of seizure. Our enrichment study model presented several advantages. The dose was adjustable to age, bodyweight and co-medication. The lowest effective dose was used, which is similar to how patients with epilepsy are treated in clinical practice. Ethically, all patients were able to try the new drug and only clinical "responders" would continue in a double-blind crossover study with placebo. This trial minimised the exposure of children to placebo. We found no relationship between plasma LTG concentrations and clinical efficacy. However, our results suggest that therapeutic drug monitoring (TDM) of LTG is of value for optimising the dose because of large interindividual differences caused by interactions between LTG and other AEDs. TDM may also be of great importance, especially in patients with rapid elimination who may require medication three times daily to ensure optimal treatment with LTG. We found LTG to be more effective than placebo when we looked at the average monthly seizure frequency (p<0.0001). Our findings in the group of children with Lennox-Gastaut syndrome are encouraging. Thirteen patients with Lennox-Gastaut syndrome showed an overall improvement when LTG was added. Seven of the 20 children responded with a more than 50% seizure reduction. Two patients became seizure-free and three showed a more than 75% reduction in seizure frequency. Assessments of the short-term effects of AEDs by measuring free amino acids in the CSF are problematic, both methodologically and ethically. We could not find any changes in amino acid levels when LTG was added. Video-EEG may be a complementary method for assessing AED efficacy in children with frequent epileptiform discharges in the EEG. Our findings support the assumption that reduction of the amount of interictal epileptiform activity and/or periods of more than 30s of repetitive, epileptiform discharges is a possible reason for the observed improvement in behaviour. Measures of seizure severity and quality of life are of great importance in assessing the efficacy outcome when a new AED is studied. Therapeutic decisions based only on seizure frequency are not sufficient for adequate management of patients with epilepsy. Increased alertness, resulting in a corresponding improvement in social interaction and educational progress, is as important as a reduction of clinical seizures. Altogether, these results have important implications for practical patient management. Failure to control clinical seizures does not necessarily mean complete failure of the treatment.
|
|
| 8. |
- Andersson, Siv GE, et al.
(författare)
-
The genome sequence of Rickettsia prowazekii and the origin of mitochondria
- 1998
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 396:6707, s. 133-140
-
Tidskriftsartikel (refereegranskat)abstract
- We describe here the complete genome sequence (1,111,523 base pairs) of the obligate intracellular parasite Rickettsia prowazekii, the causative agent of epidemic typhus. This genome contains 834 protein-coding genes. The functional profiles of these genes show similarities to those of mitochondrial genes: no genes required for anaerobic glycolysis are found in either R. prowazekii or mitochondrial genomes, but a complete set of genes encoding components of the tricarboxylic acid cycle and the respiratory-chain complex is found in R. prowazekii. In effect, ATP production in Rickettsia is the same as that in mitochondria. Many genes involved in the biosynthesis and regulation of biosynthesis of amino acids and nucleosides in free-living bacteria are absent from R. prowazekii and mitochondria. Such genes seem to have been replaced by homologues in the nuclear (host) genome. The R. prowazekii genome contains the highest proportion of non-coding DNA (24%) detected so far in a microbial genome. Such non-coding sequences may be degraded remnants of 'neutralized' genes that await elimination from the genome. Phylogenetic analyses indicate that R. prowazekii is more closely related to mitochondria than is any other microbe studied so far.
|
|
| 9. |
|
|
| 10. |
|
|
