Frankia strains are nitrogen-fixing soil actinobacteria that can form root symbioses with actinorhizal plants. Phylogenetically, symbiotic frankiae can be divided into three clusters, and this division also corresponds to host specificity groups. The strains of cluster II which form symbioses with actinorhizal Rosales and Cucurbitales, thus displaying a broad host range, show suprisingly low genetic diversity and to date can not be cultured. The genome of the first representative of this cluster, Candidatus Frankia datiscae Dg1 (Dg1), a microsymbiont of Datisca glomerata, was recently sequenced. A phylogenetic analysis of 50 different housekeeping genes of Dg1 and three published Frankia genomes showed that cluster II is basal among the symbiotic Frankia clusters. Detailed analysis showed that nodules of D. glomerata, independent of the origin of the inoculum, contain several closely related cluster II Frankia operational taxonomic units. Actinorhizal plants and legumes both belong to the nitrogen-fixing plant clade, and bacterial signaling in both groups involves the common symbiotic pathway also used by arbuscular mycorrhizal fungi. However, so far, no molecules resembling rhizobial Nod factors could be isolated from Frankia cultures. Alone among Frankia genomes available to date, the genome of Dg1 contains the canonical nod genes nodA, nodB and nodC known from rhizobia, and these genes are arranged in two operons which are expressed in D. glomerata nodules. Furthermore, Frankia Dg1 nodC was able to partially complement a Rhizobium leguminosarum A34 nodC::Tn5 mutant. Phylogenetic analysis showed that Dg1 Nod proteins are positioned at the root of both α- and β-rhizobial NodABC proteins. NodA-like acyl transferases were found across the phylum Actinobacteria, but among Proteobacteria only in nodulators. Taken together, our evidence indicates an Actinobacterial origin of rhizobial Nod factors.

Advances in microbiome science require a better understanding of how beneficial microbes adapt to hosts. We tested whether hosts select for more-cooperative microbial strains with a year-long evolution experiment and a cross-inoculation experiment designed to explore how nitrogen-fixing bacteria (rhizobia) adapt to legumes. We paired the bacterium Ensifer meliloti with one of five Medicago truncatula genotypes that vary in how strongly they “choose” bacterial symbionts. Independent of host choice, E. meliloti rapidly adapted to its local host genotype, and derived microbes were more beneficial when they shared evolutionary history with their host. This local adaptation was mostly limited to the symbiosis plasmids, with mutations in putative signaling genes. Thus, cooperation depends on the match between partner genotypes and increases as bacteria adapt to their local host.

The objective of this article was to review the outcome of assessments performed at a recently established nurseled one-stop male lower urinary tract symptom (LUTS) assessment clinic. Retrospective audit was performed on 107 patients assessed between December 2006 and August 2007. Information obtained included demographics, symptoms, International Prostatic Symptom Score (IPSS), prostate-specific antigen (PSA), electrolyte profile, mid-stream sample of urine (MSSU), ultrasound scan of renal tracts, uroflowmetry (urinary flow studies), management plan and clinical outcome. The mean age of the patient was 65Á8 years, and patients waited 15Á7 weeks (previously up to 2 years) for consultation. Symptomatically, 51% had moderate (IPSS score 8-19) and 38% had marked symptoms (score 20-35), and 43Á5% reported sexual dysfunction. The mean PSA, prostatic volume and postvoid residual urine volume were 4Á9 ng/mL, 50Á4 cc and 101Á9 mL, respectively. The average maximum urinary flow was 14Á9 mL/s, and only 1% of all MSSU obtained revealed urinary tract infection. The final clinical outcomes identified nine prostate cancers, three renal cancers, three bladder calculi, two urethral strictures, two atonic bladders, one new-onset diabetes and one pelvi-ureteric junction obstruction. From a treatment perspective, 70Á1% patients had alpha-blockers, 42Á9% had a 5-alpha reductase inhibitor, 15% had anticholinergics, 1% had transurethral incision of prostate, 2% had optical urethrotomy, 3% had cystolitholapaxy, 3% had radical nephrectomy and 8% had transurethral resection of prostate. This clinic had significantly reduced the waiting time for first assessment in people with LUTS. Additionally, it has highlighted areas for further refinement and revision and firmly establishes the need for ongoing reaudit. We tentatively suggest the inclusion of ultrasound renal tracts as part of LUTS assessment.

This study compares Breast Cancer 1 (BRCA1) and excision repair cross complementation group 1 (ERCC1) expression as predictive markers and evaluates the in vitro enhancement of platinum sensitivity using targeted agents in sporadic ovarian cancer (OC). A retrospective study was performed of advanced stage OC patients receiving platinum-based chemotherapy. BRCA1 and ERCC1 mRNA expression was determined from frozen tissue of 51 patients. Median overall survival (OS) was longer for patients with lower BRCA1 vs. higher BRCA1 (46 vs.33 months, p 5 0.03). High BRCA1 was predictive of poorer OS specifically in patients with residual disease (RD) <2 cm (p 5 0.03). There was a non-significant association for patients with lower ERCC1 and RD <2 cm in favor of improved OS and time to progression. Patients who expressed higher levels of both BRCA1 and ERCC1 mRNA had a shorter OS compared to patients with lower levels of either or both transcript (33 vs.46 months, p 5 0.04). When Cox proportional modeling was used by representing BRCA1 and ERCC1 mRNA expression as a continuous variable, both emerge as potential predictors of survival. OC cell lines were exposed to chemotherapy in combination with DNA repair pathway inhibitors and cell viability was assessed. In vitro histone deacetylase (HDAC) inhibition increased the sensitivity of A2780s/cp cells to cisplatin and carboplatin but not to taxol, coincident with a significant decrease in BRCA1 and ERCC1 expression, suggesting that this compound directly targets DNA repair. In summary, this study shows that low BRCA1 and ERCC1 expression correlate with improved survival in advanced OC and HDAC inhibition induces synergistic cytotoxicity with platinum in vitro. ' 2008 Wiley-Liss, Inc.Key words: BRCA1; ERCC1; sporadic ovarian cancer; DNA repair; predictive marker Epithelial ovarian cancer (OC) is generally diagnosed at advanced stage resulting in a 5-year survival of only 20-30%. The standard treatment of OC is surgical debulking followed by platinum and taxane chemotherapy. Although 70% of patients with advanced disease initially respond to the first-line regimen, early recurrences and platinum resistance are common obstacles in the management of this disease. Identifying reliable predictors of response and the use of novel therapeutic agents to enhance platinum efficacy are needed to improve the management of OC. Platinum resistance is multifactorial, 1 and an important mechanism of resistance is increased tolerance to platinum-DNA damage and enhanced repair of damaged DNA. In a variety of malignancies including OC, enhanced expression of the DNA repair proteins, Breast Cancer 1 (BRCA1) and excision repair cross complementation group 1 (ERCC1), have correlated with resistance to platinum. [2][3][4][5][6] In vitro models have shown that targeting the expression of both BRCA1 and ERCC1 sensitizes cells to platinum-based chemotherapeutic agents, suggesting a potential clinical application to help overcome platinum resistance in OC.Mutations in the BRCA1 tumor suppressor gene are ...

Species belonging to the genera Aloysia and Acantholippia are difficult to place within Lantaneae due to gene tree incongruence and limited sampling in previous studies. We use an expanded sample of both genera, and DNA sequence data from six loci, to reveal that Aloysia and Acantholippia species occur in five consistently inferred, well-supported clades. The precise relationships of these clades to one another are still enigmatic, due to gene tree incongruence. However, coalescent-based species tree inference supports the inclusion of most of Acantholippia in an expanded Aloysia sensu lato, with a 4-lobed calyx as its defining feature. Five new combinations are proposed to reflect this relationship: Aloysia deserticola, Aloysia riojana, Aloysia salsoloides, Aloysia tarapacana, and Aloysia trifida. Geographic range shifts from subtropical South America to North America have occurred at least twice in Aloysia. Shifts between determinate and indeterminate inflorescence arrangement have occurred at least twice independently. The elongate, lax inflorescence, which is characteristic of most of Aloysia, is hypothesized to be derived from a condensed inflorescence.

Evolutionary biologists typically envision a trait’s genetic basis and fitness effects occurring within a single species. However, traits can be determined by and have fitness consequences for interacting species, thus evolving in multiple genomes. This is especially likely in mutualisms, where species exchange fitness benefits and can associate over long periods of time. Partners may experience evolutionary conflict over the value of a multi-genomic trait, but such conflicts may be ameliorated by mutualism’s positive fitness feedbacks. Here, we develop a simulation model of a host–microbe mutualism to explore the evolution of a multi-genomic trait. Coevolutionary outcomes depend on whether hosts and microbes have similar or different optimal trait values, strengths of selection and fitness feedbacks. We show that genome-wide association studies can map joint traits to loci in multiple genomes and describe how fitness conflict and fitness feedback generate different multi-genomic architectures with distinct signals around segregating loci. Partner fitnesses can be positively correlated even when partners are in conflict over the value of a multi-genomic trait, and conflict can generate strong mutualistic dependency. While fitness alignment facilitates rapid adaptation to a new optimum, conflict maintains genetic variation and evolvability, with implications for applied microbiome science.

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