Complex subsurface hydrothermal fluid mixing at a submarine arc volcano supports distinct and highly diverse microbial communities.

Hydrothermally active submarine volcanoes are mineral-rich biological oases contributing significantly to chemical fluxes in the deep sea, yet little is known about the microbial communities inhabiting these systems. Here we investigate the diversity of microbial life in hydrothermal deposits and their metagenomics-inferred physiology in light of the geological history and resulting hydrothermal fluid paths in the subsurface of Brothers submarine volcano north of New Zealand on the southern Kermadec arc. From metagenome-assembled genomes we identified over 90 putative bacterial and archaeal genomic families and nearly 300 previously unknown genera, many potentially endemic to this submarine volcanic environment. While magmatically influenced hydrothermal systems on the volcanic resurgent cones of Brothers volcano harbor communities of thermoacidophiles and diverse members of the superphylum "DPANN," two distinct communities are associated with the caldera wall, likely shaped by two different types of hydrothermal circulation. The communities whose phylogenetic diversity primarily aligns with that of the cone sites and magmatically influenced hydrothermal systems elsewhere are characterized predominately by anaerobic metabolisms. These populations are probably maintained by fluids with greater magmatic inputs that have interacted with different (deeper) previously altered mineral assemblages. However, proximal (a few meters distant) communities with gene-inferred aerobic, microaerophilic, and anaerobic metabolisms are likely supported by shallower seawater-dominated circulation. Furthermore, mixing of fluids from these two distinct hydrothermal circulation systems may have an underlying imprint on the high microbial phylogenomic diversity. Collectively our results highlight the importance of considering geologic evolution and history of subsurface processes in studying microbial colonization and community dynamics in volcanic environments.

SAXS studies of the thermally-induced fusion of diblock copolymer spheres: formation of hybrid nanoparticles of intermediate size and shape.

Dilute dispersions of poly(lauryl methacrylate)-poly(benzyl methacrylate) (PLMA-PBzMA) diblock copolymer spheres (a.k.a. micelles) of differing mean particle diameter were mixed and thermally annealed at 150 °C to produce spherical nanoparticles of intermediate size. The two initial dispersions were prepared via reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate in n-dodecane at 90 °C. Systematic variation of the mean degree of polymerization of the core-forming PBzMA block enabled control over the mean particle diameter: small-angle X-ray scattering (SAXS) analysis indicated that PLMA39-PBzMA97 and PLMA39-PBzMA294 formed well-defined, non-interacting spheres at 25 °C with core diameters of 21 ± 2 nm and 48 ± 5 nm, respectively. When heated separately, both types of nanoparticles regained their original dimensions during a 25-150-25 °C thermal cycle. However, the cores of the smaller nanoparticles became appreciably solvated when annealed at 150 °C, whereas the larger nanoparticles remained virtually non-solvated at this temperature. Moreover, heating caused a significant reduction in mean aggregation number for the PLMA39-PBzMA97 nanoparticles, suggesting their partial dissociation at 150 °C. Binary mixtures of PLMA39-PBzMA97 and PLMA39-PBzMA294 nanoparticles were then studied over a wide range of compositions. For example, annealing a 1.0% w/w equivolume binary mixture led to the formation of a single population of spheres of intermediate mean diameter (36 ± 4 nm). Thus we hypothesize that the individual PLMA39-PBzMA97 chains interact with the larger PLMA39-PBzMA294 nanoparticles to form the hybrid nanoparticles. Time-resolved SAXS studies confirm that the evolution in copolymer morphology occurs on relatively short time scales (within 20 min at 150 °C) and involves weakly anisotropic intermediate species. Moreover, weakly anisotropic nanoparticles can be obtained as a final copolymer morphology over a restricted range of compositions (e.g. for PLMA39-PBzMA97 volume fractions of 0.20-0.35) when heating dilute dispersions of such binary nanoparticle mixtures up to 150 °C. A mechanism involving both chain expulsion/insertion and micelle fusion/fission is proposed to account for these unexpected observations.

Marine-influenced microbial communities inhabit terrestrial hot springs on a remote island volcano.

Raoul Island is a subaerial island volcano approximately 1000 km northeast of New Zealand. Its caldera contains a circumneutral closed-basin volcanic lake and several associated pools, as well as intertidal coastal hot springs, all fed by a hydrothermal system sourced from both meteoric water and seawater. Here, we report on the geochemistry, prokaryotic community diversity, and cultivatable abundance of thermophilic microorganisms of four terrestrial features and one coastal feature on Raoul. Hydrothermal fluid contributions to the volcanic lake and pools make them brackish, and consequently support unusual microbial communities dominated by Planctomycetes, Chloroflexi, Alphaproteobacteria, and Thaumarchaeota, as well as up to 3% of the rare sister phylum to Cyanobacteria, Candidatus Melainabacteria. The dominant taxa are mesophilic to moderately thermophilic, phototrophic, and heterotrophic marine groups related to marine Planctomycetaceae. The coastal hot spring/shallow hydrothermal vent community is similar to other shallow systems in the Western Pacific Ocean, potentially due to proximity and similarities of geochemistry. Although rare in community sequence data, thermophilic methanogens, sulfur-reducers, and iron-reducers are present in culture-based assays.

Reduce bladder cancer recurrence in patients treated for upper urinary tract urothelial carcinoma: The REBACARE-trial.

BACKGROUND: Following radical nephro-ureterectomy for urothelial carcinoma of the upper urinary tract (UUT), the reported bladder recurrence rate of urothelial carcinoma is 22-47%. A single intravesical instillation of chemotherapy within 10 days following nephro-ureterectomy has the potential to decrease the risk of a bladder recurrence significantly. Despite recommendation by the European Association of Urology guideline to administer a single instillation postoperatively, the compliance rate is low because the risk of extravasation of chemotherapy. AIM: To reduce the risk of bladder cancer recurrence by a single intravesical instillation of Mitomycin immediately (within 3 h) before radical nephro-ureterectomy or partial ureterectomy. METHODS: Adult patients (age ≥ 18 years) with a (suspicion of a) urothelial carcinoma of the UUT undergoing radical nephro-ureterectomy or partial ureterectomy will be eligible and will receive a single intravesical instillation of Mitomycin within 3 h before surgery. In total, 170 patients will be included in this prospective, observational study. Follow-up will be according to current guidelines. RESULTS: The primary endpoint is the bladder cancer recurrence rate up to two years after surgery. Secondary endpoints are: a) the compliance rate; b) oncological outcome; c) possible side-effects; d) the quality of life; e) the calculation of costs of a single neoadjuvant instillation with Mitomycin and f) molecular characterization of UUT tumors and intravesical recurrences. CONCLUSIONS: A single intravesical instillation of Mitomycin before radical nephro-ureterectomy or partial ureterectomy may reduce the risk of a bladder recurrence in patients treated for UUT urothelial carcinoma and will circumvent the disadvantages of current therapy.

Subduction of the oceanic Hikurangi Plateau and its impact on the Kermadec arc.

Large igneous province subduction is a rare process on Earth. A modern example is the subduction of the oceanic Hikurangi Plateau beneath the southern Kermadec arc, offshore New Zealand. This segment of the arc has the largest total lava volume erupted and the highest volcano density of the entire Kermadec arc. Here we show that Kermadec arc lavas south of ~32°S have elevated Pb and Sr and low Nd isotope ratios, which argues, together with increasing seafloor depth, forearc retreat and crustal thinning, for initial Hikurangi Plateau-Kermadec arc collision ~250 km north of its present position. The combined data set indicates that a much larger portion of the Hikurangi Plateau (the missing Ontong Java Nui piece) than previously believed has already been subducted. Oblique plate convergence caused southward migration of the thickened and buoyant oceanic plateau crust, creating a buoyant 'Hikurangi' mélange beneath the Moho that interacts with ascending arc melts.

Evaluation of the fat-tailed gerbil, Pachyuromys duprasi (Rodentia: Gerbillidae), as a new animal model for studies of Leishmania major infection and transmission.

The fat-tailed gerbil Pachyuromys duprasi is a common burrowing rodent found across the northern Sahara Desert from Morocco to Egypt. There is overlap in the geographical distribution and ecological habitats of P. duprasi, several Old World Leishmania species, and numerous sand fly vectors of Leishmania, but there are no records that document the natural occurrence of this gerbil with any species of Leishmania or phlebotomine sand fly. Experiments were conducted to determine its potential as a natural host and laboratory animal model for Leishmania major. Captive-born P. duprasi were inoculated subcutaneously (s.c.) in the tail with promastigotes or amastigotes of an Egyptian strain of L. major and monitored for signs of infection. Local swelling and erythema was visible 10-12 days after amastigote inoculation, and within 3-4 weeks swelling had increased tail widths by up to 78%. Infections progressed more slowly and less conspicuously following inoculation with promastigotes. Tissue density of amastigotes in the gerbil's tail lesions after inoculating with either stage of L. major was significantly lower than that produced in the footpads of BALB/c mice by the same parasite and incubation period. Laboratory transmission of L. major to P. duprasi by sand fly bite was demonstrated and acquisition of L. major, by bite, from tail lesions of infected P. duprasi to laboratory-reared Phlebotomus papatasi was also achieved with 10% of biting flies developing promastigote infections. The acquisition and development of L. major infections in P. papatasi after biting an infected P. duprasi and the susceptibility of P. duprasi to L. major delivered at low densities by sand fly bites indicate that fat-tailed gerbils could serve as a natural host and reservoir of L. major.

Louisville seamount subduction and its implication on mantle flow beneath the central Tonga-Kermadec arc.

Subduction of intraplate seamounts beneath a geochemically depleted mantle wedge provides a seldom opportunity to trace element recycling and mantle flow in subduction zones. Here we present trace element and Sr, Nd and Pb isotopic compositions of lavas from the central Tonga-Kermadec arc, west of the contemporary Louisville-Tonga trench intersection, to provide new insights into the effects of Louisville seamount subduction. Elevated (206)Pb/(204)Pb, (208)Pb/(204)Pb, (86)Sr/(87)Sr in lavas from the central Tonga-Kermadec arc front are consistent with localized input of subducted alkaline Louisville material (lavas and volcaniclastics) into sub-arc partial melts. Furthermore, absolute Pacific Plate motion models indicate an anticlockwise rotation in the subducted Louisville seamount chain that, combined with estimates of the timing of fluid release from the subducting slab, suggests primarily trench-normal mantle flow beneath the central Tonga-Kermadec arc system.

Phase 2 study of adjuvant intravesical instillations of apaziquone for high risk nonmuscle invasive bladder cancer.

PURPOSE: We studied the safety and efficacy of multiple adjuvant apaziquone instillations in patients with high risk nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Patients with high risk nonmuscle invasive urothelial carcinoma of the bladder underwent transurethral resection of all bladder tumor(s), and received 6 weekly adjuvant intravesical apaziquone instillations of 4 mg in 40 ml. Patients with carcinoma in situ received 3 further maintenance instillations at months 3, 6 and 12. Followup consisted of cystoscopy, urine cytology and observation of adverse events every 3 months for 18 months. RESULTS: A total of 53 patients were enrolled in the study. Although all patients were high risk according to the definitions used when the study was initiated, according to most recent guideline criteria, 80% and 20% of these patients would now be considered intermediate and high risk for recurrence, and 50% and 44% would be considered intermediate and high risk for progression, respectively. Intent to treat analysis of 49 patients with papillary tumors showed recurrent tumors in 34.7% and 44.9% at 12 and 18 months, respectively. One patient had progression to T2 or greater urothelial carcinoma after 9 months. There were 4 patients with carcinoma in situ who had complete responses at 3 months but discontinued treatment due to cystitis, recurrent papillary disease, urinary incontinence and dysuria. Most other side effects were mild (grade 1 to 2). CONCLUSIONS: Adjuvant intravesical instillations of apaziquone are generally well tolerated. The recurrence rates of 34.7% after 12 months and 44.9% after 18 months in these patients can be considered encouraging, and warrant further study.

Benign prostatic hyperplasia as a progressive disease: a guide to the risk factors and options for medical management.

Benign prostatic hyperplasia (BPH) is a complex disease that is progressive in many men. BPH is commonly associated with bothersome lower urinary tract symptoms; progressive disease can also result in complications such as acute urinary retention (AUR) and BPH-related surgery. It is therefore important to identify men at increased risk of BPH progression to optimise therapy. Several factors are associated with progression, including age and prostate volume (PV). Serum prostate-specific antigen level is closely correlated with PV, making it useful for determining the risk of BPH progression. Medical therapy is the most frequently used treatment for BPH. 5-alpha-reductase inhibitors impact the underlying disease and decrease PV; this results in improved symptoms, urinary flow and quality of life, and a reduced risk of AUR and BPH-related surgery. Alpha-blockers achieve rapid symptom relief but do not reduce the overall risk of AUR or BPH-related surgery, presumably because they have no effect on PV. Combination therapy provides greater and more durable benefits than either monotherapy and is a recommended option in treatment guidelines. The Combination of Avodart and Tamsulosin (CombAT) study is currently evaluating the combination of dutasteride with tamsulosin over 4 years in a population of men at increased risk of BPH progression. A preplanned 2-year analysis has shown sustained symptom improvement with combination therapy, significantly greater than with either monotherapy. CombAT is also the first study to show benefit in improving BPH symptoms for combination therapy over the alpha-blocker, tamsulosin, from 9 months of treatment.

Implications of a 3.472-3.333 Gyr-old subaerial microbial mat from the Barberton greenstone belt, South Africa for the UV environmental conditions on the early Earth.

Modelling suggests that the UV radiation environment of the early Earth, with DNA weighted irradiances of about three orders of magnitude greater than those at present, was hostile to life forms at the surface, unless they lived in specific protected habitats. However, we present empirical evidence that challenges this commonly held view. We describe a well-developed microbial mat that formed on the surface of volcanic littoral sediments in an evaporitic environment in a 3.5-3.3Ga-old formation from the Barberton greenstone belt. Using a multiscale, multidisciplinary approach designed to strongly test the biogenicity of potential microbial structures, we show that the mat was constructed under flowing water by 0.25 microm filaments that produced copious quantities of extracellular polymeric substances, representing probably anoxygenic photosynthesizers. Associated with the mat is a small colony of rods-vibroids that probably represent sulphur-reducing bacteria. An embedded suite of evaporite minerals and desiccation cracks in the surface of the mat demonstrates that it was periodically exposed to the air in an evaporitic environment. We conclude that DNA-damaging UV radiation fluxes at the surface of the Earth at this period must either have been low (absorbed by CO2, H2O, a thin organic haze from photo-dissociated CH4, or SO2 from volcanic outgassing; scattered by volcanic, and periodically, meteorite dust, as well as by the upper layers of the microbial mat) and/or that the micro-organisms exhibited efficient gene repair/survival strategies.

Long-term eruptive activity at a submarine arc volcano.

Three-quarters of the Earth's volcanic activity is submarine, located mostly along the mid-ocean ridges, with the remainder along intraoceanic arcs and hotspots at depths varying from greater than 4,000 m to near the sea surface. Most observations and sampling of submarine eruptions have been indirect, made from surface vessels or made after the fact. We describe here direct observations and sampling of an eruption at a submarine arc volcano named NW Rota-1, located 60 km northwest of the island of Rota (Commonwealth of the Northern Mariana Islands). We observed a pulsating plume permeated with droplets of molten sulphur disgorging volcanic ash and lapilli from a 15-m diameter pit in March 2004 and again in October 2005 near the summit of the volcano at a water depth of 555 m (depth in 2004). A turbid layer found on the flanks of the volcano (in 2004) at depths from 700 m to more than 1,400 m was probably formed by mass-wasting events related to the eruption. Long-term eruptive activity has produced an unusual chemical environment and a very unstable benthic habitat exploited by only a few mobile decapod species. Such conditions are perhaps distinctive of active arc and hotspot volcanoes.

Evaluation of early pelvic floor physiotherapy on the duration and degree of urinary incontinence after radical retropubic prostatectomy in a non-teaching hospital.

The objective of this study was to study the effect of early pelvic floor re-education on the degree and duration of incontinence and to evaluate the results of radical retropubic prostatectomy (RRP) performed in a non-teaching hospital. This is a non-randomised study. From March 2000 to November 2003, 57 consecutive men, who underwent RRP for localized prostate cancer, participated in a pelvic floor re-educating program. Continence was defined as a loss of no more than 2-g urine on the 24-h pad test and no use of pads. The 24-h pad test was performed once in every 4 weeks until the patient indicated that he was continent. Diurnal and nocturnal continence was achieved after 1, 2, 3, 6 and 12 months post catheter removal in 40, 49, 70, 86 and 88% of all men, respectively. Comparison of our results with current literature suggest that the time period towards continence after a RRP can be shortened relevantly if pelvic floor re-education is started directly after catheter removal.

Removal of a missed polypropylene tape by a combined transurethral and transabdominal endoscopic approach.

Surgical intervention for bladder perforation caused by application of a transvaginally placed polypropylene tape is rare. Open as well as endoscopic procedures for removal from the bladder have been described earlier. In this case report we describe the removal of an intravesical polypropylene tape by a combined transurethral and transabdominal endoscopic approach 3 months after the initial surgical procedure.

Transurethral deroofing of midline prostatic cyst for subfertile men.

We evaluated the efficacy of transurethral deroofing of a midline prostatic cyst in subfertile men with one or more of the following semen abnormalities: decreased ejaculatory volume, decreased sperm motility and oligo- or azoospermia. Results from treatment of a series of 11 subfertile men with a midline prostatic cyst by transurethral deroofing of the cyst are presented. Five patients showed an improvement of seminal volume. Only one patient demonstrated an improvement of sperm count. Sperm motility was not influenced. No relationship was found between positive outcome following operation and either size of the cyst or dilatation of the seminal vesicles. Spontaneous pregnancies did not occur after transurethral deroofing of the midline prostatic cyst. In conclusion, our study suggests a poor efficacy of transurethral deroofing of a midline prostatic cyst in subfertile men with the above mentioned semen abnormalities.

Manual derotation of the twisted spermatic cord.

OBJECTIVE: To re-emphasize the safety and efficacy of manual derotation in the management of the twisted spermatic cord. PATIENTS AND METHODS: Seventeen patients (mean age 15 years, range 13-28) with acute unilateral torsion of the spermatic cord, initially treated by manual detorsion, were reviewed; all 17 patients were seen by one consulting urologist (H.F.M.K.). RESULTS: In 14 of the 17 patients the attempt resulted in successful manual derotation, i. e. the immediate relief of all symptoms and normal findings at physical examination. No testicular atrophy was detected during the follow-up (mean 22 months, range 9-72). CONCLUSIONS: These results reinforce the efficacy and safety of manual derotation with subsequent elective bilateral orchidopexy as the primary treatment for the twisted spermatic cord.

Testicular simple cyst and teratoma: asynchronous bilateral occurrence within the first year of life.

Benign and malignant testicular tumors are rare in infancy. Moreover, only a few cases of bilateral testicular tumors in children have been reported to date. To our knowledge, we report the first case of an asynchronous bilateral simple testicular cyst and testicular teratoma in an infant. This case demonstrates that although both lesions are benign in the prepubertal child, treatment decisions should be made carefully.

Overexpression of c-src and n-src in the developing Xenopus retina differentially impairs axonogenesis.

To compare the roles of the nonreceptor tyrosine kinase c-src and its neuronal splice form n-src in developing neurons, Xenopus retinal precursors were transfected in vivo with c-src, n-src, or constitutively active mutants. Axonogenesis of retinal ganglion cells was markedly impaired by the expression of constitutively active c-src and only mildly affected by the expression of constitutively active n-src. This differential phenotype could not be accounted for by raised levels of intracellular tyrosine phosphorylation alone because the average anti-phosphotyrosine staining intensity of retinal neurons expressing mutant n-src was almost twofold greater than that of neurons expressing mutant c-src. The expression of either constitutively active isoform inhibited photoreceptor differentiation by 72% but did not influence other cell fates. These results suggest that c-src and n-src have both overlapping and distinct activities in differentiating retinal neurons.

Influence of high-intensity focused ultrasound on the development of metastases.

OBJECTIVE: The hypothesis that exposure of a solid tumor to high-intensity focused ultrasound (HIFU) could lead to an increase of metastases was investigated in an animal model. METHODS: The highly metastatic AT-6 Dunning R3327 rat prostate cancer subline was implanted into the hind limb of Fisher-Copenhagen rats and was exposed to 1 pulse/mm2 tumor (acoustical power 1,000 W/cm2) delivered by an experimental machine (Ablatherm, Technomed, France), or the animals were sham treated, as soon as the tumor had reached a volume of 175-225 mm3. The tumor-bearing leg was amputated 24 h later and the number of metastases examined 12 weeks thereafter at autopsy. RESULTS: Metastases were seen in 3 (23%) of the 13 animals exposed to HIFU and in 4 (25%) of the 16 sham-treated animals; this is not significantly different. There was also no significant difference in weight of the lungs that contained metastases between sham-treated and HIFU-treated animals. CONCLUSION: Metastatic spread of animal tumors with a high metastatic potential is not enhanced by HIFU exposure.

Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo.

The cell-cell adhesion molecule N-cadherin strongly promotes neurite outgrowth in cultured retinal neurons. To test whether cadherins regulate process outgrowth in retinal neurons in vivo, we have blocked cadherin function in single cells by expression of a dominant negative N-cadherin mutant. We report that when cadherin function is inhibited, axon and dendrite outgrowth are severely impaired, particularly in retinal ganglion cells. Laminar migration and cell type specification, by contrast, appear unaffected. Further, expression of the catenin-binding domain of N-cadherin, which blocks cadherin-mediated adhesion in early embryos, does not affect axon outgrowth, suggesting that outgrowth and adhesion are mediated by distinct regions of the cytoplasmic domain. These findings indicate that cadherins play an essential role in the initiation and extension of axons from retinal ganglion cells in vivo.

Inhibition of FGF receptor activity in retinal ganglion cell axons causes errors in target recognition.

Native fibroblast growth factor receptor (FGFR) function was inhibited in developing Xenopus retinal ganglion cells (RGCs) by in vivo transfection of a dominant negative FGFR. Axons expressing the dominant negative protein advanced at 60% of the normal speed, but nevertheless navigated appropriately in the embryonic optic pathway. When they neared the optic tectum, however, many axons made erroneous turns, causing them to bypass rather than enter their target. By contrast, RGC axons expressing nonfunctional FGFR mutants entered the tectum correctly. These findings demonstrate a role for FGFR signaling in the extension and targeting of RGC axons and suggest that receptor tyrosine kinase/growth factor interactions play a critical function in establishing initial connectivity in the vertebrate visual system.