Soil net nitrogen mineralisation across global grasslands.

Soil nitrogen mineralisation (Nmin), the conversion of organic into inorganic N, is important for productivity and nutrient cycling. The balance between mineralisation and immobilisation (net Nmin) varies with soil properties and climate. However, because most global-scale assessments of net Nmin are laboratory-based, its regulation under field-conditions and implications for real-world soil functioning remain uncertain. Here, we explore the drivers of realised (field) and potential (laboratory) soil net Nmin across 30 grasslands worldwide. We find that realised Nmin is largely explained by temperature of the wettest quarter, microbial biomass, clay content and bulk density. Potential Nmin only weakly correlates with realised Nmin, but contributes to explain realised net Nmin when combined with soil and climatic variables. We provide novel insights of global realised soil net Nmin and show that potential soil net Nmin data available in the literature could be parameterised with soil and climate data to better predict realised Nmin.

TetR-family transcription factors in Gram-negative bacteria: conservation, variation and implications for efflux-mediated antimicrobial resistance.

BACKGROUND: TetR-family transcriptional regulators (TFTRs) are DNA binding factors that regulate gene expression in bacteria. Well-studied TFTRs, such as AcrR, which regulates efflux pump expression, are usually encoded alongside target operons. Recently, it has emerged that there are many TFTRs which act as global multi-target regulators. Our classical view of TFTRs as simple, single-target regulators therefore needs to be reconsidered. As some TFTRs regulate essential processes (e.g. metabolism) or processes which are important determinants of resistance and virulence (e.g. biofilm formation and efflux gene expression) and as TFTRs are present throughout pathogenic bacteria, they may be good drug discovery targets for tackling antimicrobial resistant infections. However, the prevalence and conservation of individual TFTR genes in Gram-negative species, has to our knowledge, not yet been studied. RESULTS: Here, a wide-scale search for TFTRs in available proteomes of clinically relevant pathogens Salmonella and Escherichia species was performed and these regulators further characterised. The majority of identified TFTRs are involved in efflux regulation in both Escherichia and Salmonella. The percentage variance in TFTR genes of these genera was found to be higher in those regulating genes involved in efflux, bleach survival or biofilm formation than those regulating more constrained processes. Some TFTRs were found to be present in all strains and species of these two genera, whereas others (i.e. TetR) are only present in some strains and some (i.e. RamR) are genera-specific. Two further pathogens on the WHO priority pathogen list (K. pneumoniae and P. aeruginosa) were then searched for the presence of the TFTRs conserved in Escherichia and Salmonella. CONCLUSIONS: Through bioinformatics and literature analyses, we present that TFTRs are a varied and heterogeneous family of proteins required for the regulation of numerous important processes, with consequences to antimicrobial resistance and virulence, and that the roles and responses of these proteins are frequently underestimated.

Author Correction: Crowther et al. reply.

In this Brief Communications Arising Reply, the affiliation for author P. H. Templer was incorrectly listed as 'Department of Ecology & Evolutionary Biology, University of California Irvine, Irvine, California 92697, USA' instead of 'Department of Biology, Boston University, Boston, Massachusetts 02215, USA'. This has been corrected online.

Quantifying global soil carbon losses in response to warming.

The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.

RANK ligand.

RANK ligand (RANKL), a key mediator of bone resorption in normal and pathological states, is expressed as membrane-bound or soluble forms by tissues as diverse as lymph nodes, spleen, thymus and bone-forming cells. In normal bone turnover and in bone metastasis, RANKL stimulates the formation and activity of bone-removing cells, osteoclasts, by binding to its cognate receptor, RANK, on osteoclasts and their progenitors; these processes are disrupted by binding of RANKL to osteoprotegerin (OPG), a soluble decoy receptor. Whilst no mutations in the RANKL gene have yet been identified in human disease, mutations that result in enhanced RANK signalling through inactivation of OPG or activation of RANK are associated with Juvenile Paget's disease and familial expansile osteolysis, respectively. This review focuses on the central role of RANKL in bone resorption and on the therapeutic targeting of RANKL in osteoporosis, humoral hypercalcaemia of malignancy and bone metastasis.

Androgen decreases osteoprotegerin expression in prostate cancer cells.

Osteoprotegerin (OPG), a key regulator of bone resorption, is hypothesized to have a role in prostate cancer (CaP) bone metastasis. As advanced CaP is treated by androgen ablation, we examined if androgen modulates OPG expression by CaP cell lines in vitro. Basal levels of secreted OPG protein were significantly greater in androgen-independent PC-3 cells compared with androgen-responsive LNCaP-FGC cells (P<0.001); OPG was not detected in the androgen-responsive CaP cell lines LAPC-4 or DuCaP. Treatment with 5alpha-dihydrotestosterone (5alpha-DHT) significantly decreased OPG protein levels in both PC-3 and LNCaP-FGC, with maximal suppression using 10(-9)-10(-7) M 5alpha-DHT in PC-3 (P<0.01; day 3), and using 10(-10)-10(-9) M 5alpha-DHT in LNCaP-FGC cells (P<0.01; day 6). OPG messenger RNA levels were not significantly altered by this 5alpha-DHT treatment. Co-treatment with 10(-6) M flutamide blocked 5alpha-DHT inhibition of OPG protein expression in LNCaP-FGC cells. These data suggest that androgen may modulate OPG protein levels in CaP cell lines in vitro using a post-transcriptional mechanism.

Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo.

This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous "take rate" in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation.

Patient controlled analgesia for labour: a comparison of remifentanil with pethidine.

We compared the analgesic efficacy and safety of remifentanil and pethidine via patient controlled analgesia for women in established uncomplicated labour. Women received either remifentanil 40 microg with a 2-min lockout (n = 20) or pethidine 15 mg with a 10-min lockout (n = 19). Visual analogue scores for pain during the study and for overall pain were similar for both groups (mean (SD) 6.4 (1.5) cm for remifentanil and 6.9 (1.7) cm for pethidine). The area under the curve for visual analogue scores of satisfaction with analgesia was higher for remifentanil than for pethidine (p = 0.001). Maternal arterial oxygen saturation was similar in both groups. Neurologic and Adaptive Capacity Scores at 30 min were higher for remifentanil than for pethidine (median (interquartile range [range]) 36 (34.5-37 [32-39]) vs 34 (33-35 [30-35]), respectively; p = 0.003).

Plant community responses to resource availability and heterogeneity during restoration.

Availability and heterogeneity of resources have a strong influence on plant community structure in undisturbed systems, as well as those recovering from disturbance. Less is known about the role of resource availability and heterogeneity in restored communities, although restoration provides a valuable opportunity to test our understanding of factors that influence plant community assembly. We altered soil nitrogen (N) availability and soil depth during a prairie restoration to determine if the availability and/or heterogeneity of soil resources influenced plant community composition in restored grassland communities. Plant community responses to three levels of N availability (ambient, enriched by fertilization, and reduced by carbon amendment) and two levels of soil depth (deep and shallow) were evaluated. In addition, we evaluated plant community responses to four whole plot heterogeneity treatments created from the six possible combinations of soil N availability and soil depth. The soil depth treatment had little influence on community structure during the first 3 years of restoration. Total diversity and richness declined over time under annual N enrichment, whereas diversity was maintained and richness increased over time in soil with reduced N availability. Non-native species establishment was lowest in reduced-N soil in the initial year, but their presence was negligible in all of the soil N treatments by the second year of restoration. Panicum virgatum, a native perennial C(4) grass, was the dominant species in all soil N treatments by year three, but the magnitude of its dominance was lowest in the reduced-N soil and highest in enriched-N soil. Consequently, the relative cover of P. virgatum was strongly correlated with community dominance and inversely related to diversity. The differential growth response of P. virgatum to soil N availability led to a higher degree of community similarity to native prairie in the reduced-N treatment than in the enriched-N treatment. There were no differences in plant community structure among the four whole plot-level heterogeneity treatments, which all exhibited the same degree of similarity to native prairie. Diversity and community heterogeneity in the whole-plot treatments appeared to be regulated by the dominant species' effect on light availability, rather than soil N heterogeneity per se. Our results indicate that a strong differential response of a dominant species to resource availability in a restored community can regulate community structure, diversity, and similarity to the native (or target) community, but the importance of resource heterogeneity in restoring diversity may be dampened in systems where a dominant species can successfully establish across a range of resource availability.

Assessment of tracheal intubation in children after induction with propofol and different doses of remifentanil.

Tracheal intubating conditions were assessed in 112 children after induction of anaesthesia with propofol and remifentanil 1.0, 2.0 or 3.0 micro g.kg-1. Subjects in a control group were given propofol and mivacurium 0.2 mg.kg-1. Haemodynamic and respiratory parameters were recorded. Plasma catecholamine levels were measured in a subgroup of 40 children. Intubating conditions were acceptable in 14/28 (50%), 18/26 (69%) and 22/27 (82%) in those subjects given remifentanil 1.0, 2.0 or 3.0 micro g.kg-1, respectively, and in 27/28 (96%) of the control group. Intubating conditions in subjects given remifentanil 3.0 micro g.kg-1 were better than in those given remifentanil 1.0 micro g.kg-1 (p < 0.05). There were no significant differences in intubating conditions between those given remifentanil 3.0 micro g.kg-1 and the control group. Systolic blood pressure and heart rate increased in response to tracheal intubation in subjects given remifentanil 1.0 micro g.kg-1 and in the control group (p < 0.05). Time to resumption of spontaneous respiration was prolonged in subjects given remifentanil 3.0 micro g.kg-1 (p < 0.001). In conclusion, remifentanil 2 micro g.kg-1 provides acceptable intubating conditions and haemodynamic stability without prolonging the return of spontaneous respiration.

The extent of bisexual behaviour in HIV-infected men and implications for transmission to their female sex partners.

Heterosexual transmission of HIV is a growing problem for women, but many women do not know how their partners acquired HIV. We described a group of HIV-infected men and women, and focused on: (1) sexual identity and bisexual behaviour in men, and (2) the proportion of women who acknowledged having a bisexual male partner. This study examined HIV-infected persons who participated in a cross-sectional interview project from January 1995 through July 2000; 5,156 men who have sex with men (MSM), and 3,139 women. The proportion of MSM who reported having sex with women (MSM/MSW) varied by race: 34% of black MSM, 26% of Hispanic MSM, and 13% of white MSM. While 14% of white women acknowledged having a bisexual partner, only 6% of black and 6% of Hispanic women reported having a bisexual partner. Most behaviourally bisexual men identified as either bisexual (59%) or homosexual (26%). Among MSM/MSW, 30% had more female partners than male partners, while only 10% had more male partners than female partners. These data suggest that bisexual activity is relatively common among black and Hispanic HIV-infected MSM, few identify as heterosexual, and their female partners may not know of their bisexual activity.

Does resource availability, resource heterogeneity or species turnover mediate changes in plant species richness in grazed grasslands?

Grazing by large ungulates often increases plant species richness in grasslands of moderate to high productivity. In a mesic North American grassland with and without the presence of bison ( Bos bison), a native ungulate grazer, three non-exclusive hypotheses for increased plant species richness in grazed grasslands were evaluated: (1) bison grazing enhances levels of resource (light and N) availability, enabling species that depend on higher resource availability to co-occur; (2) spatial heterogeneity in resource availability is enhanced by bison, enabling coexistence of a greater number of plant species; (3) increased species turnover (i.e. increased species colonization and establishment) in grazed grassland is associated with enhanced plant species richness. We measured availability and spatial heterogeneity in light, water and N, and calculated species turnover from long-term data in grazed and ungrazed sites in a North American tallgrass prairie. Both regression and path analyses were performed to evaluate the potential of the three hypothesized mechanisms to explain observed patterns of plant species richness under field conditions. Experimental grazing by bison increased plant species richness by 25% over an 8-year period. Neither heterogeneity nor absolute levels of soil water or available N were related to patterns of species richness in grazed and ungrazed sites. However, high spatial heterogeneity in light and higher rates of species turnover were both strongly related to increases in plant species richness in grazed areas. This suggests that creation of a mosaic of patches with high and low biomass (the primary determinant of light availability in mesic grasslands) and promotion of a dynamic species pool are the most important mechanisms by which grazers affect species richness in high productivity grasslands.

Patient-controlled analgesia for labour using remifentanil: a feasibility study.

We have investigated the efficacy and safety of remifentanil in a patient-controlled analgesia device for labour in 21 women. Remifentanil was available in increasing doses (bolus doses 0.25-1.0 microg x kg(-1)) with and without a background infusion (0.025-0.05 microg x kg(-1) x min(-1)). A lockout time of 2 min was used. Thirteen out of 21 (62%) women chose to continue using remifentanil up to and during delivery. Nineteen out of 21 (90%) achieved a reduction in pain score from baseline. Using a VAS of 0-10 cm the median maximum reduction in pain score was 3 cm (range 0-8 cm). There was a significant reduction (P<0.05) from baseline pain scores (median= 8 cm) to scores at bolus doses in the range 0.25-0.5 microg x kg(-1) (median=5 cm). There were no significant reductions in the fetal heart rate. Apgar scores and cord blood gas analyses remained within normal limits. We conclude that a remifentanil patient-controlled analgesia system (bolus doses 0.25-0.5 microg x kg(-1), without a background infusion) may safely provide worthwhile, although incomplete, analgesia for labour.

Tracheal intubating conditions after induction with sevoflurane 8% in children. A comparison with two intravenous techniques.

We studied tracheal intubating conditions in 120 healthy children, aged 3-12 years, in a blinded, randomised clinical trial. Children were randomly allocated to one of three groups: group PS, propofol 3 mg.kg-1 and succinylcholine 1 mg.kg-1 (n = 40); group PA, propofol 3 mg.kg-1 and alfentanil 10 microg.kg-1 (n = 40); group SF, sevoflurane 8% in 60% nitrous oxide in oxygen for 3 min (n = 40). Tracheal intubating conditions were graded according to ease of laryngoscopy, position of vocal cords, coughing, jaw relaxation and movement of limbs. Overall intubating conditions were acceptable in 39 of 40 children in the propofol/succinylcholine group, 21 of 40 children in the propofol/alfentanil group and 35 of 40 children in the sevoflurane group. Children receiving propofol and succinylcholine or sevoflurane had better intubating conditions overall than those given propofol and alfentanil (p < 0.01). In conclusion, anaesthetic induction and tracheal intubation using sevoflurane 8% for 3 min is a satisfactory alternative to propofol with succinylcholine in children.

The natural history of asymptomatic thoracic disc herniations.

STUDY DESIGN: Magnetic resonance imaging was used to determine the natural history of asymptomatic thoracic disc herniations. OBJECTIVES: To determine whether thoracic disc herniations change in size over time. SUMMARY OF BACKGROUND DATA: Based on previous work by the authors of the present study, the incidence of asymptomatic thoracic disc herniations is approximately 37%. The natural history of thoracic disc herniations is unknown. The natural history of lumbar and cervical disc herniations in symptomatic individuals who become asymptomatic has been shown in multiple studies frequently to result in a decrease in size of the herniation. METHODS: Twenty patients with 48 asymptomatic thoracic herniations previously diagnosed with magnetic resonance imaging underwent repeat magnetic resonance imaging using sagittal T1-weighted spine echo and axial multiplanar gradient refocused images at each thoracic disc level from T1 to T12 for a mean follow-up period of 26 months. Midsagittal canal diameter was recorded, and disc herniation square area was measured using a computer-assisted digitizing program. Disc herniations were categorized according to percentage of canal compromise. The change in size of the disc herniations over time was analyzed. RESULTS: All patients remained asymptomatic during the follow-up period. A total of 48 disc herniations were identified from the original magnetic resonance images. There were 21 small (0-10% canal compromise) disc herniations, 20 medium (> 10-20%) disc herniations, and seven large (> 20%) disc herniations. Of the 21 small disc herniations, 18 showed no significant change in size, whereas three showed a measurable increase in size. Of the 20 medium-sized disc herniations, 16 showed either a small or no change in size, one showed a significant increase in size, and three showed a significant decrease in size. Of the seven large disc herniations, three demonstrated no change in size, and four demonstrated a significant decrease in size. In addition, five new disc herniations were detected in four patients; one was small, and four were moderate in size. CONCLUSIONS: Based on the results of this study, the authors believe that asymptomatic disc herniations may well exist in a state of relative flux, yet exhibit little change in size and remain asymptomatic. There was a trend, however, for small disc herniations either to remain unchanged or increase in size and for large disc herniations often to decrease in size.

A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives.

OBJECTIVE: To examine bone density among adolescents receiving different forms of hormonal contraception along with that of control subjects. METHODS: Baseline and 1-year measures of lumbar vertebral bone density were obtained in girls receiving depot medroxyprogesterone acetate (Depo-Provera) (n = 15), levonorgestrel (Norplant) (n = 7), or oral contraceptives (n = 9) and in girls receiving no hormonal treatment (n = 17). In a subsample of Depo-Provera users (n = 8), Norplant users (n = 3), and control subjects (n = 4), bone density measurements were repeated after 2 years. Bone density was measured by dual-energy x-ray absorptiometry. RESULTS: Body mass indexes, level of pubertal development, substance use, and reproductive histories were not significantly different among the groups. More black girls were represented in the initial Depo-Provera group (p < 0.02), girls in the Norplant group exercised more hours per week (p < 0.02), and control subjects were older (p < 0.01) than those in the other groups. These variables did not significantly affect bone density results. After 1 year, bone density decreased 1.5% in Depo-Provera users, compared with increases of 2.5% in Norplant users, 1.5% in oral contraceptive users, and 2.9% control subjects (p < 0.02). After 2 years, bone density increased a total of 9.3% in Norplant users and 9.5% in control subjects but decreased a total of 3.1% in Depo-Provera users (p < 0.0001). CONCLUSION: These data suggest that Depo-Provera may, at least temporarily, suppress the expected skeletal bone mineralization in adolescents, whereas Norplant and oral contraceptives are associated with the expected increase in bone density in this population.

PIP: In Ohio, data on 31 postmenarcheal women, 12-21 years old and using hormonal contraception (Norplant = 7, Depo Provera = 15, and oral contraceptives [OCs] = 9) were compared with data on 17 controls of similar age to prospectively examine lumbar bone density in girls before and after 1 and 2 years of hormonal contraceptive use and to compare the results with young women not using hormonal contraceptives. The subjects attended a general adolescent clinic at Children's Hospital in Columbus. There was an insufficient number of OC users at 2 years, so they were not included in second year analyses. Initial height and weight were significantly associated with bone density values (p 0.05). Weight accounted for the most variance both at baseline (p 0.001) and after 1 year of treatment (p 0.01). At baseline and 1 year, bone density values between patient groups were not significantly different. At 2 years, however, Norplant users had higher bone density than Depo- Provera users and controls (1.308 vs. 1.004 and 1.087, respectively; p 0.01). After 1 year, Depo-Provera users experienced a decrease (1.53%) in bone density while Norplant users, OC users, and controls experienced an increase in bone density (2.46%, 1.52%, and 2.85%, respectively). The change in bone density between Depo-Provera users and controls was significant (p 0.02). At 2 years, Depo Provera users experienced a decrease in bone density while Norplant users and controls experienced an increase (-3.12% vs. 9.33% and 9.49%, respectively; p 0.0001). This study is important because 50% of adult bone mass is accrued during adolescence. In fact, bone mass peaks during adolescence. It is not known whether bone loss during Depo Provera use is reversible after treatment discontinuation. These findings show that Depo Provera inhibits skeletal bone mineralization in adolescents, at least temporarily, while Norplant and OCs appear to increase bone density.