Receptor-mediated activation of phospholipase D by sphingosine 1-phosphate in skeletal muscle C2C12 cells. A role for protein kinase C.

The present study showed that sphingosine 1-phosphate (SPP) induced rapid stimulation of phospholipase D (PLD) in skeletal muscle C2C12 cells. The effect was receptor-mediated since it was fully inhibited by pertussis toxin. All known SPP-specific receptors, Edg-1, Edg-3 and AGR16/H218, resulted to be expressed in C2C12 myoblasts, although at a different extent. SPP-induced PLD activation did not involve membrane translocation of PLD1 or PLD2 and appeared to be fully dependent on protein kinase C (PKC) catalytic activity. SPP increased membrane association of PKCalpha, PKCdelta and PKClambda, however, only PKCalpha and PKCdelta played a role in PLD activation since low concentrations of GF109203X and rottlerin, a selective inhibitor of PKCdelta, prevented PLD stimulation.     

A global analysis of the determinants of alien geographical range size in birds

Aim Determining the causes of range size variation in the distributions of alien species is important for understanding the spread of invasive species. Factors influencing alien range size have been explored for some species at a regional level, but to date there has been no global analysis of an entire class. Here, we present such an analysis for birds, testing for the effects of introduction event, location and species‐level variables on alien range sizes. Location Global. Methods We used a novel dataset on the global distributions of alien bird species to test for relationships between alien range size and colonization pressure, residence time, extent of the global climatic niche, native range size, body mass and specialization, using a statistical approach based on phylogenetic generalized least squares models. We performed this analysis globally, and for separate biogeographical realms. Results Approximately half of the variation in alien bird range size is explained by colonization pressure in univariate analysis. We identified consistent effects of higher colonization pressure at global and realm levels, as well as support for effects of native range size and residence time. We found less support for effects of body mass, specialization or extent of the global climatic niche on alien range size. Main conclusions Alien bird range sizes are generally small relative to their native range sizes, and many are continuing to expand. Nevertheless, current variation is predictable, most strongly by the event‐level factor of colonization pressure. Whether a species is widespread is a better predictor of alien range size than whether a species could be widespread (estimated by global climatic niche extent), while we also find effects of residence time on alien range size. These relationships may help to identify those alien species that are more likely to spread and hence have greater environmental and economic impacts where they have been introduced.     

Effects of experimentally induced cyanobacterial blooms on crustacean zooplankton communities

SUMMARY 1. Large in situ enclosures were used to study the effects of experimentally induced cyanobacterial blooms on zooplankton communities. A combination of N and P was added to shallow (2 m) and deep enclosures (5 m) with the goal of reducing the TN : TP ratio to a low level (∼5 : 1) to promote cyanobacterial growth. After nutrient additions, high biomass of cyanobacteria developed rapidly in shallow enclosures reaching levels only observed during bloom events in eutrophic lakes.
2. In the shallow enclosures, particulate phosphorus (PP) was on average 35% higher in comparison with deep enclosures, suggesting that depth plays a key role in P uptake by algae. Phytoplankton communities in both deep and shallow enclosures were dominated by three cyanobacteria species – Aphanizomenon flos-aquae , Anabaena flos-aquae and Microcystis aeruginosa – which accounted for up to 70% of total phytoplankton biomass. However, the absolute biomass of the three species was much higher in shallow enclosures, especially Aphanizomenon flos-aquae . The three cyanobacteria species responded in contrasting ways to nutrient manipulation because of their different physiology.
3. Standardised concentrations of the hepatotoxic microcystin-LR increased as a result of nutrient manipulations by a factor of four in the treated enclosures. Increased biomass of inedible and toxin producing cyanobacteria was associated with a decline in Daphnia pulicaria biomass caused by a reduction in the number of individuals with a body length of >1 mm. Zooplankton biomass did not decline at moderate cyanobacteria biomass, but when cyanobacteria reached high biomass large cladocerans were reduced.
4. Our results demonstrate that zooplankton communities can be negatively affected by cyanobacterial blooms and therefore the potential to use herbivory to reduce algal blooms in such eutrophic lakes appears limited.     

Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae – Identification of LYS228

Metallo-β-lactamases (MBLs), such as New Delhi metallo-β-lactamase (NDM-1) have spread world-wide and present a serious threat. Expression of MBLs confers resistance in Gram-negative bacteria to all classes of β-lactam antibiotics, with the exception of monobactams, which are intrinsically stable to MBLs. However, existing first generation monobactam drugs like aztreonam have limited clinical utility against MBL-expressing strains because they are impacted by serine β-lactamases (SBLs), which are often co-expressed in clinical isolates. Here, we optimized novel monobactams for stability against SBLs, which led to the identification of LYS228 (compound 31). LYS228 is potent in the presence of all classes of β-lactamases and shows potent activity against carbapenem-resistant isolates of Enterobacteriaceae (CRE).     

Serum bactericidal activities of moxifloxacin and levofloxacin against aerobic and anaerobic intra-abdominal pathogens

We studied the serum bactericidal activity (SBA) of moxifloxacin and levofloxacin against common pathogens associated with complicated intra-abdominal infections. Ten healthy volunteers received a single dose of moxifloxacin (400 mg) and levofloxacin (750 mg) and serum samples were collected at 2, 4, 8, 12, and 24h after the dose of each drug. Bactericidal titers in serum over time were determined for aerobic gram-negative bacilli (Escherichia coli, Klebseilla pneumoniae, and Enterobacter cloacae) and anaerobic bacteria (Bacteroides fragilis, Bacteroides thetaiotaomicron, Prevotella bivia, and Finegoldia magna). Both fluoroquinolones provided rapid (2h) attainment and prolonged (24h) SBA (titers > or = 1:8) against each of the aerobic bacilli studied. SBA was observed for at least 12h against B. fragilis strains with MICs < or = 2 microg/ml to moxifloxacin and < or = 4 microg/ml to levofloxacin. Prolonged (12h) SBA (titers > or = 1:2) was also observed against isolates of B. thetaiotaomicron, P. bivia, and F. magna with moxifloxacin < or = MICs 2 microg/ml.     

Adenylate cyclase stimulating agents and mitogens raise fructose 2,6-bisphosphate levels in human fibroblasts. Evidence for a dual control of the metabolite

Fructose 2,6-bisphosphate, the most potent activator of 6-phosphofructo-1-kinase, has been demonstrated to mediate the increase of glycolytic flux induced by mitogens human fibroblasts. In the present work the molecular basis of transmembrane control of fructose 2,6-bisphosphate has been investigated. Prostacyclin and isoprenaline, known to activate adenylate cyclase, are able to increase fructose 2,6-bisphosphate levels, indicating that in human fibroblasts cyclic AMP plays a positive role in the control of the metabolite concentration, opposite to that exerted in hepatocytes. Substances known to activate protein kinase C such as phorbol 12-myristate 13-acetate, or to stimulate phosphoinositide turnover such as thrombin and bradykinin are also effective in raising fructose 2,6-bisphosphate. Therefore, we conclude that cyclic AMP and protein kinase C are likely involved in the control of fructose 2,6-bisphosphate levels in human fibroblasts.     

Some T-cell leukemia lines express surface markers related to a restricted set of human VH determinants

Serological studies were carried out to obtain information regarding the relationship of the VH-related determinants expressed by certain permanent in vitro T-cell leukemia lines and corresponding determinants expressed by characterized human serum immunoglobulins. A panel of conventional (goat and rabbit) antisera, produced against various Fab-related fragments of monoclonal human Waldenstrom macroglobulins and polyclonal IgG molecules, bound to certain in vitro T-cell leukemia lines, notably, 70-N2, MT-1, YT4E, and HUT78, as shown by microhemagglutination. Inhibition studies using characterized myeloma proteins to inhibit this agglutination indicated the expression of a restricted VH-related determinant by these T-cell lines. Parallel studies performed using conventional (rabbit) and murine monoclonal/hybridoma antibodies produced against the isolated 68,000-Da VH-related product synthesized by the 70-N2 line showed that the determinant expressed by this molecule was restricted in expression, comprising 2-3% of the normal, polyclonal human Fab pool, and that the determinants found on the other positive T-cell leukemias were cross-reactive rather than identical. The inhibition studies suggest that the determinant resides between residue 22 and the end of the VH region. These results further define the antigenic nature of the VH-related marker found on the surfaces of certain normal and neoplastic T-cell lines.     

VARIABILITY OF THE HEPATOTOXIN MICROCYSTIN-LR IN HYPEREUTROPHIC DRINKING WATER LAKES1

The patterns of occurrence of the peptide hepatotoxin microcystin-LR (MC-LR) was studied in three hypereu-trophic hardwater lakes (Coal, Driedmeat, and Little Beaver) in central Alberta, Canada, over three open-water seasons. MC-LR concentration was based on high-performance liquid chromatography detection and expressed as μg.g^?1 of total plankton biomass, ng.L^?1 of lake water, and μg.g^?1 of Microcystis aeruginosa Kuetz. emend. Elenkin. MC-LR was highly variable temporally (differences up to 3 orders of magnitude) within each lake over an individual year, between years in an individual lake, and between lakes in any year. Seasonal (within-year) changes in MC-LR concentration (expressed in the preceding units) were positively correlated to the abundance and biomass Of the cyanobacterium M. aeruginosa (r =0.60–0.77), total and total dissolved phosphorus concentration (r =0.46–0.59), pH (r=0.38–0.58), and chlorophyll a (r=0.25–0.59). Surprisingly, there was no relationship between MC-LR concentration and water temperature (range: 7°-24°C, r =-0.13 to 0.02) and a negative correlation with nitrate concentration (r =–0.27 to -0.34). In two synoptic surveys examining spatial variability, MC-LR concentrations were quite variable (CV of 185 and 36% between sampling sites for Coal and Little Beaver lakes, respectively). Spatial distribution of MC-LR on any one day was correlated with the abundance and biomass of M. aeruginosa. Over a 24-h period, MC-LR concentration in M. aeruginosa decreased more than 6-fold at night relative to daytime concentrations. In general, analytical and within-site variation of MC-LR was relatively small (CV < 4 and 9%, respectively) but greatest both within and between years in a lake followed by diel and spatial variation.     

A Comparison of Midwife-Led and Medical-Led Models of Care and Their Relationship to Adverse Fetal and Neonatal Outcomes: A Retrospective Cohort Study in New Zealand

BackgroundInternationally, a typical model of maternity care is a medically led system with varying levels of midwifery input. New Zealand has a midwife-led model of care, and there are movements in other countries to adopt such a system. There is a paucity of systemic evaluation that formally investigates safety-related outcomes in relationship to midwife-led care within an entire maternity service. The main objective of this study was to compare major adverse perinatal outcomes between midwife-led and medical-led maternity care in New Zealand.ConclusionsThere is an unexplained excess of adverse events in midwife-led deliveries in New Zealand where midwives practice autonomously. The findings are of concern and demonstrate a need for further research that specifically investigates the reasons for the apparent excess of adverse outcomes in mothers with midwife-led care. These findings should be interpreted in the context of New Zealand’s internationally comparable birth outcomes and in the context of research that supports the many benefits of midwife-led care, such as greater patient satisfaction and lower intervention rates.