Anthropogenic alteration of nutrient supply increases the global freshwater carbon sink.

Lakes have a disproportionate effect on the global carbon (C) cycle relative to their area, mediating C transfer from land to atmosphere, and burying organic-C in their sediments. The magnitude and temporal variability of C burial is, however, poorly constrained, and the degree to which humans have influenced lake C cycling through landscape alteration has not been systematically assessed. Here, we report global and biome specific trajectories of lake C sequestration based on 516 lakes and show that some lake C burial rates (i.e., those in tropical forest and grassland biomes) have quadrupled over the last 100 years. Global lake C-sequestration (~0.12 Pg year-1) has increased by ~72 Tg year-1 since 1900, offsetting 20% of annual CO2 freshwater emissions rising to ~30% if reservoirs are included and contributing to the residual continental C sink. Nutrient availability explains ~70% of the observed increase, while rising temperatures have a minimal effect.

Marine resource abundance drove pre-agricultural population increase in Stone Age Scandinavia.

How climate and ecology affect key cultural transformations remains debated in the context of long-term socio-cultural development because of spatially and temporally disjunct climate and archaeological records. The introduction of agriculture triggered a major population increase across Europe. However, in Southern Scandinavia it was preceded by ~500 years of sustained population growth. Here we show that this growth was driven by long-term enhanced marine production conditioned by the Holocene Thermal Maximum, a time of elevated temperature, sea level and salinity across coastal waters. We identify two periods of increased marine production across trophic levels (P1 7600-7100 and P2 6400-5900 cal. yr BP) that coincide with markedly increased mollusc collection and accumulation of shell middens, indicating greater marine resource availability. Between ~7600-5900 BP, intense exploitation of a warmer, more productive marine environment by Mesolithic hunter-gatherers drove cultural development, including maritime technological innovation, and from ca. 6400-5900 BP, underpinned a ~four-fold human population growth.

Activation of the insulin-signaling pathway in sciatic nerve and hippocampus of type 1 diabetic rats.

Peripheral neuropathy is a major complication associated with diabetes and central neuropathy characterized by Alzheimer's disease-like features in the brain is associated with increased dementia risk for patients with diabetes. Although glucose uptake into the cells of the nervous system is insulin-independent, contribution of impaired insulin support is clearly recognized to play a role, however not yet fully understood, in the development of neuropathy. In this study, we assessed the direct role of insulin on the peripheral nervous system (PNS) and central nervous system (CNS) of insulin-dependent type 1 diabetic rats. Fresh sciatic nerve and hippocampus from control and diabetic rats were incubated with varied ex vivo concentrations of insulin and phosphorylation levels of insulin receptor and glycogen synthase kinase-3 (GSK3ß) were assessed by Western blot analysis. Both the sciatic nerve and hippocampus from type 1 diabetic rats were highly responsive to exogenous insulin with a significantly increased phosphorylation of insulin receptor and GSK3 compared to tissues from control rats. Further, sustained in vivo insulin delivery, not sufficient to restore normal blood glucose, normalized the activation of both insulin receptor and GSK3 in both PNS and CNS tissues. These results suggest that the insulin-signaling pathway is responsive to exogenous insulin in the nervous system of insulin-deficient type 1 diabetic rats and that constant insulin delivery restore normal nerve function and may protect PNS and CNS from damage.

Long-Term Persistence of an Anxiolytic Drug (Oxazepam) in a Large Freshwater Lake.

Production and human consumption of pharmaceuticals result in contamination of surface waters worldwide. Little is known about the long-term (i.e., over decades) fate of pharmaceuticals in aquatic systems. Here, we show that the most prescribed anxiolytic in Sweden (oxazepam) persists in its therapeutic form for several decades after being deposited in a large freshwater lake. By comparing sediment cores collected in 1995 and 2013, we demonstrate that oxazepam inputs from the early 1970s remained in the sediments until sampling in 2013, despite in situ degradation processes and sediment diagenesis. In laboratory and pond experiments, we further reveal that therapeutic forms of oxazepam can persist over several months in cold (5 °C) lake water free from UV light. We conclude that oxazepam can persist in lakes over a time scale much longer than previously realized and that levels can build up in lakes due to both a legacy of past inputs and a growing urban population.

The ecology of the planktonic diatom Cyclotella and its implications for global environmental change studies.

The fossil record of diatoms in lake sediments can be used to assess the effects of climate variability on lake ecosystems if ecological relationships between diatom community structure and environmental parameters are well understood. Cyclotella sensu lato taxa are a key group of diatoms that are frequently dominant members of phytoplankton communities in low- to moderate-productivity lakes. Their relative abundances have fluctuated significantly in palaeolimnological records spanning over a century in arctic, alpine, boreal and temperate lakes. This suggests that these species are sensitive to environmental change and may serve as early indicators of ecosystem effects of global change. Yet patterns of change in Cyclotella species are not synchronous or unidirectional across, or even within, regions, raising the question of how to interpret these widespread changes in diatom community structure. We suggest that the path forward in resolving seemingly disparate records is to identify clearly the autecology of Cyclotella species, notably the role of nutrients, dissolved organic carbon and light, coupled with better consideration of both the mechanisms controlling lake thermal stratification processes and the resulting effects of changing lake thermal regimes on light and nutrients. Here we begin by reviewing the literature on the resource requirements of common Cyclotella taxa, illustrating that many studies reveal the importance of light, nitrogen, phosphorus, and interactions among these resources in controlling relative abundances. We then discuss how these resource requirements can be linked to shifts in limnological processes driven by environmental change, including climate-driven change in lakewater temperature, thermal stratification and nutrient loading, as well as acidification-driven shifts in nutrients and water clarity. We examine three case studies, each involving two lakes from the same region that have disparate trends in the relative abundances of the same species, and illustrate how the mechanisms by which these species abundances are changing can be deciphered. Ultimately, changes in resource availability and water clarity are key factors leading to shifts in Cyclotella abundances. Tighter integration of the autecology of this important group of diatoms with environmental change and subsequent alterations in limnological processes will improve interpretations of palaeolimnological records, and clarify the drivers of seemingly disparate patterns in fossil records showing widespread and rapid changes across the northern hemisphere.

Lake eutrophication and its implications for organic carbon sequestration in Europe.

The eutrophication of lowland lakes in Europe by excess nitrogen (N) and phosphorus (P) is severe because of the long history of land-cover change and agricultural intensification. The ecological and socio-economic effects of eutrophication are well understood but its effect on organic carbon (OC) sequestration by lakes and its change overtime has not been determined. Here, we compile data from ~90 culturally impacted European lakes [~60% are eutrophic, Total P (TP) >30 µg P l(-1) ] and determine the extent to which OC burial rates have increased over the past 100-150 years. The average focussing corrected, OC accumulation rate (C ARFC ) for the period 1950-1990 was ~60 g C m(-2) yr(-1) , and for lakes with >100 µg TP l(-1) the average was ~100 g C m(-2) yr(-1) . The ratio of post-1950 to 1900-1950 C AR is low (~1.5) indicating that C accumulation rates have been high throughout the 20th century. Compared to background estimates of OC burial (~5-10 g C m(-2) yr(-1) ), contemporary rates have increased by at least four to fivefold. The statistical relationship between C ARFC and TP derived from this study (r(2) = 0.5) can be used to estimate OC burial at sites lacking estimates of sediment C-burial. The implications of eutrophication, diagenesis, lake morphometry and sediment focussing as controls of OC burial rates are considered. A conservative interpretation of the results of the this study suggests that lowland European meso- to eutrophic lakes with >30 µg TP l(-1) had OC burial rates in excess of 50 g C m(-2) yr(-1) over the past century, indicating that previous estimates of regional lake OC burial have seriously underestimated their contribution to European carbon sequestration. Enhanced OC burial by lakes is one positive side-effect of the otherwise negative impact of the anthropogenic disruption of nutrient cycles.

Land-use change, not climate, controls organic carbon burial in lakes.

Lakes are a central component of the carbon cycle, both mineralizing terrestrially derived organic matter and storing substantial amounts of organic carbon (OC) in their sediments. However, the rates and controls on OC burial by lakes remain uncertain, as do the possible effects of future global change processes. To address these issues, we derived OC burial rates in (210)Pb-dated sediment cores from 116 small Minnesota lakes that cover major climate and land-use gradients. Rates for individual lakes presently range from 7 to 127 g C m(-2) yr(-1) and have increased by up to a factor of 8 since Euro-American settlement (mean increase: 2.8×). Mean pre-disturbance OC burial rates were similar (14-22 g C m(-2) yr(-1)) across all land-cover categories (prairie, mixed deciduous and boreal forest), indicating minimal effect of the regional temperature gradient (approx. 4 °C) on background carbon burial. The relationship between modern OC burial rates and temperature was also not significant after removal of the effect of total phosphorus. Contemporary burial rates were strongly correlated with lake-water nutrients and the extent of agricultural land cover in the catchment. Increased OC burial, documented even in relatively undisturbed boreal lake ecosystems, indicates a possible role for atmospheric nitrogen deposition. Our results suggest that globally, future land-cover change, intensification of agriculture and associated nutrient loading together with atmospheric N-deposition will enhance OC sequestration by lakes.

Reductions in paradoxical sleep time in adult rats treated neonatally with low dose domoic acid.

One hallmark of neurological dysfunction is a reduction in paradoxical sleep (PS) time. To determine if adult rats treated neonatally with low dose domoic acid have altered sleep patterns, a home cage analysis of electroencephalogram (EEG) waveforms was performed using radio telemetry. Domoate treated rats spent significantly less time in PS than controls during daytime hours even though they spent the same total amount of time sleeping, and showed no difference in stage shifts into the PS stage.

Valacyclovir for the management of herpes viral infections.

The Herpesviridae family (Types 1-8) continues to inflict considerable morbidity and social stigma upon humanity. Once infected with the herpes viruses, especially Types 1-3, they establish permanent residence within our nervous system and reactivate during periods of stress, trauma, and/or other precipitating factors. To date, there is no cure for herpes viral infections but antivirals can attenuate the symptoms and duration of episodic outbreaks. Prophylactic therapy can suppress recurrences. The first antiviral with selective activity against virus-infected cells is considered to be acyclovir. Our article will highlight the clinical indications of the current generation, valacyclovir, which is a prodrug of acyclovir. We consider valacyclovir as a second-generation antiviral, having taken into account the initial selectivity and safety profile of its progenitor, acyclovir.

Assessing population structure and gene flow in Montana wolverines (Gulo gulo) using assignment-based approaches.

In North America, wolverines once occupied a continuous range from Alaska southward to New Mexico. In the lower 48 states, small remnant populations remain only in the northwestern United States. Among these remnant populations, the Montana population has the highest probability of long-term persistence given its size and proximity to healthy populations in Canada. In this study, we evaluate population genetic structure and gene flow among Montana wolverines using 10 polymorphic microsatellite loci. Bayesian and frequency-based assignment tests revealed significant population substructure and provide support for at least three subpopulations in Montana. FST values between subpopulations ranged from 0.08 to 0.10 and provide evidence for male-biased dispersal. The high degree of population substructure and low levels of gene flow contrast results from wolverine population genetic studies in less fragmented landscapes of Alaska and Canada. This study provides additional support for the hypothesis that large carnivore populations of Montana are becoming increasingly fragmented due to human development and disturbance.

Endogenous beta-carbolines as clonidine-displacing substances.

Endogenous beta-carbolines, such as harmane, are known to occur in mammalian species including humans. Radioligand binding studies have revealed that certain beta-carbolines display high affinity for both I(1) and I(2) imidazoline-binding sites (IBS). Functional studies have shown that the beta-carboline harmane elicits many characteristics expected of an endogenous ligand IBS. This article discusses the evidence relating to beta-carbolines as endogenous ligands and presents a case for harmane and related compounds as endogenous ligands for IBS.

Characterization of [(3)H]harmane binding to rat whole brain membranes.

This study investigates the binding of [(3)H]harmane to rat whole brain homogenates. Saturation studies revealed [(3)H]harmane labels a single, saturable, high-capacity population with high affinity. All the test compounds displaced [(3)H]harmane completely and in an apparently monophasic manner. The displacement profile of the test ligands indicated labeling of MAO-A. Given the high level of MAO-A binding, it is unlikely that a low-capacity I(2) site would be distinguishable from the total [(3)H]harmane population.

Complete characterisation of thermally treated sludges.

As disposal options for sludges become more difficult to find and more expensive to operate, those relying on some form of thermal treatment are becoming more commercially attractive. The incentive, especially for more heavily populated countries, is the production of treated solids suitable for beneficial application to land. It is the level of treatment required to achieve this cost effectively which has been the focus of much of the research in this field. There are now several commercially available plants designed to thermally treat sludges and many have been in full scale operation for a number of years. One of the auxiliary claims often made by proponents of such treatments, is that the resultant sludges are more amenable to dewatering and therefore easier and cheaper to handle. In this work we have used a novel filtration rig to obtain complete sets of filtration data for different sludges. Historically sludge characterisation has been achieved by measurement of an empirical Capillary Suction Time (CST) parameter, however with the new filtration apparatus it is now possible to obtain fundamental sludge characteristics across a wide range of volume fractions in hours not days. We have applied this technology to characterise different sludge samples before and after thermal treatment under different sets of operating conditions (pH, temperature and pressure) to simulate some of the commercially available thermal treatment technologies. We have also examined the effects of various chemical oxidants (hydrogen peroxide and Fenton's reagent) used as pretreatments to the thermal process and attempted to compare their cost efficiencies. The results show that the physical structure of the sludge is irreversibly altered by decreasing the pH or heating to temperatures in excess of 150 degrees C in a way which significantly enhances the dewaterability of the material. The treated sludge not only has a higher permeability but also has a higher final per cent solids (often in the autothermal region). In contrast the amounts of chemical additives used in pretreatment to achieve similar effects are cost prohibitive.

Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome.

OBJECTIVE: To investigate the natural history and predictors of outcome of posthaemorrhagic ventriculomegaly in the very low birthweight (VLBW) infant. METHODS: All VLBW infants admitted between September 1994 and September 1997 to the neonatal intensive care units of Brigham and Women's Hospital (Boston), Children's Hospital (Boston), and Christchurch Women's Hospital (New Zealand) with germinal matrix intraventricular haemorrhage (IVH) were identified. All charts and ultrasound scans were reviewed to define the natural history and perinatal and/or postnatal factors of value in prediction of the course of posthaemorrhagic ventriculomegaly. Progressive ventricular dilatation (PVD) was defined from the results of serial cranial ultrasound scans. RESULTS: A total of 248 VLBW infants had evidence of IVH (22% of all VLBW infants, mean (SD) gestational age 26.8 (2.6) weeks). A quarter of the infants exhibited PVD. Spontaneous arrest of PVD occurred without treatment in 38% of infants with PVD. Of the remaining 62% with persistent PVD, 48% received non-surgical treatment only (pharmacological and/or drainage of cerebrospinal fluid by serial lumbar punctures), 34% received surgical treatment with insertion of a ventriculoperitoneal reservoir and/or shunt, and 18% died. The development of PVD after IVH and adverse short term outcome, such as the requirement for surgery, were predicted most strongly by the severity of IVH. CONCLUSIONS: These data reflect the natural history of PVD in the 1990s and show that, despite a slight reduction in its overall incidence, there appears to be a more aggressive course, with appreciable mortality and morbidity in the extremely premature infant. The major predictor of adverse short term outcome, defined as death or need for surgical intervention, was the severity of IVH. These findings may be valuable for the management of very small premature infants.

Pharmacokinetics of norelgestromin and ethinyl estradiol from two consecutive contraceptive patches.

The primary objective of this open-label study was to determine the pharmacokinetics of norelgestromin (NGMN) and ethinyl estradiol (EE)following two consecutive applications of a contraceptive patch (ORTHO EVRA/EVRA). Twelve healthy women wore the first patch on their abdomen for 7 days and, after removal at 168 hours (day 7), wore a second patch for 10 days (i.e., 3 days beyond the intended 7-day wear period). Blood samples were collected before and at various times up to 456 hours (day 19) after application of the first patch for analysis of NGMN and EE. Mean serum concentrations of NGMN and EE remained within the reference ranges, 0.6 to 1.2 ng/ml and 25 to 75 pg/ml, respectively, during the entire 7-day wear period after application of the first patch and for 10 days after application of the second patch; reference ranges are based on studies with ORTHO-CYCLEN/ Cilest. No patch detached spontaneously. No subject discontinued or experienced a serious adverse event.

Mercury accumulation rates and spatial patterns in lake sediments from west Greenland: a coast to ice margin transect.

The Arctic is recognized as an important focus for long-range transport of contaminants, such as mercury (Hg), from industrial regions at lower latitudes. In addition to large geographic gaps, there are few long-term retrospective time trends in arctic research, besides the Greenland ice record, to assess the onset of atmospheric pollution as well as to establish the rates of change in the terrestrial environment. In a study of sediments from 21 lakes along a 150 km transect from the coast to the ice sheet margin in the Søndre Strømfjord (Kangerlussuaq) region, we present stratigraphic evidence for elevated Hg inputs to this ice-free region on Greenland's west coast. Nineteen study lakes showed Hg concentration enrichments (HgEFconc) in surface compared to deeper sediments, with a mean HgEFconc of 3. Higher HgEFconc are found in lakes closest to the ice margin. The existence of this Hg gradient is supported by pollution Hg inventories in three 210Pb-dated cores. While 210Pb inventories and Pb pollution are higher at the coast, pollution Hg inventories are nearly 3-fold higher at the ice margin (570 micrograms m-2) than at the coast (210 micrograms m-2). These dated cores also indicate an onset of Hg pollution in the region beginning at least by the late 19th century but possibly as early as the 17th century.

Modeling diffuse phosphorus loads from land to freshwater using the sedimentary record.

Diffuse phosphorus (P) loads to a small lake, Friary Lough, in a 1 km2 agricultural subcatchment were quantified over 90 years using a palaeolimnological model. The model assumes that lake total phosphorus (TP) is lost to the sediments and to the lake outflow during periods of steady-state or is also stored within the water column during periods of non-steady-state behavior. Reconstructed TP loads during the 1991-1995 time interval of 2.05-2.53 g m-2 yr-1 are verified by hydrochemical monitoring results from the lake inflow during 1997-1998. This provides evidence for the accuracy of the palaeolomnological model and also that TP loads to the lake can be accounted for from external catchment runoff. An analysis of the TP load data in terms of catchment exports shows that there was a linear rate of increase from ca. 1946 to 1995 of 1.20-1.56 kg km-2 yr-1. The rate of increase is similar to river P load data in the larger 1480 km2 catchment taken over 17 years. The rate of TP increase to the lake is interpreted with regard to current soil P models that propose increasing and threshold soil P concentrations as the cause for increasing diffuse P loss in runoff.

The determination of RWJ-38705 (tramadol N-oxide) and its metabolites in preclinical pharmacokinetic studies using LC-MS/MS.

A rapid and reliable analytical method is described for the simultaneous determination of RWJ-38705 (tramadol N-oxide) and several of its major metabolites in the plasma of Sprague-Dawley rats and Beagle dogs. Sample preparation using solid phase extraction was followed by reversed phase liquid chromatography (LC) coupled with tandem mass spectrometric (MS/MS) detection in the positive ionization mode. The assay was linear for all analytes over concentrations ranging from approximately 6 to 2000 ng/ml. The inter-assay reproducibility was generally less than 15% while accuracy values were within 13% of theoretical. The overall recovery of the analytes ranged from approximately 40 to 64% in rat plasma and 53-75% in dog plasma. This assay has proven to be sensitive, specific and reproducible, and it has been readily implemented in preclinical PK studies. Representative plasma concentration versus time profiles resulting from administration of TNO to rats and dogs are presented in this communication.