Current Practices in Reporting Uncertainty in Ecosystem Ecology

Ecosystem budgets of water and elements can be difficult to estimate and are often unreplicated, making it challenging to provide confidence in estimates of ecosystem pools and fluxes. We conducted a survey to learn about current practices in reporting uncertainties in precipitation, streamflow, soils, and vegetation. Uncertainty derives from natural variation, which is commonly characterized by replicate samples, and from imperfect knowledge, which includes measurement error and model error (model fit and model selection). We asked questions about whether researchers report uncertainties in these sources, whether they know how to do so, and how important they believe the sources to be. We also asked questions about identifying missing or unusable values, filling gaps in data, and dealing with analytical concentrations below detection limits. We obtained responses from 140 researchers representing 90 research sites around the world. Natural variation was the most important source of uncertainty in calculations of biomass and soil pools, according to respondents in these fields, and sampling error was the source they most often reported. In contrast, uncertainty in the chemical analysis of precipitation and stream water was the source most commonly reported by hydrologists, although they rated this one of the least important sources of uncertainty to calculations of hydrologic flux. Awareness of types of uncertainty can help identify sources of uncertainty that may have been overlooked, and quantifying them will help determine which sources are most important to report.     

Protein kinase A site-specific phosphorylation regulates ATP-binding cassette A1 (ABCA1)-mediated phospholipid efflux

ATP-binding cassette A1 (ABCA1) is a key mediator of cholesterol and phospholipid efflux to apolipoprotein particles. We show that ABCA1 is a constitutively phosphorylated protein in both RAW macrophages and in a human embryonic kidney cell line expressing ABCA1. Furthermore, we demonstrate that phosphorylation of ABCA1 is mediated by protein kinase A (PKA) or a PKA-like kinase in vivo. Through site-directed mutagenesis studies of consensus PKA phosphorylation sites and in vitro PKA kinase assays, we show that Ser-1042 and Ser-2054, located in the nucleotide binding domains of ABCA1, are major phosphorylation sites for PKA. ApoA-I-dependent phospholipid efflux was decreased significantly by mutation of Ser-2054 alone and Ser-1042/Ser-2054 but was not significantly impaired with Ser-1042 alone. The mechanism by which ABCA1 phosphorylation affected ApoA-I-dependent phospholipid efflux did not involve either alterations in ApoA-I binding or changes in ABCA1 protein stability. These studies demonstrate a novel serine (Ser-2054) on the ABCA1 protein crucial for PKA phosphorylation and for regulation of ABCA1 transporter activity.     

Quorum Sensing in <Emphasis Type="Italic">Aeromonas</Emphasis> Species Isolated from Patients in Malaysia

Bacterial quorum sensing signal molecules called N-acylhomoserine lactone (AHL) controls the expression of virulence determinants in many Gram-negative bacteria. We determined AHL production in 22 Aeromonas strains isolated from various infected sites from patients (bile, blood, peritoneal fluid, pus, stool and urine). All isolates produced the two principal AHLs, N-butanoylhomoserine lactone (C4-HSL) and N-hexanoyl homoserine lactone (C6-HSL). Ten isolates also produced additional AHLs. This report is the first documentation of Aeromonas sobria producing C6-HSL and two additional AHLs with N-acyl side chain longer than C₆. Our data provides a better understanding of the mechanism(s) of this environmental bacterium emerging as a human pathogen.     

Polarization Orientation,Piezoelectricity, and Energy Harvesting Performance of Ferroelectric PVDF‐TrFE Nanotubes Synthesized by Nanoconfinement

1D nanostructures of soft ferroelectric materials exert promising potential in the fields of energy harvesting and flexible and printed nanoelectronics. Here, improved piezoelectric properties, energy‐harvesting performance, lower coercive fields, and the polarization orientation of poly(vinylidene fluoride–trifluoroethylene) (PVDF‐TrFE) nanotubes synthesized with nanoconfinement effect are reported. X‐ray diffraction (XRD) patterns of the nanotubes show the peak corresponding to the planes of (110)/(200), which is a signature of ferroelectric beta phase formation. Piezoforce spectroscopy measurements on the free‐standing horizontal nanotubes bundles reveal that the effective polarization direction is oriented at an inclination to the long axis of the nanotubes. The nanotubes exhibit a coercive field of 18.6 MV m^?1 along the long axis and 40 MV m^?1 (13.2 MV m^?1 considering the air gap) in a direction perpendicular to the long axis, which is lower than the film counterpart of 50 MV m^?1. The poled 200 nm nanotubes, with 40% reduction in poling field, give larger piezoelectric d₃₃ coefficient values of 44 pm V^?1, compared to poled films (≈20 pm V^?1). The ferroelectric nanotubes deliver superior energy harvesting performance with an output voltage of ≈4.8 V and power of 2.2 μW cm^?2, under a dynamic compression pressure of 0.075 MPa at 1 Hz.     

Focal Radiation Therapy Combined with 4-1BB Activation and CTLA-4 Blockade Yields Long-Term Survival and a Protective Antigen-Specific Memory Response in a Murine Glioma Model

Background

Glioblastoma (GBM) is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4) blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against a variety of solid tumors. 4-1BB (CD137) is expressed by activated T lymphocytes and served as a co-stimulatory signal, which promotes cytotoxic function. Here, we evaluate a combination immunotherapy regimen involving 4-1BB activation, CTLA-4 blockade, and focal radiation therapy in an immune-competent intracranial GBM model.

Methods

GL261-luciferace cells were stereotactically implanted in the striatum of C57BL/6 mice. Mice were treated with a triple therapy regimen consisted of 4-1BB agonist antibodies, CTLA-4 blocking antibodies, and focal radiation therapy using a small animal radiation research platform and mice were followed for survival. Numbers of brain-infiltrating lymphocytes were analyzed by FACS analysis. CD4 or CD8 depleting antibodies were administered to determine the relative contribution of T helper and cytotoxic T cells in this regimen. To evaluate the ability of this immunotherapy to generate an antigen-specific memory response, long-term survivors were re-challenged with GL261 glioma en B16 melanoma flank tumors.

Results

Mice treated with triple therapy had increased survival compared to mice treated with focal radiation therapy and immunotherapy with 4-1BB activation and CTLA-4 blockade. Animals treated with triple therapy exhibited at least 50% long-term tumor free survival. Treatment with triple therapy resulted in a higher density of CD4⁺ and CD8⁺ tumor infiltrating lymphocytes. Mechanistically, depletion of CD4⁺ T cells abrogated the antitumor efficacy of triple therapy, while depletion of CD8⁺ T cells had no effect on the treatment response.

Conclusion

Combination therapy with 4-1BB activation and CTLA-4 blockade in the setting of focal radiation therapy improves survival in an orthotopic mouse model of glioma by a CD4⁺ T cell dependent mechanism and generates antigen-specific memory.     

Epidemiology and management of gout in Taiwan: a nationwide population study

IntroductionGout is the most common inflammatory arthritis worldwide and is the only type of chronic arthritis that potentially can be ‘cured’. However, data on gout incidence, prevalence and management, assessed at multiple time points in the same population, are sparse, particularly in Asian populations. The aim of this study was to describe trends in the epidemiology of gout in the general population of Taiwan.MethodsThe National Health Insurance Research Database was used to identify patients with gout and to estimate the prevalence and incidence of gout for each calendar year from 2005 to 2010. The pattern of gout management was also examined.ResultsOf 23,371,362 beneficiaries in 2010, there were 1,458,569 prevalent and 56,595 incident cases of gout, giving a prevalence of 6.24% (95% confidence interval (CI), 6.23% to 6.25%) and an incidence of 2.74 (95% CI, 2.72 to 2.76) per 1,000 person-years. The annual percentage change (APC) of the standardised prevalence was −0.7% (95% CI, −1.7% to 0.3%; P = 0.14), suggesting that the prevalence of gout was essentially the same throughout the study period. However, The APC of incidence was −13.4 (95% CI, −16.1 to −10.6) between 2005 and 2007 and −2.1 (95% CI, −10.4 to 7.1) between 2007 and 2010. Regions with the highest prevalence and incidence were eastern coastal counties and offshore islets, where indigenous people are clustered. Among prevalent gout cases in 2010, only 22.93% (95% CI, 22.87% to 23.00%) were prescribed urate-lowering treatment (ULT), which remained unchanged between 2005 and 2010 at an APC of 0.0 (95% CI, −3.8 to 4.0). Uricosuric agents were more commonly prescribed than xanthine oxidase inhibitors in Taiwan.ConclusionsIn Taiwan, 1 in 16 people have gout. Whereas the incidence has decreased recently, the prevalence remains unchanged. Management of gout in Taiwan is poor, with only one in five affected people being treated with ULT.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0522-8) contains supplementary material, which is available to authorized users.     

Chronic neuroleptic treatment in rats produces persisting changes in GABAA and dopamine D-2, but not dopamine D-1 receptors

The effects of continuous treatment with haloperidol (HAL) or fluphenazine (FLU) for 10 months on dopamine and GABA receptors in the rat brain was examined using in vitro autoradiography. Rats treated with HAL, but not FLU, showed an increase in D-2 receptor binding in the caudate-putamen as revealed by [3H]spiperone. Labeling of D-1 receptors by [3H]SCH23390 revealed no changes in either drug-treated group. Both drug-treated groups, however, exhibited a significant increase in [3H]muscimol binding in substantia nigra, pars reticulata (SNR). These dopaminergic-GABAergic receptor alterations may be related to previously reported changes in oral movement activity seen in these neuroleptic-treated animals.     

Partial purification and properties of rat liver mitochondrial polynucleotide phosphorylase

1. Polynucleotide phosphorylase was partially purified from the inner membrane of rat liver mitochondria. 2. The partially purified particulate enzyme catalyses phosphorolysis of poly(A), poly(C), poly(U) and RNA to nucleoside diphosphates. 3. It is devoid of nucleoside diphosphate-polymerization activity. 4. Variable amounts of ADP/P(i)-exchange activity are associated with the polynucleotide phosphorylase and are probably due to a different enzyme. 5. ADP is the preferred substrate for exchange, and little or no reaction occurs with other nucleoside diphosphates, but ATP/P(i)-exchange takes place at one-third the rate observed with ADP. 6. The partially purified enzyme is free from the phosphatases found in the crude mitochondrial inner membrane, but is associated with an endonuclease activity and some adenylate kinase activity; no cytidylate kinase activity analogous to the latter was detectable.     

Translocation and binding of adenine nucleotides by rat liver mitochondria partially depleted of phospholipids.

1. Rat liver mitochondria were partially depleted of their phospholipids using phospholipase A prepared from porcine pancreas (substrate specificity, cardiolipin greater than phosphatidylethanolamine greater than phosphatidylcholine) or from Crotalus adamanteus venom (substrate specificity, phosphatidylethanolamine = phosphatidylcholine greater than cardiolipin). 2. Removal of only about 1% of the mitochondrial phospholipid with the pancreatic enzyme leads to 50% and 25% losses in ADP and ATP translocation, respectively. Concomitant with the loss in translocation is a decline in the ability of both carbonylcyanide m-chlorophenylhydrazone and Ca2+ to stimulate ATP translocation. 3. To achieve comparable losses in ADP and ATP translocation with the venom enzyme, it is necessary to remove about 8% of the total mitochondrial phospholipid. Following such treatment, carbonylcyanide m-chlorophenylhydrazone and Ca2+ are still capable of stimulating ATP translocation. 4. Control experiments involving treatment of the mitochondria with the products of phospholipase digestion indicate that the effects observed on the translocase reflect a loss of phospholipid from the membrane. 5. Binding studies indicate that the loss in adenine nucleotide translocation following phospholipase treatment cannot be accoundted for by an altered ability to bind adenine nucleotides to atractyloside-sensitive sites. 6. The data are interpreted in terms of a mechanism of adenine nucleotide translocation involving a lipoprotein carrier system, consisting of the translocator protein and phospholipids, possibly cardiolipin and phosphatidylethanolamine.