Integrated landscape approaches to managing social and environmental issues in the tropics: learning from the past to guide the future

Poverty, food insecurity, climate change and biodiversity loss continue to persist as the primary environmental and social challenges faced by the global community. As such, there is a growing acknowledgement that conventional sectorial approaches to addressing often inter‐connected social, environmental, economic and political challenges are proving insufficient. An alternative is to focus on integrated solutions at landscape scales or ‘landscape approaches’. The appeal of landscape approaches has resulted in the production of a significant body of literature in recent decades, yet confusion over terminology, application and utility persists. Focusing on the tropics, we systematically reviewed the literature to: (i) disentangle the historical development and theory behind the framework of the landscape approach and how it has progressed into its current iteration, (ii) establish lessons learned from previous land management strategies, (iii) determine the barriers that currently restrict implementation of the landscape approach and (iv) provide recommendations for how the landscape approach can contribute towards the fulfilment of the goals of international policy processes. This review suggests that, despite some barriers to implementation, a landscape approach has considerable potential to meet social and environmental objectives at local scales while aiding national commitments to addressing ongoing global challenges.     

A consensus view of the proteome of the last universal common ancestor

The availability of genomic and proteomic data from across the tree of life has made it possible to infer features of the genome and proteome of the last universal common ancestor (LUCA). A number of studies have done so, all using a unique set of methods and bioinformatics databases. Here, we compare predictions across eight such studies and measure both their agreement with one another and with the consensus predictions among them. We find that some LUCA genome studies show a strong agreement with the consensus predictions of the others, but that no individual study shares a high or even moderate degree of similarity with any other individual study. From these observations, we conclude that the consensus among studies provides a more accurate depiction of the core proteome of the LUCA and its functional repertoire. The set of consensus LUCA protein family predictions between all of these studies portrays a LUCA genome that, at minimum, encoded functions related to protein synthesis, amino acid metabolism, nucleotide metabolism, and the use of common, nucleotide‐derived organic cofactors.     

Enzyme kinetic and molecular modelling studies of sulphur-containing substrates of phenylalanine 4-monooxygenase

Previous investigations into the binding of substrates/cofactors to the PAH active site have only concentrated on Phe, thienylalanine and BH₄. This is the first reported investigation to model aliphatic thioether amino acid substrates to PAH. The clearance of the thioether substrates (4.82-79.09% of Phe) in the rat and human (1.19-37.41% of Phe) showed species differences. The xenobiotic thioether substrates (SMC and SCMC) were predicted to be poor substrates for PAH by the molecular modelling investigation and this has now been confirmed by the in vitro enzyme kinetic data. However, reaction phenotyping investigations have found that PAH was the major enzyme involved in the metabolism of SCMC in vitro and in vivo.     

Inclusion of Plasma Lipid Species Improves Classification of Individuals at Risk of Type 2 Diabetes

Background

A significant proportion of individuals with diabetes or impaired glucose tolerance have fasting plasma glucose less than 6.1 mmol/L and so are not identified with fasting plasma glucose measurements. In this study, we sought to evaluate the utility of plasma lipids to improve on fasting plasma glucose and other standard risk factors for the identification of type 2 diabetes or those at increased risk (impaired glucose tolerance).

Methods and Findings

Our diabetes risk classification model was trained and cross-validated on a cohort 76 individuals with undiagnosed diabetes or impaired glucose tolerance and 170 gender and body mass index matched individuals with normal glucose tolerance, all with fasting plasma glucose less than 6.1 mmol/L. The inclusion of 21 individual plasma lipid species to triglycerides and HbA1c as predictors in the diabetes risk classification model resulted in a statistically significant gain in area under the receiver operator characteristic curve of 0.049 (p<0.001) and a net reclassification improvement of 10.5% (p<0.001). The gain in area under the curve and net reclassification improvement were subsequently validated on a separate cohort of 485 subjects.

Conclusions

Plasma lipid species can improve the performance of classification models based on standard lipid and non-lipid risk factors.     

Phenotypic,Ultra-Structural,and Functional Characterization of Bovine Peripheral Blood Dendritic Cell Subsets

Dendritic cells (DC) are multi-functional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets directly ex vivo, without further in vitro manipulation. Multi-color flow cytometric analysis revealed that three DC subsets could be identified. Bovine plasmacytoid DC were phenotypically identified by a unique pattern of cell surface protein expression including CD4, exhibited an extensive endoplasmic reticulum and Golgi apparatus, efficiently internalized and degraded exogenous antigen, and were the only peripheral blood cells specialized in the production of type I IFN following activation with Toll-like receptor (TLR) agonists. Conventional DC were identified by expression of a different pattern of cell surface proteins including CD11c, MHC class II, and CD80, among others, the display of extensive dendritic protrusions on their plasma membrane, expression of very high levels of MHC class II and co-stimulatory molecules, efficient internalization and degradation of exogenous antigen, and ready production of detectable levels of TNF-alpha in response to TLR activation. Our investigations also revealed a third novel DC subset that may be a precursor of conventional DC that were MHC class II⁺ and CD11c⁻. These cells exhibited a smooth plasma membrane with a rounded nucleus, produced TNF-alpha in response to TLR-activation (albeit lower than CD11c⁺ DC), and were the least efficient in internalization/degradation of exogenous antigen. These studies define three bovine blood DC subsets with distinct phenotypic and functional characteristics which can be analyzed during immune responses to pathogens and vaccinations of cattle.     

Longitudinal trends in concentration and composition of dissolved organic nitrogen (DON) in a largely unregulated river system

Dissolved organic nitrogen (DON) can comprise up to 80% of the dissolved N pool in riverine ecosystems, but concentration and compositional responses to catchment conditions has received limited attention. We examined the suite of nitrogenous nutrients along the length of the Ovens River, Victoria, Australia, a river with identifiable regions of native vegetation, agricultural activity and floodplain forest connection, carrying out longitudinal surveys in winter during a period of high flow and in summer during a period of stable base flow. We examined: the concentrations of DON, the proportion of DON that occurs as dissolved combined amino acids (DCAAs), whether concentration and DCAA composition varied between flow and whether land-use and tributaries have an impact upon nutrient concentration and DON composition. DON concentrations were greater than dissolved inorganic nitrogen under both base flow and high flow conditions. Under base flow DON exhibited a continuous increase in concentration downstream (ranging from 50 to 300 μg/L), compared to a much larger increase under high flow (150–600 μg/L) coupled with a major discrete increase of ~?350 μg/L at a tributary input (King River). Concentrations of NO_x (oxides of nitrogen) species were much higher under high flow conditions (range 50–250 μg/L) compared to 0–50 µg/L at base flow, and showed a significant increase in concentration with distance downstream. A discrete change in NO_x concentrations was also observed at the King River confluence under high flow, although in this case causing a decrease in concentration of ~100 µg/L. DCAA concentrations varied little along the length of the river at base flow but increased with distance downstream at high flow. The DCAA concentrations were of the same order of magnitude as ammonium at both base and high flows and nitrate concentrations at base flow. The proportion of DON that was in the form of DCAA was reasonably uniform during high flow (3–6%), but highly variable at base flow (5–44%). The amino acid (AA) composition of the DCAA varied along the river and differed between flow regimes (except below the confluence with the King River where AA composition under the two flow conditions converged) suggesting a strong influence of land use. We show that DON is potentially a large component (4–81%) of the total N budget and given that 5–23% is in the form of peptide/protein, represents an important source of N. DON and more specifically DCAAs should therefore be considered both when constructing N budgets and monitoring levels of in-stream nitrogen.     

The effect of selective phosphodiesterase inhibitors,alone and in combination,on a murine model of allergic asthma

BackgroundThe anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control.MethodsControl and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days.ResultsWhen used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-α, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice. Treatment with cilostazol or sildenafil did not significantly inhibit any markers of inflammation measured. Combining any of these PDE inhibitors produced no additive or synergistic effects. Indeed, the anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of either cilostazol or sildenafil.ConclusionsThese results suggest that concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti-inflammatory effectiveness of a PDE 4 inhibitor.     

Star-PAP control of BIK expression and apoptosis is regulated by nuclear PIPKIα and PKCδ signaling

BIK protein is an initiator of mitochondrial apoptosis, and BIK expression is induced by proapoptotic signals, including DNA damage. Here, we demonstrate that 3' end processing and expression of BIK mRNA are controlled by the nuclear PI4,5P(2)-regulated poly(A) polymerase Star-PAP downstream of DNA damage. Nuclear PKCδ is a key mediator of apoptosis, and DNA damage stimulates PKCδ association with the Star-PAP complex where PKCδ is required for Star-PAP-dependent BIK expression. PKCδ binds the PI4,5P(2)-generating enzyme PIPKIα, which is essential for PKCδ interaction with the Star-PAP complex, and PKCδ activity is directly stimulated by PI4,5P(2). Features in the BIK 3' UTR uniquely define Star-PAP specificity and may block canonical PAP activity toward BIK mRNA. This reveals a nuclear phosphoinositide signaling nexus where PIPKIα, PI4,5P(2), and PKCδ regulate Star-PAP control of BIK expression and induction of apoptosis. This pathway is distinct from the Star-PAP-mediated oxidative stress pathway indicating signal-specific regulation of mRNA 3' end processing.