The photosynthesis of young Panicum C4 leaves is not C3-like

Evidence is presented contrary to the suggestion that C₄ plants grow larger at elevated CO₂ because the C₄ pathway of young C₄ leaves has C₃-like characteristics, making their photosynthesis O₂ sensitive and responsive to high CO₂. We combined PAM fluorescence with gas exchange measurements to examine the O₂ dependence of photosynthesis in young and mature leaves of Panicum antidotale (C₄, NADP-ME) and P. coloratum (C₄, NAD-ME), at an intercellular CO₂ concentration of 5 Pa. P. laxum (C₃) was used for comparison. The young C₄ leaves had CO₂ and light response curves typical of C₄ photosynthesis. When the O₂ concentration was gradually increased between 2 and 40%, CO₂ assimilation rates (A) of both mature and young C₄ leaves were little affected, while the ratio of the quantum yield of photosystem II to that of CO₂ assimilation (Φ_PSII/Φ_CO2) increased more in young (up to 31%) than mature (up to 10%) C₄ leaves. A of C₃ leaves decreased by 1·3 and Φ_PSII/Φ_CO2 increased by 9-fold, over the same range of O₂ concentrations. Larger increases in electron transport requirements in young, relative to mature, C₄ leaves at low CO₂ are indicative of greater O₂ sensitivity of photorespiration. Photosynthesis modelling showed that young C₄ leaves have lower bundle sheath CO₂ concentration, brought about by higher bundle sheath conductance relative to the activity of the C₄ and C₃ cycles and/or lower ratio of activities of the C₄ to C₃ cycles.     

Detection heterogeneity in underwater visual‐census data

This study shows how capture–mark–recapture (CMR) models can provide robust estimates of detection heterogeneity (sources of bias) in underwater visual‐census data. Detection biases among observers and fish family groups were consistent between fished and unfished reef sites in Kenya, even when the overall level of detection declined between locations. Species characteristics were the greatest source of detection heterogeneity and large, highly mobile species were found to have lower probabilities of detection than smaller, site‐attached species. Fish family and functional‐group detectability were also found to be lower at fished locations, probably due to differences in local abundance. Because robust CMR models deal explicitly with sampling where not all species are detected, their use is encouraged for studies addressing reef‐fish community dynamics.     

Cost-Effectiveness of a Specialist Geriatric Medical Intervention for Frail Older People Discharged from Acute Medical Units: Economic Evaluation in a Two-Centre Randomised Controlled Trial (AMIGOS)

BackgroundPoor outcomes and high resource-use are observed for frail older people discharged from acute medical units. A specialist geriatric medical intervention, to facilitate Comprehensive Geriatric Assessment, was developed to reduce the incidence of adverse outcomes and associated high resource-use in this group in the post-discharge period.ObjectiveTo examine the costs and cost-effectiveness of a specialist geriatric medical intervention for frail older people in the 90 days following discharge from an acute medical unit, compared with standard care.MethodsEconomic evaluation was conducted alongside a two-centre randomised controlled trial (AMIGOS). 433 patients (aged 70 or over) at risk of future health problems, discharged from acute medical units within 72 hours of attending hospital, were recruited in two general hospitals in Nottingham and Leicester, UK. Participants were randomised to the intervention, comprising geriatrician assessment in acute units and further specialist management, or to control where patients received no additional intervention over and above standard care. Primary outcome was incremental cost per quality adjusted life year (QALY) gained.ResultsWe undertook cost-effectiveness analysis for 417 patients (intervention: 205). The difference in mean adjusted QALYs gained between groups at 3 months was -0.001 (95% confidence interval [CI]: -0.009, 0.007). Total adjusted secondary and social care costs, including direct costs of the intervention, at 3 months were £4412 (€5624, $6878) and £4110 (€5239, $6408) for the intervention and standard care groups, the incremental cost was £302 (95% CI: 193, 410) [€385, $471]. The intervention was dominated by standard care with probability of 62%, and with 0% probability of cost-effectiveness (at £20,000/QALY threshold).ConclusionsThe specialist geriatric medical intervention for frail older people discharged from acute medical unit was not cost-effective. Further research on designing effective and cost-effective specialist service for frail older people discharged from acute medical units is needed.

Trial Registration

ISRCTN registry ISRCTN21800480 http://www.isrctn.com/ISRCTN21800480     

Serum-Induced Differentiation of Glioblastoma Neurospheres Leads to Enhanced Migration/Invasion Capacity That Is Associated with Increased MMP9

Glioblastoma (GBM) is a highly infiltrative brain tumor in which cells with properties of stem cells, called glioblastoma stem cells (GSCs), have been identified. In general, the dominant view is that GSCs are responsible for the initiation, progression, invasion and recurrence of this tumor. In this study, we addressed the question whether the differentiation status of GBM cells is associated with their invasive capacity. For this, several primary GBM cell lines were used, cultured either as neurospheres known to enrich for GSCs or in medium supplemented with 10% FCS that promotes differentiation. The differentiation state of the cells was confirmed by determining the expression of stem cell and differentiation markers. The migration/invasion potential of these cells was tested using in vitro assays and intracranial mouse models. Interestingly, we found that serum-induced differentiation enhanced the invasive potential of GBM cells, which was associated with enhanced MMP9 expression. Chemical inhibition of MMP9 significantly reduced the invasive potential of differentiated cells in vitro. Furthermore, the serum-differentiated cells could revert back to an undifferentiated/stem cell state that were able to form neurospheres, although with a reduced efficiency as compared to non-differentiated counterparts. We propose a model in which activation of the differentiation program in GBM cells enhances their infiltrative potential and that depending on microenvironmental cues a significant portion of these cells are able to revert back to an undifferentiated state with enhanced tumorigenic potential. Thus, effective therapy should target both GSCs and differentiated offspring and targeting of differentiation-associated pathways may offer therapeutic opportunities to reduce invasive growth of GBM.     

The contribution of genetic variation and infection to the pathogenesis of ANCA-associated systemic vasculitis

The aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis has not been well defined. Here we review two factors which may play a role in the pathogenesis of the disease: genetics and infection. In particular, we discuss the role of autoantibodies to LAMP-2, which may arise following infection with Gram-negative bacteria, and may contribute to the development of ANCA-associated systemic vasculitis in genetically susceptible individuals.     

Diseases, parasites and survival of coyotes in south-central Georgia.

Serologic testing, radio-telemetry and post-mortem diagnostic evaluations were used to investigate survival and causes of mortality among 17 coyotes (Canis latrans) in south-central Georgia (USA). Prevalence of canine heartworm (Dirofilaria immitis) microfilariae was lower (P = 0.057) among fall-captured (22%) than among winter-captured (75%) coyotes. Prevalence of heartworm was higher among adults than juveniles in the fall, but no significant difference was detected between animals captured in winter. Antibodies were found against canine parvovirus (65%), canine parainfluenza virus (59%), infectious canine hepatitis virus (41%), and Toxoplasma gondii (18%). Antibodies were not found to Brucella canis, canine coronavirus, five serovars of Leptospira interrogans, or canine distemper virus. Seroprevalence of canine parvovirus was lower (P = 0.009) among fall-captured animals (33%) than winter-captured animals (100%). The Kaplan-Meier estimate of annual survival was 0.500 for all animals. Juvenile survival did not differ (P = 0.79) from adult survival, but male survival (S = 0.217) was lower (P = 0.11) than female survival (S = 0.804). Two of nine (22%) mortalities were human-caused, one was due to concurrent canine parvovirus and canine distemper virus infections, one animal died of trauma, two were considered natural mortalities of unknown cause, and no cause of death could be determined for the remaining three animals. Natural mortality may be significant for coyotes in south-central Georgia, although there was no apparent link between exposure to pathogens and the animals' subsequent fate in our small sample.     

Bronchoabsorption; a novel bronchoscopic technique to improve biomarker sampling of the airway

Background

Current techniques used to obtain lung samples have significant limitations and do not provide reproducible biomarkers of inflammation. We have developed a novel technique that allows multiple sampling methods from the same area (or multiple areas) of the lung under direct bronchoscopic vision. It allows collection of mucosal lining fluid and bronchial brushing from the same site; biopsy samples may also be taken. The novel technique takes the same time as standard procedures and can be conducted safely.

Methods

Eight healthy smokers aged 40–65 years were included in this study. An absorptive filter paper was applied to the bronchial mucosa under direct vision using standard bronchoscopic techniques. Further samples were obtained from the same site using bronchial brushings. Bronchoalveolar lavage (BAL) was obtained using standard techniques. Chemokine (C-C Motif) Ligand 20 (CCL20), CCL4, CCL5, Chemokine (C-X-C Motif) Ligand 1 (CXCL1), CXCL8, CXCL9, CXCL10, CXCL11, Interleukin 1 beta (IL-1β), IL-6, Vascular endothelial growth factor (VEGF), Matrix metalloproteinase 8 (MMP-8) and MMP-9 were measured in exudate and BAL. mRNA was collected from the bronchial brushings for gene expression analysis.

Results

A greater than 10 fold concentration of all the biomarkers was detected in lung exudate in comparison to BAL. High yield of good quality RNA with RNA integrity numbers (RIN) between 7.6 and 9.3 were extracted from the bronchial brushings. The subset of genes measured were reproducible across the samples and corresponded to the inflammatory markers measured in exudate and BAL.

Conclusions

The bronchoabsorption technique as described offers the ability to sample lung fluid direct from the site of interest without the dilution effects caused by BAL. Using this method we were able to successfully measure the concentrations of biomarkers present in the lungs as well as collect high yield mRNA samples for gene expression analysis from the same site. This technique demonstrates superior sensitivity to standard BAL for the measurement of biomarkers of inflammation. It could replace BAL as the method of choice for these measurements. This method provides a systems biology approach to studying the inflammatory markers of respiratory disease progression.

Trial registration

NHS Health Research Authority (13/LO/0256).     

SCNVSim: somatic copy number variation and structure variation simulator

Background

Somatically acquired structure variations (SVs) and copy number variations (CNVs) can induce genetic changes that are directly related to tumor genesis. Somatic SV/CNV detection using next-generation sequencing (NGS) data still faces major challenges introduced by tumor sample characteristics, such as ploidy, heterogeneity, and purity. A simulated cancer genome with known SVs and CNVs can serve as a benchmark for evaluating the performance of existing somatic SV/CNV detection tools and developing new methods.

Results

SCNVSim is a tool for simulating somatic CNVs and structure variations SVs. Other than multiple types of SV and CNV events, the tool is capable of simulating important features related to tumor samples including aneuploidy, heterogeneity and purity.

Conclusions

SCNVSim generates the genomes of a cancer cell population with detailed information of copy number status, loss of heterozygosity (LOH), and event break points, which is essential for developing and evaluating somatic CNV and SV detection methods in cancer genomics studies.     

Complement activation: a critical mediator of adverse fetal outcomes in placental malaria?

Malaria infection is a significant risk factor for low birth weight outcomes in pregnancy. Despite efforts to define the molecular mechanisms that cause low birth weight as a result of intrauterine growth restriction, the roles of inflammation and mononuclear cells in the process are incompletely understood. Data from adverse pregnancy outcomes in humans and from murine models of pathological pregnancies suggest that C5a could be an important upstream regulator of placental angiogenesis, and excessive C5a could lead to functional placental insufficiency by impairing adequate vascularization of the placenta. Based on recent evidence, we hypothesize that complement factor C5a is a central initiator of poor birth outcomes associated with placental malaria by promoting mononuclear cell migration, activation and dysregulated angiogenesis.     

Finding fossils in new ways: an artificial neural network approach to predicting the location of productive fossil localities

Chance and serendipity have long played a role in the location of productive fossil localities by vertebrate paleontologists and paleoanthropologists. We offer an alternative approach, informed by methods borrowed from the geographic information sciences and using recent advances in computer science, to more efficiently predict where fossil localities might be found. Our model uses an artificial neural network (ANN) that is trained to recognize the spectral characteristics of known productive localities and other land cover classes, such as forest, wetlands, and scrubland, within a study area based on the analysis of remotely sensed (RS) imagery. Using these spectral signatures, the model then classifies other pixels throughout the study area. The results of the neural network classification can be examined and further manipulated within a geographic information systems (GIS) software package. While we have developed and tested this model on fossil mammal localities in deposits of Paleocene and Eocene age in the Great Divide Basin of southwestern Wyoming, a similar analytical approach can be easily applied to fossil-bearing sedimentary deposits of any age in any part of the world. We suggest that new analytical tools and methods of the geographic sciences, including remote sensing and geographic information systems, are poised to greatly enrich paleoanthropological investigations, and that these new methods should be embraced by field workers in the search for, and geospatial analysis of, fossil primates and hominins.