Characterizing the effect of glutamine supplementation on asparagine and glutamine metabolism using 13C metabolic flux analysis

Upstream development efforts often focus on improved productivity. Among those efforts, improvements in medium formulations have translated into greater titers. To continue this historical trend, a better understanding of the cell metabolism is warranted for guiding efficient utilization of medium components to improve titer while minimizing byproducts. 13C Metabolic Flux Analysis (13C MFA) offers opportunities to study metabolic phenotypes by applying isotope tracers to estimate the intracellular fluxes through metabolic pathways. In this work, 13C MFA was applied to study the effects of glutamine supplementation by 13C parallel labelling of cultures with [U-13C]asparagine, [U-13C]glutamine and an a mixture of [U-13C]glucose with [1,2-13C]glucose. The study was focused on two metabolic states characterized by glutamine consumption in the early exponential phase and glutamine production in the late exponential phase of a fed-batch culture. To quantify individual metabolic pathway activity, metabolic flux maps were generated for the glutamine supplemented feeds compared to a control case with glutamine in the initial medium. The glutamine supplementation condition resulted in redistribution of the fluxes in the TCA cycle. Furthermore, measurements of the enrichment of cell protein indicate different allocations of the fed nutrients into generated biomass for the glutamine supplemented condition. Comparison between the early and the late exponential phases provided novel insights on how glutamine modulates CHO central carbon metabolism and supports the important role of glutamine as a major source of energy for cell proliferation. These findings contribute towards an improved characterization of the metabolism of industrial cells with useful implications for optimizing medium and feed development

Prevalence of pre-cancerous lesions and cervical cancer in South Africa - A multicentre study

Objectives. To describe the age-specific prevalence rates of cancer of the cervix in South African women presenting for screening.Design. A multicentre prevalence survey in 10 geographically defined areas following a common core protocol. Services were located in existing service sites, with the exception of KwaZulu-Natal which used a mobile service. Women aged 20 years and above were eligible for inclusion.Outcome measures. Age-specific cervical cytologically diagnosed abnormality rates according to the Bethesda classification.Results. During the study 20 603 women participated. Eighty per cent of the sample had never had a Pap smear before and just over 91 % had not had a Pap smear in the last 5 years. Inthis study population 468 women screened (2.42%) were found to have low-grade squamous intra-epithelial lesions (LSIL) and the average age of these women was 33.1 years; 366 (1.8%) had high-grade SIL (HSIL) and these women were statistically significantly older at 37.97 years of age; and 92 women (0.47%) were found to have cytologically diagnosed invasive cancer. These women were significantly older, with an average age of 51.3 years. A clear relationship was found between age and LSIL, with younger women having a high rate of LSIL which decreases with increasing age. A similar but inverse relationship between age and invasive cancer is described, with the rate being low in young women and increasing with increasing age. A clear relationship between HSIL and age is not described in these data. The adequacy rate (satisfactory and satisfactory but limited) of the slides was 95%, and just under 92% of the study sample received their results. Not all women were appropriately referred and it was not possible to assess if women referred for treatment received it.Conclusions. These data indicate that cancer of the cervix is a common disease and that, similar to other countries, it is a disease of older women. These data give some positive indicators for future screening - older women will present for screening and the majority of women received their results. However, improvements in health system functioning are needed. A uniform national cytology reporting system is required as well as clear guidelines for providers on what action to take based on cytology reports. Linkage between the site of screening and treatment centre is inadequate and requires urgent attention in order to decrease cervical cancer mortality

Global no net loss of natural ecosystems

A global goal of no net loss of natural ecosystems or better has recently been proposed, but such a goal would require equitable translation to country-level contributions. Given the wide variation in ecosystem depletion, these could vary from net gain (for countries where restoration is needed), to managed net loss (in rare circumstances where natural ecosystems remain extensive and human development imperative is greatest). National contributions and international support for implementation also must consider non-area targets factors such as the capacity to conserve and the imperative for human development

Measuring Global Trends in the Status of Biodiversity: Red List Indices for Birds

The rapid destruction of the planet's biodiversity has prompted the nations of the world to set a target of achieving a significant reduction in the rate of loss of biodiversity by 2010. However, we do not yet have an adequate way of monitoring progress towards achieving this target. Here we present a method for producing indices based on the IUCN Red List to chart the overall threat status (projected relative extinction risk) of all the world's bird species from 1988 to 2004. Red List Indices (RLIs) are based on the number of species in each Red List category, and on the number changing categories between assessments as a result of genuine improvement or deterioration in status. The RLI for all bird species shows that their overall threat status has continued to deteriorate since 1988. Disaggregated indices show that deteriorations have occurred worldwide and in all major ecosystems, but with particularly steep declines in the indices for Indo-Malayan birds (driven by intensifying deforestation of the Sundaic lowlands) and for albatrosses and petrels (driven by incidental mortality in commercial longline fisheries). RLIs complement indicators based on species population trends and habitat extent for quantifying global trends in the status of biodiversity. Their main weaknesses are that the resolution of status changes is fairly coarse and that delays may occur before some status changes are detected. Their greatest strength is that they are based on information from nearly all species in a taxonomic group worldwide, rather than a potentially biased subset. At present, suitable data are only available for birds, but indices for other taxonomic groups are in development, as is a sampled index based on a stratified sample from all major taxonomic groups

Photographic protocol for image acquisition in craniofacial microsomia

Craniofacial microsomia (CFM) is a congenital condition associated with orbital, mandibular, ear, nerve, and soft tissue anomalies. We present a standardized, two-dimensional, digital photographic protocol designed to capture the common craniofacial features associated with CFM

Protecting Important Sites for Biodiversity Contributes to Meeting Global Conservation Targets

Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as ‘important sites’). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45–1.14% annually since 1950 for IBAs and 0.79–1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends

Local conditions and policy design determine whether ecological compensation can achieve No Net Loss goals.

Funder: Science for Nature and People Partnership Australian Research Council Discovery Early Career Research Award (DE170100684) Australian Research Council Future Fellowship (FT140100516) The Australian Government’s National Environmental Science Program through the Threatened Species Recovery Hub Agence Française de Développement Fonds Français pour l'environnement Mondial Mava FoundationFunder: Science for Nature and People Partnership Australian Research Council Future Fellowship FT140100516 National Environmental Science Program's Threatened Species Recovery HubMany nations use ecological compensation policies to address negative impacts of development projects and achieve No Net Loss (NNL) of biodiversity and ecosystem services. Yet, failures are widely reported. We use spatial simulation models to quantify potential net impacts of alternative compensation policies on biodiversity (indicated by native vegetation) and two ecosystem services (carbon storage, sediment retention) across four case studies (in Australia, Brazil, Indonesia, Mozambique). No policy achieves NNL of biodiversity in any case study. Two factors limit their potential success: the land available for compensation (existing vegetation to protect or cleared land to restore), and expected counterfactual biodiversity losses (unregulated vegetation clearing). Compensation also fails to slow regional biodiversity declines because policies regulate only a subset of sectors, and expanding policy scope requires more land than is available for compensation activities. Avoidance of impacts remains essential in achieving NNL goals, particularly once opportunities for compensation are exhausted

Synergies between the key biodiversity area and systematic conservation planning approaches

Systematic conservation planning and Key Biodiversity Areas (KBAs) are the two most widely used approaches for identifying important sites for biodiversity. However, there is limited advice for conservation policy makers and practitioners on when and how they should be combined. Here we provide such guidance, using insights from the recently developed Global Standard for the Identification of KBAs and the language of decision science to review and clarify their similarities and differences. We argue the two approaches are broadly similar, with both setting transparent environmental objectives and specifying actions. There is however greater contrast in the data used and actions involved, as the KBA approach uses biodiversity data alone and identifies sites for monitoring and vigilance actions at a minimum, whereas systematic conservation planning combines biodiversity and implementation‐relevant data to guide management actions. This difference means there is much scope for combining approaches, so conservation planners should use KBA data in their analyses, setting context‐specific targets for each KBA type, and planners and donors should use systematic conservation planning techniques when prioritizing between KBAs for management action. In doing so, they will benefit conservation policy, practice and research by building on the collaborations formed through the KBA Standard's development