Individual variation in levels of haptoglobin-related protein in children from Gabon

Background: Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of highdensity lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas. Methods and Principal Findings: We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP

Classical and quantum: a conflict of interest

We highlight three conflicts between quantum theory and classical general relativity, which make it implausible that a quantum theory of gravity can be arrived at by quantising classical gravity. These conflicts are: quantum nonlocality and space-time structure; the problem of time in quantum theory; and the quantum measurement problem. We explain how these three aspects bear on each other, and how they point towards an underlying noncommutative geometry of space-time.Comment: 15 pages. Published in `Gravity and the quantum' [Essays in honour of Thanu Padmanabhan on the occasion of his sixtieth birthday] Eds. Jasjeet Singh Bagla and Sunu Engineer (Springer, 2017

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability

Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance

Trypanosoma brucei rhodesiense (Tbr) and T. b. gambiense (Tbg), causative agents of Human African Trypanosomiasis (sleeping sickness) in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs), components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA) protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR). HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb), a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1) and not found in related taxa, which are either human serum susceptible (Tbb) or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2). We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR functio

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

Using geonarratives to explore the diverse temporalities of therapeutic landscapes: perspectives from ‘green’ and ‘blue’ settings

This is the author accepted manuscript. The final version is available from Taylor and Francis via the DOI in this record.A growing evidence base highlights “green” and “blue” spaces as examples of “therapeutic landscapes” incorporated into people’s lives to maintain a sense of wellbeing. A commonly overlooked dimension within this corpus of work concerns the dynamic nature of people’s therapeutic place assemblages over time. This article provides these novel temporal perspectives, drawing on the findings of an innovative three-stage interpretive geo-narrative study conducted in south-west England from May to November 2013, designed to explore the complex spatial-temporal ordering of people’s lives. Activity maps produced using accelerometer and Global Positioning system (GPS) data were used to guide in-depth geonarrative interviews with 33 participants, followed by a subset of go-along interviews in therapeutic places deemed important by participants. Concepts of “fleeting time”, “restorative time” and “biographical time” are used, alongside notions of individual agency, to examine participants’ green and blue space experiences in the context of the temporal structures characterising their everyday lives and the biographical experiences contributing to the perceived importance of such settings over time. In a culture that by and large prioritises speed, dominated by social ideals of, for example, the “productive worker” and the “good parent”, participants conveyed a desire to shift from “fleeting time” to “restorative time”, seeking a balance between embodied stillness and therapeutic mobility. This was deemed particularly important during more stressful life transitions, such as parenthood, employment shifts and the onset of illness or impairment, when participants worked hard to tailor their therapeutic geographies to shifting wellbeing needs and priorities.This work was supported by the European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

Estimating the incidence of acute infectious intestinal disease in the community in the UK:A retrospective telephone survey

Objectives: To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design. Design/Setting: A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days. Participants: 14,813 individuals for all of whom we had a legible recording of their agreement to participate Outcomes: Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause. Results: The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135 – 2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377 – 778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time. Conclusions: The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates

Testing A (Stringy) Model of Quantum Gravity

I discuss a specific model of space-time foam, inspired by the modern non-perturbative approach to string theory (D-branes). The model views our world as a three brane, intersecting with D-particles that represent stringy quantum gravity effects, which can be real or virtual. In this picture, matter is represented generically by (closed or open) strings on the D3 brane propagating in such a background. Scattering of the (matter) strings off the D-particles causes recoil of the latter, which in turn results in a distortion of the surrounding space-time fluid and the formation of (microscopic, i.e. Planckian size) horizons around the defects. As a mean-field result, the dispersion relation of the various particle excitations is modified, leading to non-trivial optical properties of the space time, for instance a non-trivial refractive index for the case of photons or other massless probes. Such models make falsifiable predictions, that may be tested experimentally in the foreseeable future. I describe a few such tests, ranging from observations of light from distant gamma-ray-bursters and ultra high energy cosmic rays, to tests using gravity-wave interferometric devices and terrestrial particle physics experients involving, for instance, neutral kaons.Comment: 25 pages LATEX, four figures incorporated, uses special proceedings style. Invited talk at the third international conference on Dark Matter in Astro and Particle Physics, DARK2000, Heidelberg, Germany, July 10-15 200

Gravitational Waves from Gravitational Collapse

Gravitational wave emission from the gravitational collapse of massive stars has been studied for more than three decades. Current state of the art numerical investigations of collapse include those that use progenitors with realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non--axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Interpretation of Binary Pulsar Observations

The nature, dynamics and evolution of the three known radio pulsar binaries are discussed. The system containing 1913+16 appears to comprise two ~1.4 M⊙ components, and to undergo orbital decay as predicted by general relativity. It is proposed that 1913+16 has a neutron star companion and that 0655+64 and 0820+02 have white dwarf companions which should be observable optically