Lateglacial and Early Holocene palaeoenvironmental change and human activity at Killerby Quarry, North Yorkshire, UK

The hunter-gatherers that entered the British peninsula after ice-retreat were exploiting a dynamic, rapidly changing environment. Records of vegetation change and human occupation during the Lateglacial to Early Holocene in northern Britain are more commonly found at upland and cave sites. However, recent research highlights many areas of the Swale–Ure Washlands that preserve extensive environmental sequences in low-lying ice-wastage basins, channels and depressions. The Lateglacial–Early Holocene environment of Killerby Quarry, North Yorkshire, is investigated here using a multi-proxy approach of sedimentary ancient DNA (sedaDNA), pollen, sedimentological (geochemistry and portable optically stimulated luminescence), and rare and well-preserved archaeology (Lavvu structures and lithics). Results show that the wetland basins and kettleholes were small lakes or ponds in the Lateglacial surrounded by sedge-fen and birch woodland. A gradual (centennial scale) succession to reed-swamp and then marsh is seen by the Early Holocene. This environment formed the resource-scape for hunter-gatherer transitory settlement in both the Lateglacial (Late Upper Palaeolithic) and Holocene (Early Mesolithic), attracted by the rich communities of pond-related flora and fauna as well as easy strategic landscape access by way of the River Swale, an arterial route through the landscape connecting the North Sea Basin with the Pennine uplands via the palaeolakes around Killerby

Call-Tracking Data and the Public Health Response to Bioterrorism-Related Anthrax

After public notification of confirmed cases of bioterrorism-related anthrax, the Centers for Disease Control and Prevention’s Emergency Operations Center responded to 11,063 bioterrorism-related telephone calls from October 8 to November 11, 2001. Most calls were inquiries from the public about anthrax vaccines (58.4%), requests for general information on bioterrorism prevention (14.8%), and use of personal protective equipment (12.0%); 882 telephone calls (8.0%) were referred to the state liaison team for follow-up investigation. Of these, 226 (25.6%) included reports of either illness clinically confirmed to be compatible with anthrax or direct exposure to an environment known to be contaminated with Bacillus anthracis. The remaining 656 (74.4%) included no confirmed illness but reported exposures to “suspicious” packages or substances or the receipt of mail through a contaminated facility. Emergency response staff must handle high call volumes following suspected or actual bioterrorist attacks. Standardized health communication protocols that address contact with unknown substances, handling of suspicious mail, and clinical evaluation of suspected cases would allow more efficient follow-up investigations of clinically compatible cases in high-risk groups

Learning in large learning spaces:the academic engagement of a diverse group of students

Teaching larger groups of students is a growing phenomenon in HE and this brings with it, its own challenges not least for the students themselves but also their lecturers. Demographic factors as well as the experiences that characterise us as individuals will impact upon our ability to learn. The pilot study reported here considered the “academic engagement” of a diverse group of students where their course is delivered in large learning environments. As a pilot study, the paper concludes with the identification of two areas which are worthy of further research. Firstly, the study highlighted that mature students were more likely to engage in learning strategies that are associated with surface learning – the binary opposite to which practitioners often strive to achieve. Secondly, the research suggests that students who appear to know their tutors well indicate a preference for study approaches that are likely to develop deeper learning

Structures of CD6 and Its Ligand CD166 Give Insight into Their Interaction

SummaryCD6 is a transmembrane protein with an extracellular region containing three scavenger receptor cysteine rich (SRCR) domains. The membrane proximal domain of CD6 binds the N-terminal immunoglobulin superfamily (IgSF) domain of another cell surface receptor, CD166, which also engages in homophilic interactions. CD6 expression is mainly restricted to T cells, and the interaction between CD6 and CD166 regulates T-cell activation. We have solved the X-ray crystal structures of the three SRCR domains of CD6 and two N-terminal domains of CD166. This first structure of consecutive SRCR domains reveals a nonlinear organization. We characterized the binding sites on CD6 and CD166 and showed that a SNP in CD6 causes glycosylation that hinders the CD6/CD166 interaction. Native mass spectrometry analysis showed that there is competition between the heterophilic and homophilic interactions. These data give insight into how interactions of consecutive SRCR domains are perturbed by SNPs and potential therapeutic reagents

Using salt counterions to modify β2-agonist behaviour in vivo

This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. © 2016 American Chemical Society.There is a paucity of data describing the impact of salt counterions on the biological performance of inhaled medicines in vivo. The aim of this study was to determine if the coadministration of salt counterions influenced the tissue permeability and airway smooth muscle relaxation potential of salbutamol, formoterol, and salmeterol. The results demonstrated that only salbutamol, when formulated with an excess of the 1-hydroxy-2-naphthoate (1H2NA) counterion, exhibited a superior bronchodilator effect (p < 0.05) compared to salbutamol base. The counterions aspartate, maleate, fumarate, and 1H2NA had no effect on the ability of formoterol or salmeterol to reduce airway resistance in vivo. Studies using guinea pig tracheal sections showed that the salbutamol:1H2NA combination resulted in a significantly faster (p < 0.05) rate of tissue transport compared to salbutamol base. Furthermore, when the relaxant activity of salbutamol was assessed in vitro using electrically stimulated, superfused preparations of guinea pig trachea, the inhibition of contraction by salbutamol in the presence of 1H2NA was greater than with salbutamol base (a total inhibition of 94.13%, p < 0.05). The reason for the modification of salbutamol’s behavior upon administration with 1H2NA was assigned to ion-pair formation, which was identified using infrared spectroscopy. Ion-pair formation is known to modify a drug’s physicochemical properties, and the data from this study suggested that the choice of counterion in inhaled pharmaceutical salts should be considered carefully as it has the potential to alter drug action in vivo.Peer reviewe

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

Comparison of 3 Infrared Thermal Detection Systems and Self-Report for Mass Fever Screening

In a hospital setting, the systems had reasonable utility for fever detection

Lead exposure in adult males in urban Transvaal Province, South Africa during the apartheid era

Human exposure to lead is a substantial public health hazard worldwide and is particularly problematic in the Republic of South Africa given the country’s late cessation of leaded petrol. Lead exposure is associated with a number of serious health issues and diseases including developmental and cognitive deficiency, hypertension and heart disease. Understanding the distribution of lifetime lead burden within a given population is critical for reducing exposure rates. Femoral bone from 101 deceased adult males living in urban Transvaal Province (now Gauteng Province), South Africa between 1960 and 1998 were analyzed for lead concentration by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Of the 72 black and 29 white individuals sampled, chronic lead exposure was apparent in nearly all individuals. White males showed significantly higher median bone lead concentration (ME = 10.04 µg·g−1), than black males (ME = 3.80 µg·g−1) despite higher socioeconomic status. Bone lead concentration covaries significantly, though weakly, with individual age. There was no significant temporal trend in bone lead concentration. These results indicate that long-term low to moderate lead exposure is the historical norm among South African males. Unexpectedly, this research indicates that white males in the sample population were more highly exposed to lead

Progesterone receptor modulates ERα action in breast cancer.

Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-α (ERα) function and breast cancer prognosis. Here we show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited oestrogen-mediated growth of ERα(+) cell line xenografts and primary ERα(+) breast tumour explants, and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ERα(+) breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.We would like to acknowledge the support of the University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. Research reported in this manuscript was supported by the National Cancer Institute of the National Institutes of Health under award number 5P30CA142543 (to UT Southwestern) and Department of Defense grants W81XWH-12-1-0288-03 (GVR). W.D.T. is supported by grants from the National Health and Medical Research Council of Australia (ID 1008349; ID 1084416) and Cancer Australia (ID 627229) T.E.H held a Fellowship Award from the US Department of Defense Breast Cancer Research Program (BCRP; #W81XWH-11-1-0592) and currently is supported by a Florey Fellowship from the Royal Adelaide Hospital Research Foundation. J.S.C is supported by an ERC starting grant and an EMBO Young investigator award.This is the accepted manuscript. The final version is available at www.nature.com/nature/journal/v523/n7560/full/nature14583.htm

Non-Detection of Human Herpesvirus 8 (HHV-8) DNA in HHV-8-Seropositive Blood Donors from Three Brazilian Regions

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the etiologic agent of all forms of Kaposi's sarcoma, primary effusion lymphoma and the plasmablastic cell variant of multicentric Castleman disease. In endemic areas of sub-Saharan Africa, blood transfusions have been associated with a substantial risk of HHV-8 transmission. By contrast, several studies among healthy blood donors from North America have failed to detect HHV-8 DNA in samples of seropositive individuals. In this study, using a real-time PCR assay, we investigated the presence of HHV-8 DNA in whole-blood samples of 803 HHV-8 blood donors from three Brazilian states (São Paulo, Amazon, Bahia) who tested positive for HHV-8 antibodies, in a previous multicenter study. HHV-8 DNA was not detected in any sample. Our findings do not support the introduction of routine HHV-8 screening among healthy blood donors in Brazil. (WC = 140)