Animal movement on the hoof and on the cart and its implications for understanding exchange within the Indus Civilisation.

Movement of resources was essential to the survival and success of early complex societies. The sources and destinations of goods and the means of transportation - be it by boats, carts and/or foot - can often be inferred, but the logistics of these movements are inherently more difficult to ascertain. Here, we use strontium isotopic analysis to test hypotheses about the role of animal and animal-powered transport in medium and long-distance movement and exchange, using the Indus Civilization as a case study. Across the wide geographical spread of the Indus Civilisation, there is strong evidence for long-distance exchange of raw materials and finished objects and this process is presumed to involve boats and animal-driven transport, although there is little evidence as to the relative importance of each mode of movement. Strontium isotopic analysis of animal remains from four sites analysed for this study combined with results from nine other sites indicates limited long-distance animal movement between different geological zones within the Indus Civilisation. These findings suggest that individual animals primarily moved short- or medium-distances, though there are several significant exceptions seen in some pigs and cattle found at two large urban sites. We infer that long-distance transport of goods, be it raw materials, finished objects, other goods, or the animals themselves, could have occurred through the use of boats and waterways, by traction animals moving over long distances that did not end up in the archaeological record, and/or by different animals participating in many short to medium-distance movements.

Effects of fat loss and low energy availability on the serum cardiometabolic profile of physique athletes.

Low energy availability (LEA) is a health concern for athletes, although it may paradoxically lead to improved cardiometabolic health in the general population. We investigated the associations between LEA, body composition, and serum cardiometabolic profile in 23 physique athletes (DIET) and 21 controls (CONT) during a 5-month pre-competition diet (MID), followed by 1 week of increased energy availability (COMP) and a 5-month weight regain period (POST). Quantification of 250 serum metabolome variables was conducted by NMR spectroscopy, body composition by dual-energy x-ray absorptiometry, dietary intake by food diaries, and exercise levels by training logs. Body fat percentage decreased from 19.5 ± 7.0% to 8.3 ± 5.3% (p < 0.001) in DIET through increased exercise levels and decreased energy intake, while CONT maintained those constant. In MID, DIET had increased (FDR < 0.01) HDL cholesterol, HDL particle size and number, and decreased (FDR < 0.05) VLDL lipids, serum triglycerides, and low-grade inflammation (glycoprotein acetyls) compared to baseline and CONT. The changes were associated with reduced android fat mass (-78 ± 13%) and energy intake (-28 ± 10%). In COMP, most of the metabolic changes found in MID persisted, except for altered triglycerides in all lipoprotein classes. After weight regain in POST, serum metabolome, body composition, energy intake, and exercise levels had reverted to baseline levels. In conclusion, fat loss and LEA may have beneficial yet transient effects on the serum cardiometabolic profile of lean individuals. Especially the HDL lipidome and lipoprotein triglycerides offer potential novel biomarkers for detecting LEA in athletes.

Taurine, an osteocyte metabolite, protects against oxidative stress-induced cell death and decreases inhibitors of the Wnt/ß-catenin signaling pathway.

Taurine has been shown to have positive effects on bone mass, which are thought to be due in part to its cytoprotective effects on osteoblasts and here we show that taurine also protects osteocytes against cell death due to reactive oxygen species. Using the IDG-SW3 cell line, the expression of the taurine uptake transporter Taut/Slc6a6 is increased during osteoblast to osteocyte differentiation. Taurine had no effect on genes associated with osteoblast to osteocyte differentiation such as Dmp1, Phex or osteocalcin, even at high doses, but a slight yet significant inhibition of alkaline phosphatase was observed at the highest dose (50 mM). No effect was seen on the osteoclast regulatory genes Rankl and Opg, however the wnt antagonist Sost/sclerostin was potently and dose-dependently downregulated in response to taurine supplementation. Taurine also significantly inhibited Dkk1 mRNA expression, but only at 50 mM. Interestingly, osteocytes were found to also be able to synthesize taurine intracellularly, potentially as a self-protective mechanism, but do not secrete the metabolite. A highly significant increase in the expression of cysteine dioxygenase (Cdo), a key enzyme necessary for the production of taurine, was observed with osteoblast to osteocyte differentiation along with a decrease in methionine, the precursor of taurine. For the first time, we describe the synthesis of taurine by osteocytes, potentially to preserve viability and to regulate bone formation through inhibition of sclerostin.

Beam-Target Helicity Asymmetry for γ[over →]n[over →]→π

We report the first beam-target double-polarization asymmetries in the γ+n(p)→π^{-}+p(p) reaction spanning the nucleon resonance region from invariant mass W=1500 to 2300 MeV. Circularly polarized photons and longitudinally polarized deuterons in solid hydrogen deuteride (HD) have been used with the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The exclusive final state has been extracted using three very different analyses that show excellent agreement, and these have been used to deduce the E polarization observable for an effective neutron target. These results have been incorporated into new partial wave analyses and have led to significant revisions for several γnN^{*} resonance photocouplings.

'Trophic' and 'source' amino acids in trophic estimation: a likely metabolic explanation.

Amino acid nitrogen isotopic analysis is a relatively new method for estimating trophic position. It uses the isotopic difference between an individual's 'trophic' and 'source' amino acids to determine its trophic position. So far, there is no accepted explanation for the mechanism by which the isotopic signals in 'trophic' and 'source' amino acids arise. Yet without a metabolic understanding, the utility of nitrogen isotopic analyses as a method for probing trophic relations, at either bulk tissue or amino acid level, is limited. I draw on isotopic tracer studies of protein metabolism, together with a consideration of amino acid metabolic pathways, to suggest that the 'trophic'/'source' groupings have a fundamental metabolic origin, to do with the cycling of amino-nitrogen between amino acids. 'Trophic' amino acids are those whose amino-nitrogens are interchangeable, part of a metabolic amino-nitrogen pool, and 'source' amino acids are those whose amino-nitrogens are not interchangeable with the metabolic pool. Nitrogen isotopic values of 'trophic' amino acids will reflect an averaged isotopic signal of all such dietary amino acids, offset by the integrated effect of isotopic fractionation from nitrogen cycling, and modulated by metabolic and physiological effects. Isotopic values of 'source' amino acids will be more closely linked to those of equivalent dietary amino acids, but also modulated by metabolism and physiology. The complexity of nitrogen cycling suggests that a single identifiable value for 'trophic discrimination factors' is unlikely to exist. Greater consideration of physiology and metabolism should help in better understanding observed patterns in nitrogen isotopic values.

High pitch, low voltage dual source CT pulmonary angiography: assessment of image quality and diagnostic acceptability with hybrid iterative reconstruction.

Increased use of CT Pulmonary angiography in suspected pulmonary embolism (PE) has driven research to minimize radiation dose while maintaining image quality and diagnostic accuracy. Following institutional review board approval, we performed a retrospective comparison study in patients with suspected PE. Patients were scanned using an ultra high pitch dual source technique (pitch = 2.6) using 120 kV (SVCTPA) (n = 54) or 100 kV (RV-CTPA) (n = 52). SV-CTPA images were reconstructed using filtered back projection (SV-wFBP) and RV-CTPA images were reconstructed using both FBP (RV-wFBP) and Iterative Reconstruction (RV-IR). Comparison of radiation dose, diagnostic ability, subjective image noise, quality, and sharpness, diagnostic agreement, signal to noise (SNR) and contrast to noise ratios (CNR) were performed. Mean effective dose was 2.56 ± 0.19 mSv for the RV protocol compared to 5.36 ± 0.60 mSv for the SV. The RV-CTPA protocol resulted in a mean DLP reduction of 52 % and mean CTDI reduction of 51 %. Pulmonary artery SNR and CNR were significantly higher on RV-IR images than SV-wFBP (p = 0.007, p = 0.003). Mean subjective image noise, quality and sharpness scores did not differ significantly between the SV-wFBP and RVIR images (p > 0.05). Subjective quality scores were significantly better for the RV-IR group compared to the RV-wFBP group (p < 0.001). Agreement between readers for presence or absence of pulmonary emboli on RV-IR images was almost perfect (κ = 0.891, p < 0.001). Iterative reconstruction complements ultra high pitch dual source CTPA examinations acquired using a reduced voltage resulting in higher mean pulmonary artery SNR and CNR when compared to both RV-wFBP and SV-CTPA.

Water consumption in Iron Age, Roman, and Early Medieval Croatia.

Patterns of water consumption by past human populations are rarely considered, yet drinking behavior is socially mediated and access to water sources is often socially controlled. Oxygen isotope analysis of archeological human remains is commonly used to identify migrants in the archeological record, but it can also be used to consider water itself, as this technique documents water consumption rather than migration directly. Here, we report an oxygen isotope study of humans and animals from coastal regions of Croatia in the Iron Age, Roman, and Early Medieval periods. The results show that while faunal values have little diachronic variation, the human data vary through time, and there are wide ranges of values within each period. Our interpretation is that this is not solely a result of mobility, but that human behavior can and did lead to human oxygen isotope ratios that are different from that expected from consumption of local precipitation.

Review of Irish Civil Service sickness absence referrals 2008-10.

BACKGROUND: Long-term sickness absence can have negative consequences for individuals and for their employers. Occupational health has an important role in assisting workplace rehabilitation in such cases. AIMS: To investigate long-term sickness absence referrals in the Irish Civil Service in terms of epidemiological profile, illness categories and eventual outcomes. METHODS: A retrospective review of consecutive new long-term sickness absence cases referred between January 2008 and April 2008 and followed up to July 2010, using review of electronic and paper medical records and personnel department data to establish case outcomes. RESULTS: Three hundred and one cases were available for analysis. There were more long-term sickness absence cases among older employees, with female employees and clerical officer grades more likely to be referred. The principal diagnostic groups were mental health issues (30%), musculoskeletal disorders (13%) and cancer (11%). The eventual outcomes were the following: return to work (83%) and ill-health retirement (8%); 2% were still on sick leave and the remaining 7% had left civil service employment for other reasons at the end of the study period. CONCLUSIONS: The final outcome in a large majority of case referrals was to resume work, with only a small proportion retiring on ill-health grounds. Mental health disorders, musculoskeletal disorders and cancers were the principal reasons for absence.

The diet-body offset in human nitrogen isotopic values: a controlled dietary study.

The "trophic level enrichment" between diet and body results in an overall increase in nitrogen isotopic values as the food chain is ascended. Quantifying the diet-body Δ(15) N spacing has proved difficult, particularly for humans. The value is usually assumed to be +3-5‰ in the archaeological literature. We report here the first (to our knowledge) data from humans on isotopically known diets, comparing dietary intake and a body tissue sample, that of red blood cells. Samples were taken from 11 subjects on controlled diets for a 30-day period, where the controlled diets were designed to match each individual's habitual diet, thus reducing problems with short-term changes in diet causing isotopic changes in the body pool. The Δ(15) N(diet-RBC) was measured as +3.5‰. Using measured offsets from other studies, we estimate the human Δ(15) N(diet-keratin) as +5.0-5.3‰, which is in good agreement with values derived from the two other studies using individual diet records. We also estimate a value for Δ(15) N(diet-collagen) of ≈6‰, again in combination with measured offsets from other studies. This value is larger than usually assumed in palaeodietary studies, which suggests that the proportion of animal protein in prehistoric human diet may have often been overestimated in isotopic studies of palaeodiet.

Changing cultures, changing cuisines: Cultural transitions and dietary change in Iron Age, Roman, and Early Medieval Croatia.

Food is well-known to encode social and cultural values, for example different social groups use different consumption patterns to act as social boundaries. When societies and cultures change, whether through drift, through population replacement or other factors, diet may also alter despite unchanging resource availability within a region. This study investigates the extent to which dietary change coincides with cultural change, to understand the effects of large-scale migrations on the populations' diets. Through stable carbon and nitrogen isotope analysis of Iron Age, Roman, and Early Medieval human bone collagen, we show that in Croatia large-scale cultural change led to significant changes in diet. The isotopic evidence indicates that Iron Age diet consisted of C(3) foodstuffs with no isotopic evidence for the consumption of C(4) or marine resources. With the Roman conquest, marine resources were added to the diet, although C(3) foodstuffs continued to play an important role. In the Early Medieval period, this marine component was lost and varying amounts of C(4) foodstuffs, probably millet, were added to the otherwise C(3) diet. In both of these transitions it is likely that the changes in diet are related to the arrival of a new people into the area.

The application of metabonomics to predict drug-induced liver injury.

The occurrence of drug-induced liver injury (DILI) presents a significant safety issue for patients and represents a major cause of regulatory action. The methods that are in current use for early detection and prediction of DILI in patients are not adequate. The liver is the major site of synthesis of endogenous metabolites, and data suggest that alterations in the profiles of endogenous metabolites ("the metabolome") may precede development of clinically overt DILI. Metabonomics involves the application of analytical technologies such as nuclear magnetic resonance and mass spectrometry to detect changes in the metabolome. In this review, we describe the emerging role of metabonomics in predicting and understanding the mechanisms underlying DILI. Recent human clinical trials of drugs, including acetaminophen (APAP) and ximelagatran, have shown that the metabonomics of biofluids (plasma and urine) collected before and immediately after dosing can identify individual patients who are likely to develop DILI. These studies support the need to include metabonomic investigations in clinical trials of potentially hepatotoxic medications.

Use of pharmaco-metabonomics for early prediction of acetaminophen-induced hepatotoxicity in humans.

Achieving the ability to identify individuals who are susceptible to drug-induced liver injury (DILI) would represent a major advance in personalized medicine. Clayton et al. demonstrated that the pattern of endogenous metabolites in urine could predict susceptibility to acetaminophen-induced liver injury in rats. We designed a clinical study to test this approach in healthy adults who received 4 g of acetaminophen per day for 7 days. Urine metabolite profiles obtained before the start of treatment were not sufficient to distinguish which of the subjects would develop mild liver injury, as indicated by a rise in alanine aminotransferase (ALT) to a level more than twice the baseline value (responders). However, profiles obtained shortly after the start of treatment, but prior to ALT elevation, could distinguish responders from nonresponders. Statistical analyses revealed that predictive metabolites included those derived from the toxic metabolite N-acetyl paraquinone imine (NAPQI), but that the inclusion of endogenous metabolites was required for significant prediction. This "early-intervention pharmaco-metabonomics" approach should now be tested in clinical trials of other potentially hepatotoxic drugs.

Occupational sharps injuries in a Dublin teaching hospital.

Contaminated sharps injuries pose a risk of infection to health care workers and represent a major workload for hospital occupational health departments (OHDs). The aim of this study was to review the epidemiology and management of sharps injuries in an Irish tertiary referral centre, which has not been previously described. Occupational health records of sharps injuries occurring between January 1998 and December 2000 inclusive were reviewed from the hospital OHD. A total of 332 sharps injuries were reported to the OHD in this period. More than two-thirds of injuries involved medical or nursing staff. Support staff such as cleaners and porters accounted for 13.5% of injuries. The majority of sharps injury recipients (86%) were immune to hepatitis B. Of those injured, 22% were not wearing gloves at the time of their injury. Eight source patients were hepatitis C antibody positive, two were HIV antibody positive and one was hepatitis B surface antigen positive. No instances of occupational acquisition of blood borne viruses were documented. The results of this study confirm that health care workers need further education to prevent sharps injuries, and that the risk of blood borne virus acquisition through an occupational sharps injury is low but not negligible.

Synthesis and structure-activity relationships of thiotetronic acid analogues of thiolactomycin.

3-Acetyl analogues of thiolactomycin, a thiotetronic acid natural product, were synthesized and profiled against livestock pathogens. Some analogues showed improved activity over thiolactomycin against Staphylococcus aureus and comparable activity against Pasteurella multocida. Several semisynthetically modified analogues of thiolactomycin showed no improvement in activity over thiolactomycin.

A transcript encoding a nucleic acid-binding protein specifically expressed in maize seeds.

A cDNA clone has been obtained for a low-abundance, seed-specific mRNA that encodes a polypeptide which defines a novel family of plant proteins with some similarities to the DnaJ class of molecular chaperones. The MEM1 (Maize Endosperm Motif binding protein) protein is capable of binding to the endosperm motif and activating transcription in the yeast one-hybrid system. Recombinant MEM1 was shown to bind in vitro to nucleic acids, with a preference for RNA over DNA. MEM1 is capable of forming homodimers, a property that is dependent on a domain close to the C-terminus of the protein. The protein is expressed in mid- to late-term endosperm cells. Subcellular fractionation and size fractionation under non-denaturing conditions indicate that the protein is present in the cytosol of endosperm cells. Possible roles of MEM1 in endosperm and protein body development are discussed.

Aspects of mental health among older lesbian, gay, and bisexual adults.

This study examined aspects of mental health among 416 lesbian, gay, and bisexual adults aged 60 to 91 years old, attending social and recreational programs. Mental health indicators were perceived mental health status; self-esteem; internalized homophobia; loneliness; alcohol and drug abuse; and suicidality. Better mental health was correlated with higher self-esteem, less loneliness, and lower internalized homophobia. Compared to women, men reported significantly more internalized homophobia, alcohol abuse, and suicidality related to their sexual orientation. Less lifetime suicidal ideation was associated with lower internalized homophobia, less loneliness, and more people knowing about participants' sexual orientation.

Oral fluid collection by post for viral antibody testing.

BACKGROUND: The objective of this study was to estimate the prevalence of hepatitis B virus exposure (HBV) in the population of the Republic of Ireland, by using oral fluid (saliva) collection by post for hepatitis B anti-core antibody (anti-HBc). This paper discusses the methodological approach used and the strategies that were adopted to improve response rates. METHODS: The sampling frame used was the Register of Electors for Irish parliamentary elections. A multistage stratified cluster sample was taken, and a total of 962 households were selected nationally. A four-letter approach was employed for sample collection. Households received an initial letter outlining the purpose of the study. This was followed by a letter containing six swabs for oral fluid collection, along with easy-to-follow instructions. Non-respondents received two reminder letters, and were also telephoned where possible. A telephone helpline was provided. All testing was anonymous and unlinked. RESULTS: The study achieved a good household response rate (60.4%), and more than 98% of the 1738 specimens received were suitable for testing. The prevalence of anti-HBc in the Irish population was estimated to be 0.51%. The observed design effect was 1.29. DISCUSSION: From a review of the literature, this is the first study where a representative sample of a national population was asked to self-collect oral fluid samples and return these by post for serological testing. The technique may have many future applications in epidemiological research.

Cloning and characterization of the mouse alpha1C/A-adrenergic receptor gene and analysis of an alpha1C promoter in cardiac myocytes: role of an MCAT element that binds transcriptional enhancer factor-1 (TEF-1).

alpha1-Adrenergic receptor (AR) subtypes in the heart are expressed by myocytes but not by fibroblasts, a feature that distinguishes alpha1-ARs from beta-ARs. Here we studied myocyte-specific expression of alpha1-ARs, focusing on the subtype alpha1C (also called alpha1A), a subtype implicated in cardiac hypertrophic signaling in rat models. We first cloned the mouse alpha1C-AR gene, which consisted of two exons with an 18 kb intron, similar to the alpha1B-AR gene. The receptor coding sequence was >90% homologous to that of rat and human. alpha1C-AR transcription in mouse heart was initiated from a single Inr consensus sequence at -588 from the ATG; this and a putative polyadenylation sequence 8.5 kb 3' could account for the predominant 11 kb alpha1C mRNA in mouse heart. A 5'-nontranscribed fragment of 4.4 kb was active as a promoter in cardiac myocytes but not in fibroblasts. Promoter activity in myocytes required a single muscle CAT (MCAT) element, and this MCAT bound in vitro to recombinant and endogenous transcriptional enhancer factor-1. Thus, alpha1C-AR transcription in cardiac myocytes shares MCAT dependence with other cardiac-specific genes, including the alpha- and beta-myosin heavy chains, skeletal alpha-actin, and brain natriuretic peptide. However, the mouse alpha1C gene was not transcribed in the neonatal heart and was not activated by alpha1-AR and other hypertrophic agonists in rat myocytes, and thus differed from other MCAT-dependent genes and the rat alpha1C gene.

Maize endosperm secretes a novel antifungal protein into adjacent maternal tissue.

A series of endosperm transfer layer-specific transcripts has been identified in maize by differential screening of a cDNA library of transcripts at 10 days after pollination. Sequence comparisons revealed among this class of cDNAs a novel, small gene family of highly diverged sequences encoding basal layer antifungal proteins (BAPs). The bap genes mapped to two loci on chromosomes 4 and 10. So far, bap-homologous sequences have been detected only in maize, teosinte and sorghum, and are not present in grasses outside the Andropogoneae tribe. BAP2 is synthesized as a pre-proprotein, and is processed by successive removal of a signal peptide and a 29-residue prodomain. The proprotein can be detected exclusively in microsomal membrane-containing fractions of kernel extracts. Immunolocalization reveals BAP2 to be predominantly located in the placentochalazal cells of the pedicel, adjacent to the basal endosperm transfer layer (BETL) cells, although the BAP2 transcript is found only in the BETL cells. The biological roles of BAP2 propeptide and mature peptide have been investigated by heterologous expression of the proprotein in Escherichia coli, and by tests of its fungistatic activity and that of the fully processed form in vitro. The mature BAP2 peptide exhibits potent broad-range activity against a range of filamentous fungi, including several plant pathogens.