Rate of Decline of the Oriental White-Backed Vulture Population in India Estimated from a Survey of Diclofenac Residues in Carcasses of Ungulates

The non-steroidal anti-inflammatory drug diclofenac is a major cause of the rapid declines in the Indian subcontinent of three species of vultures endemic to South Asia. The drug causes kidney failure and death in vultures. Exposure probably arises through vultures feeding on carcasses of domesticated ungulates treated with the drug. However, before the study reported here, it had not been established from field surveys of ungulate carcasses that a sufficient proportion was contaminated to cause the observed declines. We surveyed diclofenac concentrations in samples of liver from carcasses of domesticated ungulates in India in 2004–2005. We estimated the concentration of diclofenac in tissues available to vultures, relative to that in liver, and the proportion of vultures killed after feeding on a carcass with a known level of contamination. We assessed the impact of this mortality on vulture population trend with a population model. We expected levels of diclofenac found in ungulate carcasses in 2004–2005 to cause oriental white-backed vulture population declines of 80–99% per year, depending upon the assumptions used in the model. This compares with an observed rate of decline, from road transect counts, of 48% per year in 2000–2003. The precision of the estimate based upon carcass surveys is low and the two types of estimate were not significantly different. Our analyses indicate that the level of diclofenac contamination found in carcasses of domesticated ungulates in 2004–2005 was sufficient to account for the observed rapid decline of the oriental white-backed vulture in India. The methods we describe could be used again to assess changes in the effect on vulture population trend of diclofenac and similar drugs. In this way, the effectiveness of the recent ban in India on the manufacture and importation of diclofenac for veterinary use could be monitored

An Eight-Week Trial Investigating the Efficacy and Tolerability of Atorvastatin for Children and Adolescents With Heterozygous Familial Hypercholesterolemia

This study aimed to assess the efficacy and tolerability of atorvastatin in Tanner stage (TS) 1 patients ages 6 to 10 years and TS ≥2 patients ages 10 to <18 years with genetically confirmed heterozygous familial hypercholesterolemia (HeFH) and a low density lipoprotein cholesterol (LDL-C) level of 4 mmol/l (155 mg/dl) or higher. In this open-label, 8-week study, 15 TS 1 children were treated initially with atorvastatin 5 mg/day and 24 TS ≥2 children with 10 mg/day. Doses were doubled at week 4 if the LDL-C target (<3.35 mmol/l [130 mg/dl]) was not achieved. The efficacy variables were the percentage change from baseline in LDL-C, total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), and apolipoprotein (Apo) A-I and Apo B. Safety evaluations included clinical monitoring, subject-reported adverse events (AEs), vital signs, and clinical laboratory tests. The mean values for LDL-C, TC, VLDL-C, and Apo B decreased by week 2 among all TS 1 and TS ≥2 patients, whereas TG, HDL-C, and Apo A-I varied considerably from week to week. After 8 weeks, the mean reduction in LDL-C was −40.7% ± 8.4 for the TS 1 children and −39.7% ± 10.3 for the TS ≥2 children. For the TS 1 patients, the mean reductions were −34.1% ± 6.9 for TC and −6.0% ± 32.1 for TG. The corresponding changes for the TS ≥2 patients were −35.6% ± 9.5 for TC and −21.1% ± 29.7 for TG. Four patients experienced mild to moderate treatment-related AEs. No serious AEs or discontinuations were reported. Overall, no difference in safety or tolerability was observed between the younger and older cohorts. Across the range of exposures after atorvastatin 5 to 10 mg (TS 1) or atorvastatin 10 to 20 mg (TS ≥2) doses for 8 weeks, clinically meaningful reductions in LDL-C, TC, VLDL-C, and Apo were observed with atorvastatin in pediatric patients who had HeFH. Atorvastatin also was well tolerated in this population

Buying Years to Extinction: Is Compensatory Mitigation for Marine Bycatch a Sufficient Conservation Measure for Long-Lived Seabirds?

Along the lines of the ‘polluter pays principle’, it has recently been proposed that the local long-line fishing industry should fund eradication of terrestrial predators at seabird breeding colonies, as a compensatory measure for the bycatch caused by the fishing activity. The measure is economically sound, but a quantitative and reliable test of its biological efficacy has never been conducted. Here, we investigated the demographic consequences of predator eradication for Cory's shearwater Calonectris diomedea, breeding in the Mediterranean, using a population model that integrates demographic rates estimated from individual life-history information with experimental measures of predation and habitat structure. We found that similar values of population growth rate can be obtained by different combinations of habitat characteristics, predator abundance and adult mortality, which explains the persistence of shearwater colonies in islands with introduced predators. Even so, given the empirically obtained values of survival, all combinations of predator abundance and habitat characteristics projected a decline in shearwater numbers. Perturbation analyses indicated that the value and the sensitivity of shearwater population growth rates were affected by all covariates considered and their interactions. A decrease in rat abundance delivered only a small increase in the population growth rate, whereas a change in adult survival (a parameter independent of rat abundance) had the strongest impact on population dynamics. When adult survival is low, rat eradication would allow us to “buy” years before extinction but does not reverse the process. Rat eradication can therefore be seen as an emergency measure if threats on adult survival are eliminated in the medium-term period. For species with low fecundity and long life expectancy, our results suggest that rat control campaigns are not a sufficient, self-standing measure to compensate the biological toll of long-line fisheries

Energy expenditure, intake and availability in female soccer players via doubly labelled water: Are we misrepresenting low energy availability?

Female soccer players have been identified as presenting with low energy availability (LEA), though the prevalence of LEA may be overestimated given inaccuracies associated with self-reporting dietary intakes. Accordingly, we aimed to quantify total daily energy expenditure (TDEE) via the doubly labelled water (DLW) method, energy intake (EI) and energy availability (EA). Adolescent female soccer players (n = 45; 16 ± 1 years) completed a 9–10 day ‘training camp’ representing their national team. Absolute and relative TDEE was 2683 ± 324 and 60 ± 7 kcal kg−1 fat free mass (FFM), respectively. Mean daily EI was lower (P < 0.01) when players self-reported using the remote food photography method (RFPM) (2047 ± 383 kcal day−1) over a 3-day period versus DLW derived EI estimates accounting for body mass (BM) changes (2545 ± 518 kcal day−1) over 7–8 days, representing a mean daily Δ of 499 ± 526 kcal day−1 and 22% error when using the RFPM. Estimated EA was different (P < 0.01) between methods (DLW: 48 ± 14 kcal kg−1 FFM, range: 22–82; RFPM: 37 ± 8 kcal kg−1 FFM, range: 22–54), such that prevalence of LEA (<30 kcal kg−1 FFM) was lower in DLW compared with RFPM (5% vs. 15%, respectively). Data demonstrate the potential to significantly underestimate EI when using self-report methods. This approach can therefore cause a misrepresentation and an over-prevalence of LEA, which is the underlying aetiology of ‘relative energy deficiency in sport’ (REDs)

Effectiveness of Action in India to Reduce Exposure of Gyps Vultures to the Toxic Veterinary Drug Diclofenac

Contamination of their carrion food supply with the non-steroidal anti-inflammatory drug diclofenac has caused rapid population declines across the Indian subcontinent of three species of Gyps vultures endemic to South Asia. The governments of India, Pakistan and Nepal took action in 2006 to prevent the veterinary use of diclofenac on domesticated livestock, the route by which contamination occurs. We analyse data from three surveys of the prevalence and concentration of diclofenac residues in carcasses of domesticated ungulates in India, carried out before and after the implementation of a ban on veterinary use. There was little change in the prevalence and concentration of diclofenac between a survey before the ban and one conducted soon after its implementation, with the percentage of carcasses containing diclofenac in these surveys estimated at 10.8 and 10.7%, respectively. However, both the prevalence and concentration of diclofenac had fallen markedly 7–31 months after the implementation of the ban, with the true prevalence in this third survey estimated at 6.5%. Modelling of the impact of this reduction in diclofenac on the expected rate of decline of the oriental white-backed vulture (Gyps bengalensis) in India indicates that the decline rate has decreased to 40% of the rate before the ban, but is still likely to be rapid (about 18% year−1). Hence, further efforts to remove diclofenac from vulture food are still needed if the future recovery or successful reintroduction of vultures is to be feasible

Genetic Insight into Yield-Associated Traits of Wheat Grown in Multiple Rain-Fed Environments

Background: Grain yield is a key economic driver of successful wheat production. Due to its complex nature, little is known regarding its genetic control. The goal of this study was to identify important quantitative trait loci (QTL) directly and indirectly affecting grain yield using doubled haploid lines derived from a cross between Hanxuan 10 and Lumai 14. Methodology/Principal Findings: Ten yield-associated traits, including yield per plant (YP), number of spikes per plan

Diving of Great Shearwaters (Puffinus gravis) in Cold and Warm Water Regions of the South Atlantic Ocean

BACKGROUND: Among the most widespread seabirds in the world, shearwaters of the genus Puffinus are also some of the deepest diving members of the Procellariiformes. Maximum diving depths are known for several Puffinus species, but dive depths or diving behaviour have never been recorded for great shearwaters (P. gravis), the largest member of this genus. This study reports the first high sampling rate (2 s) of depth and diving behaviour for Puffinus shearwaters. METHODOLOGY/PRINCIPAL FINDINGS: Time-depth recorders (TDRs) were deployed on two female great shearwaters nesting on Inaccessible Island in the South Atlantic Ocean, recording 10 consecutive days of diving activity. Remote sensing imagery and movement patterns of 8 males tracked by satellite telemetry over the same period were used to identify probable foraging areas used by TDR-equipped females. The deepest and longest dive was to 18.9 m and lasted 40 s, but most (>50%) dives were <2 m deep. Diving was most frequent near dawn and dusk, with <0.5% of dives occurring at night. The two individuals foraged in contrasting oceanographic conditions, one in cold (8 to 10°C) water of the Sub-Antarctic Front, likely 1000 km south of the breeding colony, and the other in warmer (10 to 16°C) water of the Sub-tropical Frontal Zone, at the same latitude as the colony, possibly on the Patagonian Shelf, 4000 km away. The cold water bird spent fewer days commuting, conducted four times as many dives as the warm water bird, dived deeper on average, and had a greater proportion of bottom time during dives. CONCLUSIONS/SIGNIFICANCE: General patterns of diving activity were consistent with those of other shearwaters foraging in cold and warm water habitats. Great shearwaters are likely adapted to forage in a wide range of oceanographic conditions, foraging mostly with shallow dives but capable of deep diving

Functional Role of Dimerization of Human Peptidylarginine Deiminase 4 (PAD4)

Peptidylarginine deiminase 4 (PAD4) is a homodimeric enzyme that catalyzes Ca2+-dependent protein citrullination, which results in the conversion of arginine to citrulline. This paper demonstrates the functional role of dimerization in the regulation of PAD4 activity. To address this question, we created a series of dimer interface mutants of PAD4. The residues Arg8, Tyr237, Asp273, Glu281, Tyr435, Arg544 and Asp547, which are located at the dimer interface, were mutated to disturb the dimer organization of PAD4. Sedimentation velocity experiments were performed to investigate the changes in the quaternary structures and the dissociation constants (Kd) between wild-type and mutant PAD4 monomers and dimers. The kinetic data indicated that disrupting the dimer interface of the enzyme decreases its enzymatic activity and calcium-binding cooperativity. The Kd values of some PAD4 mutants were much higher than that of the wild-type (WT) protein (0.45 µM) and were concomitant with lower kcat values than that of WT (13.4 s−1). The Kd values of the monomeric PAD4 mutants ranged from 16.8 to 45.6 µM, and the kcat values of the monomeric mutants ranged from 3.3 to 7.3 s−1. The kcat values of these interface mutants decreased as the Kd values increased, which suggests that the dissociation of dimers to monomers considerably influences the activity of the enzyme. Although dissociation of the enzyme reduces the activity of the enzyme, monomeric PAD4 is still active but does not display cooperative calcium binding. The ionic interaction between Arg8 and Asp547 and the Tyr435-mediated hydrophobic interaction are determinants of PAD4 dimer formation