Time perception and patience: individual differences in interval timing precision predict choice impulsivity in European starlings, Sturnus vulgaris.

Impulsivity, in the sense of the extent rewards are devalued as the time until their realization increases, is linked to various negative outcomes in humans, yet understanding of the cognitive mechanisms underlying it is limited. Variation in the imprecision of interval timing is a possible contributor to variation in impulsivity. We use a numerical model to generate predictions concerning the effect of timing imprecision on impulsivity. We distinguish between fixed imprecision (the imprecision that applies even when timing the very shortest time intervals) and proportional imprecision (the rate at which imprecision increases as the interval becomes longer). The model predicts that impulsivity should increase with increasing fixed imprecision, but decrease with increasing proportional imprecision. We present data from a cohort of European starlings (Sturnus vulgaris, n = 28) in which impulsivity had previously been measured through an intertemporal choice paradigm. We tested interval timing imprecision in the same individuals using a tri-peak temporal reproduction procedure. We found repeatable individual differences in both fixed and proportional imprecision. As predicted, birds with greater proportional imprecision in interval timing made fewer impulsive choices, whilst those with greater fixed imprecision tended to make more. Contradictory observations in the literature regarding the direction of association between timing imprecision and impulsivity might be clarified by distinguishing between fixed and proportional components of imprecision.

Developmental history, energetic state and choice impulsivity in European starlings, Sturnus vulgaris.

Impulsivity-the extent to which a reward is devalued by the amount of time until it is realized-can be affected by an individual's current energetic state and long-term developmental history. In European starlings (Sturnus vulgaris), a previous study found that birds that were lighter for their skeletal size, and birds that had undergone greater shortening of erythrocyte telomeres over the course of development, were more impulsive as adults. Here, we studied the impulsivity of a separate cohort of 29 starlings hand-reared under different combinations of food amount and begging effort. The task involved repeated choice between a key yielding one pellet after 3 s and another key yielding two pellets after 8 s. Impulsivity was operationalised as the proportion of choices for the short-delay option. We found striking variation in impulsivity. We did not replicate the results of the previous study concerning developmental telomere attrition, though combining all the evidence to date in a meta-analysis did support that robustness of that association. We also found that early-life conditions and mass for skeletal size interacted in predicting impulsivity. Specifically, birds that had experienced the combination of high begging effort and low food amount were less impulsive than other groups, and the usual negative relationship between impulsivity and body mass was abolished in birds that had experienced high begging effort. We discuss methodological differences between our study and studies that measure impulsivity using an adjusting-delay procedure.

Genetic variation in the matrix metalloproteinase genes and diabetic nephropathy in type 1 diabetes.

Genetic data support the notion that polymorphisms in members of the matrix metalloproteinase (MMP) family of genes play an important role in extracellular matrix remodeling and contribute to the pathogenesis of vascular disease. To identify novel genetic markers for diabetic nephropathy (DN), we examined the relationship between MMP gene polymorphisms and DN in the Genetics of Kidneys in Diabetes (GoKinD) population. Genotypic data from the Genetic Association Information Network (GAIN) type 1 DN project were analyzed for associations across 21 MMP genes in 1705 individual with type 1 diabetes, including 885 normoalbuminuric control subjects and 820 advanced DN case subjects. In total, we investigated the role of 1283 SNPs (198 genotyped SNPs and 1085 imputed SNPs) mapping to the MMP genes. We identified associations at several correlated SNPs across a 29.2kb interval on chromosome 11q at the MMP-3/MMP-12 locus. The strongest associations occurred at 2 highly-correlated SNPs, rs610950 (OR=0.50, P=1.6×10(-5)) and rs1277718 (OR=0.50, P=2.1×10(-5)). Further examination of this locus identified 17 SNPs (2 genotyped SNPs and 15 imputed SNPs) in complete linkage disequilibrium associated with DN (P-values<2.5×10(-4)), including a non-synonymous SNP (rs652438, Asn357Ser) located in exon 8 of MMP-12 that significantly reduced the risk of DN among carriers of the serine substitution relative to homozygous carriers of asparagine (OR=0.51; 95% CI=0.37-0.71, P=6.2×10(-5)). Taken together, our study suggests that genetic variations within the MMP-3/MMP-12 locus influence susceptibility of DN in type 1 diabetes.

Food insecurity increases energetic efficiency, not food consumption: an exploratory study in European starlings.

Food insecurity-defined as limited or unpredictable access to nutritionally adequate food-is associated with higher body mass in humans and birds. It is widely assumed that food insecurity-induced fattening is caused by increased food consumption, but there is little evidence supporting this in any species. We developed a novel technology for measuring foraging, food intake and body mass in small groups of aviary-housed European starlings (Sturnus vulgaris). Across four exploratory experiments, we demonstrate that birds responded to 1-2 weeks of food insecurity by increasing their body mass despite eating less. Food-insecure birds therefore increased their energetic efficiency, calculated as the body mass maintained per unit of food consumed. Mass gain was greater in birds that were lighter at baseline and in birds that faced greater competition for access to food. Whilst there was variation between experiments in mass gain and food consumption under food insecurity, energetic efficiency always increased. Bomb calorimetry of guano showed reduced energy density under food insecurity, suggesting that the energy assimilated from food increased. Behavioural observations of roosting showed inconsistent evidence for reduced physical activity under food insecurity. Increased energetic efficiency continued for 1-2 weeks after food security was reinstated, indicating an asymmetry in the speed of the response to food insecurity and the recovery from it. Future work to understand the mechanisms underlying food insecurity-induced mass gain should focus on the biological changes mediating increased energetic efficiency rather than increased energy consumption.

GalliForm, a database of Galliformes occurrence records from the Indo-Malay and Palaearctic, 1800-2008.

Historical as well as current species distribution data are needed to track changes in biodiversity. Species distribution data are found in a variety of sources, each of which has its own distinct bias toward certain taxa, time periods or places. We present GalliForm, a database that comprises 186687 galliform occurrence records linked to 118907 localities in Europe and Asia. Records were derived from museums, peer-reviewed and grey literature, unpublished field notes, diaries and correspondence, banding records, atlas records and online birding trip reports. We describe data collection processes, georeferencing methods and quality-control procedures. This database has underpinned several peer-reviewed studies, investigating spatial and temporal bias in biodiversity data, species' geographic range changes and local extirpation patterns. In our rapidly changing world, an understanding of long-term change in species' distributions is key to predicting future impacts of threatening processes such as land use change, over-exploitation of species and climate change. This database, its historical aspect in particular, provides a valuable source of information for further studies in macroecology and biodiversity conservation.

Evaluating the cyclic ratio schedule as an assay of feeding behaviour in the European starling (Sturnus vulgaris).

The cyclic ratio (CR) schedule is a behavioural assay developed to study feeding in rats, in which the number of operant responses required to obtain food reward (the ratio requirement) increases and then decreases in a repeating cycle. In a recent study, we used the CR schedule with European starlings (Sturnus vulgaris) to investigate the effects of an early-life manipulation on adult feeding behaviour. As this was the first time the CR schedule had been used with any bird species, a more in-depth evaluation is warranted. Here, we performed a fuller CR experiment with the same birds as the prior study, a year later. First, we examine the individual consistency of feeding behaviour between experimental sessions and also between CR schedules comprising different ratio requirement progressions. We found that between-session consistency was poor to moderate, and that a geometric ratio progression provided greater between-session consistency than an arithmetic ratio progression. Second, we tried to replicate some of the canonical findings from rats working on CR schedules. In contrast to findings from rats, we found that defence of feeding rates did not increase when starlings were acutely food deprived. However, as in rats, we found that the post-reinforcement pause increased linearly with the upcoming ratio requirement, suggesting that starlings were able to learn the cyclic nature of the schedule. Third, we compared the results from the present study concerning the impacts of our early-life treatment with those from our earlier study. We found that the majority of our previous findings were replicated in the same individuals one year on, reinforcing our previous conclusion that the early-life manipulation had canalised our birds into two groups with different patterns of feeding rate defence.

Early-life begging effort reduces adult body mass but strengthens behavioural defence of the rate of energy intake in European starlings.

Animals require strategies for coping with periods when food is scarce. Such strategies include storing fat as a buffer, and defending the rate of energy intake by changing foraging behaviour when food becomes difficult to obtain. Storage and behavioural defence may constitute alternative strategies for solving the same problem. We would thus expect any developmental influences that limit fat storage in adulthood to also induce a compensatory alteration in adult foraging behaviour, specifically when food is hard to obtain. In a cohort of hand-reared European starlings, we found that higher manipulated early-life begging effort caused individuals to maintain consistently lower adult body mass over a period of two years. Using an operant foraging task in which we systematically varied the costs of obtaining food, we show that higher early-life begging effort also caused stronger behavioural defence of the rate of energy intake when food was more costly to obtain. Among individuals with the same developmental history, however, those individuals who defended their rate of energy intake most strongly were also the heaviest. Our results are relevant to understanding why there are marked differences in body weight and foraging behaviour even among individuals inhabiting the same environment.

A genome-wide linkage scan for genes controlling variation in renal function estimated by serum cystatin C levels in extended families with type 2 diabetes.

We performed a variance components linkage analysis of renal function, measured as glomerular filtration rate (GFR), in 63 extended families with multiple members with type 2 diabetes. GFR was estimated from serum concentrations of cystatin C and creatinine in 406 diabetic and 428 nondiabetic relatives. Results for cystatin C were summarized because they are superior to creatinine results. GFR aggregates in families with significant heritability (h(2)) in diabetic (h(2) = 0.45, P < 1 x 10(-5)) and nondiabetic (h(2) = 0.36, P < 1 x 10(-3)) relatives. Genetic correlation (r(G) = 0.35) between the GFR of diabetic and nondiabetic relatives was less than one (P = 0.01), suggesting that genes controlling GFR variation in these groups are different. Linkage results supported this interpretation. In diabetic relatives, linkage was strong on chromosome 2q (logarithm of odds [LOD] = 4.1) and suggestive on 10q (LOD = 3.1) and 18p (LOD = 2.2). In nondiabetic relatives, linkage was suggestive on 3q (LOD = 2.2) and 11p (LOD = 2.1). When diabetic and nondiabetic relatives were combined, strong evidence for linkage was found only on 7p (LOD = 4.0). In conclusion, partially distinct sets of genes control GFR variation in relatives with and without diabetes on chromosome 2q, possibly on 10q and 18p in the former, and on 7p in both. None of these genes overlaps with genes controlling variation in urinary albumin excretion.

Examination of candidate chromosomal regions for type 2 diabetes reveals a susceptibility locus on human chromosome 8p23.1.

In a panel of large Caucasian pedigrees, we genotyped markers in eight chromosomal regions previously reported as supporting linkage with type 2 diabetes. We previously reported significant linkage on chromosome 20q (maximum logarithm of odds score [MLS] = 2.79) in this panel. In the present analysis, candidate regions on 1q, 2q, 3q, 5q, 9q, and 10q yielded little evidence for linkage; a region on 2p (MLS = 1.64, P = 0.01 at position 9.0 cM) gave suggestive evidence of linkage; and a region on 8p (MLS = 3.67, P = 2.8 x 10(-5), at position 7.6 cM) gave significant evidence of linkage. Conditional analyses were performed for both 2p and 8p regions and the region reported on 20q. The MLS for 2p increased from 1.64 to 1.79 (empirical P = 0.142) when conditioned for heterogeneity on 20q. The case was similar for 8p, where the MLS increased from 3.67 to 4.51 (empirical P = 0.023) when conditioned on families without evidence of linkage at 20q. In conclusion, our data support a type 2 diabetes susceptibility locus on chromosome 8p that appears to be independent from other susceptibility loci. Although we were able to replicate linkage in our pedigrees on chromosome 2p, we did not find evidence of linkage for regions on 1q, 2q, 3q, 5q, 9q, or 10q.

Genome-wide association scan for diabetic nephropathy susceptibility genes in type 1 diabetes.

OBJECTIVE: Despite extensive evidence for genetic susceptibility to diabetic nephropathy, the identification of susceptibility genes and their variants has had limited success. To search for genes that contribute to diabetic nephropathy, a genome-wide association scan was implemented on the Genetics of Kidneys in Diabetes collection. RESEARCH DESIGN AND METHODS: We genotyped approximately 360,000 single nucleotide polymorphisms (SNPs) in 820 case subjects (284 with proteinuria and 536 with end-stage renal disease) and 885 control subjects with type 1 diabetes. Confirmation of implicated SNPs was sought in 1,304 participants of the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, a long-term, prospective investigation of the development of diabetes-associated complications. RESULTS: A total of 13 SNPs located in four genomic loci were associated with diabetic nephropathy with P < 1 x 10(-5). The strongest association was at the FRMD3 (4.1 protein ezrin, radixin, moesin [FERM] domain containing 3) locus (odds ratio [OR] = 1.45, P = 5.0 x 10(-7)). A strong association was also identified at the CARS (cysteinyl-tRNA synthetase) locus (OR = 1.36, P = 3.1 x 10(-6)). Associations between both loci and time to onset of diabetic nephropathy were supported in the DCCT/EDIC study (hazard ratio [HR] = 1.33, P = 0.02, and HR = 1.32, P = 0.01, respectively). We demonstratedexpression of both FRMD3 and CARS in human kidney. CONCLUSIONS: We identified genetic associations for susceptibility to diabetic nephropathy at two novel candidate loci near the FRMD3 and CARS genes. Their identification implicates previously unsuspected pathways in the pathogenesis of this important late complication of type 1 diabetes.

Exclusion of polymorphisms in carnosinase genes (CNDP1 and CNDP2) as a cause of diabetic nephropathy in type 1 diabetes: results of large case-control and follow-up studies.

OBJECTIVES: Recently, an association was found between diabetic nephropathy and the D18S880 microsatellite, located in the carnosinase gene (CNDP1) on chromosome 18q. Alleles of this microsatellite encode for a variable number of leucine residues (from four to seven) in the leader peptide of the carnosinase precursor. The frequency of subjects homozygous for the five leucines was higher in control subjects than in case subjects in studies focusing on type 2 diabetic patients. To test whether this finding can be extended to type 1 diabetic patients, we carried out a comprehensive study on association between diabetic nephropathy and the D18S880 microsatellite and 21 additional SNPs that tagged the genomic region containing CNDP1 and CNDP2. RESEARCH DESIGN AND METHODS: Overall, 1,269 Caucasian patients with type 1 diabetes were included in the study, including 613 patients with normoalbuminuria and a long duration of diabetes, 445 patients with persistent proteinuria, and 211 patients with end-stage renal disease (ESRD). All patients were genotyped for selected polymorphisms, the associations with diabetic nephropathy were tested by a chi(2) test, and odds ratios were calculated. RESULTS: We did not find any significant association between diabetic nephropathy and any examined genetic markers. The negative findings of the case-control study were supported further by negative findings obtained from the 6-year follow-up study of 445 patients with persistent proteinuria, during which 135 patients developed ESRD. CONCLUSIONS: Our large, comprehensive study did not find an association between the D18S880 microsatellite or any other polymorphisms in the CNDP2-CNDP1 genomic region and susceptibility for diabetic nephropathy in type 1 diabetes.

High-density single nucleotide polymorphism genome-wide linkage scan for susceptibility genes for diabetic nephropathy in type 1 diabetes: discordant sibpair approach.

OBJECTIVE: Epidemiological and family studies have demonstrated that susceptibility genes play an important role in the etiology of diabetic nephropathy, defined as persistent proteinuria or end-stage renal disease (ESRD) in type 1 diabetes. RESEARCH DESIGN AND METHODS: To efficiently search for genomic regions harboring diabetic nephropathy genes, we conducted a scan using 5,382 informative single nucleotide polymorphisms on 100 sibpairs concordant for type 1 diabetes but discordant for diabetic nephropathy. In addition to being powerful for detecting linkage to diabetic nephropathy, this design allows linkage analysis on type 1 diabetes via traditional affected sibpair (ASP) analysis. In weighing the evidence for linkage, we considered maximum logarithm of odds score (maximum likelihood score [MLS]) values and corresponding allelic sharing patterns, calculated and viewed graphically using the software package SPLAT. RESULTS: Our primary finding for diabetic nephropathy, broadly defined, is on chromosome 19q (MLS = 3.1), and a secondary peak exists on chromosome 2q (MLS = 2.1). Stratification of discordant sibpairs based on whether disease had progressed to ESRD suggested four tertiary peaks on chromosome 1q (ESRD only), chromosome 20p (proteinuria only), and chromosome 3q (two loci 58 cm apart, one for ESRD only and another for proteinuria only). Additionally, analysis of 130 ASPs for type 1 diabetes confirmed the linkage to the HLA region on chromosome 6p (MLS = 9.2) and IDDM15 on chromosome 6q (MLS = 3.1). CONCLUSIONS: This study identified several novel loci as candidates for diabetic nephropathy, none of which appear to be the sole genetic determinant of diabetic nephropathy in type 1 diabetes. In addition, this study confirms two previously reported type 1 diabetes loci.