On discriminating temporal relations: Is it relational?

Pigeons were presented on each trial with a pair of keylight stimuli that varied in duration. One of two subsequent choices was reinforced, depending on which of the two stimuli was longer. For some pairs, the duration of one stimulus was predictive of relative duration, but for other pairs, absolute duration was unpredictive. Choice responses depended on relative differences between the stimuli, but were also controlled to some degree by absolute duration of the second member of the pair. Individual differences in control by absolute and relative duration were evident. Those pigeons whose behavior was most influenced by absolute duration showed poorer transfer to a different set of duration pairs

Accommodating Dynamic Oceanographic Processes and Pelagic Biodiversity in Marine Conservation Planning

Pelagic ecosystems support a significant and vital component of the ocean's productivity and biodiversity. They are also heavily exploited and, as a result, are the focus of numerous spatial planning initiatives. Over the past decade, there has been increasing enthusiasm for protected areas as a tool for pelagic conservation, however, few have been implemented. Here we demonstrate an approach to plan protected areas that address the physical and biological dynamics typical of the pelagic realm. Specifically, we provide an example of an approach to planning protected areas that integrates pelagic and benthic conservation in the southern Benguela and Agulhas Bank ecosystems off South Africa. Our aim was to represent species of importance to fisheries and species of conservation concern within protected areas. In addition to representation, we ensured that protected areas were designed to consider pelagic dynamics, characterized from time-series data on key oceanographic processes, together with data on the abundance of small pelagic fishes. We found that, to have the highest likelihood of reaching conservation targets, protected area selection should be based on time-specific data rather than data averaged across time. More generally, we argue that innovative methods are needed to conserve ephemeral and dynamic pelagic biodiversity

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe

Personal Papers (MS 80-0002)

Letter from Leon R. Dreyfus to Harris L. Kempner expressing appreciation for an answer and question session from the Galveston Rotary Club

Duration comparison: relative stimulus differences stimulus age, and stimulus predictiveness.

Under a psychophysical trials procedure, pigeons were presented with a red light of one duration followed by a green light of a second duration. Eight geometrically spaced base durations were paired with one of four shorter and four longer durations as the alternate member of a duration pair, with different pairs randomly intermixed. One choice was reinforced if red had lasted longer than green, and a second choice was reinforced if green had lasted longer. Performance was compared when all the base durations and their pair members were included (entire-range condition) or when only the four longest base durations and their comparison durations (restricted-range condition) were used. Discrimination sensitivity decreased for longer duration pairs under both conditions, supporting a memory-based account. Sensitivity was lower under the restricted-range condition. Under both conditions, a bias to report "green as longer" increased as the second green duration increased. Bias changed as a matching function of the green-duration predictiveness of the correct choice. The results are related to a quantitative model of timing and remembering proposed by Staddon

Choice with a fixed requirement for food, and the generality of the matching relation

Pigeons were trained on choice procedures in which responses on each of two keys were reinforced probabilistically, but only after a schedule requirement had been met. Under one arrangement, a fixed-interval choice procedure was used in which responses were not reinforced until the interval was over; then a response on one key would be reinforced, with the effective key changing irregularly from interval to interval. Under a second, fixed-ratio choice procedure, responses on either key counted towards completion of the ratio and then, once the ratio had been completed, a response on the probabilistically selected key would produce food. In one experiment, the schedule requirements were varied for both fixed-interval and fixed-ratio schedules. In the second experiment, relative reinforcement rate was varied. And in a third experiment, the duration of an intertrial interval separating choices was varied. The results for 11 pigeons across all three experiments indicate that there were often large deviations between relative response rates and relative reinforcement rates. Overall performance measures were characterized by a great deal of variability across conditions. More detailed measures of choice across the schedule requirement were also quite variable across conditions. In spite of this variability, performance was consistent across conditions in its efficiency of producing food. The absence of matching of behavior allocation to reinforcement rate indicates an important difference between the present procedures and other choice procedures; that difference raises questions about the specific conditions that lead to matching as an outcome