Explore the vast range of titles available.

The heterochromatin loss model of aging suggests there is an age-dependent reduction in epigenetic factors that form and maintain the heterochromatin state of chromosomes. Position Effect Variegation (PEV) can visually report phenotypes of heterochromatin mediated silencing in Drosophila Melanogaster eyes and we use PEV to examine the association between heterochromatin state changes and aging. Pericentric inserts causing PEV showed suppressed variegation phenotypes in old age compared to young age and were confirmed to be associated with progressively increasing transcription, indicating loss of heterochromatin mediated silencing. Within a single population, animals with enhanced PEV phenotypes live longer than those with more suppressed PEV phenotypes, suggesting that small differences in environmental or genetic factors within this population could be responsible for differences in heterochromatin and lifespan. Environmental factors could enhance heterochromatin, reduced nutrient diet and lower temperature coincided with enhanced heterochromatin and longer life. Furthermore, genetic variants associated with long life, including chico mutants, lead to increased heterochromatin and enhanced PEV phenotypes. Therefore, aging can be linked to heterochromatin loss and developmental increases in heterochromatin are associated with longevity. Thus, PEV reporters act as aging clocks demonstrating loss of heterochromatin that progresses with age and epigenetic alterations that can promote longevity.

The ordinal position effect refers to a phenomenon in which items positioned early in an ordinal sequence receive a faster response with the left key than with the right key, and the opposite response pattern occurs when items are positioned later in an ordinal sequence. Previous studies have suggested that ordinal symbols are spatially represented from left to right, thus leading to the ordinal position effect; however, the spatial coding mechanism of ordinal symbols remains unclear. Therefore, the present study explored the ordinal position effect as an index to judge the spatial coding of ordinal symbols, and three experiments were performed to investigate the spatial coding mechanism of ordinal symbols. In particular, a novel transitory ordinal sequence was induced by presenting successive dots of different colors centrally (Experiment 1 ), from left to right or from right to left (Experiments 2 and 3 ), and participants were asked to memorize the successive dots in the correct order. Then, the participants were asked to press a key to provide a response corresponding to a probe dot’s ordinal position (Experiments 1 and 2 ) or its spatial location (Experiment 3 ). The following results were identified: (1) The ordinal position effect occurred when responses were based on the ordinal position regardless of the presentation direction, and (2) the ordinal position effect was overridden when responses were based on the spatial locations of the ordinal symbols. From these results, we concluded that the spatial coding of ordinal symbols is flexible and that ordinal symbols are encoded depending on the specific experimental context.

From drop-down computer menus to department-store aisles, people in everyday life often choose from simultaneous displays of products or options. Studies of position effects in such choices show seemingly inconsistent results. For example, in restaurant choice, items enjoy an advantage when placed at the beginning or end of the menu listings, but in multiple-choice tests, answers are more popular when placed in the middle of the offered list. When reaching for a bottle on a supermarket shelf, bottles in the middle of the display are more popular. But on voting ballots, first is the most advantageous position. Some of the effects are quite sensible, whereas others are harder to justify and can aptly be regarded as biases. This article attempts to put position effects into a unified and coherent framework and to account for them simply by using a small number of familiar psychological principles.

Serial position effects involve the differential recall of information based on its temporal order at encoding. Previous research indicates that learners may be aware of these effects under certain encoding conditions, but it is unclear whether metacognitive control is sensitive to serial position effects. The current study examined whether there are serial position effects in participants’ study time and whether they can learn about serial position effects under fixed encoding conditions and then transfer what they have learned to self-paced study conditions. Specifically, participants were given lists of to-be-remembered words and studied each word for a fixed duration on initial lists, but self-paced their study time on later lists. Results revealed that self-paced study times oppositely mirrored serial position effects (i.e., briefer study times in the beginning and end of each list), and serial position effects were reduced in self-paced study conditions, particularly in participants initially studying under fixed conditions before self-pacing their study time. Specifically, participants may have monitored their output and, based on observations of forgetting middle items, transferred their learning of serial position effects from prior lists. Thus, participants may use forgetting and serial position information to guide encoding, indicating that fundamental properties of the memory system can be incorporated into the processes that guide metacognitive control.

The present study examined if disruption of serial position effects in list recall could serve as an early marker of Alzheimer's disease (AD) in Spanish-English bilinguals. We tested 20 participants initially diagnosed as cognitively normal or with mild cognitive impairment who declined and eventually received a diagnosis of AD (decliners), and 37 who remained cognitively stable (controls) over at least 2 years. Participants were tested on the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test in English or Spanish as part of an annual neuropsychological evaluation. Compared to controls, decliners exhibited significantly reduced recall including reduced primacy scores (i.e., items recalled from the three list items on Trial 1), whereas recency scores (i.e., items recalled from the 3 list items on Trial 1) were equivalent in decliners and controls. Further analyses suggested that the sensitivity of the primacy effect to preclinical AD was initially stronger in participants tested in Spanish, a surprising finding given that the CERAD was developed for English speakers. However, in the subsequent year of testing, primacy scores declined to the same level regardless of language of testing. Several list learning measures may facilitate early diagnosis of AD in Spanish-English bilinguals, possibly including the relatively understudied primacy effect. Additional studies are needed to investigate the possibility that linguistic or demographic variables might modulate sensitivity of list learning tests to preclinical AD, which could lead to broader improvements in their utility for early diagnosis of AD in all populations.

Position effect variegation (PEV) in Drosophila results from new juxtapositions of euchromatic and heterochromatic chromosomal regions, and manifests as striking bimodal patterns of gene expression. The semirandom patterns of PEV, reflecting clonal relationships between cells, have been interpreted as gene-expression states that are set in development and thereafter maintained without change through subsequent cell divisions. The rate of instability of PEV is almost entirely unexplored beyond the final expression of the modified gene; thus the origin of the expressivity and patterns of PEV remain unexplained. Many properties of PEV are not predicted from currently accepted biochemical and theoretical models. In this work we investigate the time at which expressivity of silencing is set, and find that it is determined before heterochromatin exists. We employ a mathematical simulation and a corroborating experimental approach to monitor switching (i.e., gains and losses of silencing) through development. In contrast to current views, we find that gene silencing is incompletely set early in embryogenesis, but nevertheless is repeatedly lost and gained in individual cells throughout development. Our data support an alternative to locus-specific “epigenetic” silencing at variegating gene promoters that more fully accounts for the final patterns of PEV.

Ballot position effects have been documented across a variety of political and electoral systems. In general, knowledge of the underlying mechanisms is limited. There is also little research on such effects in preferential-list PR systems, in which parties typically present ranked lists and thus signaling is important. This study addresses both gaps. Theoretically, we formalize four models of voter decision-making: pure appeal-based utility maximization, implying no position effects; rank-taking, where voters take cues from ballot position per se; satisficing, where choice is a function of appeal, but voters consider the options in the order of their appearance; and a hybrid “satisficing-with-rank-taking” variant. From these, we derive differential observable implications. Empirically, we exploit a quasi-experiment, created by the mixed-member electoral system that is used in the state of Bavaria, Germany. Particular electoral rules induce variation in both the observed rank and the set of competitors, and allow for estimating effects at all ranks. We find clear evidence for substantial position effects, which are strongest near the top, but discernible even for the 15th list position. In addition, a candidate’s vote increases when the average appeal of higher-placed (but not that of lower-placed) competitors is lower. Overall, the evidence is most compatible with the hybrid satisficing-with-rank-taking model. Ballot position thus affects both judgment and choice of candidates.

Background Integration of heterogeneous genes is widely applied in synthetic biology and metabolic engineering. However, knowledge about the effect of integrative position on gene expression remains limited. Results We established a genome-wide landscape of position effect on gene expression in Saccharomyces cerevisiae. The expression cassette of red fluorescence protein (RFP) gene was constructed and inserted at 1044 loci, which were scattered uniformly in the yeast genome. Due to the different integrative loci on the genome, the maximum relative intensity of RFP is more than 13-fold over the minimum. Plots of the number of strains to RFP relative intensity showed normal distribution, indicating significant position effect on gene expression in yeast. Furthermore, changing the promoters or reporter genes, as well as carbon sources, revealed little consequences on reporter gene expression, indicating chromosomal location is the major determinant of reporter gene expression. Conclusions We have examined the position effects to integration genes expression in large number loci around whole genome in S. cerevisiae. The results could guide the design of integration loci for exogenous genes and pathways to maximize their expression in metabolic engineering.

Development of transgenic cell lines or organisms for industrial, agricultural, or medicinal applications involves inserting DNA into the target genome in a way that achieves efficacious transgene expression without a deleterious impact on fitness. The genomic insertion site is widely recognized as an important determinant of success. However, the effect of chromosomal location on transgene expression and fitness has not been systematically investigated in plants. Here we evaluate the importance of transgene insertion site in maize and soybean using both random and site-specific transgene integration. We have compared the relative contribution of genomic location on transgene expression levels with other factors, including cis-regulatory elements, neighboring transgenes, genetic background, and zygosity. As expected, cis-regulatory elements and the presence/absence of nearby transgene neighbors can impact transgene expression. Surprisingly, we determined not only that genomic location had the least impact on transgene expression compared to the other factors that were investigated but that the majority of insertion sites recovered supported transgene expression levels that were statistically not distinguishable. All 68 genomic sites evaluated were capable of supporting high-level transgene expression, which was also consistent across generations. Furthermore, multilocation field evaluation detected no to little decrease in agronomic performance as a result of transgene insertion at the vast majority of sites we evaluated with a single construct in five maize hybrid backgrounds.

Exogenous genes are generally expressed by integration into the chromosomes of Pichia pastoris. However, systematic studies on the chromosomal position effect are lacking, and locations that are conducive to the high expression of foreign genes are rarely reported. In this study, a genomic random insertion mutagenesis library for P. pastoris was successfully constructed using the piggyBac (PB) transposon system. Through sequencing, the sequence TTAA was identified as the major recognition site of the PB transposon, which exhibited relatively high coverage on P. pastoris chromosomes, making it a valuable tool for studying position effect variegation in P. pastoris. Using the enhanced green fluorescent protein gene (eGFP) as a reporter, two libraries including low-expression positions and high-expression positions were obtained by flow cytometry. The low-expression sites were mainly located upstream of ORFs around the promoter region and downstream near the terminator region, while the high-expression sites were predominantly located at the gene interior. KEGG and GO analyses showed that genes in high-expression positions were significantly enriched in the ATP-dependent chromatin remodeling and histone binding pathways, and genes in low-expression positions were significantly enriched in the MAPK signaling pathway, autophagy, mitochondrial autophagy, ABC transporters, and the arginine synthesis pathway. This study has clarified the genome-wide landscape of position effect variegation in P. pastoris. Additionally, it has provided novel insights into high-throughput screening strategies for strains with high exogenous gene expression.