The Accumulation of Deficits with Age and Possible Invariants of Aging

This paper extends a method of apprising health status to a broad range of ages from adolescence to old age. The “frailty index” is based on the accumulation of deficits (symptoms, signs, disease classifications) as analyzed in the National Population Health Survey, a representative Canadian population sample (n = 81,859). The accumulation of deficits has both an age-independent (background) component and an age-dependent (exponential) component, akin to the well-known Gompertz-Makeham model for the risk of mortality. While women accumulate more deficits than men of the same age, on average, their rate of accumulation is lower, so the difference in the level of deficits between men and women decreases with age. Two possible invariants of the process of accumulation of deficits were found: (1) the age at which the average proportion of deficits coincides for men and women is 94 years, which closely matches the species-specific lifespan in humans (95 ± 2); (2) the value of the frailty index (proportion of deficits), which corresponds to that age (0.18). The similarity between mortality kinetics and the accumulation of deficits (frailty kinetics), and the coincidence of the time parameters in the frailty and mortality models make it possible to express mortality risk in terms of accumulated deficits. This provides a simple and accessible tool that might have potential in a number of biomedical applications

Information theory analysis of Australian humpback whale song

Songs produced by migrating whales were recorded off the coast of Queensland, Australia, over six consecutive weeks in 2003. Forty-eight independent song sessions were analyzed using information theory techniques. The average length of the songs estimated by correlation analysis was approximately 100 units, with song sessions lasting from 300 to over 3100 units. Song entropy, a measure of structural constraints, was estimated using three different methodologies: (1) the independently identically distributed model, (2) a first-order Markov model, and (3) the nonparametric sliding window match length (SWML) method, as described by Suzuki et al. [(2006). “Information entropy of humpback whale song,” J. Acoust. Soc. Am. 119, 1849–1866]. The analysis finds that the song sequences of migrating Australian whales are consistent with the hierarchical structure proposed by Payne and McVay [(1971). “Songs of humpback whales,” Science 173, 587–597], and recently supported mathematically by Suzuki et al. (2006) for singers on the Hawaiian breeding grounds. Both the SWML entropy estimates and the song lengths for the Australian singers in 2003 were lower than that reported by Suzuki et al. (2006) for Hawaiian whales in 1976–1978; however, song redundancy did not differ between these two populations separated spatially and temporally. The average total information in the sequence of units in Australian song was approximately 35 bits/song. Aberrant songs (8%) yielded entropies similar to the typical songs

Earlier age of dementia onset and shorter survival times in dementia patients with diabetes

Diabetes is a risk factor for dementia, but relatively little is known about the epidemiology of the association. A retrospective population study using Western Australian hospital inpatient, mental health outpatient, and death records was used to compare the age at index dementia record (proxy for onset age) and survival outcomes in dementia patients with and without preexisting diabetes (n = 25,006; diabetes, 17.3%). Inpatient records from 1970 determined diabetes history in this study population with incident dementia in years 1990–2005. Dementia onset and death occurred an average 2.2 years and 2.6 years earlier, respectively, in diabetic compared with nondiabetic patients. Age-specific mortality rates were increased in patients with diabetes. In an adjusted proportional hazard model, the death rate was increased with long-duration diabetes, particularly with early age onset dementia. In dementia diagnosed before age 65 years, those with a ≥15-year history of diabetes died almost twice as fast as those without diabetes (hazard ratio = 1.9, 95% confidence interval: 1.3, 2.9). These results suggest that, in patients with diabetes, dementia onset occurs on average 2 years early and survival outcomes are generally poorer. The effect of diabetes on onset, survival, and mortality is greatest when diabetes develops before middle age and after 15 years’ diabetes duration. The impact of diabetes on dementia becomes progressively attenuated in older age groups

Mid- and Late-Life Diabetes in Relation to the Risk of Dementia: A Population-Based Twin Study

OBJECTIVE—We aimed to verify the association between diabetes and the risk of dementia, Alzheimer's disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association

Ratio-Based Analysis of Differential mRNA Processing and Expression of a Polyadenylation Factor Mutant pcfs4 Using Arabidopsis Tiling Microarray

US National Institutes of Health [1R15GM07719201A1]; US National Science Foundation [IOS-0817818]; Ohio Plant Biotech Consortium; National Natural Science Foundation of China [60774033]; Specialized Research Fund for the Doctoral Program of Higher EducatiBackground: Alternative polyadenylation as a mechanism in gene expression regulation has been widely recognized in recent years. Arabidopsis polyadenylation factor PCFS4 was shown to function in leaf development and in flowering time control. The function of PCFS4 in controlling flowering time was correlated with the alternative polyadenylation of FCA, a flowering time regulator. However, genetic evidence suggested additional targets of PCFS4 that may mediate its function in both flowering time and leaf development. Methodology/Principal Findings: To identify further targets, we investigated the whole transcriptome of a PCFS4 mutant using Affymetrix Arabidopsis genomic tiling 1.0R array and developed a data analysis pipeline, termed RADPRE (Ratio-based Analysis of Differential mRNA Processing and Expression). In RADPRE, ratios of normalized probe intensities between wild type Columbia and a pcfs4 mutant were first generated. By doing so, one of the major problems of tiling array data-variations caused by differential probe affinity-was significantly alleviated. With the probe ratios as inputs, a hierarchy of statistical tests was carried out to identify differentially processed genes (DPG) and differentially expressed genes (DEG). The false discovery rate (FDR) of this analysis was estimated by using the balanced random combinations of Col/pcfs4 and pcfs4/Col ratios as inputs. Gene Ontology (GO) analysis of the DPGs and DEGs revealed potential new roles of PCFS4 in stress responses besides flowering time regulation. Conclusion/Significance: We identified 68 DPGs and 114 DEGs with FDR at 1% and 2%, respectively. Most of the 68 DPGs were subjected to alternative polyadenylation, splicing or transcription initiation. Quantitative PCR analysis of a set of DPGs confirmed that most of these genes were truly differentially processed in pcfs4 mutant plants. The enriched GO term "regulation of flower development'' among PCFS4 targets further indicated the efficacy of the RADPRE pipeline. This simple but effective program is available upon request

Differential Interactions of the Autonomous Pathway RRM Proteins and Chromatin Regulators in the Silencing of Arabidopsis Targets

We have recently shown that two proteins containing RRM-type RNA-binding domains, FCA and FPA, originally identified through their role in flowering time control in Arabidopsis, silence transposons and other repeated sequences in the Arabidopsis genome. In flowering control, FCA and FPA function in the autonomous pathway with conserved chromatin regulators, the histone demethylase FLD and the MSI1-homologue FVE, a conserved WD-repeat protein found in many chromatin complexes. Here, we investigate how the RRM proteins interact genetically with these chromatin regulators at a range of loci in the Arabidopsis genome. We also investigate their interaction with the DNA methylation pathway. In several cases the RRM protein activity at least partially required a chromatin regulator to effect silencing. However, the interactions of the autonomous pathway components differed at each target analysed, most likely determined by certain properties of the target loci and/or other silencing pathways. We speculate that the RNA-binding proteins FCA and FPA function as part of a transcriptome surveillance mechanism linking RNA recognition with chromatin silencing mechanisms

Patterns of Polymorphism and Demographic History in Natural Populations of Arabidopsis lyrata

Many of the processes affecting genetic diversity act on local populations. However, studies of plant nucleotide diversity have largely ignored local sampling, making it difficult to infer the demographic history of populations and to assess the importance of local adaptation. Arabidopsis lyrata, a self-incompatible, perennial species with a circumpolar distribution, is an excellent model system in which to study the roles of demographic history and local adaptation in patterning genetic variation.We studied nucleotide diversity in six natural populations of Arabidopsis lyrata, using 77 loci sampled from 140 chromosomes. The six populations were highly differentiated, with a median FST of 0.52, and structure analysis revealed no evidence of admixed individuals. Average within-population diversity varied among populations, with the highest diversity found in a German population; this population harbors 3-fold higher levels of silent diversity than worldwide samples of A. thaliana. All A. lyrata populations also yielded positive values of Tajima's D. We estimated a demographic model for these populations, finding evidence of population divergence over the past 19,000 to 47,000 years involving non-equilibrium demographic events that reduced the effective size of most populations. Finally, we used the inferred demographic model to perform an initial test for local adaptation and identified several genes, including the flowering time gene FCA and a disease resistance locus, as candidates for local adaptation events.Our results underscore the importance of population-specific, non-equilibrium demographic processes in patterning diversity within A. lyrata. Moreover, our extensive dataset provides an important resource for future molecular population genetic studies of local adaptation in A. lyrata

Repression of FLOWERING LOCUS C and FLOWERING LOCUS T by the Arabidopsis Polycomb Repressive Complex 2 Components

Polycomb group (PcG) proteins are evolutionarily conserved in animals and plants, and play critical roles in the regulation of developmental gene expression. Here we show that the Arabidopsis Polycomb repressive complex 2 (PRC2) subunits CURLY LEAF (CLF), EMBRYONIC FLOWER 2 (EMF2) and FERTILIZATION INDEPENDENT ENDOSPERM (FIE) repress the expression of FLOWERING LOCUS C (FLC), a central repressor of the floral transition in Arabidopsis and FLC relatives. In addition, CLF directly interacts with and mediates the deposition of repressive histone H3 lysine 27 trimethylation (H3K27me3) into FLC and FLC relatives, which suppresses active histone H3 lysine 4 trimethylation (H3K4me3) in these loci. Furthermore, we show that during vegetative development CLF and FIE strongly repress the expression of FLOWERING LOCUS T (FT), a key flowering-time integrator, and that CLF also directly interacts with and mediates the deposition of H3K27me3 into FT chromatin. Our results suggest that PRC2-like complexes containing CLF, EMF2 and FIE, directly interact with and deposit into FT, FLC and FLC relatives repressive trimethyl H3K27 leading to the suppression of active H3K4me3 in these loci, and thus repress the expression of these flowering genes. Given the central roles of FLC and FT in flowering-time regulation in Arabidopsis, these findings suggest that the CLF-containing PRC2-like complexes play a significant role in control of flowering in Arabidopsis

Mobility, Expansion and Management of a Multi-Species Scuba Diving Fishery in East Africa

Background: Scuba diving fishing, predominantly targeting sea cucumbers, has been documented to occur in an uncontrolled manner in the Western Indian Ocean and in other tropical regions. Although this type of fishing generally indicates a destructive activity, little attention has been directed towards this category of fishery, a major knowledge gap and barrier to management. Methodology and Principal Findings: With the aim to capture geographic scales, fishing processes and social aspects the scuba diving fishery that operate out of Zanzibar was studied using interviews, discussions, participant observations and catch monitoring. The diving fishery was resilient to resource declines and had expanded to new species, new depths and new fishing grounds, sometimes operating approximately 250 km away from Zanzibar at depths down to 50 meters, as a result of depleted easy-access stock. The diving operations were embedded in a regional and global trade network, and its actors operated in a roving manner on multiple spatial levels, taking advantage of unfair patron-client relationships and of the insufficient management in Zanzibar. Conclusions and Significance: This study illustrates that roving dynamics in fisheries, which have been predominantly addressed on a global scale, also take place at a considerably smaller spatial scale. Importantly, while proposed management of the sea cucumber fishery is often generic to a simplified fishery situation, this study illustrates