Traditional and Emerging Lifestyle Risk Behaviors and All-Cause Mortality in Middle-Aged and Older Adults: Evidence from a Large Population-Based Australian Cohort

Background

Lifestyle risk behaviors are responsible for a large proportion of disease burden worldwide. Behavioral risk factors, such as smoking, poor diet, and physical inactivity, tend to cluster within populations and may have synergistic effects on health. As evidence continues to accumulate on emerging lifestyle risk factors, such as prolonged sitting and unhealthy sleep patterns, incorporating these new risk factors will provide clinically relevant information on combinations of lifestyle risk factors.

Methods and Findings

Using data from a large Australian cohort of middle-aged and older adults, this is the first study to our knowledge to examine a lifestyle risk index incorporating sedentary behavior and sleep in relation to all-cause mortality. Baseline data (February 2006– April 2009) were linked to mortality registration data until June 15, 2014. Smoking, high alcohol intake, poor diet, physical inactivity, prolonged sitting, and unhealthy (short/long) sleep duration were measured by questionnaires and summed into an index score. Cox proportional hazards analysis was used with the index score and each unique risk combination as exposure variables, adjusted for socio-demographic characteristics.During 6 y of follow-up of 231,048 participants for 1,409,591 person-years, 15,635 deaths were registered. Of all participants, 31.2%, 36.9%, 21.4%, and 10.6% reported 0, 1, 2, and 3+ risk factors, respectively. There was a strong relationship between the lifestyle risk index score and all-cause mortality. The index score had good predictive validity (c index = 0.763), and the partial population attributable risk was 31.3%. Out of all 96 possible risk combinations, the 30 most commonly occurring combinations accounted for more than 90% of the participants. Among those, combinations involving physical inactivity, prolonged sitting, and/or long sleep duration and combinations involving smoking and high alcohol intake had the strongest associations with all-cause mortality. Limitations of the study include self-reported and under-specified measures, dichotomized risk scores, lack of long-term patterns of lifestyle behaviors, and lack of cause-specific mortality data.

Conclusions

Adherence to healthy lifestyle behaviors could reduce the risk for death from all causes. Specific combinations of lifestyle risk behaviors may be more harmful than others, suggesting synergistic relationships among risk factors.     

Technical advance: a high throughput system for transposon tagging and promoter trapping in tomato

We describe new tools for functional analysis of the tomato genome based on insertional mutagenesis with the maize Ac/Ds transposable elements in the background of the miniature cultivar Micro-Tom. 2932 F3 families, in which Ds elements transposed and were stabilized, were screened for phenotypic mutations. Out of 10 families that had a clear mutant phenotype, only one mutant was Ds-tagged. In addition, we developed promoter trapping using the firefly luciferase reporter gene and enhancer trapping, using beta-glucuronidase (GUS). We show that luciferase can be used as a non-invasive reporter to identify, isolate and regenerate somatic sectors, to study the time course of mutant expression, and to identify inducible genes. Out of 108 families screened for luciferase activity 55% showed expression in the flower, 11% in the fruit and 4% in seedlings, suggesting a high rate of Ds insertion into genes. Preferential insertion into genes was supported by the analysis of Ds flanking sequences: 28 out of 50 sequenced Ds insertion sites were similar to known genes or to ESTs. In summary, the 2932 lines described here contain 2-3 Ds inserts per line, representing a collection of approximately 7500 Ds insertions. This collection has potential for use in high-throughput functional analysis of genes and promoter isolation in tomato.     

Mechanisms of sexual selection: sexual swellings and estrogen concentrations as fertility indicators and cues for male consort decisions in wild baboons

Male mate-guarding episodes ('consortships'), are taxonomically widespread, yet costly to individual males. Consequently, males should bias consortships toward females with whom the probability of conception is high. We combined data on consortships with visual scoring of sexual swellings and assays of fecal estrogen concentrations (fE) in a wild population of baboons (Papio cynocephalus) to test the hypotheses that sexual swellings are reliable indicators of (1) within-cycle timing of ovulation, (2) differences in conception probability among females that differ in maturational stage, and (3) conceptive versus non-conceptive cycles of parous females. We also evaluated whether adult males might rely on swellings or other estrogen-dependent signals (e.g., fE) for mate-guarding decisions. We found that sexual swellings reflected conception probability within and among cycles. Adult males limited their consortships to the turgescent phase of cycles, and consorted more with adult females than with newly cycling adolescents. The highest ranking (alpha) males discriminated more than did males of other ranks; they (1) limited their consortships to the 5-day peri-ovulatory period, (2) consorted more with adult than with adolescent females, and (3) consorted more with adult females on conceptive cycles than on non-conceptive cycles, all to a greater extent than did males of other ranks. Male mate choice based on sexual swellings and other estrogenic cues of fertility may result in sexual selection on these female traits and enhance dominance-based reproductive skew in males. Alpha males are the least constrained in their mating behavior and can best take advantage of these cues to mate selectively.     

The Membrane Topology of ALMT1, an Aluminum-Activated Malate Transport Protein in Wheat (Triticum aestivum)

The wheat ALMT1 gene encodes an aluminum (Al)-activated malate transport protein which confers Al-resistance. We investigated the membrane topology of this plasma-membrane localized protein with immunocytochemical techniques. Several green fluorescent protein (GFP)-fused and histidine (His)-tagged chimeras of ALMT1 were prepared based on a computer-predicted secondary structure and transiently expressed in cultured mammalian cells. Antibodies raised to polypeptide epitopes of ALMT1 were used in conjunction with the antibody to the His-tags to determine the topology of ALMT1. This study shows that the ALMT1 protein contains six transmembrane domains with the amino and carboxyl termini located on the extracellular side of the plasma membrane.Key Words: ALMT1, aluminum resistance, immunofluorescent staining, malate transporter, topology, Triticum aestivum     

Whole-genome sequences of Borrelia bissettii, Borrelia valaisiana, and Borrelia spielmanii

It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Borrelia spielmanii, and Borrelia bissettii have been associated with Lyme disease. We report the complete genome sequences of B. valaisiana VS116, B. spielmanii A14S, and B. bissettii DN127.     

Immobilization of thermostable exo-inulinase from mutant thermophilic Aspergillus tamarii-U4 using kaolin clay and its application in inulin hydrolysis

In this study, attempts were made to immobilize purified exo-inulinase from mutant thermophic Aspergillus tamarii-U4 onto Kaolinite clay by covalent bonding cross-linked with glutaraldehyde with an immobilization yield of 66% achieved. The free and immobilized inulinases were then characterized and characterization of the enzymes revealed that temperature and pH optima for the activity of the free and immobilized enzymes were both 65?°C and pH 4.5 respectively. The free inulinase completely lost its activity after incubation at 65?°C for 6 h while the immobilized inulinase retained 16.4% of its activity under the same condition of temperature and incubation time. The estimated kinetic parameters K_m and V_max for the free inulinase as estimated from Lineweaver-Burk plots were 0.39?mM and 4.21?µmol/min for the free inulinase and 0.37?mM and 4.01?µmol/min for the immobilized inulinase respectively. Inulin at 2.5% (w/v) and a flow rate of 0.1?mL was completely hydrolysed for 10?days at 60?°C in a continuous packed bed column and the operational stability of the system revealed that the half-life of the immobilized inulinase was 51?days. These properties make the immobilized exo-inulinase from Aspergillus tamarii-U4 a potential candidate for the production of fructose from inulin hydrolysis.     

Absence of morningness alleles in non-European populations

ABSTRACT

In spite of suspected circadian differences between different ancestral groups, most human studies have used individuals of European descent. This also applies to three recent genome-wide association studies (GWAS), which pinpointed a number of chronotype loci. We investigated the distribution of these hits in different 1000 Genomes populations. We found 6 out of the 41 alleles previously identified by GWAS in European participants (in the genes RGS16, PER2 and AK5 and between the genes APH1A and CA14) to be absent from some non-European population groups. This highlights the need for ancestral diversity in circadian research and may reflect differences affecting the phenotype of individuals of East Asian ancestry.     

Phototoxic Action Spectrum on a Retinal Pigment Epithelium Model of Age-Related Macular Degeneration Exposed to Sunlight Normalized Conditions

Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the eye.     

1H-NMR and 13C-NMR lipid profiles of human renal tissues

Lipids from human renal tissues are studied by means of (1)H- and (13)C-NMR spectroscopy. The total lipid fractions obtained from healthy kidneys, malignant renal cell carcinomas, and benign oncocytomas are characterized and analyzed to elucidate the main differences between the functional and neoplastic tissues. In all cases the lipid components are well identified. The healthy kidney is characterized by high amounts of triglycerides and the presence of cholesterol in its free form. On the contrary, renal cell carcinomas contain high amounts of cholesterol that are almost completely esterified as oleate, suggesting an intracellular localization of the cholesteryl esters synthesis. Cholesteryl esters are considered markers of renal cell carcinomas, thus supporting recent theories that these compounds play a leading role in cell proliferation. Oncocytomas are particularly rich in phosphatidylcholine and, analogous to the healthy kidney, are completely lacking in cholesteryl esters. Healthy kidneys and oncocytomas appear to have other similarities if compared with renal cell carcinomas: a very high fatty acyl/cholesterol ratio, the presence of dolichols, and a higher grade of unsaturation. The (13)C data suggest a new method for the direct evaluation of the saturated/unsaturated fatty acyl ratio.