Gender differences in the pathways from childhood disadvantage to metabolic syndrome in adulthood: An examination of health lifestyles.

We investigate whether socioeconomic status (SES) in childhood shapes adult health lifestyles in domains of physical activity (leisure, work, chores) and diet (servings of healthy [i.e., nutrient-dense] vs. unhealthy [energy-dense] foods). Physical activity and food choices vary by gender and are key factors in the development of metabolic syndrome (MetS). Thus, we examined gender differences in the intervening role of these behaviors in linking early-life SES and MetS in adulthood. We used survey data (n = 1054) from two waves of the Midlife in the U.S. Study (MIDUS 1 and 2) and biomarker data collected at MIDUS 2. Results show that individuals who were disadvantaged in early life are more likely to participate in physical activity related to work or chores, but less likely to participate in leisure-time physical activity, the domain most consistently linked with health benefits. Women from low SES families were exceedingly less likely to complete recommended amounts of physical activity through leisure. Men from low SES consumed more servings of unhealthy foods and fewer servings of healthy foods. The observed associations between childhood SES and health lifestyles in adulthood persist even after controlling for adult SES. For men, lack of leisure-time physical activity and unhealthy food consumption largely explained the association between early-life disadvantage and MetS. For women, leisure-time physical activity partially accounted for the association, with the direct effect of childhood SES remaining significant. Evidence that material deprivation in early life compromises metabolic health in adulthood calls for policy attention to improve economic conditions for disadvantaged families with young children where behavioral pathways (including gender differences therein) may be shaped. The findings also underscore the need to develop gender-specific interventions in adulthood

The Scientific Study of Positive Psychology, Religion/Spirituality, and Physical Health

Humans have long been interested in relations among religion/spirituality (R/S), positive psychological constructs, and physical health. Furthermore, many religions attempt to influence behavior through health-related prescriptions about food choices, sexual activity, substance use, and resting. Similarly, positive psychological constructs have been discussed in light of their presumed benefits on both mental and physical health (Ryff & Singer, 1998). However, R/S and positive psychological constructs have only recently become objects of scientific investigation of their associations with physical health.https://digitalcommons.chapman.edu/psychology_books/1025/thumbnail.jp

The Effect of Mass Ratio on the Morphology and Time-scales of Disc Galaxy Mergers

The majority of galaxy mergers are expected to be minor mergers. The observational signatures of minor mergers are not well understood, thus there exist few constraints on the minor merger rate. This paper seeks to address this gap in our understanding by determining if and when minor mergers exhibit disturbed morphologies and how they differ from the morphology of major mergers. We simulate a series of unequal-mass moderate gas-fraction disc galaxy mergers. With the resulting g-band images, we determine how the time-scale for identifying galaxy mergers via projected separation and quantitative morphology (the Gini coefficient G, asymmetry A, and the second-order moment of the brightest 20% of the light M20) depends on the merger mass ratio, relative orientations and orbital parameters. We find that G-M20 is as sensitive to 9:1 baryonic mass ratio mergers as 1:1 mergers, with observability time-scales ~ 0.2-0.4 Gyr. In contrast, asymmetry finds mergers with baryonic mass ratios between 4:1 and 1:1 (assuming local disc galaxy gas-fractions). Asymmetry time-scales for moderate gas-fraction major disc mergers are ~ 0.2-0.4 Gyr, and less than 0.06 Gyr for moderate gas-fraction minor mergers. The relative orientations and orbits have little effect on the time-scales for morphological disturbances. Observational studies of close pairs often select major mergers by choosing paired galaxies with similar luminosities and/or stellar masses. Therefore, the various ways of finding galaxy mergers (G-M20, A, close pairs) are sensitive to galaxy mergers of different mass ratios. By comparing the frequency of mergers selected by different techniques, one may place empirical constraints on the major and minor galaxy merger rates.Comment: 16 pages; resubmitted to MNRA

The Effect of Gas Fraction on the Morphology and Time-scales of Disc Galaxy Mergers

Gas-rich galaxy mergers are more easily identified by their disturbed morphologies than mergers with less gas. Because the typical gas fraction of galaxy mergers is expected to increase with redshift, the under-counting of low gas-fraction mergers may bias morphological estimates of the evolution of galaxy merger rate. To understand the magnitude of this bias, we explore the effect of gas fraction on the morphologies of a series of simulated disc galaxy mergers. With the resulting g-band images, we determine how the time-scale for identifying major and minor galaxy mergers via close projected pairs and quantitative morphology (the Gini coefficient G, the second-order moment of the brightest 20% of the light M20, and asymmetry A) depends on baryonic gas fraction f(gas). Strong asymmetries last significantly longer in high gas-fraction mergers of all mass ratios, with time-scales ranging from >= 300 Myr for f(gas) ~ 20% to >= 1 Gyr for f(gas) ~ 50%. Therefore the strong evolution with redshift observed in the fraction of asymmetric galaxies may reflect evolution in the gas properties of galaxies rather than the global galaxy merger rate. On the other hand, the time-scale for identifying a galaxy merger via G-M20 is weakly dependent on gas-fraction (~ 200-400 Myr), consistent with the weak evolution observed for G-M20 mergers.Comment: 15 pages; resubmitted to MNRA

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Rapamycin Response in Tumorigenic and Non-Tumorigenic Hepatic Cell Lines

The mTOR inhibitor rapamycin has anti-tumor activity across a variety of human cancers, including hepatocellular carcinoma. However, resistance to its growth inhibitory effects is common. We hypothesized that hepatic cell lines with varying rapamycin responsiveness would show common characteristics accounting for resistance to the drug.We profiled a total of 13 cell lines for rapamycin-induced growth inhibition. The non-tumorigenic rat liver epithelial cell line WB-F344 was highly sensitive while the tumorigenic WB311 cell line, originally derived from the WB-F344 line, was highly resistant. The other 11 cell lines showed a wide range of sensitivities. Rapamycin induced inhibition of cyclin E-dependent kinase activity in some cell lines, but the ability to do so did not correlate with sensitivity. Inhibition of cyclin E-dependent kinase activity was related to incorporation of p27(Kip1) into cyclin E-containing complexes in some but not all cell lines. Similarly, sensitivity of global protein synthesis to rapamycin did not correlate with its anti-proliferative effect. However, rapamycin potently inhibited phosphorylation of two key substrates, ribosomal protein S6 and 4E-BP1, in all cases, indicating that the locus of rapamycin resistance was downstream from inhibition of mTOR Complex 1. Microarray analysis did not disclose a unifying mechanism for rapamycin resistance, although the glycolytic pathway was downregulated in all four cell lines studied.We conclude that the mechanisms of rapamycin resistance in hepatic cells involve alterations of signaling downstream from mTOR and that the mechanisms are highly heterogeneous, thus predicting that maintaining or promoting sensitivity will be highly challenging

Insights into the complex regulation of rpoS in Borrelia burgdorferi

Co-ordinated regulation of gene expression is required for the transmission and survival of Borrelia burgdorferi in different hosts. The sigma factor RpoS (σS), as regulated by RpoN (σ54), has been shown to regulate key virulence factors (e.g. OspC) required for these processes. As important, multiple signals (e.g. temperature, pH, cell density, oxygen) have been shown to increase the expression of σS-dependent genes; however, little is known about the signal transduction mechanisms that modulate the expression of rpoS. In this report we show that: (i) rpoS has a σ54-dependent promoter that requires Rrp2 to activate transcription; (ii) Rrp2Δ123, a constitutively active form of Rrp2, activated σ54-dependent transcription of rpoS/P-lacZ reporter constructs in Escherichia coli; (iii) quantitative reverse transcription polymerase chain reaction (QRT-PCR) experiments with reporter cat constructs in B. burgdorferi indicated that Rrp2 activated transcription of rpoS in an enhancer-independent fashion; and finally, (iv) rpoN is required for cell density- and temperature-dependent expression of rpoS in B. burgdorferi, but histidine kinase Hk2, encoded by the gene immediately upstream of rrp2, is not essential. Based on these findings, a model for regulation of rpoS has been proposed which provides mechanisms for multiple signalling pathways to modulate the expression of the σS regulon in B. burgdorferi

Purpose in life predicts better emotional recovery from negative stimuli

Purpose in life predicts both health and longevity suggesting that the ability to find meaning from life’s experiences, especially when confronting life’s challenges, may be a mechanism underlying resilience. Having purpose in life may motivate reframing stressful situations to deal with them more productively, thereby facilitating recovery from stress and trauma. In turn, enhanced ability to recover from negative events may allow a person to achieve or maintain a feeling of greater purpose in life over time. In a large sample of adults (aged 36-84 years) from the MIDUS study (Midlife in the U.S., http://www.midus.wisc.edu/), we tested whether purpose in life was associated with better emotional recovery following exposure to negative picture stimuli indexed by the magnitude of the eyeblink startle reflex (EBR), a measure sensitive to emotional state. We differentiated between initial emotional reactivity (during stimulus presentation) and emotional recovery (occurring after stimulus offset). Greater purpose in life, assessed over two years prior, predicted better recovery from negative stimuli indexed by a smaller eyeblink after negative pictures offset, even after controlling for initial reactivity to the stimuli during the picture presentation, gender, age, trait affect, and other well-being dimensions. These data suggest a proximal mechanism by which purpose in life may afford protection from negative events and confer resilience is through enhanced automatic emotion regulation after negative emotional provocation

Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS

Summary Algorithms designed to identify canonical yeast prions predict that ~250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbor a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here, we define pathogenic mutations in PrLDs of hnRNPA2/B1 and hnRNPA1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and a case of familial ALS. Wild-type hnRNPA2 and hnRNPA1 display an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a ‘steric zipper’ motif in the PrLD, which accelerates formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Importantly, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant ‘steric zipper’ motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs must be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone

Forecasting: theory and practice

Forecasting has always been in the forefront of decision making and planning. The uncertainty that surrounds the future is both exciting and challenging, with individuals and organisations seeking to minimise risks and maximise utilities. The lack of a free-lunch theorem implies the need for a diverse set of forecasting methods to tackle an array of applications. This unique article provides a non-systematic review of the theory and the practice of forecasting. We offer a wide range of theoretical, state-of-the-art models, methods, principles, and approaches to prepare, produce, organise, and evaluate forecasts. We then demonstrate how such theoretical concepts are applied in a variety of real-life contexts, including operations, economics, finance, energy, environment, and social good. We do not claim that this review is an exhaustive list of methods and applications. The list was compiled based on the expertise and interests of the authors. However, we wish that our encyclopedic presentation will offer a point of reference for the rich work that has been undertaken over the last decades, with some key insights for the future of the forecasting theory and practice