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The effects of resource subsidies on a recipient ecosystem depends on a variety of factors. Firstly, increasing the supply of limiting nutrients tends to increase the accumulation of biomass across different compartments of the recipient food web. Secondly, in the case of aquatic microorganisms, this accumulation may also be contingent on inputs of energy through light, mediating interactions between heterotrophic bacteria and autotrophic algae. Thirdly, macroscopic consumers feed upon microorganisms and recycle nutrients through excretion and egestion, profoundly affecting nutrient cycling.In order to examine the context‐dependency of nutrient cycling in aquatic systems, we performed an experiment in mesocosms where we followed the responses of dissolved nutrients, microorganisms, and larvae of the cosmopolitan mosquito Culex quinquefasciatus (Diptera: Culicidae) to two terrestrial subsidies differing in carbon (C):nutrient, in combination with two light intensities.We found that the interactions amongst bacteria and algae themselves remained generally unimportant after accounting for treatment effects, and that light did mediate some of the effects of nutrient subsidies on microorganisms. We also found that the presence of mosquito larvae was associated with altered concentrations of nitrogen (N) in some treatments, ultimately benefitting algae. Finally, we found that low C:nutrient subsidies generally increased the development rate of mosquito larvae, and that increased light exposure led to higher mosquito survival.Overall, these patterns may be explained by strong nitrogen limitation in our system, causing both group of microorganisms to respond similarly to variations in nutrient supply without direct covariation, and to the key role of N recycling by mosquito larvae in sustaining algal densities in exposed treatments.The context‐dependency in our study may reflect elemental or molecular constraints other than phosphorus. Our experiment thus calls for greater synthesis amongst ecological theories. [ABSTRACT FROM AUTHOR]

Abstract It is commonly known that the MAPK pathway is involved in translating environmental inputs, regulating downstream reactions, and maintaining the intrinsic dynamic balance. Numerous essential elements and regulatory processes are included in this pathway, which are essential to its functionality. Among these, MAP3K4, a member of the serine/threonine kinases family, plays vital roles throughout the organism's life cycle, including the regulation of apoptosis and autophagy. Moreover, MAP3K4 can interact with key partners like GADD45, which affects organism's growth and development. Notably, MAP3K4 functions as both a tumor promotor and suppressor, being activated by a variety of factors and triggering diverse downstream pathways that differently influence cancer progression. The aim of this study is to provide a brief overview of physiological functions of MAP3K4 and shed light on its contradictory roles in tumorigenesis.

[Display omitted] • KMT2 methyltransferases are responsible for methylation on H3K4. • KMT2 family include six members: KMT2A/B, KMT2C/D, and KMT2F/G. • KMT2s play important roles in gene regulation, differentiation, and development. • KMT2 methyltransferases have enzymatic activity-dependent and -independent functions. Histone-lysine N -methyltransferase 2 (KMT2) methyltransferases are critical for gene regulation, cell differentiation, animal development, and human diseases. KMT2 biological roles are often attributed to their methyltransferase activities on lysine 4 of histone H3 (H3K4). However, recent data indicate that KMT2 proteins also possess non-enzymatic functions. In this review, we discuss the current understanding of KMT2 family, with a focus on their enzymatic activity-dependent and -independent functions. Six mammalian KMT2 proteins of three subgroups, KMT2A/B (MLL1/2), KMT2C/D (MLL3/4), and KMT2F/G (SETD1A/B or SET1A/B), have shared and distinct protein domains, catalytic substrates, genomic localizations, and associated complex subunits. Recent studies have revealed the importance of KMT2C/D in enhancer regulation, differentiation, development, tumor suppression and highlighted KMT2C/D enzymatic activity-dependent and -independent roles in mouse embryonic development and cell differentiation. Catalytic dependent and independent functions for KMT2A/B and KMT2F/G in gene regulation, differentiation, and development are less understood. Finally, we provide our perspectives and lay out future research directions that may help advance the investigation on enzymatic activity-dependent and -independent biological roles and working mechanisms of KMT2 methyltransferases. [ABSTRACT FROM AUTHOR]

Big Five personality traits are assumed to be linked with attitudes toward own aging. Since both constructs have central importance for the aging process, it is surprising that to our knowledge no study so far comprehensively addressed their mutual connection over time. We used data from the ILSE study, a longitudinal study capturing personality and attitudes toward own aging at four measurement occasions, spanning 20 years and including two participant cohorts in midlife (n = 501; born 1950–52) and later life (n = 500; born 1930–32). Dual latent change score models showed that personality was longitudinally related to change in attitudes toward own aging: Lower Neuroticism, higher Conscientiousness, and higher Openness predicted more positive attitudes, whereas the direction of the effect for Extraversion varied by time. Furthermore, the role of personality seems to be confined to certain sensitive periods in midlife and early old age. Contrary to our expectations, attitudes toward own aging had only marginal longitudinal impact on the Big Five. Our results shed light on the developmental co-dynamics of personality and subjective perceptions of aging across the second half of the lifespan. [ABSTRACT FROM AUTHOR]

CDGSH iron-sulfur domain-containing protein 2 (Cisd2) is pivotal to mitochondrial integrity and intracellular Ca2+ homeostasis. In the heart of Cisd2 knockout mice, Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Furthermore, Cisd2 deficiency disrupts Ca2+ homeostasis via dysregulation of sarco/endoplasmic reticulum Ca2+-ATPase (Serca2a) activity, resulting in an increased level of basal cytosolic Ca2+ and mitochondrial Ca2+ overload in cardiomyocytes. Most strikingly, in Cisd2 transgenic mice, a persistently high level of Cisd2 is sufficient to delay cardiac aging and attenuate age-related structural defects and functional decline. In addition, it results in a younger cardiac transcriptome pattern during old age. Our findings indicate that Cisd2 plays an essential role in cardiac aging and in the heart’s electromechanical functioning. They highlight Cisd2 as a novel drug target when developing therapies to delay cardiac aging and ameliorate age-related cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Understanding cell differentiation—the process of generation of distinct cell-types—plays a pivotal role in developmental and evolutionary biology. Transcriptomic information and epigenetic marks are useful to elucidate hierarchical developmental relationships among cell-types. Standard phylogenetic approaches such as maximum parsimony, maximum likelihood and neighbor joining have previously been applied to ChIP-Seq histone modification data to infer cell-type trees, showing how diverse types of cells are related. In this study, we demonstrate the applicability and suitability of quartet-based phylogenetic tree estimation techniques for constructing cell-type trees. We propose two quartet-based pipelines for constructing cell phylogeny. Our methods were assessed for their validity in inferring hierarchical differentiation processes of various cell-types in H3K4me3, H3K27me3, H3K36me3, and H3K27ac histone mark data. We also propose a robust metric for evaluating cell-type trees. [ABSTRACT FROM AUTHOR]

Background: Vitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are involved in fetal skeletal development. A positive association between maternal vitamin D levels and offspring bone mineral density (BMD) at adulthood has been observed. The impact of maternal vitamin A status in pregnancy on offspring peak bone mass remains unclear. Method and findings: Forty-one mother-child pairs were recruited from a population-based prospective cohort study in Trondheim, Norway, where pregnant women were followed from gestational week 17. Their term-born infants were followed from birth (1986–88). Regression analyses were performed for vitamin A (retinol), 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in maternal serum (gestational weeks 17, 33, 37) and cord blood. Offspring BMD and spine trabecular bone score (TBS), a measure of bone quality, were analyzed by dual x-ray absorptiometry at 26 years. Average levels during pregnancy of retinol, 25(OH)D and 1,25(OH)2D were 1.66 (0.32) μmol/L, 59.0 (20.6) nmol/L, and 251.3 (62.4) pmol/L, respectively. 1,25(OH)2D levels were similar in those with 25(OH)D levels <30 and >75 nmol/L. After adjustment for maternal age, BMI, smoking, and education, and offspring birth weight, maternal serum retinol was positively associated with offspring spine BMD [mean change 30.8 (CI 7.6, 54.0) mg/cm2 per 0.2 μmol/L retinol], and with offspring TBS, although non-significant (p = 0.08). No associations were found between maternal 25(OH)D and 1,25(OH)2D levels and offspring bone parameters. Vitamin levels in cord blood were not associated with offspring BMD or TBS. Conclusions: This is the first study to show an association between maternal vitamin A status and offspring peak bone mass. Our findings may imply increase future risk for osteoporotic fracture in offspring of mothers with suboptimal vitamin A level. No associations were observed between 25(OH)D and 1,25(OH)2D and offspring BMD. [ABSTRACT FROM AUTHOR]

Accurate age estimation in wildlife conservation is an important diagnostic tool in the interpretation of biological data, necropsy examination, reproductive status and population demographics. The most frequently utilized methods to age bottlenose dolphins (Tursiops truncatus) include tooth extraction; counting dental growth layer groups and dental radiography. These methods are inaccurate in dolphins > 13 years old, due to overlapping of the growth layer groups in dolphins and worn teeth. Establishing a non-invasive method of accurately aging bottlenose dolphins across the entire age range is important to long term conservation efforts to understand health status, lifespan, reproduction and survivability. A database of 126 radiographs from 94 dolphins of known chronological age was utilized to establish the stages of skeletal ossification over time. A numerical score from -1 to 8 was assigned to 16 anatomic locations on the pectoral radiograph, to create a formula to estimate age. The most informative areas to evaluate morphologically were the metaphyseal regions of the radius and ulna, and the proximal and distal epiphysis of metacarpals II and III. Third order polynomial regression calculated separate age predictor formulas for male and female dolphins, with females reaching sexual maturity earlier than males. Completion of epiphyseal closure of the long bones correlated with average sexual maturity. Managed care dolphin ages could be properly estimated with decreasing precision from within 3 months in animals < 5 years old, to within 5 years in animals > 30 years old. This diagnostic tool could also be applied to diagnose atypical ossification patterns consistent with nutritional, developmental or growth abnormalities, and identifying subclinical health issues. In conclusion, knowledge of the lifespan and the onset of sexual maturity for each species will allow this model to be applied to other cetaceans, facilitating age estimation via pectoral radiography in future research. [ABSTRACT FROM AUTHOR]

Background: Though mass evacuation may increase the need for long-term care (LTC) services, how the need for LTC services increases and how the public LTC system affects it is not well understood. We evaluated changes in public LTC benefits for the people living in the mandatory evacuation areas established after the 2011 Fukushima nuclear disaster and examined the roles of the universal LTC insurance system in Japan. Methods: In order to evaluate the effect of the mandatory evacuation on LTC benefits, we examined the trends of LTC benefits in the Fukushima evacuation group and the nationwide non-evacuation group. We first decomposed per-elderly-individual benefits at the municipality level into the LTC certification rate and per-certified-individual benefits, and then implemented difference-in-differences analysis using these variables as outcomes. Results: Per-elderly-individual benefits significantly increased from 2012 onward in the evacuation group, and this was explained by an increase in the certification rate rather than in per-certified-individual benefits. Increases in per-elderly-individual benefits and the certification rate in the post-disaster period were observed in all but the highest care level, and the corresponding outcomes for the highest care level decreased immediately after the disaster. We also found that the increase in the certification rate had been mostly realized by an increase in the number of certified individuals. Conclusions: The increase in LTC benefits can be associated with the impact of the increase in the number of people newly certified to receive LTC benefits after the mandatory evacuation. In order to cope with the increase in utilization of long-term care and associated costs after disasters in aging societies, both formal long-term care services and social support for informal care for evacuees should be considered important. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) disease reactivates from distant latent infection or recent (re)infection. Progression risks increase with age. Across the World Health Organisation Western Pacific region, many populations are ageing and have the highest per capita TB incidence rates in older age groups. However, methods for analysing age-specific TB incidence and forecasting epidemic trends while accounting for demographic change remain limited. Methods: We applied the Lee-Carter models, which were originally developed for mortality modelling, to model the temporal trends in age-specific TB incidence data from 2005 to 2018 in Taiwan. Females and males were modelled separately. We combined our demographic forecasts, and age-specific TB incidence forecasts to project TB incidence until 2035. We compared TB incidence projections with demography fixed in 2018 to projections accounting for demographic change. Results: Our models quantified increasing incidence rates with age and declining temporal trends. By 2035, the forecast suggests that the TB incidence rate in Taiwan will decrease by 54% (95% Prediction Interval (PI): 45%-59%) compared to 2015, while most age-specific incidence rates will reduce by more than 60%. In 2035, adults aged 65 and above will make up 78% of incident TB cases. Forecast TB incidence in 2035 accounting for demographic change will be 39% (95% PI: 36%-42%) higher than without population ageing. Conclusions: Age-specific incidence forecasts coupled with demographic forecasts can inform the impact of population ageing on TB epidemics. The TB control programme in Taiwan should develop plans specific to older age groups and their care needs. [ABSTRACT FROM AUTHOR]

Reverse engineering of gene regulatory networks (GRNs) is a central task in systems biology. Most of the existing methods for GRN inference rely on gene co-expression analysis or TF-target binding information, where the determination of co-expression is often unreliable merely based on gene expression levels, and the TF-target binding data from high-throughput experiments may be noisy, leading to a high ratio of false links and missed links, especially for large-scale networks. In recent years, the microscopy images recording spatial gene expression have become a new resource in GRN reconstruction, as the spatial and temporal expression patterns contain much abundant gene interaction information. Till now, the spatial expression resources have been largely underexploited, and only a few traditional image processing methods have been employed in the image-based GRN reconstruction. Moreover, co-expression analysis using conventional measurements based on image similarity may be inaccurate, because it is the local-pattern consistency rather than global-image-similarity that determines gene-gene interactions. Here we present GripDL (ene egulatory nteraction rediction via eep earning), which incorporates high-confidence TF-gene regulation knowledge from previous studies, and constructs GRNs for Drosophila eye development based on Drosophila embryonic gene expression images. Benefitting from the powerful representation ability of deep neural networks and the supervision information of known interactions, the new method outperforms traditional methods with a large margin and reveals new intriguing knowledge about Drosophila eye development. [ABSTRACT FROM AUTHOR]

The concept of actuarial senescence (defined here as the increase in mortality hazard with age) is often confounded with life span duration, which obscures the relative role of age-dependent and age-independent processes in shaping the variation in life span. We use the opportunity afforded by the Species360 database, a collection of individual life span records in captivity, to analyze age-specific mortality patterns in relation to variation in life span. We report evidence of actuarial senescence across 96 mammal species. We identify the life stage (juvenile, prime-age, or senescent) that contributes the most to the observed variation in life span across species. Actuarial senescence only accounted for 35%–50% of the variance in life span across species, depending on the body mass category. We computed the sensitivity and elasticity of life span to five parameters that represent the three stages of the age-specific mortality curve—namely, the duration of the juvenile stage, the mean juvenile mortality, the prime-age (i.e., minimum) adult mortality, the age at the onset of actuarial senescence, and the rate of actuarial senescence. Next, we computed the between-species variance in these five parameters. Combining the two steps, we computed the relative contribution of each of the five parameters to the variance in life span across species. Variation in life span was increasingly driven by the intensity of actuarial senescence and decreasingly driven by prime-age adult mortality from small to large species because of changes in the elasticity of life span to these parameters, even if all the adult survival parameters consistently exhibited a canalization pattern of weaker variability among long-lived species than among short-lived ones. Our work unambiguously demonstrates that life span cannot be used to measure the strength of actuarial senescence, because a substantial and variable proportion of life span variation across mammals is not related to actuarial senescence metrics. [ABSTRACT FROM AUTHOR]

Visual and proprioceptive information is used differently at different phases of a reach. The time at which a target perturbation occurs during a reach therefore has a significant impact on how an individual can compensate for this perturbation though online control. With healthy ageing, there are notable changes to both sensory and motor control that impact motor performance. However, how the online control process changes with age is not yet fully understood. We used a target perturbation paradigm and manipulated the time at which a target perturbation occurred during the reach to investigate how healthy ageing impacts sensorimotor control. We measured how the latency of the correction and the magnitude of the corrective response changed with perturbation time and quantified the difference across groups using a percentage difference measure. For both groups, online corrections to early perturbations were more easily accounted for than those to late perturbations, despite late perturbations eliciting faster correction latencies. While there was no group difference in accuracy, older participants were slower overall and produced a correction to a change in target location proportionally less often despite similar correction latencies. We speculate that the differences in the time during the reach that the correction is first identified may explain the differences in correction latencies observed between the perturbation time conditions. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is the result of chronic injury where fibroblasts become activated and secrete large amounts of extracellular matrix (ECM), leading to impaired fibroblasts degradation followed by stiffness and loss of lung function. Fructose-1,6-bisphosphate (FBP), an intermediate of glycolytic pathway, decreases PF development, but the underlying mechanism is unknown. To address this issue, PF was induced in vivo using a mouse model, and pulmonary fibroblasts were isolated from healthy and fibrotic animals. In PF model mice, lung function was improved by FBP as revealed by reduced collagen deposition and downregulation of ECM gene expression such as collagens and fibronectin. Fibrotic lung fibroblasts (FLF) treated with FBP for 3 days in vitro showed decreased proliferation, contraction, and migration, which are characteristic of myofibroblast to fibroblast phenotype reversal. ECM-related genes and proteins such as collagens, fibronectin and α-smooth muscle actin, were also downregulated in FBP-treated FLF. Moreover, matrix metalloproteinase (MMP) 1, responsible for ECM degradation, was produced only in fibroblasts obtained from healthy lungs (HLF) and FBP did not alter its expression. On the other hand, tissue inhibitor of metalloproteinase (TIMP)-1, a MMP1 inhibitor, and MMP2, related to fibroblast tissue-invasion, were predominantly produced by FLF and FBP was able to downregulate its expression. These results demonstrate that FBP may prevent bleomycin-induced PF development through reduced expression of collagen and other ECM components mediated by a reduced TIMP-1 and MMP2 expression. [ABSTRACT FROM AUTHOR]

Background: Frailty is a major health issue which impacts the life of older people, posing a significant challenge to the health system. One of the key emerging areas is the development of frailty interventions to halt or reverse the progression of the condition. In many countries, economic evidence is required to inform public funding decisions for such interventions, and cost-effectiveness models are needed to estimate long-term costs and effects. Such models should capture current clinical understanding of frailty, its progression and its health consequences. The objective of this paper is to present a conceptual model of frailty that can be used to inform the development of a cost-effectiveness model to evaluate frailty interventions. Methods: After critical analysis of the clinical and economic literature, a Delphi study consisting of experts from the disciplines of clinical medicine and epidemiology was undertaken to inform the key components of the conceptual model. We also identified relevant databases that can be used to populate and validate the model. Results: A list of significant health states/events for which frailty is a strong independent risk factor was identified (e.g., hip fracture, hospital admission, delirium, death). We also identified a list of important patient attributes that may influence disease progression (e.g., age, gender, previous hospital admissions, depression). A number of large-scale relevant databases were also identified to populate and validate the cost-effectiveness model. Face validity of model structure was confirmed by experts. Discussion and conclusions: The proposed conceptual model is being used as a basis for developing a new cost-effectiveness model to estimate lifetime costs and outcomes associated with a range of frailty interventions. Using an appropriate model structure, which more accurately reflects the natural history of frailty, will improve model transparency and accuracy. This will ultimately lead to better informed public funding decisions around interventions to manage frailty. [ABSTRACT FROM AUTHOR]

Background: Leprosy has a global presence; more than 180 thousand new cases were registered in 2013, 15% of which were found in the Americas. The elderly are a very susceptible demographic in terms of developing illnesses, mainly because of characteristics natural to the senescence of the human organism. This study’s goals were to analyze leprosy in an elderly population from a hyperendemic region of the Brazilian Amazon in a historical series from 2004 to 2013 and to determine the clinical and epidemiological profile of a series of leprosy cases of elderly people in the period spanning from 2009 to 2013. Methods: To achieve these goals, an observational, longitudinal, retrospective and descriptive study was put together to analyze leprosy in elderly people from data acquired from the Notification Aggravations Information System. Furthermore, a profile of the disease from a retrospective cohort based on data collected from medical records was developed. Results: The number of new cases and the leprosy detection rate decreased across the observed period but remained stable among the elderly. The trend for the next ten years indicates decreases in the number of cases and in the detection rate in the general population and an increase in only the elderly. The overall profile was characterized by a predominance of males (64.32%), the multibacillary clinical form (87.57%), Type 1 reaction episodes (37.50%) and some physical incapacity at diagnosis (49.19%). The risk of reaction was greater in the first six months of multidrug therapy, and the positive result from the skin smear was associated with the greater chance of reactional condition development. Conclusions: The resulting data demonstrate that leprosy amongst the elderly deserves attention because of the increased susceptibility to disability in this age group, with their higher risk of reaction and their greater level of co-morbidity. [ABSTRACT FROM AUTHOR]

Regenerative medicine using umbilical cord blood (UCB) cells shows promise for the treatment of cerebral palsy. Although the efficacy of this therapy has been seen in the clinic, the mechanisms by which UCB cells interact and aid in the improvement of symptoms are not clear. We explored the chemokine expression profile in damaged brain tissue in the neonatal mouse ischemia-reperfusion (IR) brain injury model that was infused with human UCB (hUCB) cells. IR brain injury was induced in 9-day-old NOD/SCID mice. hUCB cells were administered 3 weeks post brain injury. Chemokine expression profiles in the brain extract were determined at various time points. Inflammatory chemokines such as CCL1, CCL17, and CXCL12 were transiently upregulated by 24 hours post brain injury. Upregulation of other chemokines, including CCL5, CCL9, and CXCL1 were prolonged up to 3 weeks post brain injury, but most chemokines dissipated over time. There were marked increases in levels of CCL2, CCL12, CCL20, and CX3CL1 in response to hUCB cell treatment, which might be related to the new recruitment and differentiation of neural stem cells, leading to the induction of tissue regeneration. We propose that the chemokine expression profile in the brain shifted from responding to tissue damage to inducing tissue regeneration. hUCB cell administration further enhanced the production of chemokines, and chemokine networks may play an active role in tissue regeneration in neonatal hypoxic-ischemic brain injury. [ABSTRACT FROM AUTHOR]

Similarity between targets and distracters is a key factor in generating distractibility, and exerts a large detrimental effect on aging. The present EEG study tested the role of a new stimulus dimension in generating distractibility in visual Working Memory (vWM), namely numerical similarity. In a change detection paradigm a varying number of relevant and irrelevant stimuli were presented simultaneously in opposite hemifields. Behavioral results indicated that young participants outperformed older individuals; however, in both groups numerical similarity per se did not modulate performance. At the electrophysiological level, in young participants the Contralateral Delay Activity (CDA, a proxy for item maintenance in vWM) was modulated by the numerosity of the relevant items regardless of numerical similarity. In older participants, the CDA was modulated by target numerosity only in the same numerical condition, where the total number of (relevant and irrelevant) items increased with increasing target numerosities. No effect was present in the dissimilar numerical condition, where the total number of items did not vary substantially across target numerosity. This pattern was suggestive of an age-related effect of the total number of (relevant and irrelevant) items on vWM. The additional analyses on alpha-band lateralization measures support this interpretation by revealing that older adults lacked selective deployment of attentional and vWM resources towards the relevant hemifield. Overall, the results indicate that, while numerical similarity does not modulate distractibility, there is an age-related redistribution of vWM resources across the two visual fields, ultimately leading to a general decrease in task performance of older adults. [ABSTRACT FROM AUTHOR]

Karrikins are smoke-derived compounds presumed to mimic endogenous signalling molecules (KAI2-ligand, KL), whose signalling pathway is closely related to that of strigolactones (SLs), important regulators of plant development. Both karrikins/KLs and SLs are perceived by closely related α/β hydrolase receptors (KAI2 and D14 respectively), and signalling through both receptors requires the F-box protein MAX2. Furthermore, both pathways trigger proteasome-mediated degradation of related SMAX1-LIKE (SMXL) proteins, to influence development. It has previously been suggested in multiple studies that SLs are important regulators of root and root hair development in Arabidopsis, but these conclusions are based on phenotypes observed in the non-specific max2 mutants and by use of racemic-GR24, a mixture of stereoisomers that activates both D14 and KAI2 signalling pathways. Here, we demonstrate that the majority of the effects on Arabidopsis root development previously attributed to SL signalling are actually mediated by the KAI2 signalling pathway. Using mutants defective in SL or KL synthesis and/or perception, we show that KAI2-mediated signalling alone regulates root hair density and root hair length as well as root skewing, straightness and diameter, while both KAI2 and D14 pathways regulate lateral root density and epidermal cell length. We test the key hypothesis that KAI2 signals by a non-canonical receptor-target mechanism in the context of root development. Our results provide no evidence for this, and we instead show that all effects of KAI2 in the root can be explained by canonical SMAX1/SMXL2 activity. However, we do find evidence for non-canonical GR24 ligand-receptor interactions in D14/KAI2-mediated root hair development. Overall, our results demonstrate that the KAI2 signalling pathway is an important new regulator of root hair and root development in Arabidopsis and lays an important basis for research into a molecular understanding of how very similar and partially overlapping hormone signalling pathways regulate different phenotypic outputs. [ABSTRACT FROM AUTHOR]

This study investigated the influence of age and visual occlusion on fast reach-to-grasp movements. The effect of visual occlusion on reach-to-grasp movement was examined using a task that heavily relies on feed-forward control. Three groups of healthy adults aged 22, 49 and 65 on average performed fast reach-to-grasp movements with full visual and partial visual occlusion conditions of the hand during the initial part of movement. Regarding the effect of age, the all parameters of reach-to-grasp movement were deteriorated with age, except relative time to maximum velocity and spatial coordination. Regarding the effect of visual condition, participants reached with prolonged movement time, lower peak velocity, and later occurrences of peak velocity and peak aperture, as well as decrease in spatial coordination. Regarding the effect of age on visual condition, visual occlusion resulted in a longer movement time and delayed time to maximum velocity in middle-aged and older groups compared to full vision, but the difference was not observed in the younger groups. Conclusion: Reach-to-grasp performance deteriorated with age and the performance was affected when vision of the hand at initial movement was occluded. Overall, movement performance in middle-aged and older adults was affected by visual occlusion, whereas it was unaffected in younger adults. The results indicate that visual feedback of the hand at initial movement is important to control reach-to-grasp movement of middle-aged and older adults during real tasks. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed at analyzing the cycling safety-related factors and the mental health indicators of elderly cyclists in comparison with other age groups. Methods: For this cross-sectional study, we analyzed the data of 911 bicyclists from two Latin American countries that have been experiencing a substantial growth of urban cycling during the last few years: Colombia and Argentina. Participants responded to an e-questionnaire on bicycling behaviors, mental health and cycling safety. Results: Aging adults reported lower rates of risky behaviors and traffic crashes (around .38 in five years), and, on the other hand, more cycling protective behaviors, a higher risk perception and a better knowledge of traffic norms than both other adults (26–50 years old) and young cyclists (<26). Cycling behaviors and crashes were found to be significantly related to mental health indicators, the latter being higher in aging cyclists. However, this population remains more prone to distractions experienced while cycling than other age groups. Conclusions: Although the behavioral features of aging adults were comparatively “safer” than the ones displayed by other age groups, factors such as cycling distractions and this population’s over-representation in traffic crashes suggest the need of enforcing policymaking for a better integration of this age segment in alternative transportation dynamics. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to describe bone formation and resorption markers in generally healthy prepubertal children using total alkaline phosphatase (tALP), osteocalcin (OC) and β-isomerized C-terminal telopeptides of type I collagen (β-CTx) serum concentrations and to estimate markers’ correlations with anthropometric growth (height, weight, body mass index and trajectories of weight gain) as well as bone mineral content (BMC) and areal density (aBMD). Methods: We assessed 395 7-year-old children from the Generation XXI cohort with tALP, OC and β-CTx concentrations determined from a fasting venous blood sample and BMC/aBMD measured by dual-energy X-ray absorptiometry. Gender-specific reference intervals for tALP, OC and β-CTx in 7-year-old children were established by calculating the 2.5th and 97.5th percentiles. Pearson and partial correlation coefficients (controlling for sex, age, body size and season) between bone markers and growth measures were computed. Results: tALP increased with height (rpartial controlled for sex = 0.26, 95%CI: 0.17, 0.35), was higher in overweight than in healthy weight children, and in children who gained weight above average during infancy. No correlations were found between OC or β-CTx and growth. In girls, OC was slightly correlated with subtotal BMC (rpartial = 0.22, 95%CI: 0.08, 0.35), subtotal aBMD (rpartial = 0.20, 95%CI: 0.06, 0.33) and lumbar spine aBMD (rpartial = 0.23, 95%CI: 0.09, 0.36). tALP and β-CTx were not correlated with any of the DXA-derived bone measures. Conclusion: This study contributed to the description of bone turnover at 7 years of age and suggested that bone metabolism markers measured in a single point in time have limited ability to describe anthropometric growth and overall bone status in generally healthy prepubertal children. [ABSTRACT FROM AUTHOR]

Laminopathies are tissue-selective diseases that affect differently in organ systems. Mutations in nuclear envelopes, emerin (Emd) and lamin A/C (Lmna) genes, cause clinically indistinguishable myopathy called Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy. Several murine models for EDMD have been generated; however, emerin-null (Emd) mice do not show obvious skeletal and cardiac muscle phenotypes, and Lmna H222P/H222P mutant (H222P) mice show only a mild phenotype in skeletal muscle when they already have severe cardiomyopathy. Thus, the underlying molecular mechanism of muscle involvement due to nuclear abnormalities is still unclarified. We generated double mutant (Emd-/-/LmnaH222P/H222P; EH) mice to characterize dystrophic changes and to elucidate interactions between emerin and lamin A/C in skeletal and cardiac muscles. As H222P mice, EH mice grow normally and have breeding productivity. EH mice showed severer muscle involvement compared with that of H222P mice which was an independent of cardiac abnormality at 12 weeks of age. Nuclear abnormalities, reduced muscle fiber size and increased fibrosis were prominent in EH mice. Roles of emerin and lamin A/C in satellite cells function and regeneration of muscle fiber were also evaluated by cardiotoxin-induced muscle injury. Delayed increases in myog and myh3 expression were seen in both H222P and EH mice; however, the expression levels of those genes were similar with control and regenerated muscle fiber size was not different at day 7 after injury. These results indicate that EH mouse is a suitable model for studying skeletal muscle involvement, independent of cardiac function, in laminopathies and an interaction between emerin and lamin A/C in different tissues. [ABSTRACT FROM AUTHOR]

Limb girdle muscular dystrophy (LGMD) types 2D and 2F are caused by mutations in the genes encoding for α- and δ-sarcoglycan, respectively, leading to progressive muscle weakness. Mouse models exist for LGMD2D (Sgca-/-) and 2F (Sgcd-/-). In a previous natural history study, we described the pathology in these mice at 34 weeks of age. However, the development of muscle pathology at younger ages has not been fully characterised yet. We therefore performed a study into age-related changes in muscle function and pathology by examining mice at different ages. From 4 weeks of age onwards, male mice were subjected to functional tests and sacrificed at respectively 8, 16 or 24 weeks of age. Muscle histopathology and expression of genes involved in muscle pathology were analysed for several skeletal muscles, while miRNA levels were assessed in serum. In addition, for Sgcd-/- mice heart pathology was assessed. Muscle function showed a gradual decline in both Sgca-/- and Sgcd-/- mice. Respiratory function was also impaired at all examined timepoints. Already at 8 weeks of age, muscle pathology was prominent, and fibrotic, inflammatory and regenerative markers were elevated, which remained relatively constant with age. In addition, Sgcd-/- mice showed signs of cardiomyopathy from 16 weeks of age onwards. These results indicate that Sgca-/- and Sgcd-/- are relevant disease models for LGMD2D and 2F. [ABSTRACT FROM AUTHOR]

Providing a broiler chicken embryo with a lighting schedule during incubation may stimulate leg bone development. Bone development may be stimulated through melatonin, a hormone released in darkness that stimulates bone development, or increased activity in embryos exposed to a light-dark rhythm. Aim was to investigate lighting conditions during incubation and leg bone development in broiler embryos, and to reveal the involved mechanisms. Embryos were incubated under continuous cool white 500 lux LED light (24L), continuous darkness (24D), or 16h of light, followed by 8h of darkness (16L:8D) from the start of incubation until hatching. Embryonic bone development largely takes place through cartilage formation (of which collagen is an important component) and ossification. Expression of genes involved in cartilage formation (col1α2, col2α1, and col10α1) and ossification (spp1, sparc, bglap, and alpl) in the tibia on embryonic day (ED)13, ED17, and at hatching were measured through qPCR. Femur and tibia dimensions were determined at hatch. Plasma growth hormone and corticosterone and pineal melatonin concentrations were determined every 4h between ED18.75 and ED19.5. Embryonic heart rate was measured twice daily from ED12 till ED19 as a reflection of activity. No difference between lighting treatments on gene expression was found. 24D resulted in higher femur length and higher femur and tibia weight, width, and depth at hatch than 16L:8D. 24D furthermore resulted in higher femur length and width and tibia depth than 24L. Embryonic heart rate was higher for 24D and 16L:8D in both its light and dark period than for 24L, suggesting that 24L embryos may have been less active. Melatonin and growth hormone showed different release patterns between treatments, but the biological significance was hard to interpret. To conclude, 24D resulted in larger leg bones at hatch than light during incubation, but the underlying pathways were not clear from present data. [ABSTRACT FROM AUTHOR]

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the improvements in annotation enrichment by re-interpreting edges that would otherwise be omitted by traditional ancestor path-tracing methods. Specifically, we show that GOcats’ unique handling of relations improves enrichment over conventional methods in the analysis of two different gene-expression datasets: a breast cancer microarray dataset and several horse cartilage development RNAseq datasets. With the breast cancer microarray dataset, we observed significant improvement (one-sided binomial test p-value = 1.86E-25) in 182 of 217 significantly enriched GO terms identified from the conventional path traversal method when GOcats’ path traversal was used. We also found new significantly enriched terms using GOcats, whose biological relevancy has been experimentally demonstrated elsewhere. Likewise, on the horse RNAseq datasets, we observed a significant improvement in GO term enrichment when using GOcat’s path traversal: one-sided binomial test p-values range from 1.32E-03 to 2.58E-44. [ABSTRACT FROM AUTHOR]

Regenerating the periodontal ligament (PDL) is a crucial factor for periodontal tissue regeneration in the presence of traumatized and periodontally damaged teeth. Various methods have been applied for periodontal regeneration, including tissue substitutes, bioactive materials, and synthetic scaffolds. However, all of these treatments have had limited success in structural and functional periodontal tissue regeneration. To achieve the goal of complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized scaffolds fabricated via tissue engineering. The aim of this study was to fabricate a decellularized periodontal scaffold of human tooth slices and determine its regeneration potential. We evaluated two different protocols applied to tooth slices obtained from human healthy third molars. The extracellular matrix scaffold decellularized using sodium dodecyl sulfate and Triton X-100, which are effective in removing nuclear components, was demonstrated to preserve an intact structure and composition. Furthermore, the decellularized scaffold could support repopulation of PDL stem cells near the cementum and expressed cementum and periodontal-ligament-related genes. These results show that decellularized PDL scaffolds of human teeth are capable of inducing the proliferation and differentiation of mesenchymal stem cells, thus having regeneration potential for use in future periodontal regenerative tissue engineering. [ABSTRACT FROM AUTHOR]

Regulators of G Protein Signaling (RGS proteins) inhibit G protein-coupled receptor (GPCR) signaling by accelerating the GTP hydrolysis rate of activated Gα subunits. Some RGS proteins exert additional signal modulatory functions, and RGS12 is one such protein, with five additional, functional domains: a PDZ domain, a phosphotyrosine-binding domain, two Ras-binding domains, and a Gα·GDP-binding GoLoco motif. RGS12 expression is temporospatially regulated in developing mouse embryos, with notable expression in somites and developing skeletal muscle. We therefore examined whether RGS12 is involved in the skeletal muscle myogenic program. In the adult mouse, RGS12 is expressed in the tibialis anterior (TA) muscle, and its expression is increased early after cardiotoxin-induced injury, suggesting a role in muscle regeneration. Consistent with a potential role in coordinating myogenic signals, RGS12 is also expressed in primary myoblasts; as these cells undergo differentiation and fusion into myotubes, RGS12 protein abundance is reduced. Myoblasts isolated from mice lacking Rgs12 expression have an impaired ability to differentiate into myotubes ex vivo, suggesting that RGS12 may play a role as a modulator/switch for differentiation. We also assessed the muscle regenerative capacity of mice conditionally deficient in skeletal muscle Rgs12 expression (via Pax7-driven Cre recombinase expression), following cardiotoxin-induced damage to the TA muscle. Eight days post-damage, mice lacking RGS12 in skeletal muscle had attenuated repair of muscle fibers. However, when mice lacking skeletal muscle expression of Rgs12 were cross-bred with mdx mice (a model of human Duchenne muscular dystrophy), no increase in muscle degeneration was observed over time. These data support the hypothesis that RGS12 plays a role in coordinating signals during the myogenic program in select circumstances, but loss of the protein may be compensated for within model syndromes of prolonged bouts of muscle damage and repair. [ABSTRACT FROM AUTHOR]

There is no cure or beneficial management option for Limb-Girdle muscular dystrophy (MD) type 2B (LGMD2B). Losartan, a blood pressure (BP) lowering angiotensin II (AngII) receptor type 1 (ATR1) blocker (ARB) with unique anti-transforming growth factor-β (TGF-β) properties, can protect muscles in various types of MD such as Duchenne MD, suggesting a potential benefit for LGMD2B patients. Herein, we show in a mild, dysferlin-null mouse model of LGMD2B that losartan increased quadriceps muscle fibrosis (142%; P<0.0001). In a severe, atherogenic diet-fed model of LGMD2B recently described by our group, losartan further exacerbated dysferlin-null mouse muscle wasting in quadriceps and triceps brachii, two muscles typically affected by LGMD2B, by 40% and 51%, respectively (P<0.05). Lower TGF-β signalling was not observed with losartan, therefore plasma levels of atherogenic lipids known to aggravate LGMD2B severity were investigated. We report that losartan increased both plasma triglycerides and cholesterol concentrations in dysferlin-null mice. Other protective properties of losartan, such as increased nitric oxide release and BP lowering, were also reduced in the absence of dysferlin expression. Our data suggest that LGMD2B patients may show some resistance to the primary BP-lowering effects of losartan along with accelerated muscle wasting and dyslipidemia. Hence, we urge caution on the use of ARBs in this population as their ATR1 pathway may be dysfunctional. [ABSTRACT FROM AUTHOR]

Reaction-diffusion schemes are widely used to model and interpret phenomena in various fields. In that context, phenomena driven by Turing instabilities are particularly relevant to describe patterning in a number of biological processes. While the conditions that determine the appearance of Turing patterns and their wavelength can be easily obtained by a linear stability analysis, the estimation of pattern amplitudes requires cumbersome calculations due to non-linear terms. Here we introduce an expansion method that makes possible to obtain analytical, approximated, solutions of the pattern amplitudes. We check and illustrate the reliability of this methodology with results obtained from numerical simulations. [ABSTRACT FROM AUTHOR]

Development of white striping (WS) and wooden breast (WB) in broiler breast meat have been linked to hypoxia, but their etiologies are not fully understood. This study aimed at investigating absolute expression of hypoxia-inducible factor-1 alpha subunit (HIF1A) and genes involved in stress responses and muscle repair using a droplet digital polymerase chain reaction. Total RNA was isolated from pectoralis major collected from male 6-week-old medium (carcass weight ≤ 2.5 kg) and heavy (carcass weight > 2.5 kg) broilers. Samples were classified as “non-defective” (n = 4), “medium-WS” (n = 6), “heavy-WS” (n = 7) and “heavy-WS+WB” (n = 3) based on abnormality scores. The HIF1A transcript was up-regulated in all of the abnormal groups. Transcript abundances of genes encoding 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4), lactate dehydrogenase-A (LDHA), and phosphorylase kinase beta subunit (PHKB) were increased in heavy-WS but decreased in heavy-WS+WB. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was up-regulated in non-defective samples. The muscle-specific mu-2 isoform of glutathione S-transferases (GSTM2) was up-regulated in the abnormal samples, particularly in the heavy groups. The genes encoding myogenic differentiation (MYOD1) and myosin light chain kinase (MYLK) exhibited similar expression pattern, of which medium-WS and heavy-WS significantly increased compared to non-defective whereas expression in heavy-WS+WB was not different from either non-defective or WS-affected group. The greatest and the lowest levels of calpain-3 (CAPN3) and delta-sarcoglycan (SCGD) were observed in heavy-WS and heavy-WS+WB, respectively. Based on micrographs, the abnormal muscles primarily comprised fibers with cross-sectional areas ranging from 2,000 to 3,000 μm2. Despite induced glycolysis at the transcriptional level, lower stored glycogen in the abnormal muscles corresponded with the reduced lactate and higher pH within their meats. The findings support hypoxia within the abnormal breasts, potentially associated with oversized muscle fibers. Between WS and WB, divergent glucose metabolism, cellular detoxification and myoregeneration at the transcriptional level could be anticipated. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play pivotal roles in growth, development, and stress responses. However, the regulatory function of miRNAs in early weaned goats remains unclear. Deep sequencing comparison of mRNA and miRNA expression profiles showed that 18 miRNAs and 373 genes were differentially expressed in pre- and post-weaning Chongming white goats. Bioinformatics analysis indicated that these differentially expressed genes are involved in cellular processes, developmental processes, and growth in terms of biological process analysis. KEGG analysis showed that downregulated genes were enriched in salivary secretion, bile secretion, vascular smooth muscle contraction, and calcium signaling pathways. Additionally, a miRNA-mRNA co-expression network of the 18 dysregulated miRNAs and their 107 target mRNAs was constructed using a combination of Pearson’s correlation analysis and prediction by miRanda software. Among the downregulated miRNAs, two (chi-miR-206 and chi-miR-133a/b) were muscle development-related and the others were cell proliferation associated. Further RT-qPCR analysis confirmed that downregulated miRNAs (chi-miR-99b-3p, chi-miR-224, and chi-miR-10b-5p) were highly expressed in muscle tissues (heart, spleen, or kidney) of the rapid growth period (7-month old) in Chongming white goats. The results of the present study suggested that weaning induced cell proliferation repression in post-weaning goats, providing new insight into the mechanism of muscle development of goats, although additional details remain to be elucidated in the future. [ABSTRACT FROM AUTHOR]

It has been suggested that Jmjd6 plays an important role in gene regulation through its demethylation or hydroxylation activity on histone and transcription factors. In addition, Jmjd6 has been shown to regulate RNA splicing by interaction with splicing factors. In this study, we demonstrated that Jmjd6a is expressed in developing Xenopus laevis eye during optic vesicle formation and retinal layer differentiation stages. Knockdown of Jmjd6a by an antisense morpholino resulted in eye malformation including a deformed retinal layer and no lens formation. We further found down-regulation of gene expression related to eye development such as Rx1, Otx2, and Pax6 in Jmjd6a morpholino injected embryos. Jmjd6 interacts with splicing factor U2AF25 and GSK3β RNA in the anterior region of Xenopus embryos. Knockdown of Jmjd6a led to deletion of GSK3β RNA exon 1 and 2, which resulted in generation of N’-terminal truncated GSK3β protein. This event further caused decreased phosphorylation of β-catenin and subsequently increased β-catenin stability. Therefore, our result may suggest that Jmjd6a plays an important role in Xenopus eye development through regulation of GSK3β RNA splicing and canonical Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Environmental changes can modify the phenotypic characteristics of populations, which in turn can influence their evolutionary trajectories. In ectotherms like fishes, temperature is a particularly important environmental variable that is known to have significant impacts on the phenotype. Here, we raised specimens of the surface ecomorph of Astyanax mexicanus at temperatures of 20°C, 23°C, 25°C, and 28°C to examine how temperature influenced vertebral number and body shape. To increase biological realism, specimens were also subjected to two water turbulence regimes. Vertebral number was counted from x-rays and body shape variation was analysed using geometric morphometric methods. Temperature significantly impacted mean total vertebral number, which increased at the lowest and highest temperatures. Fish reared at lower temperatures had relatively more precaudal vertebrae while fish reared at higher temperatures had relatively more caudal vertebrae. Vertebral anomalies, especially vertebral fusions, were most frequent at the extreme temperature treatments. Temperature significantly impacted body shape as well, with fish reared at 20°C being particularly divergent. Water turbulence also impacted body shape in a generally predictable manner, with specimens reared in high turbulence environments being more streamlined and having extended dorsal and anal fin bases. Variation in environmental variables thus resulted in significant changes in morphological traits known to impact fish fitness, indicating that A. mexicanus has the capacity to exhibit a range of phenotypic plasticity when challenged by environmental change. Understanding the biochemical mechanisms underlying this plasticity and whether adaptive plasticity has influenced the evolutionary radiation of the Characidae, are major directions for future research. [ABSTRACT FROM AUTHOR]

Background: Ageing is becoming a considerable public health burden in China, which produces great societal development challenges. Healthy and active longevity could ease the ageing burden on families and communities. To date, most studies of the oldest-old distribution are focused on a simple scale from spatial perspective, and the multi-scale spatio-temporal clusters trend in the oldest-old population has not yet been determined. Thus, the objective in present study is to use a new method to evaluate the spatio-temporal pattern and detect the risk clusters in the oldest-old population from three scales. Methods: Individuals aged 65 years or older and individuals aged 80 years or older on three scales in China from 2000 to 2010 were used. The exploratory spatial data analysis was performed using Moran’s I statistic, and the pattern of the oldest-old clusters among humans was examined by using the spatial scan statistical method. Then, spatial stratified heterogeneity was used to explore the factors affecting the spatial heterogeneity of the oldest-old population. Results: The oldest-old index in the southeast coastal areas is higher than that in the northwest inland areas in China. A three-ladder terrain distribution of the oldest-old index from west to east is obvious. The overall pattern of the oldest-old index evolves from a “concave” shape to an “east-west uplift, and northern collapse” shape. Space-time analysis revealed that high-risk areas were concentrated in five regions: the Yangtze River Delta, the Pearl River Delta, the Southeast Coast, Sichuan and Chongqing, and the Central Plains. The oldest-old cluster at different scales shows a similar pattern, but local differences exist. The risk at the prefecture scale and county scale is greater than at the interprovincial scale; the sublevel can identify clusters that have not been identified at the previous level, especially the bordering areas of prefectures and counties; and more risk units and greater relative risk are found in urban areas than in rural areas. Conclusions: The results emphasized that spatial scan statistics can be used to estimate the spatial clusters of the oldest-old people. The detection of these clusters might be highly useful in the surveillance of the ageing phenomenon, thus helping local public health authorities measure the population burden at all locations, identifying geographical areas that require more attention, and evaluating the impacts of intervention programs. [ABSTRACT FROM AUTHOR]

Objective: Social participation benefits health. We assessed the relationship between self-reported visual impairment (VI) and glaucoma versus seniors’ social participation. Methods: Data from individuals aged ≥65 years responding to the Canadian Community Health Survey Healthy Aging 2008/2009 (n = 16,369) was analyzed. Participation in eight social activities by seniors with and without self-reported VI or glaucoma was compared. Results: Seniors with VI had significantly reduced participation (p<0.05) in sports/physical activities (18.0% vs. 33.6%), family/friendship activities outside the household (39.7% vs. 53.0%), service club/fraternal organization activities (11.4% vs. 18.4%), volunteer/charity work (13.4% vs. 24.9%), educational/cultural activities (16.2% vs. 24.5%), and other social recreational activities (21.6% vs. 31.0%) compared to those without VI. Differences in participation in church/religious activities (40.6% vs. 44.5%) and community/professional association activities (15.3% vs. 18.0%) were non-significant between seniors with and without VI. Seniors with glaucoma versus those without had significantly reduced participation (p<0.05) in family/friendship activities (46.6% vs. 52.9%), sports/physical activities (26.0% vs. 33.6%) and volunteer/charity work (20.4% vs. 24.9%). No participation in any social activity was significantly higher among seniors with VI versus those without (10.1% vs. 2.9%, p<0.05), but was similar among seniors with and without glaucoma (3.9% vs. 3.1%, p>0.05). After adjusting for the effects of age, sex, education, household income, ethnicity, job status and chronic diseases (adjusted odds ratio, aOR = 3.4 (95% confidence interval (CI) 2.0–5.8), seniors with VI but no glaucoma were more likely not to engage in any social activities compared to seniors without VI and no glaucoma. Seniors with glaucoma but without VI had a similar level of non-participation (aOR = 0.9, 95%% CI 0.5–1.7). Conclusions: Significantly reduced social participation was found across six community activities among seniors with self-reported VI and in three activities among those with self-reported glaucoma. Policies and programs that help seniors with VI or glaucoma engage in social activities are needed. [ABSTRACT FROM AUTHOR]

Longitudinal studies of bone adaptation in mice using in vivo micro-computed tomography (μCT) have been commonly used for pre-clinical evaluation of physical and pharmacological interventions. The main advantage of this approach is to use each mouse as its own control, reducing considerably the sample size required by statistical power analysis. To date, multi-scale estimation of bone adaptations become essential since the bone activity that takes place at different scales may be associated with different bone mechanisms. Measures of bone adaptations at different time scales have been attempted in a previous study. This paper extends quantification of bone activity at different spatial scales with a proposition of a novel framework. The method involves applying level-set method (LSM) to track the geometric changes from the longitudinal in vivo μCT scans of mice tibia. Bone low- and high-spatial frequency patterns are then estimated using multi-resolution analysis. The accuracy of the framework is quantified by applying it to two times separated scanned images with synthetically manipulated global and/or local activity. The Root Mean Square Deviation (RMSD) was approximately 1.5 voxels or 0.7 voxels for the global low-spatial frequency or local high-spatial frequency changes, respectively. The framework is further applied to the study of bone changes in longitudinal datasets of wild-type mice tibiae over time and space. The results demonstrate the ability for the spatio-temporal quantification and visualisation of bone activity at different spatial scales in longitudinal studies thus providing further insight into bone adaptation mechanisms. [ABSTRACT FROM AUTHOR]

We describe a network-based method to obtain a subset of representative variables from clinical data of subjects of the second Singapore Longitudinal Aging Study (SLAS-2), while preserving to a good extent the predictive performance of the full set with regards to a multi-faceted index of successful aging, SAGE. To examine differences in predictive performance of high-degree nodes (“hubs”) and high-centrality ones (“cores”), we implement four subsetting strategies (two degree-based, two centrality-based) and obtain four surrogate sets of variables, which we use as input features for machine learning models to predict the SAGE index of subjects. All four models have variables belonging to the physical, cardiovascular, cognitive and immunological domains among their fifteen most important predictors. A fifth domain (leisure-time activities, LTA) is also present in some form. From a comparison of the surrogate sets’ size and predictive performance, a centrality-based approach (selection of the most central variable-nodes within each cluster) yielded the smallest-sized surrogate set, while having high prediction accuracy (measured by its model’s area-under-curve, AUC) in comparison to its analogous degree-based strategy (selection of the highest-degree nodes per cluster). Inclusion of the next most-central variables yielded negligible changes in predictive performance while more than doubling the surrogate set size. The centrality-based approach thus yields a surrogate set which offers a good balance between number of variables and prediction performance, and can act as a representative subset of the SLAS-2 clinical dataset. [ABSTRACT FROM AUTHOR]

Conotruncal heart defects (CTDs) are among the most common and severe groups of congenital heart defects. Despite evidence of an inherited genetic contribution to CTDs, little is known about the specific genes that contribute to the development of CTDs. We performed gene-based genome-wide analyses using microarray-genotyped and imputed common and rare variants data from two large studies of CTDs in the United States. We performed two case-parent trio analyses (N = 640 and 317 trios), using an extension of the family-based multi-marker association test, and two case-control analyses (N = 482 and 406 patients and comparable numbers of controls), using a sequence kernel association test. We also undertook two meta-analyses to combine the results from the analyses that used the same approach (i.e. family-based or case-control). To our knowledge, these analyses are the first reported gene-based, genome-wide association studies of CTDs. Based on our findings, we propose eight CTD candidate genes (ARF5, EIF4E, KPNA1, MAP4K3, MBNL1, NCAPG, NDFUS1 and PSMG3). Four of these genes (ARF5, KPNA1, NDUFS1 and PSMG3) have not been previously associated with normal or abnormal heart development. In addition, our analyses provide additional evidence that genes involved in chromatin-modification and in ribonucleic acid splicing are associated with congenital heart defects. [ABSTRACT FROM AUTHOR]

Albeit osteoporosis is one of the most prevalent disorders in the aged population, treatment options stimulating the activity of bone-forming osteoblasts are still limited. We and others have previously identified sphingosine-1-phosphate (S1P) as a bone remodeling coupling factor, which is released by bone-resorbing osteoclasts to stimulate bone formation. Moreover, S1pr3, encoding one of the five known S1P receptors (S1P3), was found differentially expressed in osteoblasts, and S1P3 deficiency corrected the moderate high bone mass phenotype of a mouse model (deficient for the calcitonin receptor) with increased S1P release from osteoclasts. In the present study we addressed the question, if S1P3 deficiency would also influence the skeletal phenotype of mice lacking S1P-lyase (encoded by Sgpl1), which display markedly increased S1P levels due to insufficient degradation. Consistent with previous reports, the majority of Sgpl1-deficient mice died before or shortly after weaning, and this lethality was not influenced by additional S1P3 deficiency. At 3 weeks of age, Sgpl1-deficient mice displayed increased trabecular bone mass, which was associated with enhanced osteoclastogenesis and bone resorption, but also with increased bone formation. Most importantly however, none of the skeletal parameters assessed by μCT, histomorphometry and serum analyses were significantly influenced by additional S1P3 deficiency. Taken together, our findings fully support the concept that S1P is a potent osteoanabolic molecule, although S1P3 is not the sole receptor mediating this influence. Since S1P receptors are considered excellent drug targets, it is now required to screen for the impact of other family members on bone formation. [ABSTRACT FROM AUTHOR]

Attitudes towards aging are often negative, a phenomenon known as ageism. However, personal contact with older adults and intergenerational exchange in the context of close families may mitigate such negative tendencies. So far, these effects have been studied in Western and industrialized contexts. The present study extended this work to the Cook Islands archipelago, a group of islands in the South Pacific characterized by low levels of industrialization and relative isolation from foreign influences. We tested the hypothesis that attitudes toward aging in the Cook Islands would be more positive than in the world at large, and that, within the archipelago, attitudes towards aging would be more positive in smaller, less industrialized communities with closer family ties. Participants (n = 70), were recruited from three islands varying in community size and strength of the family ties among inhabitants. They rated their aging attitudes on four dimensions. Contrary to our hypotheses, attitudes in the Cook Islands did not differ from those reported in industrialized nations and did not vary significantly across islands, even after controlling for personal contact to older adults. Potential limitations and implications for future research are discussed. [ABSTRACT FROM AUTHOR]

Self-reported memory problems are often the first indicator of cognitive decline; however, they are inconsistently associated with objective memory performance and are known to be influenced by individual factors, such as personality. The current study examined the relationships between personality traits and self-reported memory problems in cognitively intact older adults, and whether these associations differ across Black and White older adults. Data were collected annually via in-person comprehensive medical and neuropsychological examinations as part of the Einstein Aging Study. Community-dwelling older adults in an urban, multi-ethnic area of New York City were interviewed. The current study included a total of 425 older adults (Mage = 76.68, SD = 4.72, 62.59% female; 72.00% White). Multilevel modeling tested the associations of neuroticism, conscientiousness, extraversion, openness, and agreeableness with self-reported memory problems. Results showed that neuroticism was positively related to frequency of memory problems and perceived ten-year memory decline only when other personality traits were not accounted for. Extraversion was negatively related to frequency of memory problems and perceived ten-year decline for both White and Black participants. However, conscientiousness was negatively related to perceived ten-year decline for Black participants only. Our findings highlight the importance of examining the association of all five personality traits with self-reported memory problems, as well as examining whether these associations differ for participants from different race/ethnicities. [ABSTRACT FROM AUTHOR]

Background: Lifestyle factors predicting successful aging as a unified concept or as separate components of successful aging are important for understanding healthy aging, interventions and preventions. The main objective was to investigate the effect of midlife predictors on subsequent successful aging 20 years later. Materials and methods: Data were from a population-based health survey, the Nord-Trøndelag Health Study (HUNT), with an average follow-up of 22.6 years. Individuals free of major disease at baseline in 1984–86 with complete datasets for the successful aging components in HUNT3 in 2006–08, were included (n = 4497; mean age at baseline 52.7, range 45–59, years). Successful aging was defined either as a unified category or as three components: being free of nine specified diseases and depression, having no physical or cognitive impairment, and being actively engaged with life. The midlife predictors (smoking, physical activity, alcohol consumption, obesity and social support) were analysed both as separate predictors and combined into a lifestyle index controlling for sociodemographic variables, using multivariable regression analysis. Results: Successful aging as a unified concept was related to all the lifestyle factors in the unadjusted analyses, and all except alcohol consumption in the adjusted analyses. The individual components of successful aging were differently associated with the lifestyle factors; engagement with life was less associated with the lifestyle factors. Non- smoking and good social support were the most powerful predictors for successful aging as a unified concept. When the lifestyle factors were summed into a lifestyle index, there was a trend for more positive lifestyle to be related to higher odds for successful aging. Conclusions: Lifestyle factors predicted an overall measure of SA, as well as the individual components, more than 20 years later. Modifiable risk factors in midlife, exemplified by social support, may be used for interventions to promote overall health and specific aspects of health in aging. [ABSTRACT FROM AUTHOR]

Elderly people show a decline in the ability to decode facial expressions, but also experience age-related facial structure changes that may render their facial expressions harder to decode. However, to date there is no empirical evidence to support the latter mechanism. The objective of this study was to assess the effects of age on facial morphology at rest and during smiling, in younger (n = 100; age range, 18–32 years) and older (n = 30; age range, 55–65 years) Japanese women. Three-dimensional images of each subject’s face at rest and during smiling were obtained and wire mesh fitting was performed on each image to quantify the facial surface morphology. The mean node coordinates in each facial posture were compared between the groups using t-tests. Further, the node coordinates of the fitted mesh were entered into a principal component analysis (PCA) and a multifactor analysis of variance (MANOVA) to examine the direct interactions of aging and facial postures on the 3D facial morphology. The results indicated that there were significant age-related 3D facial changes in facial expression generation and the transition from resting to smiling produced a smaller amount of soft tissue movement in the older group than in the younger group. Further, 185 surface configuration variables were extracted and the variables were used to create four discriminant functions: the age-group discrimination for each facial expression, and the facial expression discrimination for each age group. For facial expression discrimination, the older group showed 80% accuracy with 2 of 66 significant variables, whereas the younger group showed 99% accuracy with 15 of 144 significant variables. These results indicate that in both facial expressions, the facial morphology was distinctly different in the younger and older subjects, and that in the older group, the facial morphology during smiling could not be as easily discriminated from the morphology at rest as in the younger group. These results may help to explain one aspect of the communication dysfunction observed in older people. [ABSTRACT FROM AUTHOR]

A growing body of literature shows that neighborhood characteristics influence older adults’ mental health. Therefore, the aim of this study was to examine the association between structural and social characteristics of the neighborhood, and depression in Mexican older adults. A longitudinal study was conducted based on waves 1 (2009–2010) and 2 (2014) of the Mexican sample from the Study on global AGEing and adult health (SAGE). A street-network buffer around each participant’s household was used to define neighborhood, so that built environment and social characteristics were assessed within it. Depression was ascertained by using an algorithm based on the Composite International Diagnostic Interview. In the analysis, multilevel logistic regression models were constructed separately for each built and social environments measurement, adjusted for socioeconomic, demographic and health-related covariates, and stratified by area of residence (urban versus rural). The results showed that a length of space between 15–45 meters restricted to vehicles was significantly associated with a lower risk of depression in older adults from the urban area (OR: 0.44; IC 95% 0.23–0.83) and the protective association appeared to be larger with increasing space with this restriction, although it lacked significance. Contrarily, the built environment measures were not predictive of depression in the rural setting. On the other hand, none of the variables from the social environment had a significant association, although safety appeared to behave as a risk factor in the overall (OR: 1.48; CI 95% 0.96–2.30; p = 0.08) and rural (OR: 3.44; CI 95% 0.95–12.45; p = 0.06) samples, as it reached marginal significance. Research about neighborhood effects on older adults’ mental health is an emergent field that has shown that depression might be treated not only from the individual-level, but also from the neighborhood-level. Additionally, further research is needed, especially in low- and middle-income countries, to help guide neighborhood policies. [ABSTRACT FROM AUTHOR]

Male genitalia show considerable morphological variation among animals with internal fertilization and exhibit a high level of evolvability in lizards. Studies have suggested that sexual selection may be driving hemipenial evolution against natural selection and pleiotropy. Given the direct interaction of male and female genitals, coevolution of the aforementioned is posited by several hypotheses of genital evolution. However, there are only a few studies on female genitalia morphology, resulting in a lack of coevolution description and understanding. Studies of allometric patterns have filled some gaps by answering questions about male genital evolution and could prove a powerful tool in clarifying coevolution between male and female genitals. Here, we studied the genital morphology of Tropidurus torquatus. This Tropidurus lizard species is an emerging Neotropical lizard model organism notable for having enlarged hemipenial lobes in contrast with other tropidurid species. In this study, we analyzed hemipenial development in early and late stages, describing both morphological variation and ontogenetic allometric pattern. We used quantitative traits to describe male and female genital morphology, examining their static allometric patterns and correspondence. Our study provides a quantitative discussion on the evolution of lizard genitals, suggesting that sexual selection plays an important role in genital evolution in Tropidurus lizards. [ABSTRACT FROM AUTHOR]

Disconnected interacting protein 2 homolog A (DIP2A) is highly expressed in nervous system and respiratory system of developing embryos. However, genes regulated by Dip2a in developing brain and lung have not been systematically studied. Transcriptome of brain and lung in embryonic 19.5 day (E19.5) were compared between wild type and Dip2a-/- mice. An average of 50 million reads per sample was mapped to the reference sequence. A total of 214 DEGs were detected in brain (82 up and 132 down) and 1900 DEGs in lung (1259 up and 641 down). GO enrichment analysis indicated that DEGs in both Brain and Lung were mainly enriched in biological processes ‘DNA-templated transcription and Transcription from RNA polymerase II promoter’, ‘multicellular organism development’, ‘cell differentiation’ and ‘apoptotic process’. In addition, COG classification showed that both were mostly involved in ‘Replication, Recombination, and Repair’, ‘Signal transduction and mechanism’, ‘Translation, Ribosomal structure and Biogenesis’ and ‘Transcription’. KEGG enrichment analysis showed that brain was mainly enriched in ‘Thyroid cancer’ pathway whereas lung in ‘Complement and Coagulation Cascades’ pathway. Transcription factor (TF) annotation analysis identified Zinc finger domain containing (ZF) proteins were mostly regulated in lung and brain. Interestingly, study identified genes Skor2, Gpr3711, Runx1, Erbb3, Frmd7, Fut10, Sox11, Hapln1, Tfap2c and Plxnb3 from brain that play important roles in neuronal cell maturation, differentiation, and survival; genes Hoxa5, Eya1, Errfi1, Sox11, Shh, Igf1, Ccbe1, Crh, Fgf9, Lama5, Pdgfra, Ptn, Rbp4 and Wnt7a from lung are important in lung development. Expression levels of the candidate genes were validated by qRT-PCR. Genome wide transcriptional analysis using wild type and Dip2a knockout mice in brain and lung at embryonic day 19.5 (E19.5) provided a genetic basis of molecular function of these genes. [ABSTRACT FROM AUTHOR]