Whole-genome methylation analysis of aging human tissues identifies age-related changes in developmental and neurological pathways

Age-associated changes in the DNA methylation state can be used to assess the pace of aging. However, it is not understood what mechanisms drive these changes and whether these changes affect the development of aging phenotypes and the aging process in general. This study was aimed at gaining a more comprehensive understanding of aging-related methylation changes across the whole genome, and relating these changes to biological functions. It has been shown that skeletal muscle and blood monocytes undergo typical changes with aging. Using whole-genome bisulfite sequencing, we sought to characterize the genome-wide changes in methylation of DNA derived from both skeletal muscle and blood monocytes, and link these changes to specific genes and pathways through enrichment analysis. We found that methylation changes occur with aging at the locations enriched for developmental and neuronal pathways regulated in these two peripheral tissues. These results contribute to our understanding of changes in epigenome in human aging.     

Abrupt Climate-Independent Fire Regime Changes

Wildfires have played a determining role in distribution, composition and structure of many ecosystems worldwide and climatic changes are widely considered to be a major driver of future fire regime changes. However, forecasting future climatic change induced impacts on fire regimes will require a clearer understanding of other drivers of abrupt fire regime changes. Here, we focus on evidence from different environmental and temporal settings of fire regimes changes that are not directly attributed to climatic changes. We review key cases of these abrupt fire regime changes at different spatial and temporal scales, including those directly driven (i) by fauna, (ii) by invasive plant species, and (iii) by socio-economic and policy changes. All these drivers might generate non-linear effects of landscape changes in fuel structure; that is, they generate fuel changes that can cross thresholds of landscape continuity, and thus drastically change fire activity. Although climatic changes might contribute to some of these changes, there are also many instances that are not primarily linked to climatic shifts. Understanding the mechanism driving fire regime changes should contribute to our ability to better assess future fire regimes.     

Impacts of changes in climate variability on regional vegetation in China: NDVI-based analysis from 1982 to 2000

Three methods were used to distinguish the characteristics of changes in climate variability and normalized difference vegetation index (NDVI) during the period from 1982 to 2000 in China. Great changes in climate variability and an increased trend in NDVI were observed. The changes in precipitation variability were greater than the changes in temperature variability in each month, which is attributed to changes in the monsoon system in East Asia. The abrupt changes in climate and NDVI were more significant in 1983 than in the other years due to the impacts of El Niño/Southern Oscillation (ENSO). Using these results, the influences of changes in climate variability on vegetation were studied in the whole nation, and eight regions were defined according to the vegetation division map of China. The results show that abrupt climate changes at a small scale cannot cause abrupt NDVI changes directly. At a nationwide level, over a longer time scale the persistence of above/below average temperature determines the changes in NDVI; at a shorter time scale, changes in the magnitude of precipitation influence NDVI significantly. Such regional climate variability affects vegetation in different ways owing to the diversity of vegetation types, climatic conditions and topography of the land.     

Epigenetic changes during aging and their reprogramming potential

The aging process results in significant epigenetic changes at all levels of chromatin and DNA organization. These include reduced global heterochromatin, nucleosome remodeling and loss, changes in histone marks, global DNA hypomethylation with CpG island hypermethylation, and the relocalization of chromatin modifying factors. Exactly how and why these changes occur is not fully understood, but evidence that these epigenetic changes affect longevity and may cause aging, is growing. Excitingly, new studies show that age-related epigenetic changes can be reversed with interventions such as cyclic expression of the Yamanaka reprogramming factors. This review presents a summary of epigenetic changes that occur in aging, highlights studies indicating that epigenetic changes may contribute to the aging process and outlines the current state of research into interventions to reprogram age-related epigenetic changes.     

Survey of virally mediated permeability changes.

1. Sendai virus causes permeability changes when added to freshly isolated brain cells (cerebellum or ependymal cells) or to a culture of forebrain cells. 2. Sendai virus causes permeability changes when added to organ cultures of ferret lung or nasal turbinate. Influenza virus causes no permeability changes under these conditions. 3. Rabies virus and vesicular-stomatitis virus, in contrast with Sendai virus, do not cause permeability changes in BHK cells or Lettrée cells. 4. Serum from patients suffering from viral hepatitis does not cause permeability changes in human leucocytes; addition to Sendai virus causes permeability changes. 5. It is concluded that permeability changes accompanying viral entry occur only with certain types of paramyxovirus, but that there is little restriction on cell type. 6. MDBK cells infected with Sendai virus show permeability changes during viral release, similar to those that occur during viral entry. Because these changes do not appear to be restricted to paramyxoviruses, they may have considerable clinical significance.     

Selected genetic polymorphisms and plasma coagulation factor VII changes with exercise training.

We assessed the effects of coagulation factor VII (FVII) gene polymorphisms, lipid-related polymorphisms, and exercise training-induced plasma lipoprotein lipid changes on FVII level changes with exercise training in middle- to older-aged men and women. Forty-six healthy sedentary men and women were stabilized on a low-fat diet and then underwent baseline testing, 6 mo of endurance exercise training, and final testing. Plasma FVII-Ag levels decreased with exercise training (106.7 +/- 1.4 vs. 104.2 +/- 1.6%, P = 0.005). There were no significant differences in FVII-Ag changes with exercise training between -323 (0/10 bp)/-401 (G/T) haplotype or -402 (G/A) genotype groups. FVII-Ag changes with training were not correlated with changes in plasma lipoprotein lipids. In linear regression analyses, FVII-Ag changes with training remained significant after adjusting for training-induced plasma lipoprotein lipid changes (P = 0.01). FVII changes with training were associated with apolipoprotein E genotype (P = 0.012); this relationship was still evident after adjusting for training-induced plasma lipoprotein lipid changes (P = 0.047). FVII changes with training also were significantly associated with human ATPase binding cassette-1 genotype (P = 0.018); this relationship persisted after accounting for the effect of the training-induced plasma lipoprotein lipid changes (P = 0.045). We conclude that plasma FVII-Ag changes with exercise training are more closely related to selected lipid-related genotypes than FVII gene promoter variants.     

Arthropod Hox genes: insights on the evolutionary forces that shape gene functions

Comparative studies suggest that gene duplication, changes in cis-regulatory elements and changes in protein sequence all contribute to the evolution of Hox gene functions, but the evolutionary dynamics of these changes are probably different. It seems likely that gene duplications arise as neutral changes and acquire an adaptive significance later on. By contrast, some changes in regulatory and protein-coding sequences can have immediate consequences in morphological evolution.     

Registration by dynamic phase microscopy of characteristic frequencies of phase height fluctuations of the myelin nerve fiber at rest and under stimulation

The method of dynamic phase microscopy was used to study the dynamics of changes in the structure of paranodal and nodal regions of a myelin nerve fiber of brown frog Rana temporaria at rest and under stimulation. Regular structural changes with frequencies of 5.3 and 10.8 Hz in the nodal region of the myelin nerve fiber were detected. A rhythmic excitation leads to additional changes in the structure of the nodal region with a new frequency of 5.6 Hz. It is likely that the regular changes in the nodal region of the myelin nerve induced by rhythmic excitation are due to slow changes in the axolemma (changes in the mode of lateral diffusion of membrane phospholipids), induced by developing trace changes in the membrane potential of the axolemma. The fact that these changes do not occur in the paranodal region of the fibre may indicate either the localization of regular structural changes in the axolemma or the difficulties that arise during the registration of the useful signal in the vicinity of myelin by this method.     

Individual aging and mortality rate: how are they related?

Many researchers working in the area of aging and longevity base their conclusions on the behavior of empirical age trajectories of mortality rates. In such analyses, changes in the slope of the logarithm of the mortality curve are often associated with changes in the rate of individual aging. We show that such interpretation may be incorrect: the changes in the slope of this curve do not necessarily correspond to the changes in the rate of individual aging. We use three models of mortality and aging to illustrate this statement. The first one is based on the idea of frailty. We show that changes in frailty distribution alone may be responsible for changes in the slope. The second model exploits the idea of saving lives. It evaluates changes in mortality rate after elimination of lethal stressful events. The third model uses the idea of Strehler and Mildvan (1960). It shows that changes in the rate of individual aging may take place without changes in the slope of the logarithm of the mortality curve.     

Life changes and menstrual discomfort.

The present study addressed the relationship between the accumulation of life changes and problems with menstruation. Female college students completed a Life Experiences Survey, which assesses desirable and undesirable life changes, and a menstruation questionnaire, which contains items relevant to menstrual discomfort and irregularity. Correlational analyses showed that undersirable life changes were correlated with reports of number of symptoms of menstrual discomfort, but not irregularity. Separate analyses among oral contraceptive users and nonusers showed that the relationship between life changes and menstrual discomfort occurred only among nonusers. A regression of contraceptive use, desirable life changes, and undersirable life changes on factors derived from the menstruation questionnaire indicated that undesirable life changes was the strongest predictor of menstrual problems.     

Vegetation succession in lakes of West Connemara,Ireland: comparing predicted and actual changes

Abstract. Changes in the vegetation of lakes and wetlands were investigated over a period of 18 years. It was assumed that changes in vegetation were related to changes in agricultural land use resulting in increased phosphate levels in surface waters. Data were collected in 1975, 1988 and 1993. Multivariate techniques were used to relate changes in vegetation to changes in environmental factors. With the use of a Markovian chain model, vegetation development was projected into the future. Projections based on vegetation dynamics between 1975 and 1988 were compared with actual changes in the vegetation. The vegetation dynamics appeared stable on a regional scale but quite dynamic on a local scale. A continuous decline in species diversity was noted as well as an overall increase of phosphate level. However, only minor changes in vegetation could be attributed to this increase of phosphate. Major changes were a result of fluctuations in water level. These changes coincide with periods of drier and wetter climate. Because of the fluctuating nature of these changes, predicted vegetation change did deviate from the observed change.     

Heritable Epigenetic Changes Alter Transgenerational Waveforms Maintained by Cycling Stores of Information

Our view of heredity can potentially be distorted by the ease of introducing heritable changes in the replicating gene sequences but not in the cycling assembly of regulators around gene sequences. Here, key experiments that have informed the understanding of heredity are reinterpreted to highlight this distortion and the possible variety of heritable changes are considered. Unlike heritable genetic changes, which are always associated with mutations in gene sequence, heritable epigenetic changes can be associated with physical or chemical changes in molecules or only changes in the system. The transmission of cycling stores along the continuous lineage of cells that connects successive generations creates waves of activity and localization of the molecules that together form the cell code for development in each generation. As a result, heritable epigenetic changes can include any that can alter a wave such as changes in form, midline, frequency, amplitude, or phase. Testing this integrated view of all heritable information will require the concerted application of multiple experimental approaches across generations.     

Hemodynamic mechanisms of the pulmonary artery pressure and blood flow changes following vasoactive depressor drugs injection

The character and values of changes of the pulmonary hemodynamics and venous return following acetylcholine, histamine and isoproterenol intravenous injection were studied in acute experiments on the anesthetized cats. After depressor drugs injection the character and values of changes of pulmonary artery pressure and flow were different. In 67% cases the pulmonary artery pressure was decreased, and in 33%--it was elevated, meanwhile the pulmonary artery flow was decreased in 48% cases and it was increased in 52%, i.e., in the equal number of observations. Thus, following depressor drugs intravenous injection, hemodynamic mechanisms of the changes of pulmonary artery pressure and flow are different. The character and values of changes of the pulmonary artery pressure are correlated with the changes of pulmonary vascular resistance and are not dependent with the left atrial pressure shifts. The changes of the pulmonary artery blood flow are caused by the changes of the venous return and are not correlated with the changes of the right and left atrial pressure.     

Effect of chemoreceptor modification on assembly and activity of the receptor-kinase complex in Escherichia coli

Bacterial chemoreceptors are embedded in the inner cell membrane in tight clusters. We show that changes in receptor methylation that generate large changes in kinase activity have relatively little effect on cluster morphology. Thus, changes in receptor activity do not appear to be mediated by changes in receptor-kinase assembly.     

Identification of molecular pathologies sufficient to cause neuropathic excitability in primary somatosensory afferents using dynamical systems theory

Pain caused by nerve injury (i.e. neuropathic pain) is associated with development of neuronal hyperexcitability at several points along the pain pathway. Within primary afferents, numerous injury-induced changes have been identified but it remains unclear which molecular changes are necessary and sufficient to explain cellular hyperexcitability. To investigate this, we built computational models that reproduce the switch from a normal spiking pattern characterized by a single spike at the onset of depolarization to a neuropathic one characterized by repetitive spiking throughout depolarization. Parameter changes that were sufficient to switch the spiking pattern also enabled membrane potential oscillations and bursting, suggesting that all three pathological changes are mechanistically linked. Dynamical analysis confirmed this prediction by showing that excitability changes co-develop when the nonlinear mechanism responsible for spike initiation switches from a quasi-separatrix-crossing to a subcritical Hopf bifurcation. This switch stems from biophysical changes that bias competition between oppositely directed fast- and slow-activating conductances operating at subthreshold potentials. Competition between activation and inactivation of a single conductance can be similarly biased with equivalent consequences for excitability. "Bias" can arise from a multitude of molecular changes occurring alone or in combination; in the latter case, changes can add or offset one another. Thus, our results identify pathological change in the nonlinear interaction between processes affecting spike initiation as the critical determinant of how simple injury-induced changes at the molecular level manifest complex excitability changes at the cellular level. We demonstrate that multiple distinct molecular changes are sufficient to produce neuropathic changes in excitability; however, given that nerve injury elicits numerous molecular changes that may be individually sufficient to alter spike initiation, our results argue that no single molecular change is necessary to produce neuropathic excitability. This deeper understanding of degenerate causal relationships has important implications for how we understand and treat neuropathic pain.     

Study of structural changes of contractile muscle proteins with the aid of polarization ultraviolet fluorescence microscopy. 1. Conformational changes of F-actin in the muscle fiber caused by ATP and its analogs]

Increase of anisotropy of F-actin fluorescence of balanus and rabbit muscle fibers under the influence of ATP, AMP and pyrophosphate in EGTA presence was detected by means of the polarized ultraviolet (UV) fluorescent microscopy methods. The fluorescence anisotropy changes are assumed to be associated with the conformational changes in the actin. ATP cause more noticeable changes of actin structure, than pyrophosphate and AMP. The conformational changes in the actin of balanus and rabbit muscle fibres were similar. ATP and its analogs induced also decrease of UV fluorescence anisotropy of A-band which appears to be associated with conformational changes in myosin. It was siggested that the changes in fluorescence of anisotropy of A-bands are due to structural changes in both HMM and LMM parts of myosin molecule.     

Modeling implications of food resource aggregation on animal migration phenology

The distribution of poikilotherms is determined by the thermal structure of the marine environment that they are exposed to. Recent research has indicated that changes in migration phenology of beluga whales in the Arctic are triggered by changes in the thermal structure of the marine environment in their summering area. If sea temperatures reflect the spatial distribution of food resources, then changes in the thermal regime will affect how homogeneous or clumped food is distributed. We explore, by individual‐based modelling, the hypothesis that changes in migration phenology are not necessarily or exclusively triggered by changes in food abundance, but also by changes in the spatial aggregation of food. We found that the level of food aggregation can significantly affect the relationship between the timing of the start of migration to the winter grounds and the total prey capture of individuals. Our approach strongly indicates that changes in the spatial distribution of food resources should be considered for understanding and quantitatively predicting changes in the phenology of animal migration.     

Are long‐term widespread avian body size changes related to food availability? A test using contemporaneous changes in carotenoid‐based color

Recent changes in global climate have been linked with changes in animal body size. While declines in body size are commonly explained as an adaptive thermoregulatory response to climate warming, many species do not decline in size, and alternative explanations for size change exist. One possibility is that temporal changes in animal body size are driven by changes in environmental productivity and food availability. This hypothesis is difficult to test due to the lack of suitable estimates that go back in time. Here, we use an alternative, indirect, approach and assess whether continent‐wide changes over the previous 100 years in body size in 15 species of Australian birds are associated with changes in their yellow carotenoid‐based plumage coloration. This type of coloration is strongly affected by food availability because birds cannot synthesize carotenoids and need to ingest them, and because color expression depends on general body condition. We found significant continent‐wide intraspecific temporal changes in body size (wing length) and yellow carotenoid‐based color (plumage reflectance) for half the species. Direction and magnitude of changes were highly variable among species. Meta‐analysis indicated that neither body size nor yellow plumage color showed a consistent temporal trend and that changes in color were not correlated with changes in size over the past 100 years. We conclude that our data provide no evidence that broad‐scale variation in food availability is a general explanation for continent‐wide changes in body size in this group of species. The interspecific variability in temporal changes in size as well as color suggests that it might be unlikely that a single factor drives these changes, and more detailed studies of museum specimens and long‐term field studies are required to disentangle the processes involved.     

Conformational changes in antigen-stimulated lymphocytes detected with 1-anilino-8-naphthalene sulphonate

The hydrophobic fluorescent probe, 1-anilino-8-naphthalene sulphonate (ANS), has been used to study conformational changes of mouse antigen-stimulated lymphocytes in vivo. Studies revealed that early conformational changes appear in Bovine Serum Albumin-- or Sheep Erythrocytes-- stimulated splenic and thymic lymphocytes. These conformational changes are detected by fluorescence intensity changes, when ANS is bound to lymphocytes. The kinetic studies further indicate that the course of conformational changes may vary considerably depending on antigens.     

Flowering range changes across an elevation gradient in response to warming summer temperatures

Many studies have demonstrated plant response to warming temperatures, both as advancement in the timing of phenological events and in range shifts. Mountain gradients are ideal laboratories for studying species range changes. In this study of 363 plant species in bloom collected in five segments across a 1200 m (4158 ft) elevation gradient, we look for changes in species flowering ranges over a 20-year period. Ninety-three species (25.6%) exhibited a significant change in the elevation at which they flowered from the first half to the second half of the record, with many of these changes occurring at higher elevations. Most of the species exhibiting the changes were perennial plants. Interestingly, though many changes in flowering range were specific to higher elevations, range changes occurred all across the gradient. The changes reported in this study are concurrent with significant increases in summer temperatures across the region and are consistent with observed changes around the globe.