Ticking Rate Research Articles

Developmental Tuning of Epigenetic Clock.

Research in the field of gerontology has traditionally focused on later life stages. There is increasing evidence, however, that both the rate of age-related functional decline and the later-life health status can be programmed during early development. The central role of epigenetic mechanisms (methylation of DNA, histone modifications and regulation by non-coding RNAs) in mediating these long-term effects has been elucidated. Both rate and direction of age-associated change of epigenetic patterns (“epigenetic drift”) were shown to be largely dependent on early-life environmental conditions. Inter-individual divergences in epigenetic profiles may arise following the stochastic errors in maintaining epigenetic marks, but they may also be adaptively mediated by specific environmental cues. Recent cohort studies indicate that ticking rate of epigenetic clock, estimated by a DNA methylation-based methods, may be developmentally adjusted, and that individual’s discrepancies among epigenetic and chronological age would be likely programmed early in development. In this Perspective article, recent findings suggesting the importance of early-life determinants for life-course dynamics of epigenetic drift are summarized and discussed.

Cattle tick infestation in Brangus cattle raised with Nellore in central Brazil

The present study evaluated the behavior of Rhipicephalus microplus naturally infesting Brangus cattle raised with Nellore animals in the municipality of Água Clara, state of Mato Grosso do Sul, Central Brazil. For the field experiment composed of a group with 15 Brangus animals and 15 Nellore animals and a control group with 30 Brangus cattle, all at the post-weaning stage. The 2 groups were kept for 6 months in 2 adjacent paddocks, naturally infested with ticks, at a stocking rate of approximately 0.6 of an animal unit per hectare (AU/ha). Every 18 days, the animals were weighed, and ticks on both sides of each bovine were counted. Every 36 days, blood was collected for hematocrit measurement and molecular diagnosis of the 3 pathogens that cause tick fever. The Brangus animals had 6.8 times more ticks than the Nellore cattle. No significant difference was observed in the weight gain of the Brangus and Nellore animals, and no correlation between the number of ticks and weight was observed in either group. During the 6 months of the study, all animals presented normal hematocrit, were positive for Babesia bigemina and Anaplasma marginale, and were negative for Babesia bovis. Animals in Group 1 produced 27% fewer ticks than the animals in Group 2. The production rate of engorged female ticks in Nellore and Brangus cattle was 0.83% and 2.01%, respectively. Considering the infestation pattern required to produce 10 engorged females/day/animal, the Nellore and Brangus animals required 1,204 and 497 larvae/day, respectively. Our estimates showed that Brangus cattle need only 11.3% of the larvae in the pastures with Nellore cattle to maintain the infestation level observed in the present study. Brangus animals raised with Nellore cattle do not have a lower parasitic load and continue to suffer from tick infestation. Finally, Nellore cattle raised with Brangus cattle do not act as a cleaner because this grouping does not contribute to a reduced infestation in the Brangus animals.

Anaplasma species detected in Haemaphysalis longicornis tick from China

Anaplasma are tick-borne obligatory intracellular bacteria, which infect humans and other animals. The Anaplasma species carried by ticks in China are not well studied. We collected 3145 questing Haemaphysalis longicornis ticks including 120 larvae, 2460 nymphs and 565 adults from vegetation in Jiaonan County, Shandong Province, China from 2013 to 2015. All ticks were examined for the presence of Anaplasma species by nested PCR amplification of the 16S rRNA gene. For further differentiation of A. capra from A. centrale, gltA and msp2 genes were sequenced for A. capra. Three Anaplasma species were detected in the nymph and/or adult ticks with the minimum infection rate of ticks as follows: 1.55% for A. bovis, 0.10% for A. phagocytophilum, and 0.03% for A. capra. These results indicated that the H. longicornis tick in Jiaonan County carried multiple Anaplasma species, which may be a challenge for public health in the studying area.

Acaricidal activity of extracts from different structures of Piper tuberculatum against larvae and adults of Rhipicephalus microplus

ABSTRACT The strategies to control the cattle tick, Rhipicephalus microplus are based mainly on the use of synthetic pesticides. However, the emergence, establishment, and development of resistance of ticks is rendering the main chemical groups ineffective. Finding new molecules to effectively control infestations by R. microplus is necessary to maintain the productivity of cattle herds, particularly of taurine breeds established in equatorial and tropical regions of the world. Ethanol extracts from the leaves, stems, and fruits of Piper tuberculatum were evaluated in bioassays at concentrations of 50, 25, 12.50, 6.25, 3.12 and 1.56 mg mL-1. The concentrations lethal to 50% of the individuals (LC50) of tick larvae after 24 hours of exposure were 3.62, 3.99 and 5.30 mg mL-1 for fruit, stem and leaf extracts, respectively. Against the engorged females, the highest efficacy rates were obtained at the concentration of 50 mg mL-1, corresponding to 71.57%, 68.38% and 37.03% of the fruit, leaf and stem extracts, respectively. The main effect of the ethanol extracts was on the egg hatching rate of ticks, with a reduction of 55.63% for the fruit and leaf extracts, and 20.82% for the stem extract. The results show that P. tuberculatum is a promising source of molecules for use as active ingredients in pesticide formulations for R. microplus control.

Faster ticking rate of the epigenetic clock is associated with faster pubertal development in girls

ABSTRACTEpigenetic age is an indicator of biological aging, capturing the impact of environmental and behavioral influences across time on cellular function. Deviance between epigenetic age and chronological age (AgeAccel) is a predictor of health. Pubertal timing has similarly been associated with cancer risk and mortality rate among females. We examined the association between AgeAccel and pubertal timing and adolescent breast composition in the longitudinal Growth and Obesity Cohort Study. AgeAccel was estimated in whole blood using the Horvath method at breast Tanner 2 (B2) and 4 (B4). Total breast volume, absolute fibro-glandular volume (FGV), and %FGV were evaluated at B4 using dual X-ray absorptiometry. The impact of AgeAccel (mean: 0; SD: 3.78) across puberty on the time to breast development (thelarche), menarche, and pubertal tempo (thelarche to menarche) was estimated using accelerated failure time models; generalized estimating equations were used to evaluate associations with breast density. A five-year increase in average adolescent AgeAccel was associated with a significant decrease in time to menarche [hazard ratio (HR): 1.37; 95% confidence interval (CI): 1.04, 1.80] adjusting for birth weight, maternal pre-pregnancy body mass index, maternal height, maternal education, B2 height, fat percentage, and cell composition. AgeAccel displayed a stronger inverse association with pubertal tempo (HR: 1.48; 95% CI: 1.10, 1.99). A five-year increase in AgeAccel was associated with 5% greater %FGV, adjusting for B4 percent body fat, and maternal traits (95% CI: 1.01, 1.10). Our study provides unique insight into the influence of AgeAccel on pubertal development in girls, which may have implications for adult health.

Endosymbiosis and its significance in dermatology.

Proposed at the beginning of the twentieth century to explain the origin of eukaryotic organelles from prokaryotes, endosymbiosis is now medically defined by various interaction patterns between microorganisms and their residing hosts, best exemplified by the bacterial endosymbiont Wolbachia identified in arthropods and filarial nematodes, which can influence normal development, reproduction, survival and transmission of the hosts. Based on the transmission modes, vertical or horizontal, and the function of the endosymbionts, the host-symbiont dependence can be divided into primary or secondary. In dermatology, the role of endosymbionts in skin ectoparasitosis has aroused great interests in the past years. Riesia pediculicola is a primary bacterial endosymbiont in body lice Pediculus humanus, and supplement their hosts with vitamin B, especially pantothenic acid. In cimicosis, the Gram-negative Wolbachia can synthesize biotin and riboflavin, which are crucial for the growth and reproduction of the bedbug Cimex lectularius. In human demodicosis and rosacea, further study is required to prove the pathogenic role of the Gram-negative bacteria Bacillus oleronius or the Gram-positive bacteria Bacillus cereus demonstrated in the Demodex mites. The high infection rate of adult female ticks Ixodes ricinus with the Gram-negative bacteria Midichloria mitochondrii present in the mitochondria in diverse ovarian cells, with the high seroprevalence rate in tick-exposed subjects, raises the possibility that this non-pathogenic endosymbiont may play a role in immune response and successful transmission of the tick-borne pathogen. The anaerobic protozoan Trichomonas vaginalis and bacteria Mycoplasma hominis are two obligate parasites in the urogenital epithelium, with partially overlapping symptoms. Intracellular localization of Mycoplasma hominis can avoid host immune response and penetration of antibiotics, while Trichomonas vaginalis infected with Mycoplasma hominis seems to have a higher cytopathic activity and amoeboid transformation rate. Further study on the biology and pathogenesis of different endosymbionts in dermatological parasitosis will help for the development of new treatment modalities.

Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "geroprotective" therapies in humans, outcome measures are needed that can assess extension of disease-free life span. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented 7 methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study (New Zealand; persons born 1972-1973). We studied 11 measures in total: telomere-length and erosion, 3 epigenetic-clocks and their ticking rates, and 3 biomarker-composites. Contrary to expectation, we found low agreement between different measures of biological aging. We next compared associations between biological aging measures and outcomes that geroprotective therapies seek to modify: physical functioning, cognitive decline, and subjective signs of aging, including aged facial appearance. The 71-cytosine-phosphate-guanine epigenetic clock and biomarker composites were consistently related to these aging-related outcomes. However, effect sizes were modest. Results suggested that various proposed approaches to quantifying biological aging may not measure the same aspects of the aging process. Further systematic evaluation and refinement of measures of biological aging is needed to furnish outcomes for geroprotector trials.

Multi-tissue DNA methylation age predictor in mouse

BackgroundDNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse.ResultsWe have generated a comprehensive set of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages. Many CpG sites show significant tissue-independent correlations with age which allowed us to develop a multi-tissue predictor of age in the mouse. Our model, which estimates age based on DNA methylation at 329 unique CpG sites, has a median absolute error of 3.33 weeks and has similar properties to the recently described human epigenetic clock. Using publicly available datasets, we find that the mouse clock is accurate enough to measure effects on biological age, including in the context of interventions. While females and males show no significant differences in predicted DNA methylation age, ovariectomy results in significant age acceleration in females. Furthermore, we identify significant differences in age-acceleration dependent on the lipid content of the diet.ConclusionsHere we identify and characterise an epigenetic predictor of age in mice, the mouse epigenetic clock. This clock will be instrumental for understanding the biology of ageing and will allow modulation of its ticking rate and resetting the clock in vivo to study the impact on biological age.

Tricks for ticks

Optical-lattice clocks have pushed the limits of frequency measurement — to such an extent that a tiny difference in altitude affects the clock's tick rate, as Hidetoshi Katori elucidates.

Epidemiological study of relapsing fever borreliae detected in Haemaphysalis ticks and wild animals in the western part of Japan.

The genus Borrelia comprises arthropod-borne bacteria, which are infectious agents in vertebrates. They are mainly transmitted by ixodid or argasid ticks. In Hokkaido, Japan, Borrelia spp. were found in deer and Haemaphysalis ticks between 2011 and 2013; however, the study was limited to a particular area. Therefore, in the present study, we conducted large-scale surveillance of ticks and wild animals in the western part of the main island of Japan. We collected 6,407 host-seeking ticks from two regions and 1,598 larvae obtained from 32 engorged female ticks and examined them to elucidate transovarial transmission. In addition, we examined whole blood samples from 190 wild boars and 276 sika deer, as well as sera from 120 wild raccoons. We detected Borrelia spp. in Haemaphysalis flava, Haemaphysalis megaspinosa, Haemaphysalis kitaokai, Haemaphysalis longicornis, and Haemaphysalis formosensis. In addition, we isolated a strain from H. megaspinosa using Barbour-Stoenner-Kelly medium. The minimum infection rate of ticks was less than 5%. Transovarial transmission was observed in H. kitaokai. Phylogenetic analysis of the isolated strain and DNA fragments amplified from ticks identified at least four bacterial genotypes, which corresponded to the tick species detected. Bacteria were detected in 8.4%, 15%, and 0.8% of wild boars, sika deer, and raccoons, respectively. In this study, we found seasonal differences in the prevalence of bacterial genotypes in sika deer during the winter and summer. The tick activity season corresponds to the season with a high prevalence of animals. The present study suggests that a particular bacterial genotype detected in this study are defined by a particular tick species in which they are present.

Correlation of an epigenetic mitotic clock with cancer risk.

BackgroundVariation in cancer risk among somatic tissues has been attributed to variations in the underlying rate of stem cell division. For a given tissue type, variable cancer risk between individuals is thought to be influenced by extrinsic factors which modulate this rate of stem cell division. To date, no molecular mitotic clock has been developed to approximate the number of stem cell divisions in a tissue of an individual and which is correlated with cancer risk.ResultsHere, we integrate mathematical modeling with prior biological knowledge to construct a DNA methylation-based age-correlative model which approximates a mitotic clock in both normal and cancer tissue. By focusing on promoter CpG sites that localize to Polycomb group target genes that are unmethylated in 11 different fetal tissue types, we show that increases in DNA methylation at these sites defines a tick rate which correlates with the estimated rate of stem cell division in normal tissues. Using matched DNA methylation and RNA-seq data, we further show that it correlates with an expression-based mitotic index in cancer tissue. We demonstrate that this mitotic-like clock is universally accelerated in cancer, including pre-cancerous lesions, and that it is also accelerated in normal epithelial cells exposed to a major carcinogen.ConclusionsUnlike other epigenetic and mutational clocks or the telomere clock, the epigenetic clock proposed here provides a concrete example of a mitotic-like clock which is universally accelerated in cancer and precancerous lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1064-3) contains supplementary material, which is available to authorized users.

Geopotential measurements with synchronously linked optical lattice clocks

According to the Einstein's theory of relativity, the passage of time changes in a gravitational field. On earth, raising a clock by one centimetre increases its tick rate by 1.1 parts in 10$^{18}$, enabling optical clocks to perform precision geodesy. Here, we demonstrate geopotentiometry by determining the height difference of master and slave clocks separated by 15 km with uncertainty of 5 cm. The subharmonic of the master clock is delivered through a telecom fibre to phase-lock and synchronously interrogate the slave clock. This protocol rejects laser noise in the comparison of two clocks, which improves the stability of measuring the gravitational red shift. Such phase-coherently operated clocks facilitate proposals for linking clocks and interferometers. Over half a year, 11 measurements determine the fractional frequency difference between the two clocks to be $1,652.9(5.9)\times 10^{-18}$, or a height difference of 1,516(5) cm, consistent with an independent measurement by levelling and gravimetry. Our system is as a building block of an internet of clocks, consisting of a master and a number of slave clocks, which will provide "quantum benchmarks" that are height references with dynamic response.

Symbols of a cosmic order

The world runs on networks over which signals communicate sequences of symbols, e.g. numerals. Examining both engineered and natural communications networks reveals an unsuspected order that depends on contact with an unpredictable entity. This order has three roots. The first is a proof within quantum theory that no evidence can ever determine its explanation, so that an agent choosing an explanation must do so unpredictably. The second root is the showing that clocks that step computers do not “tell time” but serve as self-adjusting symbol-handling agents that regulate “logically synchronized” motion in response to unpredictable disturbances. Such a clock-agent has a certain independence as well as the capacity to communicate via unpredictable symbols with other clock-agents and to adjust its own tick rate in response to that communication. The third root is the noticing of unpredictable symbol exchange in natural systems, including the transmission of symbols found in molecular biology. We introduce a symbol-handling agent as a role played in some cases by a person, for example a physicist who chooses an explanation of given experimental outcomes, and in other cases by some other biological entity, and in still other cases by an inanimate device, such as a computer-based detector used in physical measurements. While we forbear to try to explain the propensity of agents at all levels from cells to civilizations to form and operate networks of logically synchronized symbol-handling agents, we point to this propensity as an overlooked cosmic order, an order structured by the unpredictability ensuing from the proof. Appreciating the cosmic order leads to a conception of agency that replaces volition by unpredictability and reconceives the notion of objectivity in a way that makes a place for agency in the world as described by physics. Some specific implications for physics are outlined.

Effects of Increasing Temperature on Acoustic Advertisement in the Tettigoniidae

Acoustic communication in insects is vital for reproduction. In the family Tettigoniidae, certain features of acoustic signals are impacted by ambient temperature. The current study investigates the correlation between increased ambient temperature and signaling behavior in four species of katydids in two subfamilies under conditions that may be encountered as environmental temperatures continue to rise due to climate change. This is the first systematic investigation into the potential effects of temperature on song parameters in these four species. Individuals were tested at five different temperatures, ranging from 20 °C to 40 °C at 5°C intervals, and measurements were taken on six acoustic parameters: buzz duration, interbuzz interval (IBI) duration, number of ticks in the IBI, tick rate in the IBI, pulse rate within a buzz, and percent time spent calling. Results indicated a statistically significant effect of temperature on pulse rate, buzz duration, and interbuzz interval duration for all species tested. The percent time calling and buzz duration increased at higher temperatures in the single species in the subfamily Tettigoniinae, in contrast with the three species in the subfamily Conocephalinae which showed decreased percent time calling and reduced buzz duration in increased temperature. These results highlight the potential differences in the behavioral responses among different species to increasing global temperatures. Further research is necessary to assess the potential impact of variable calling parameters on female choice in these and other katydid species.

Impact specimen geometry on T23 and TP347HFG steels behaviour during steam oxidation at harsh conditions

Ferritic T23 steel and austenitic TP347HFG steel have been studied with an emphasis on understanding the impact of specimen geometry on their steam oxidation behaviour. The selected materials were tested over a wide range of temperatures from 600 to 750°C. The tests were carried out in 100% steam conditions for 1000 hours. The tests indicated that the ‘curved-shaped’ specimens show slower mass gain, scale ticking and void nucleation rates than ‘bridge-shaped’ specimens (with flat and convex surfaces combined). Furthermore, a bridge TP347HFG sample showed the formation of lower amount of flaky oxide at 750°C.

A novel C-type lectin with triple carbohydrate recognition domains has critical roles for the hard tick Haemaphysalis longicornis against Gram-negative bacteria

C-type lectins (CLecs) play an important role in innate immunity against invaders. In this study, a novel CLec was identified from Haemaphysalis longicornis ticks (HlCLec). HlCLec contains a signal peptide and a transmembrane region. Interestingly, HlCLec possesses three dissimilar carbohydrate recognition domains (CRDs). Each CRD contains the mutated motif of Ca2+-binding site 2. HlCLec mRNA was up-regulated during blood feeding, and had highest expression in the midgut and ovary. HlCLec localization was also confirmed by immunofluorescent antibody test (IFAT). HlCLec was found on the cell membrane and basal lamina of midgut and ovary. In addition, the recombinant HlCLec and individual CRDs demonstrated direct binding activity to Escherichia coli and Staphylococcus aureus; however, no growth inhibition activity was observed. Furthermore, E. coli injection after silencing of HlCLec caused drastic reduction in survival rate of ticks. These results strongly suggest the key role of HlCLec in tick innate immunity against Gram-negative bacteria.

Distribution of the tick-borne encephalitis virus among naturally infected ixodid ticks and small mammals in the Novosibirsk region

A comparative analysis of the virus infection carrier state and distribution of genetic types of the virus of tick-borne encephalitis (TBE) among invertebrates (2 species of ticks, Ixodes persulcatus Schulze and Ixodes pavlovskyi Pomerantsev 1946) and vertebrate reservoir hosts (4 species of small rodents: the red vole Myodes rutilus Pallas, gray-sided vole Myodes rufocanus Sundevall, field mouse Apodemus agrarius Pallas, birch mice Sicista betulina Pallas and 1 species of insectivores - common shrew Sorex araneus L (1758)), dominating on the territory of the Novosibirsk region in 2009-14 years, was performed with the use of virological and molecular biological methods. Frequency detection of RNA and / or E protein in mammals (70,9 ± 3,0%) were shown to considerably exceed levels of virus infection carrier state rate of ticks (3,4 ± 0,4). In the circulation of three major types of TBE - Far East (FE), Siberian (NIB) and European (Eur) in natural populations in mono - or polytype forms in mites Sib type prevailed (p

Role of the tumor necrosis factor receptor-associated factor-type zinc finger domain containing protein 1 (TRAFD1) from the hard tick Haemaphysalis longicornis in immunity against bacterial infection

A tumor necrosis factor receptor-associated factor-type zinc finger domain containing protein 1 (TRAFD1) is a negative feedback regulator that controls excessive immune responses in vertebrates. The sequence of tick hemolymph TRAFD1 from the hard tick Haemaphysalis longicornis (HlTRAFD1) was analyzed after identification and cloning from the expressed sequence tag database. RT-PCR and Western blot analyses showed that HlTRAFD1 transcript and protein levels after blood feeding were present in all developmental stages, and the transcript level was consistently high in all organs examined from adult female ticks upon engorgement. Knockdown of HlTRAFD1 gene by RNA interference did not affect blood feeding or oviposition. However, HlTRAFD1 silencing affected the expression of the longicin gene, a defensin-like molecule, but not the lysozyme gene. Moreover, the survival rate of HlTRAFD1-silenced ticks was lower, and the number of E. coli was higher in the hemolymph and plasmatocytes after E. coli injection compared to the control group. These results suggested that HlTRAFD1 strongly affected both the humoral and cellular immunity of ticks.

Ground-based optical atomic clocks as a tool to monitor vertical surface motion

Abstract According to general relativity, a clock experiencing a shift in the gravitational potential ΔU will measure a frequency change given by Δf/f ≈ ΔU/c2. The best clocks are optical clocks. After about 7 hr of integration they reach stabilities of Δf/f ∼ 10−18 and can be used to detect changes in the gravitational potential that correspond to vertical displacements of the centimetre level. At this level of performance, ground-based atomic clock networks emerge as a tool that is complementary to existing technology for monitoring a wide range of geophysical processes by directly measuring changes in the gravitational potential. Vertical changes of the clock's position due to magmatic, post-seismic or tidal deformations can result in measurable variations in the clock tick rate. We illustrate the geopotential change arising due to an inflating magma chamber using the Mogi model and apply it to the Etna volcano. Its effect on an observer on the Earth's surface can be divided into two different terms: one purely due to uplift (free-air gradient) and one due to the redistribution of matter. Thus, with the centimetre-level precision of current clocks it is already possible to monitor volcanoes. The matter redistribution term is estimated to be 3 orders of magnitude smaller than the uplift term. Additionally, clocks can be compared over distances of thousands of kilometres over short periods of time, which improves our ability to monitor periodic effects with long wavelength like the solid Earth tide.

Gravitational and relativistic deflection of X-ray superradiance

A theoretical proposal for time-dependent deflection of X-rays by gravitational and relativistic effects may lead to a table-top technique for probing gravity and relativity. Einstein predicted that clocks at different altitudes tick at various rates under the influence of gravity. This effect has been observed using 57Fe Mössbauer spectroscopy over an elevation of 22.5 m (ref. 1) or by comparing accurate optical clocks at different heights on a submetre scale2. However, challenges remain in finding novel methods for the detection of gravitational and relativistic effects on more compact scales. Here, we investigate a scheme that potentially allows for millimetre- to submillimetre-scale studies of the gravitational redshift by probing a nuclear crystal with X-rays. Also, a rotating crystal can force interacting X-rays to experience inhomogeneous clock tick rates within it. We find that an association of gravitational redshift and special-relativistic time dilation with quantum interference is manifested by a time-dependent deflection of X-rays. The scheme suggests a table-top solution for probing gravitational and special-relativistic effects, which should be within the reach of current experimental technology3,4,5.