NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise

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Are Quasi-Steady-State Approximated Models Suitable for Quantifying Intrinsic Noise Accurately?

Large gene regulatory networks (GRN) are often modeled with quasi-steady-state approximation (QSSA) to reduce the huge computational time required for intrinsic noise quantification using Gillespie stochastic simulation algorithm (SSA). However, the question still remains whether the stochastic QSSA model measures the intrinsic noise as accurately as the SSA performed for a detailed mechanistic model or not? To address this issue, we have constructed mechanistic and QSSA models for few frequently observed GRNs exhibiting switching behavior and performed stochastic simulations with them. Our results strongly suggest that the performance of a stochastic QSSA model in comparison to SSA performed for a mechanistic model critically relies on the absolute values of the mRNA and protein half-lives involved in the corresponding GRN. The extent of accuracy level achieved by the stochastic QSSA model calculations will depend on the level of bursting frequency generated due to the absolute value of the half-life of either mRNA or protein or for both the species. For the GRNs considered, the stochastic QSSA quantifies the intrinsic noise at the protein level with greater accuracy and for larger combinations of half-life values of mRNA and protein, whereas in case of mRNA the satisfactory accuracy level can only be reached for limited combinations of absolute values of half-lives. Further, we have clearly demonstrated that the abundance levels of mRNA and protein hardly matter for such comparison between QSSA and mechanistic models. Based on our findings, we conclude that QSSA model can be a good choice for evaluating intrinsic noise for other GRNs as well, provided we make a rational choice based on experimental half-life values available in literature.     

Residential Exposure to Traffic Noise and Health-Related Quality of Life—A Population-Based Study

Background

Few studies have investigated the association between objectively measured traffic noise and health-related quality of life. However, as traffic noise has been associated with both cardiovascular disease and diabetes, and health-issues including sleeping problems, annoyance, and stress, it seems plausible that traffic noise is associated with health-related quality of life.

Methods

Between 1999 and 2002, a cohort of 38,964 Danes filled in the short form-36 (SF-36) questionnaire. Residential exposure to road traffic and railway noise was calculated for all historical addresses for 10 years preceding the SF-36, using the Nordic prediction method. Associations between noise exposure and SF-36 summary scales and the eight sub-scales were calculated using general linear models, adjusted for age, sex, socioeconomic status, and lifestyle.

Results

Models adjusted for age, sex and socioeconomic factors showed that a 10 dB higher road traffic noise 1 year preceding SF-36 assessment was associated with a 0.14 lower mental component summary (MCS) score (95% confidence interval (CI) -0.26, -0.01). However, further adjustment for lifestyle factors (smoking, alcohol, and waist circumference) attenuated the association: (-0.08 (95% CI: -0.20, 0.04)). Exposure to more than 55 dB of railway noise in the same time period was borderline significantly associated with lower MCS. The physical component summary was not associated with traffic noise.

Conclusion

The present study suggests a weak association between traffic noise exposure and the mental health component score of SF-36, which may operate through lifestyle. The magnitude of effect was, however, not clinically relevant.     

Inherited Biochemical Variation in DROSOPHILA MELANOGASTER: Noise or Signal? I. Single-Locus Analyses

A study was conducted using small effective population size as an experimental design to test selective neutrality of seven isozyme polymorphisms. Loci varied as to the degree to which the decay of heterozygosity over 21 generations was retarded. Selection for heterozygotes, overdominance, is implicated for at least four of seven loci. Of these ADH gave the largest heterozygote excess in the presence of inbreeding. An interaction between the small population size treatment and excess heterozygosity suggests that (1) the loci studied may be selectively neutral and linked to other loci which are under the influence of selection or (2) the selection coefficients for the loci studied are not independent of the background genotype. In either case four of the seven enzymes studied are signaling the operation of selection. The problem of distinguishing the effect of a single marker from that of a chromosome segment is emphasized. The identification of the genetic unit of selection is crucial to any interpretation of the meaning of enzyme polymorphisms.     

Noise Induces Hypothyroidism and Gonadal Dysfunction Via Stimulation of Pineal–Adrenal Axis in Chicks

Noise is a world-wide problem that causes nervous, endocrine and cardiovascular disorders, and eventually health hazards in humans and animals. Objective of the current work is to investigate endocrine interaction in noise stress, which subsequently affects other endocrine functions including gonads in a poultry bird like chicks. Gravimetric, ultrastructural and hormonal status of the endocrine organs were examined to ascertain the effects of noise stress. Acute noise at 60 dB had no effect, but at 80 and 100 dB each for 3 h, increased pineal and serum serotonin, and adrenal and serum corticosterone, epinephrine and norepinephrine concentrations, without any change in thyroid or gonadal hormones. Chronic noise exposure at 60, 80 and 100 dB each for 6 h, daily for 7 days, drastically disturbed normal behavior, and quantum of food consumption and water intake. Chronic exposure also significantly decreased body weight including thyroid, ovary and testis weight, and increased adrenal weight. Noise stress caused ultrastructural changes leading to stimulations of pinealocytes (with abundance of rough endoplasmic reticulum and mitochondria), adrenocortical cells (enlarged nuclei and abundance of smooth endoplasmic reticulum) and adrenomedullary cells (enlarged nuclei with presence of chromaffin granules) were observed in noise stress. Additionally, pineal and serum serotonin, N-acetyl serotonin and melatonin, and adrenal and serum corticosterone, epinephrine and norepinephrine levels were significantly elevated following chronic noise exposure. Contrarily, thyroid activity was suppressed with atrophied thyroid follicles followed by declined levels of serum T₃ and T₄ with elevation of TSH level. Simultaneously, serum 17β-estradiol (E₂) and testosterone (T) concentrations were also significantly declined in all the doses of chronic noise. These changes were dose dependent of noise exposure. The findings suggest that (a) adrenal and pineal glands respond primarily to noise and secondarily act on other endocrine organs including gonads in chicks, (b) adrenal directly and/or indirectly causes thyroid and gonadal dysfunctions via pineal following noise exposure in chicks.     

Mode Transitions in a Model Reaction–Diffusion System Driven by Domain Growth and Noise

Pattern formation in many biological systems takes place during growth of the underlying domain. We study a specific example of a reaction-diffusion (Turing) model in which peak splitting, driven by domain growth, generates a sequence of patterns. We have previously shown that the pattern sequences which are presented when the domain growth rate is sufficiently rapid exhibit a mode-doubling phenomenon. Such pattern sequences afford reliable selection of certain final patterns, thus addressing the robustness problem inherent of the Turing mechanism. At slower domain growth rates this regular mode doubling breaks down in the presence of small perturbations to the dynamics. In this paper we examine the breaking down of the mode doubling sequence and consider the implications of this behaviour in increasing the range of reliably selectable final patterns.     

Effects of Experimental Choices and Analysis Noise on Surveys of the “Rare Biosphere”

When planning a survey of 16S rRNA genes from a complex environment, investigators face many choices including which primers to use and how to taxonomically classify sequences. In this study, we explored how these choices affected a survey of microbial diversity in a sample taken from the aerobic basin of the activated sludge of a North Carolina wastewater treatment plant. We performed pyrosequencing reactions on PCR products generated from primers targeting the V1-V2, V6, and V6-V7 variable regions of the 16S rRNA gene. We compared these sequences to 16S rRNA gene sequences found in a whole-genome shotgun pyrosequencing run performed on the same sample. We found that sequences generated from primers targeting the V1-V2 variable region had the best match to the whole-genome shotgun reaction across a range of taxonomic classifications from phylum to family. Pronounced differences between primer sets, however, occurred in the “rare biosphere” involving taxa that we observed in fewer than 11 sequences. We also examined the results of analysis strategies comparing a classification scheme using a nearest-neighbor approach to directly classifying sequences with a naïve Bayesian algorithm. Again, we observed pronounced differences between these analysis schemes in infrequently observed taxa. We conclude that if a study is meant to probe the rare biosphere, both the experimental conditions and analysis choices will have a profound impact on the observed results.For nearly 3 decades, investigations of the distribution of microbes in complex environments have focused on the use of rRNA genes (1, 2, 4, 11, 16, 18, 19, 22, 24). Because the full-length 16S rRNA sequence can be obtained with paired-end reads via traditional Sanger sequencing, until recently most studies of the 16S rRNA gene captured most or nearly most of the 16S sequence length. New pyrosequencing technologies, however, have recently been introduced that greatly reduce the per base cost of sequencing but with shorter read lengths than traditional Sanger sequencing (17). This new approach has proven powerful, yielding a previously unobtainable view of rare taxa (7, 12-14, 25).The shorter reads produced by pyrosequencing require the choice of a particular region of the 16S rRNA gene to target for pyrosequencing as well as the choice of an algorithm to classify the taxonomy of the shorter reads. In their initial surveys of microbial diversity with pyrosequencing (12, 14, 25), Sogin and colleagues targeted the V6 variable region, in part because it is was small enough to be captured with the 100-bp reads of the pyrosequencing technology available at the time. Recently, the read length of 454 pyrosequencing machines has been increased to an average of ∼250 bp. This allows for more flexibility in primer design and opens up the possibility of targeting regions of the 16S rRNA gene other than V6. In recent work, Huse et al. took advantage of this new capability to compare the classifications made for the human gut microbiome with the V6 and longer V3 regions (13). Plotting the taxonomic abundance of these two sequence sets against each other yielded an excellent correlation (r² = 0.99), suggesting that the choice of which variable region to target makes little difference. In this report, we introduce a data set examining the performance of sets of primers targeting the V1-V2, V6, and V6-V7 regions. By using a sample for which we have also generated a whole-genome shotgun sequencing run with 250 bp reads, we were able to compare the observed 16S rRNA genes in samples with and without an initial PCR step targeting the 16S rRNA gene. Our results demonstrate that experimental choices such as which region of the 16S rRNA gene to sequence and which algorithm to use to classify taxa are much more likely to affect observations of the “rare biosphere” than more commonly observed taxa.     

Noise improves transfer of near-threshold, phase-locked activity of the cochlear nerve: evidence for stochastic resonance?

 Stochastic resonance can be described as improved detection of weak periodic stimuli by a dynamic nonlinear system, resulting from the simultaneous presentation of a restricted dynamic range of low-intensity noise. This property has been reported in simple physical and biological activities. The present study describes data consistent with the interpretation that stochastic resonance can be observed in the response of cochlear neurons. These experiments utilized low levels (−5 to 25 dB SPL) of stimuli and noise (5 to 30 dB SPL). Stimuli consisted of simultaneously presented 8 kHz (F ₁) and 8.8 kHz (F ₂) tone bursts, which generated an 800 Hz F ₂–F ₁ cochlear nerve envelope ensemble response in the gerbil. The mean response threshold was approximately −3 dB SPL. Simultaneous presentation of a low-intensity wideband noise increased the amplitude of this response. This was observed with tonal stimuli having intensities of 0–5 dB SPL; responses to stimulus levels >10 dB were attenuated by noise. Response amplitude was increased by noise levels of 10–15 dB; the amplitude was unaffected by lower levels of noise, and decreased in the presence of higher noise levels. These properties are compatible with those of stochastic resonance. Accepted: 11 March 1999     

Noise affects porpoise click detections – the magnitude of the effect depends on logger type and detection filter settings

Automatic click detectors and full-bandwidth sound recorders are widely used in passive acoustic monitoring of small cetaceans. Detection of these signals depends on a variety of factors, including signal to noise ratio. Passive acoustic monitoring is often used to study impact of underwater noise on small cetaceans, but as detection probability is affected by changes in signal to noise ratio, variable noise levels may affect conclusions drawn from these experiments. Therefore, we examine how different detectors and filters perform in varying ocean noise conditions. C-PODs and full-bandwidth recorders (Wildlife Acoustics, SM2M+) were deployed at two stations in an environment with fluctuating ambient noise for 42 days. Noise level and harbour porpoise (Phocoena phocoena) click trains simultaneously recorded on both loggers were compared. Overall, we found that porpoise click detections by the algorithm used to analyse full-band recorder data (Pamguard) paralleled detections by the C-POD. However, Pamguard detected significantly more clicks than the C-POD. A decrease in detections was seen for both loggers with increasing noise in the band 20 –160 kHz, in particular for levels above 100 dB re 1μPa rms. We also found that the Pamguard detection function changed the least over varying noise conditions when compared to the C-POD detectors. This study sheds light on the fact that inference of animal presence/absence or density that are based on echolocation cues (here, Porpoise Positive Minutes) shall account for the acoustic environments where probability of detecting signals may be affected by variability in ambient noise levels.     

Effects of 85 dB Noise Exposure on Macro and Trace Element Levels in Plasma and Brain Areas of Rats

In this study, our hypothesis was that workplace noise can alter brain element levels like immobilization and light–dark cycle shift, and we aimed to investigate the effects of workplace noise on element levels of brain areas as well as changes in blood of chronically noise-exposed rats. Twenty-four rats were randomly divided into three groups. The first group was the control. The second group (noise exposed) was subjected to daily 8 h 85 dB workplace noise for 15 days, and the third group (noise exposed plus normal condition) was also subjected to the same noise exposure and then returned to normal condition for 15 days. In noise-exposed group, Na, K, Ca, Mg , Fe, Cu, and Zn levels in plasma significantly increased when compared with controls (p?=?0.03 for Na; p?=?0.005 for K and Mg; p?=?0.002 for Ca and Fe; p?=?0.01 for Cu and Zn). In this group, Fe level of temporal lobe significantly increased (p?=?0.021) while Mg level significantly increased in frontal (p?=?0.021) and temporal (p?=?0.001) lobes when compared with controls. In the noise-exposed plus normal condition group, plasma Na, K, Fe, Cu, and Zn levels were greatly similar to controls. But, plasma Ca and Mg levels significantly decreased when compared with controls (p?=?0.002 and p?=?0.007) and noise-exposed group (p?=?0.002 and p?=?0.001). Fe level of temporal lobe significantly increased when compared with controls (p?=?0.001) and noise exposed group (p?=?0.001). These alterations may be attributed to impaired intake of water and micronutrients or their excretions, emerging by acoustic stress.     

A Preliminary Investigation Regarding the Effect of Tennis Grunting: Does White Noise During a Tennis Shot Have a Negative Impact on Shot Perception?

Background

There is a growing chorus of critics who complain that many of the top-ranked professional tennis players who grunt when they hit the ball gain an unfair advantage because the sound of the grunt interferes with their opponent''s game. However, there is no scientific evidence to support this claim.

Methodology/Principal Findings

We explored this potential detrimental effect of grunting by presenting videos of a tennis player hitting a ball to either side of a tennis court; the shot either did, or did not, contain a brief sound that occurred at the same time as contact. The participants'' task was to respond as quickly as possible, indicating whether the ball was being hit to the left- or right-side of the court. The results were unequivocal: The presence of an extraneous sound interfered with a participants'' performance, making their responses both slower and less accurate.

Conclusions/Significance

Our data suggest that a grunting player has a competitive edge on the professional tennis tour. The mechanism that underlies this effect is a topic for future investigation. Viable alternatives are discussed. For example, the possibility that the interfering auditory stimulus masks the sound of the ball being struck by the racket or it distracts an opponent''s attention away from the sound of the ball.     

Little Evidence to Support the Risk–Disturbance Hypothesis as an Explanation for Responses to Anthropogenic Noise by Pygmy Marmosets (Cebuella niveiventris) at a Tourism site in the Peruvian Amazon

The risk–disturbance hypothesis states that animals react to human stressors in the same way as they do to natural predators. Given increasing human–wildlife contact, understanding whether animals perceive anthropogenic sounds as a threat is important for assessing the long-term sustainability of wildlife tourism and proposing appropriate mitigation strategies. A study of pygmy marmoset (Cebuella niveiventris) responses to human speech found marmosets fled, decreased feeding and resting, and increased alert behaviors in response to human speech. Following this study, we investigated pygmy marmoset reactions to playbacks of different acoustic stimuli: controls (no playback, white noise and cicadas), anthropogenic noise (human speech and motorboats), and avian predators. For each playback condition, we recorded the behavior of a marmoset and looked at how the behaviors changed during and after the playback relative to behaviors before. We repeated this on ten different marmoset groups, playing each condition once to each group. The results did not replicate a previous study on the same species, at the same site, demonstrating the importance of replication in primate research, particularly when results are used to inform conservation policy. The results showed increased scanning during playbacks of the cicadas and predators compared with before the playback, and an increase in resting after playbacks of avian predators, but no evidence of behavior change in response to playbacks of human speech. There was no effect of ambient sound levels or distance between the playback source and focal animals on their behavior for all playback conditions. Although we find that noise can change the behavior of pygmy marmosets, we did not find evidence to support the risk–disturbance hypothesis.