scholarly journals Searching for fat tails in CRISPR-Cas systems: Data analysis and mathematical modeling

2021 ◽  
Vol 17 (3) ◽  
pp. e1008841
Author(s):  
Yekaterina S. Pavlova ◽  
David Paez-Espino ◽  
Andrew Yu. Morozov ◽  
Ilya S. Belalov

Understanding CRISPR-Cas systems—the adaptive defence mechanism that about half of bacterial species and most of archaea use to neutralise viral attacks—is important for explaining the biodiversity observed in the microbial world as well as for editing animal and plant genomes effectively. The CRISPR-Cas system learns from previous viral infections and integrates small pieces from phage genomes called spacers into the microbial genome. The resulting library of spacers collected in CRISPR arrays is then compared with the DNA of potential invaders. One of the most intriguing and least well understood questions about CRISPR-Cas systems is the distribution of spacers across the microbial population. Here, using empirical data, we show that the global distribution of spacer numbers in CRISPR arrays across multiple biomes worldwide typically exhibits scale-invariant power law behaviour, and the standard deviation is greater than the sample mean. We develop a mathematical model of spacer loss and acquisition dynamics which fits observed data from almost four thousand metagenomes well. In analogy to the classical ‘rich-get-richer’ mechanism of power law emergence, the rate of spacer acquisition is proportional to the CRISPR array size, which allows a small proportion of CRISPRs within the population to possess a significant number of spacers. Our study provides an alternative explanation for the rarity of all-resistant super microbes in nature and why proliferation of phages can be highly successful despite the effectiveness of CRISPR-Cas systems.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicole A. Ellis ◽  
Byoungkwan Kim ◽  
Jessica Tung ◽  
Matthias P. Machner

AbstractCatalytically inactive dCas9 imposes transcriptional gene repression by sterically precluding RNA polymerase activity at a given gene to which it was directed by CRISPR (cr)RNAs. This gene silencing technology, known as CRISPR interference (CRISPRi), has been employed in various bacterial species to interrogate genes, mostly individually or in pairs. Here, we developed a multiplex CRISPRi platform in the pathogen Legionella pneumophila capable of silencing up to ten genes simultaneously. Constraints on precursor-crRNA expression were overcome by combining a strong promoter with a boxA element upstream of a CRISPR array. Using crRNAs directed against virulence protein-encoding genes, we demonstrated that CRISPRi is fully functional not only during growth in axenic media, but also during macrophage infection, and that gene depletion by CRISPRi recapitulated the growth defect of deletion strains. By altering the position of crRNA-encoding spacers within the CRISPR array, our platform achieved the gradual depletion of targets that was mirrored by the severity in phenotypes. Multiplex CRISPRi thus holds great promise for probing large sets of genes in bulk in order to decipher virulence strategies of L. pneumophila and other bacterial pathogens.


2019 ◽  
Vol 20 (2) ◽  
pp. 266 ◽  
Author(s):  
Maria Torcia

The vaginal ecosystem is important for women’s health and for a successful reproductive life, and an optimal host-microbial interaction is required for the maintenance of eubiosis. The vaginal microbiota is dominated by Lactobacillus species in the majority of women. Loss of Lactobacillus dominance promotes the colonization by anaerobic bacterial species with an increase in microbial diversity. Vaginal dysbiosis is a very frequent condition which affects the immune homeostasis, inducing a rupture in the epithelial barrier and favoring infection by sexually transmitted pathogens. In this review, we describe the known interactions among immune cells and microbial commensals which govern health or disease status. Particular attention is given to microbiota compositions which, through interplay with immune cells, facilitate the establishment of viral infections, such as Human Immunodeficiency Virus (HIV), Human Papilloma Virus (HPV), Herpes Simplex Virus 2 (HSV2).


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Birgitta Dresp-Langley

Generic properties of curvature representations formed on the basis of vision and touch were examined as a function of mathematical properties of curved objects. Virtual representations of the curves were shown on a computer screen for visual scaling by sighted observers (experiment 1). Their physical counterparts were placed in the two hands of blindfolded and congenitally blind observers for tactile scaling. The psychophysical data show that curvature representations in congenitally blind individuals, who never had any visual experience, and in sighted observers, who rely on vision most of the time, are statistically linked to the same mathematical properties of the curves. The perceived magnitude of object curvature, sensed through either vision or touch, is related by a mathematical power law, with similar exponents for the two sensory modalities, to the aspect ratio of the curves, a scale invariant geometric property. This finding supports biologically motivated models of sensory integration suggesting a universal power law for the adaptive brain control and balance of motor responses to environmental stimuli from any sensory modality.


2006 ◽  
Vol 13 (12) ◽  
pp. 1349-1359 ◽  
Author(s):  
Scott Angell ◽  
Bennie J. Bench ◽  
Howard Williams ◽  
Coran M.H. Watanabe

2015 ◽  
Vol 24 (04) ◽  
pp. 1541001 ◽  
Author(s):  
Cheng Cheng ◽  
Qing-Guo Huang

Even though Planck data released in 2013 (P13) is not compatible with Background Imaging of Cosmic Extragalactic Polarization (B2) and some local cosmological observations, including Supernova Legacy Survey (SNLS) samples and H0 prior from Hubble Space Telescope (HST) etc. Wilkinson Microwave Anisotropy Probe 9-year data (W9) is consistent with all of them in the base six-parameter ΛCDM + tensor cosmology quite well. In this paper, we adopt the combinations of B2+W9 and B2+W9+SNLS+BAO+HST to constrain the cosmological parameters in the base six-parameter ΛCDM + tensor model with nt = -r/8, where r and nt are the tensor-to-scalar ratio and the tilt of relic gravitational wave spectrum, and BAO denotes Baryon Acoustic Oscillation (BAO). We find that the Harrison–Zel'dovich (HZ) scale invariant scalar power spectrum is consistent with both data combinations, chaotic inflation is marginally disfavored by the data at around 2σ level, but the power-law inflation model and the inflation model with inverse power-law potential can fit the data nicely.


2015 ◽  
Vol 12 (105) ◽  
pp. 20141344 ◽  
Author(s):  
Jordi Luque ◽  
Bartolo Luque ◽  
Lucas Lacasa

Speech is a distinctive complex feature of human capabilities. In order to understand the physics underlying speech production, in this work, we empirically analyse the statistics of large human speech datasets ranging several languages. We first show that during speech, the energy is unevenly released and power-law distributed, reporting a universal robust Gutenberg–Richter-like law in speech. We further show that such ‘earthquakes in speech’ show temporal correlations, as the interevent statistics are again power-law distributed. As this feature takes place in the intraphoneme range, we conjecture that the process responsible for this complex phenomenon is not cognitive, but it resides in the physiological (mechanical) mechanisms of speech production. Moreover, we show that these waiting time distributions are scale invariant under a renormalization group transformation, suggesting that the process of speech generation is indeed operating close to a critical point. These results are put in contrast with current paradigms in speech processing, which point towards low dimensional deterministic chaos as the origin of nonlinear traits in speech fluctuations. As these latter fluctuations are indeed the aspects that humanize synthetic speech, these findings may have an impact in future speech synthesis technologies. Results are robust and independent of the communication language or the number of speakers, pointing towards a universal pattern and yet another hint of complexity in human speech.


Author(s):  
Moussa Bounoughaz ◽  
Noura Touabi

The fiberglass pipes were used for transportation of water in order to maintain the pressure in the oil field of Zarzaïtine (Region of In Amenas located in the south of Algeria). During the maintenance work in summer, a season well known for its extensive heat, the deposits contained in the pipe, and after its contact with the atmosphere, have caused a smoke and it was followed by a fire that ignited a portion of the pipe. To give an answer to the causes of this phenomenon, we have first incriminated the role of specific bacterial species and therefore we have made a microbiological analysis of the deposits collected from the site of the incident. The obtained results revealed the presence of a heterogeneous microbial population with a high concentration level of sulfate-reducing bacteria (SRB), methanogenic bacteria (MB), yeasts and fungi. The interaction between the different species of bacteria and the organic matter contained in the deposits has generated the formation of methane which under the influence of the great heat burnt and the fire caused the ignition of the fiberglass line.


Hepatocellular carcinoma (HCC) is a form of cancer that is very widespread around the world and has a high mortality rate. Extensive evidence suggests that, HCC is a multifactorial disease. Hepatic cirrhosis is present, along with systemic inflammation and viral infections such as hepatitis B or C. Thus, giving rise to genetically and phenotypically heterogeneous hepatocellular carcinoma tumors. Researchers have found that bacterial and viral inhibitors can be used to silence targeted genes in hepatocellular carcinoma. Many bacterial species such as; Salmonella, Listeria, and Escherichia, proved to have anti-tumor properties. Up till now, adenoviral, retroviral, herpes-simplex viral and adeno-associated viral vectors have been modified and are being used for HCC gene therapy. In patients, up regulation of TLR signaling have also been observed showing an interesting influence on HCC’s microenvironment. TLR 4 and TLR 9 have positive relationship with tumor whereas, TLR3 is associated with anti-tumor influence. TLRs can cause an inflammatory response in the presence of foreign pathogens including bacteria and fungi. This review reflects an insight into the biology of HCC suggesting that certain signaling pathways and molecular alterations plays a very significant role in HCC development. As well as new experimental approaches, including; anti-angiogenesis, cancer therapy, oncolytic virotherapy, and suppressing the function of oncogenes, leading to apoptosis are successively being applied. The current challenge for the researchers is to identify a medicament which is selective for tumors specific cells only, having minimal noxiousness and harmless to normal tissue. We have scrutinized research articles based on how to merge viral and bacterial anticancer therapies into a single treatment for HCC.


Author(s):  
Masao Fukui ◽  
Chishio Furukawa

AbstractWhile they are rare, superspreading events (SSEs), wherein a few primary cases infect an extraordinarily large number of secondary cases, are recognized as a prominent determinant of aggregate infection rates (ℛ0). Existing stochastic SIR models incorporate SSEs by fitting distributions with thin tails, or finite variance, and therefore predicting almost deterministic epidemiological outcomes in large populations. This paper documents evidence from recent coronavirus outbreaks, including SARS, MERS, and COVID-19, that SSEs follow a power law distribution with fat tails, or infinite variance. We then extend an otherwise standard SIR model with the estimated power law distributions, and show that idiosyncratic uncertainties in SSEs will lead to large aggregate uncertainties in infection dynamics, even with large populations. That is, the timing and magnitude of outbreaks will be unpredictable. While such uncertainties have social costs, we also find that they on average decrease the herd immunity thresholds and the cumulative infections because per-period infection rates have decreasing marginal effects. Our findings have implications for social distancing interventions: targeting SSEs reduces not only the average rate of infection (ℛ0) but also its uncertainty. To understand this effect, and to improve inference of the average reproduction numbers under fat tails, estimating the tail distribution of SSEs is vital.


2007 ◽  
Vol 14 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Y. Kawada ◽  
H. Nagahama ◽  
Y. Omori ◽  
Y. Yasuoka ◽  
T. Ishikawa ◽  
...  

Abstract. Prior to large earthquakes (e.g. 1995 Kobe earthquake, Japan), an increase in the atmospheric radon concentration is observed, and this increase in the rate follows a power-law of the time-to-earthquake (time-to-failure). This phenomenon corresponds to the increase in the radon migration in crust and the exhalation into atmosphere. An irreversible thermodynamic model including time-scale invariance clarifies that the increases in the pressure of the advecting radon and permeability (hydraulic conductivity) in the crustal rocks are caused by the temporal changes in the power-law of the crustal strain (or cumulative Benioff strain), which is associated with damage evolution such as microcracking or changing porosity. As the result, the radon flux and the atmospheric radon concentration can show a temporal power-law increase. The concentration of atmospheric radon can be used as a proxy for the seismic precursory processes associated with crustal dynamics.


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