Superstatistical modelling of protein diffusion dynamics in bacteria

A recent experiment (Sadoon AA, Wang Y. 2018 Phys. Rev. E 98, 042411. (doi:10.1103/PhysRevE.98.042411)) has revealed that nucleoid-associated proteins (i.e. DNA-binding proteins) exhibit highly heterogeneous diffusion processes in bacteria where not only the diffusion constant but also the anomalous diffusion exponent fluctuates for the various proteins. The distribution of displacements of such proteins is observed to take a q-Gaussian form, which decays as a power law. Here, a statistical model is developed for the diffusive motion of the proteins within the bacterium, based on a superstatistics with two variables. This model hierarchically takes into account the joint fluctuations of both the anomalous diffusion exponents and the diffusion constants. A fractional Brownian motion is discussed as a possible local model. Good agreement with the experimental data is obtained.     

Unified model of short- and long-term HIV viral rebound for clinical trial planning

Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. Typically suspension of therapy is rapidly followed by rebound of viral loads to high, pre-therapy levels. Indeed, a recent study showed that approximately 90% of treatment interruption study participants show viral rebound within at most a few months of therapy suspension, but the remaining 10%, showed viral rebound some months, or years, after ART suspension. Some may even never rebound. We investigate and compare branching process models aimed at gaining insight into these viral dynamics. Specifically, we provide a theory that explains both short- and long-term viral rebounds, and post-treatment control, via a multitype branching process with time-inhomogeneous rates, validated with data from Li et al. (Li et al. 2016 AIDS 30, 343–353. (doi:10.1097/QAD.0000000000000953)). We discuss the associated biological interpretation and implications of our best-fit model. To test the effectiveness of an experimental intervention in delaying or preventing rebound, the standard practice is to suspend therapy and monitor the study participants for rebound. We close with a discussion of an important application of our modelling in the design of such clinical trials.     

The furrows of Rhinolophidae revisited

Rhinolophidae, a family of echolocating bats, feature very baroque noseleaves that are assumed to shape their emission beam. Zhuang & Muller (Zhuang & Muller 2006 Phys. Rev. Lett. 97, 218701 (doi:10.1103/PhysRevLett.97.218701); Zhuang & Muller 2007 Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 76(Pt. 1), 051902 (doi:10.1103/PhysRevE.76.051902)) have proposed, based on finite element simulations, that the furrows present in the noseleaves of these bats act as resonance cavities. Using Rhinolophus rouxi as a model species, they reported that a resonance phenomenon causes the main beam to be elongated at a particular narrow frequency range. Virtually filling the furrows reduced the extent of the main lobe. However, the results of Zhuang & Muller are difficult to reconcile with the ecological background of R. rouxi. In this report, we replicate the study of Zhuang & Muller, and extend it in important ways: (i) we take the filtering of the moving pinnae into account, (ii) we use a model of the echolocation task faced by Rhinolophidae to estimate the effect of any alterations to the emission beam on the echolocation performance of the bat, and (iii) we validate our simulations using a physical mock-up of the morphology of R. rouxi. In contrast to Zhuang & Muller, we find the furrows to focus the emitted energy across the whole range of frequencies contained in the calls of R. rouxi (both in simulations and in measurements). Depending on the frequency, the focusing effect of the furrows has different consequences for the estimated echolocation performance. We argue that the furrows act to focus the beam in order to reduce the influence of clutter echoes.     

Air motion sensing hairs of arthropods detect high frequencies at near-maximal mechanical efficiency

Using measurements based on particle image velocimetry in combination with a novel compact theoretical framework to describe hair mechanics, we found that spider and cricket air motion sensing hairs work close to the physical limit of sensitivity and energy transmission in a broad range of relatively high frequencies. In this range, the hairs closely follow the motion of the incoming flow because a minimum of energy is dissipated by forces acting in their basal articulation. This frequency band is located beyond the frequency at which the angular displacement of the hair is maximum which is between about 40 and 600 Hz, depending on hair length (Barth et al. [1] Phil. Trans. R. Soc. Lond. B 340, 445–461 (doi:10.1098/rstb.1993.0084)). Given that the magnitude of natural airborne signals is known to decrease with frequency, our results point towards the possible existence of spectral signatures in the higher frequency range that may be weak but of biological significance.     

Quantification of the passive and active biaxial mechanical behaviour and microstructural organization of rat thoracic ducts

Mechanical loading conditions are likely to play a key role in passive and active (contractile) behaviour of lymphatic vessels. The development of a microstructurally motivated model of lymphatic tissue is necessary for quantification of mechanically mediated maladaptive remodelling in the lymphatic vasculature. Towards this end, we performed cylindrical biaxial testing of Sprague–Dawley rat thoracic ducts (n = 6) and constitutive modelling to characterize their mechanical behaviour. Spontaneous contraction was quantified at transmural pressures of 3, 6 and 9 cmH₂O. Cyclic inflation in calcium-free saline was performed at fixed axial stretches between 1.30 and 1.60, while recording pressure, outer diameter and axial force. A microstructurally motivated four-fibre family constitutive model originally proposed by Holzapfel et al. (Holzapfel et al. 2000 J. Elast. 61, 1–48. (doi:10.1023/A:1010835316564)) was used to quantify the passive mechanical response, and the model of Rachev and Hayashi was used to quantify the active (contractile) mechanical response. The average error between data and theory was 8.9 ± 0.8% for passive data and 6.6 ± 2.6% and 6.8 ± 3.4% for the systolic and basal conditions, respectively, for active data. Multi-photon microscopy was performed to quantify vessel wall thickness (32.2 ± 1.60 µm) and elastin and collagen organization for three loading conditions. Elastin exhibited structural ‘fibre families’ oriented nearly circumferentially and axially. Sample-to-sample variation was observed in collagen fibre distributions, which were often non-axisymmetric, suggesting material asymmetry. In closure, this paper presents a microstructurally motivated model that accurately captures the biaxial active and passive mechanical behaviour in lymphatics and offers potential for future research to identify parameters contributing to mechanically mediated disease development.     

New scaling relation for information transfer in biological networks

We quantify characteristics of the informational architecture of two representative biological networks: the Boolean network model for the cell-cycle regulatory network of the fission yeast Schizosaccharomyces pombe (Davidich et al. 2008 PLoS ONE 3, e1672 (doi:10.1371/journal.pone.0001672)) and that of the budding yeast Saccharomyces cerevisiae (Li et al. 2004 Proc. Natl Acad. Sci. USA 101, 4781–4786 (doi:10.1073/pnas.0305937101)). We compare our results for these biological networks with the same analysis performed on ensembles of two different types of random networks: Erdös–Rényi and scale-free. We show that both biological networks share features in common that are not shared by either random network ensemble. In particular, the biological networks in our study process more information than the random networks on average. Both biological networks also exhibit a scaling relation in information transferred between nodes that distinguishes them from random, where the biological networks stand out as distinct even when compared with random networks that share important topological properties, such as degree distribution, with the biological network. We show that the most biologically distinct regime of this scaling relation is associated with a subset of control nodes that regulate the dynamics and function of each respective biological network. Information processing in biological networks is therefore interpreted as an emergent property of topology (causal structure) and dynamics (function). Our results demonstrate quantitatively how the informational architecture of biologically evolved networks can distinguish them from other classes of network architecture that do not share the same informational properties.     

Homological scaffolds of brain functional networks

Networks, as efficient representations of complex systems, have appealed to scientists for a long time and now permeate many areas of science, including neuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci. 10, 186–198. (doi:10.1038/nrn2618)). Traditionally, the structure of complex networks has been studied through their statistical properties and metrics concerned with node and link properties, e.g. degree-distribution, node centrality and modularity. Here, we study the characteristics of functional brain networks at the mesoscopic level from a novel perspective that highlights the role of inhomogeneities in the fabric of functional connections. This can be done by focusing on the features of a set of topological objects—homological cycles—associated with the weighted functional network. We leverage the detected topological information to define the homological scaffolds, a new set of objects designed to represent compactly the homological features of the correlation network and simultaneously make their homological properties amenable to networks theoretical methods. As a proof of principle, we apply these tools to compare resting-state functional brain activity in 15 healthy volunteers after intravenous infusion of placebo and psilocybin—the main psychoactive component of magic mushrooms. The results show that the homological structure of the brain''s functional patterns undergoes a dramatic change post-psilocybin, characterized by the appearance of many transient structures of low stability and of a small number of persistent ones that are not observed in the case of placebo.     

Non-uniform breaking of molecular bonds,peripheral morphology and releasable adhesion by elastic anisotropy in bio-adhesive contacts

Biological adhesive contacts are usually of hierarchical structures, such as the clustering of hundreds of sub-micrometre spatulae on keratinous hairs of gecko feet, or the clustering of molecular bonds into focal contacts in cell adhesion. When separating these interfaces, releasable adhesion can be accomplished by asymmetric alignment of the lowest scale discrete bonds (such as the inclined spatula that leads to different peeling force when loading in different directions) or by elastic anisotropy. However, only two-dimensional contact has been analysed for the latter method (Chen & Gao 2007 J. Mech. Phys. Solids 55, 1001–1015 (doi:10.1016/j.jmps.2006.10.008)). Important questions such as the three-dimensional contact morphology, the maximum to minimum pull-off force ratio and the tunability of releasable adhesion cannot be answered. In this work, we developed a three-dimensional cohesive interface model with fictitious viscosity that is capable of simulating the de-adhesion instability and the peripheral morphology before and after the onset of instability. The two-dimensional prediction is found to significantly overestimate the maximum to minimum pull-off force ratio. Based on an interface fracture mechanics analysis, we conclude that (i) the maximum and minimum pull-off forces correspond to the largest and smallest contact stiffness, i.e. ‘stiff-adhere and compliant-release’, (ii) the fracture toughness is sensitive to the crack morphology and the initial contact shape can be designed to attain a significantly higher maximum-to-minimum pull-off force ratio than a circular contact, and (iii) since the adhesion is accomplished by clustering of discrete bonds or called bridged crack in terms of fracture mechanics terminology, the above conclusions can only be achieved when the bridging zone is significantly smaller than the contact size. This adhesion-fracture analogy study leads to mechanistic predictions that can be readily used to design biomimetics and releasable adhesives.     

Modelling the layer-specific three-dimensional residual stresses in arteries,with an application to the human aorta

This paper provides the first analysis of the three-dimensional state of residual stress and stretch in an artery wall consisting of three layers (intima, media and adventitia), modelled as a circular cylindrical tube. The analysis is based on experimental results on human aortas with non-atherosclerotic intimal thickening documented in a recent paper by Holzapfel et al. ( Holzapfel et al. 2007 Ann. Biomed. Eng. 35, 530–545 (doi:10.1007/s10439-006-9252-z)). The intima is included in the analysis because it has significant thickness and load-bearing capacity, unlike in a young, healthy human aorta. The mathematical model takes account of bending and stretching in both the circumferential and axial directions in each layer of the wall. Previous analysis of residual stress was essentially based on a simple application of the opening-angle method, which cannot accommodate the three-dimensional residual stretch and stress states observed in experiments. The geometry and nonlinear kinematics of the intima, media and adventitia are derived and the associated stress components determined explicitly using the nonlinear theory of elasticity. The theoretical results are then combined with the mean numerical values of the geometrical parameters and material constants from the experiments to illustrate the three-dimensional distributions of the stretches and stresses throughout the wall. The results highlight the compressive nature of the circumferential stress in the intima, which may be associated with buckling of the intima and its delamination from the media, and show that the qualitative features of the stretch and stress distributions in the media and adventitia are unaffected by the presence or absence of the intima. The circumferential residual stress in the intima increases significantly as the associated residual deformation in the intima increases while the corresponding stress in the media (which is compressive at its inner boundary and tensile at its outer boundary) is only slightly affected. The theoretical framework developed herein enables the state of residual stress to be calculated directly, serves to improve insight into the mechanical response of an unloaded artery wall and can be extended to accommodate more general geometries, kinematics and states of residual stress as well as more general constitutive models.     

Identification and analysis of circRNA–miRNA–mRNA regulatory network in hepatocellular carcinoma

This study was to identify important circRNA–miRNA–mRNA (ceRNAs) regulatory mechanisms in hepatocellular carcinoma (HCC). The circRNA dataset {"type":"entrez-geo","attrs":{"text":"GSE97332","term_id":"97332"}}GSE97332 and miRNA dataset {"type":"entrez-geo","attrs":{"text":"GSE57555","term_id":"57555"}}GSE57555 were used for analyses. Functional enrichment analysis for miRNA and target gene was conducted using cluster Profiler. Survival analysis was conducted through R package Survival. The ceRNAs and drug–gene interaction networks were constructed. The ceRNAs network contained five miRNAs including hsa‐miR‐25‐3p, hsa‐miR‐3692‐5p, hsa‐miR‐4270, hsa‐miR‐331‐3p, and hsa‐miR‐125a‐3p. Among the network, hsa‐miR‐25‐3p targeted the most genes, hsa‐miR‐3692‐5p and hsa‐miR‐4270 were targeted by more circRNAs than other miRNAs, hsa‐circ‐0034326 and hsa‐circ‐0011950 interacted with three miRNAs. Furthermore, target genes, including NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were obtained in drug–gene interaction network. Survival analysis showed NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were significantly associated with prognosis of HCC. NRAS, ITGA5, and SMAD2 were significantly enriched in proteoglycans in cancer. Moreover, hsa‐circ‐0034326 and hsa‐circ‐0011950 might function as ceRNAs to play key roles in HCC. Furthermore, miR‐25‐3p, miR‐3692‐5p, and miR‐4270 might be significant for HCC development. NRAS, ITGA5, SEC14L2, SLC12A5, and SMAD2 might be prognostic factors for HCC patients via proteoglycans in cancer pathway. Taken together, the findings will provide novel insight into pathogenesis, selection of therapeutic targets and prognostic factors for HCC.Inspec keywords: cancer, cellular biophysics, patient diagnosis, bioinformatics, tumours, biochemistry, molecular biophysics, genetics, drugs, RNAOther keywords: ITGA5, SMAD2, hsa‐circ‐0034326, SEC14L2, SLC12A5, target gene, survival analysis, drug–gene interaction network, miRNAs, hsa‐miR‐25‐3p, hsa‐miR‐3692‐5p, hsa‐miR‐4270, hsa‐miR‐331‐3p, hsa‐miR‐125a‐3p, hsa‐circ‐0011950, SLC7A1, pathogenesis, therapeutic targets, prognostic factors, circRNA‐miRNA‐mRNA regulatory network, current 125.0 A     

Preparation and Calibration of Carrier-Free 209Po Solution Standards

Carrier-free ²⁰⁹Po solution standards have been prepared and calibrated. The standards, which will be disseminated by the National Institute of Standards and Technology as Standard Reference Material SRM 4326, consist of (5.1597 ±0.0024) g of a solution of polonium in nominal 2 mol · L⁻¹ hydrochloric acid (having a solution density of (1.031±0.004) g · mL⁻¹ at 22 °C) that is contained in 5 mL flame-sealed borosilicate glass ampoules, and are certified to contain a ²⁰⁹Po alpha-particle emission rate concentration of (85.42±0.29) s⁻¹ · g⁻¹ (corresponding to a ²⁰⁹Po activity concentration of (85.83 ±0.30) Bq · g⁻¹) as of the reference time of 1200 EST 15 March 1994. The calibration was based on 4πα liquid scintillation (LS) measurements with two different LS counting systems and under wide variations in measurement and sample conditions. Confirmatory measurements by 2πα gas-flow proportional counting were also performed. The only known radionuclidic impurity, based on α- and photon-emission spectrometry, is a trace quantity of ²⁰⁸Po. The ²⁰⁸Po to ²⁰⁹Po impurity ratio as of the reference time was 0.00124 ±0.00020. All of the above cited uncertainty intervals correspond to a combined standard uncertainty multiplied by a coverage factor of k = 2. Although ²⁰⁹Po is nearly a pure α emitter with only a weak electron capture branch to ²⁰⁹Bi, LS measurements of the ²⁰⁹Po a decay are confounded by an a transition to a 2.3 keV (J^π= 1/2⁻) level in ²⁰⁵Pb which was previously unknown to be a delayed isomeric state.     

Transmission models indicate Ebola virus persistence in non-human primate populations is unlikely

Infectious diseases that kill their hosts may persist locally only if transmission is appropriately balanced by susceptible recruitment. Great apes die of Ebola virus disease (EVD) and have transmitted ebolaviruses to people. However, understanding the role that apes and other non-human primates play in maintaining ebolaviruses in Nature is hampered by a lack of data. Recent serological findings suggest that few non-human primates have antibodies to EVD-causing viruses throughout tropical Africa, suggesting low transmission rates and/or high EVD mortality (Ayouba A et al. 2019 J. Infect. Dis. 220, 1599–1608 (doi:10.1093/infdis/jiz006); Mombo IM et al. 2020 Viruses 12, 1347 (doi:10.3390/v12121347)). Here, stochastic transmission models of EVD in non-human primates assuming high case-fatality probabilities and experimentally observed or field-observed parameters did not allow viral persistence, suggesting that non-human primate populations are highly unlikely to sustain EVD-causing infection for prolonged periods. Repeated introductions led to declining population sizes, similar to field observations of apes, but not viral persistence.     

Green synthesis of colloidal gold nanoparticles using latex from Hevea brasiliensis and evaluation of their in vitro cytotoxicity and genotoxicity

Latex extracted from Hevea brasiliensis tree has been used as a green alternative for preparing gold nanoparticles (Au NPs); however, no study evaluating the cytotoxic and genotoxic potential of Au NPs synthesised using H. brasiliensis has been published. The present study aimed to synthesise and characterise colloidal Au NPs using latex from H. brasiliensis and to evaluate their in vitro cytotoxicity and genotoxicity. Ideal conditions for the green synthesis of Au NPs were studied. In vitro cytotoxicity and genotoxicity of Au NPs in CHO‐K1 cells was also evaluated. Our findings indicated that the ideal synthesis conditions of pH, temperature, reduction time, and concentrations of latex and HAuCl₄ were 7.0, 85°C, 120 min, 3.3 mg/mL, and 5.0 mmol/L, respectively. LC50_{24 h} of Au NPs was 119.164 ± 5.31 μg/mL. Lowest concentration of Au NPs tested presented minimal cytotoxicity and genotoxicity. However, high concentrations of Au NPs promoted DNA damage and cell death via apoptosis. On the basis of these findings, the authors optimised the use of an aqueous solution of H. brasiliensis latex as a reducing/stabilising agent for the green synthesis of Au NPs. Low concentrations of these NPs are biocompatible in normal cell types, suggesting that these NPs may be used in biological applications.Inspec keywords: nanofabrication, biomedical materials, nanomedicine, colloids, pH, cellular biophysics, nanoparticles, gold, DNA, reduction (chemical), molecular biophysics, materials preparation, geneticsOther keywords: colloidal Au NPs, genotoxicity, green synthesis, in vitro cytotoxicity, Hevea brasiliensis, colloidal gold nanoparticle, latex concentrations, DNA damage, cell death, H. brasiliensis latex, normal cell types, Au     

Facile nano‐free electrochemiluminescence biosensor for detection of sulphamethoxazole via tris(2,2′‐bipyridyl)ruthenium(II) and N ‐methyl pyrrolidone recognition

The electrochemiluminescence (ECL) system based on the ruthenium complex has become a powerful tool in the field of analytical chemistry. However, the non‐aqueous ECL luminescence system, which does not involve complex nano‐modification, has not been widely used for the determination of analytes. In this study, N ‐methyl pyrrolidone was selected as the solvent, and it could also act as a co‐reactant of Rubpy32+. Based on this, a simple ECL system without nanomaterials was established. Strong ECL was generated. Furthermore, a quenching effect between the excited state of Rubpy32+ and sulphamethoxazole (SMZ) was observed. Based on this, a sensitive ECL sensor for detecting SMZ is constructed. A linear relationship between ECL signal quenching intensity (ΔI) and the logarithm of SMZ concentration (log C) in the concentration range of 1 × 10⁻⁷ –1 × 10⁻⁵ mol/l is obtained. The limit of detection is as low as 3.33 × 10⁻⁹ mol/l. The method has been applied to the detection of SMZ in tap water samples with different concentration levels with satisfactory results, and the recovery was 95.3–102.6%.Inspec keywords: biosensors, electrochemical sensors, electroluminescence, chemiluminescence, organic compounds, electrochemistryOther keywords: ruthenium complex, analytical chemistry, nonaqueous ECL luminescence system, complex nanomodification, quenching effect, ECL signal quenching intensity, ECL sensor system, nanofree electrochemiluminescence biosensor system, sulphamethoxazole detection, tris(2,2′‐bipyridyl)ruthenium(II), N‐methyl pyrrolidone recognition, analyte determination, nanomaterials, SMZ concentration detection     

Antimicrobial activity of silver nanoparticles synthesised by using microbial biosurfactant produced by a newly isolated Bacillus vallismortis MDU6 strain

Microbial biosurfactants has evolved as green molecules and their chemical diversity has gained momentum in recent time not only in the field of environmental and industrial sectors but also in the pharmaceutical sector. In this study, an effort was made for the biosynthesis of silver nanoparticle (AgNPs) having antimicrobial and non‐cytotoxic activities with the help of microbial biosurfactant extracted from a novel Bacillus vallismortis strain MDU6 (Genbank accession no. {"type":"entrez-nucleotide","attrs":{"text":"MH382951","term_id":"1546647362"}}MH382951) from petroleum oil logged soil sample in Dibrugarh, Assam. The isolate shows excellent potential for the production of biosurfactant by reducing the surface tension of diesel supplemented medium up to 56.57% only within 5 days. FTIR spectra of the crude biosurfactant show the presence of ʋ _CH2 (asymmetric stretching), ʋ _CH2 (symmetric stretching), ʋ _C=C (stretch), ʋ _C−C (stretch), ʋ _C−H (bending), ʋ _C−O (stretch) and ʋ _C−H (bending) functional groups and LC‐MS/MS analysis confirms it as a cyclic lipopeptide which is a mixture of surfactin and iturin. The synthesized AgNPs showed excellent antimicrobial activities against Escherichia coli (ATCC no. 25922), Listeria monocytogenes (ATCC No. BAA‐751), Staphylococcus aureus (ATCC No. 9542) and Bacillus subtilis (ATCC no. 6051) and showed no cytotoxicity against primary mouse liver cell lines.Inspec keywords: nanoparticles, molecular biophysics, silver, liver, nanofabrication, microorganisms, petroleum, biotechnology, antibacterial activity, surfactants, cellular biophysics, toxicology, surface tension, nanomedicine, Fourier transform infrared spectraOther keywords: C−H functional groups, bending, synthesised AgNPs, excellent antimicrobial activities, ATCC no, bacillus subtilis, antimicrobial activity, silver nanoparticles, bacillus vallismortis MDU6 strain, microbial biosurfactants, green molecules, chemical diversity, environmental sectors, industrial sectors, pharmaceutical sector, noncytotoxic activities, petroleum oil, soil sample, isolate, surface tension, crude biosurfactant show, asymmetric stretching, symmetric stretching, Genbank accession no. {"type":"entrez-nucleotide","attrs":{"text":"MH382951","term_id":"1546647362"}}MH382951, time 5.0 d, Ag     

Inhibition of Fusarium oxysporum by AgNPs biosynthesised using Cinnamomum camphora fruit extract

Cinnamomum camphora fruit extract was used to biosynthesise silver nanoparticles (AgNPs), and the optimised synthesis system was ascertained through solution colour change and ultraviolet–visible absorption spectra. It contained 20 ml of fruit extract, 4 mM Ag nitrate, and pH 7. AgNPs obtained based on such conditions were spherical and finely dispersed, with an average size of 20.3 nm. As‐synthesised AgNPs exhibited excellent antifungal effect against Fusarium oxysporum. At a dose of 400 μg/ml of AgNPs, the inhibition rate of colony growth reached 61.00% and an IC₅₀ value of 154.39 μg/ml. In addition, the conidia germination was totally inhibited at 100 μg/ml of AgNPs. Results of this study provide a new approach for biological control of plant pathogenic fungi, and it makes that possible for developing a brand new fungistat.Inspec keywords: nanoparticles, microorganisms, agricultural products, nanobiotechnology, silver, antibacterial activity, nanomedicine, pharmaceutical technologyOther keywords: fusarium oxysporum, cinnamomum camphora fruit extract, biosynthesis, silver nanoparticles, antifungal effect, conidia germination, plant pathogenic fungi, Ag