Live to cheat another day: bacterial dormancy facilitates the social exploitation of beta-lactamases

The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours

Nonlinear Site Response During the 7 September 1999 Athens, Greece, Earthquake (M\u3csub\u3eW\u3c/sub\u3e 5.6)

The largest available strong-motion recording (PGA=0.35g), least affected by topography, structural response and/or soil-structure interaction, is investigated for possible nonlinear site response during the M, 5.9 Athens earthquake of 7 September 1999. Smoothed horizontal-to-vertical spectral ratios (HVSR) are calculated in subsequent overlapping 3.5-s windows, thus covering a wide range of excitation levels. Mean HVSR curves are computed for a so-called “weak-“ and “strong-“ motion range (mean horizontal ground acceleration in window, MGA\u3c=10.2 cm/s/s and \u3e=20.5 cm/s/s). The two curves have similar shape, with the “strong” curve visibly shifted toward lower frequencies relative to the “weak” one; the dominant site resonance occurs at 4.0 Hz (0.25 s) and 4.7 Hz (0.21 s), respectively. Linear correlation analysis shows that the resonance frequency, f0, and MGA are significantly correlated (t=-0.661). We attribute this behaviour to the degradation of the sediment shear modulus (nonlinearity). Our results, combined with indications that sediment sites in the near-fault area were exposed to ground shaking well above PGA=0.35 g during the earthquake of 7 September 1999, imply that these sites exhibited considerable nonlinear response

Bacteria from natural populations transfer plasmids mostly towards their kin

This is the final version. Available on open access from the Royal Society via the DOI in this recordData accessibility: The datasets supporting this article are available from the Dryad Digital Repository at https://doi.org/10.5061/dryad.ff045t7 [52].Plasmids play a key role in microbial ecology and evolution, yet the determinants of plasmid transfer rates are poorly understood. Particularly, interactions between donor hosts and potential recipients are understudied. Here, we investigate the importance of genetic similarity between naturally co-occurring Escherichia coli isolates in plasmid transfer. We uncover extensive variability, spanning over five orders of magnitude, in the ability of isolates to donate and receive two different plasmids, R1 and RP4. Overall, transfer is strongly biased towards clone-mates, but not correlated to genetic distance when donors and recipients are not clone-mates. Transfer is limited by the presence of a functional restriction-modification system in recipients, suggesting sharing of strain-specific defence systems contributes to bias towards kin. Such restriction of transfer to kin sets the stage for longer-term coevolutionary interactions leading to mutualism between plasmids and bacterial hosts in natural communities.Medical Research Council (MRC

Bacteria from natural populations transfer plasmids mostly towards their kin

This is the final version. Available on open access from the Royal Society via the DOI in this recordData accessibility: The datasets supporting this article are available from the Dryad Digital Repository at https://doi.org/10.5061/dryad.ff045t7 [52].Plasmids play a key role in microbial ecology and evolution, yet the determinants of plasmid transfer rates are poorly understood. Particularly, interactions between donor hosts and potential recipients are understudied. Here, we investigate the importance of genetic similarity between naturally co-occurring Escherichia coli isolates in plasmid transfer. We uncover extensive variability, spanning over five orders of magnitude, in the ability of isolates to donate and receive two different plasmids, R1 and RP4. Overall, transfer is strongly biased towards clone-mates, but not correlated to genetic distance when donors and recipients are not clone-mates. Transfer is limited by the presence of a functional restriction-modification system in recipients, suggesting sharing of strain-specific defence systems contributes to bias towards kin. Such restriction of transfer to kin sets the stage for longer-term coevolutionary interactions leading to mutualism between plasmids and bacterial hosts in natural communities.Medical Research Council (MRC

Coronary atherosclerosis scoring with semiquantitative CCTA risk scores for prediction of major adverse cardiac events: Propensity score-based analysis of diabetic and non-diabetic patients.

AIMS:We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS:Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS:A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION:Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone

Single-Cell Multiomics Techniques: From Conception to Applications

Recent advances in methods for single-cell analyses and barcoding strategies have led to considerable progress in research. The development of multiplexed assays offers the possibility to conduct parallel analyses of multiple factors and processes for comprehensive characterization of cellular and molecular states in health and disease. These technologies have expanded extremely rapidly in the past years and constantly evolve and provide better specificity, precision and resolution. This review summarizes recent progress in single-cell multiomics approaches, and focuses, in particular, on the most innovative techniques that integrate genome, epigenome and transcriptome profiling. It describes the methodologies, discusses their advantages and limitations, and explains how they have been applied to studies on cell heterogeneity and differentiation, and epigenetic reprogramming. Keywords: chromatin accessibility; epigenomics; genomics; multiomics; single-cell; transcriptomic

Evolutionary dynamics of cancer cell populations under immune selection pressure and optimal control of chemotherapy

Increasing experimental evidence suggests that epigenetic and microenvironmental factors play a key role in cancer progression. In this respect, it is now generally recognized that the immune system can act as an additional selective pressure, which modulates tumor development and leads, through cancer immunoediting, to the selection for resistance to immune effector mechanisms. This may have serious implications for the design of effective anti-cancer protocols. Motivated by these considerations, we present a mathematical model for the dynamics of cancer and immune cells under the effects of chemotherapy and immunity-boosters. Tumor cells are modeled as a population structured by a continuous phenotypic trait, that is related to the level of resistance to receptor-induced cell death triggered by effector lymphocytes. The level of resistance can vary over time due to the effects of epigenetic modifications. In the asymptotic regime of small epimutations, we highlight the ability of the model to reproduce cancer immunoediting. In an optimal control framework, we tackle the problem of designing effective anti-cancer protocols. The results obtained suggest that chemotherapeutic drugs characterized by high cytotoxic effects can be useful for treating tumors of large size. On the other hand, less cytotoxic chemotherapy in combination with immunity-boosters can be effective against tumors of smaller size. Taken together, these results support the development of therapeutic protocols relying on combinations of less cytotoxic agents and immune-boosters to fight cancer in the early stages. © EDP Sciences, 2014

Study the Effect of UVC Radiation on Specific Regions of the SARS-CoV-2 Coronavirus Genome Encoding the Synthesis of Structural Proteins

Only AbstractThe COVID19 pandemic that terrorizes the world with terrible aggression calls for the urgent finding of tools that would quickly inactivate viruses in the environment to reduce the chance of aerosol infection and contact transmission. For the inactivation of SARS – CoV – 2 viruses we used LEDs with maximum emission on the wavelength 255 ± 5nm. All sources of UVC bactericidal radiation have emission peaks close to the center of the DNA and RNA absorption spectrum and may underlie devices and therapies to disrupt the spread of infection. We studied the inactivation of SARS – CoV – 2 viruses by annihilating the structural components of the viruses that manifest in the amplification process in the PCR procedure

Concentric double hollow grid cathode discharges

A new cathode system, consisting of two concentric spherical hollow grids with two aligned orifices, is investigated by space-resolved Langmuir probe measurements and non-linear dynamics analysis. Negative biases of this spherical hollow grids arrangement lead to the formation of two complex space charge structures in the regions of the orifices. The overall dynamics of the current-voltage characteristic (I–V characteristic) of each discharge is characterized by strong oscillatory behaviour with various waveforms correlated with jumps in the static I–V characteristics. Space-resolved measurements through the two aligned orifices of the two grids show a peak increase of the electron temperature and particle density in the regions of the two space-charge structures. The effects of the biases and Ar pressure on the overall spatial distribution of all plasma parameters are investigated. Two important working points of the concentric double hollow grid cathode discharges are revealed which could make this configuration suitable as an electron source