Direct entry by RNase E is a major pathway for the degradation and processing of RNA in Escherichia coli

Escherichia coli endoribonuclease E has a major influence on gene expression. It is essential for the maturation of ribosomal and transfer RNA as well as the rapid degradation of messenger RNA. The latter ensures that translation closely follows programming at the level of transcription. Recently, one of the hallmarks of RNase E, i.e. its ability to bind via a 5'-monophosphorylated end, was shown to be unnecessary for the initial cleavage of some polycistronic tRNA precursors. Here we show using RNA-seq analyses of ribonuclease-deficient strains in vivo and a 5'-sensor mutant of RNase E in vitro that, contrary to current models, 5'-monophosphate-independent, 'direct entry' cleavage is a major pathway for degrading and processing RNA. Moreover, we present further evidence that direct entry is facilitated by RNase E binding simultaneously to multiple unpaired regions. These simple requirements may maximize the rate of degradation and processing by permitting multiple sites to be surveyed directly without being constrained by 5'-end tethering. Cleavage was detected at a multitude of sites previously undescribed for RNase E, including ones that regulate the activity and specificity of ribosomes. A potentially broad role for RNase G, an RNase E paralogue, in the trimming of 5'-monophosphorylated ends was also revealed

Dataset related to "A multicentric, single arm, prospective, stratified clinical investigation to evaluate MammoWave’s ability in breast lesions detection"

Microwave imaging is a safe and promising new technology in breast radiology, avoiding discomfort of breast compression and usage of ionizing radiation. This dataset relates to a paper which presents the first prospective microwave breast imaging study during which both symptomatic and asymptomatic subjects were recruited. Specifically, a prospective multicentre international clinical trial was performed in 2020-2021, to investigate the capability of a microwave imaging device (MammoWave) in allowing distinction between breasts with no radiological finding (NF) and breasts with radiological findings (WF), i.e., with benign or malignant lesions. Each breast scan was performed with the volunteers lying on a dedicated examination table in a comfortable prone position. MammoWave output was compared to reference standard (i.e., radiologic study obtained within the last month and integrated with histological one if available and deemed necessary by responsible investigator) to classify breasts into NF/WF categories. MammoWave output consists of a selection of microwave images’ features (determined prior to trials’ start), which allow distinction between NF and WF breasts (using statistical significance p<0.05). 353 women were enrolled in the study (mean age 51 years ± 12 [SD], minimum age 19, maximum age 78); MammoWave data from the first 15 women of each site, all with NF breasts, were used for calibration. Following central assessor evaluation, 111 NF (48 dense) and 272 WF (136 dense) breasts were used for comparison with MammoWave output. 272 WF comprised 182 benign findings and 90 malignant histology-confirmed cancer. A sensitivity of 82.3% was achieved (95%CI: 0.78-0.87); sensitivity is maintained when limiting the investigation to histology-confirmed breasts cancer only (90 histology-confirmed breasts cancer have been included in this analysis, having sizes ranging from 3 mm to 60 mm). Specificity value of approximately 50% was achieved as expected, since thresholds were calculated (for each feature) using median value obtained after recruiting the first 15 women (of each site), all NF. This prospective trial may represent another step for introducing microwave imaging into clinical practice, for helping in breast lesion identification in asymptomatic women

Energy and Flux Measurements of Ultra-High Energy Cosmic Rays Observed During the First ANITA Flight

The first flight of the Antarctic Impulsive Transient Antenna (ANITA) experiment recorded 16 radio signals that were emitted by cosmic-ray induced air showers. For 14 of these events, this radiation was reflected from the ice. The dominant contribution to the radiation from the deflection of positrons and electrons in the geomagnetic field, which is beamed in the direction of motion of the air shower. This radiation is reflected from the ice and subsequently detected by the ANITA experiment at a flight altitude of 36km. In this paper, we estimate the energy of the 14 individual events and find that the mean energy of the cosmic-ray sample is 2.9 EeV. By simulating the ANITA flight, we calculate its exposure for ultra-high energy cosmic rays. We estimate for the first time the cosmic-ray flux derived only from radio observations. In addition, we find that the Monte Carlo simulation of the ANITA data set is in agreement with the total number of observed events and with the properties of those events.Comment: Added more explanation of the experimental setup and textual improvement

A multicentric, single arm, prospective, stratified clinical investigation to evaluate MammoWave’s ability in breast lesions detection

Microwave imaging is a safe and promising new technology in breast radiology, avoiding discomfort of breast compression and usage of ionizing radiation. This paper presents the first prospective microwave breast imaging study during which both symptomatic and asymptomatic subjects were recruited. Specifically, a prospective multicentre international clinical trial was performed in 2020-2021, to investigate the capability of a microwave imaging device (MammoWave) in allowing distinction between breasts with no radiological finding (NF) and breasts with radiological findings (WF), i.e., with benign or malignant lesions. Each breast scan was performed with the volunteers lying on a dedicated examination table in a comfortable prone position. MammoWave output was compared to reference standard (i.e., radiologic study obtained within the last month and integrated with histological one if available and deemed necessary by responsible investigator) to classify breasts into NF/WF categories. MammoWave output consists of a selection of microwave images’ features (determined prior to trials’ start), which allow distinction between NF and WF breasts (using statistical significance p<0.05). 353 women were enrolled in the study (mean age 51 years ± 12 [SD], minimum age 19, maximum age 78); MammoWave data from the first 15 women of each site, all with NF breasts, were used for calibration. Following central assessor evaluation, 111 NF (48 dense) and 272 WF (136 dense) breasts were used for comparison with MammoWave output. 272 WF comprised 182 benign findings and 90 malignant histology-confirmed cancer. A sensitivity of 82.3% was achieved (95%CI: 0.78-0.87); sensitivity is maintained when limiting the investigation to histology-confirmed breasts cancer only (90 histology-confirmed breasts cancer have been included in this analysis, having sizes ranging from 3 mm to 60 mm). Specificity value of approximately 50% was achieved as expected, since thresholds were calculated (for each feature) using median value obtained after recruiting the first 15 women (of each site), all NF. This prospective trial may represent another step for introducing microwave imaging into clinical practice, for helping in breast lesion identification in asymptomatic women

Cherenkov radio pulses from electromagnetic showers in the time-domain

The electric field of the Cherenkov radio pulse produced by a single charged particle track in a dielectric medium is derived from first principles. An algorithm is developed to obtain the pulse in the time domain for numerical calculations. The algorithm is implemented in a Monte Carlo simulation of electromagnetic showers in dense media (specifically designed for coherent radio emission applications) as might be induced by interactions of ultra-high energy neutrinos. The coherent Cherenkov radio emission produced by such showers is obtained simultaneously both in the time and frequency domains. A consistency check performed by Fourier-transforming the pulse in time and comparing it to the frequency spectrum obtained directly in the simulations yields, as expected, fully consistent results. The reversal of the time structure inside the Cherenkov cone and the signs of the corresponding pulses are addressed in detail. The results, besides testing algorithms used for reference calculations in the frequency domain, shed new light into the properties of the radio pulse in the time domain. The shape of the pulse in the time domain is directly related to the depth development of the excess charge in the shower and its width to the observation angle with respect to the Cherenkov direction. This information can be of great practical importance for interpreting actual data.Comment: 10 pages, 4 figure

Mitochondrial respiration variability and simulations in human skeletal muscle: The Gene SMART study

Mitochondrial respiration using the oxygraph‐2k respirometer (Oroboros) is widely used to estimate mitochondrial capacity in human skeletal muscle. Here, we measured mitochondrial respiration variability, in a relatively large sample, and for the first time, using statistical simulations, we provide the sample size required to detect meaningful respiration changes following lifestyle intervention. Muscle biopsies were taken from healthy, young men from the Gene SMART cohort, at multiple time points. We utilized samples for each measurement with two technical repeats using two respirometer chambers (n = 160 pairs of same muscle after removal of low‐quality samples). We measured the Technical Error of measurement (TEM) and the coefficient of variation (CV) for each mitochondrial complex. There was a high correlation between measurements from the two chambers (R > 0.7 P 15% for all complexes. We performed statistical simulations of a range of effect sizes at 80% power and found that 75 participants (with duplicate measurements) are required to detect a 6% change in mitochondrial respiration after an intervention, while for interventions with 11% effect size, ~24 participants are sufficient. The high variability in respiration suggests that the typical sample sizes in exercise studies may not be sufficient to capture exercise‐induced changes

Dielectric Characterization of Breast Biopsied Tissues as Pre-Pathological Aid in Early Cancer Detection: A Blinded Feasibility Study

Dielectric characterization has significant potential in several medical applications, providing valuable insights into the electromagnetic properties of biological tissues for disease diagnosis, treatment planning, and monitoring of therapeutic interventions. This work presents the use of a custom-designed electromagnetic characterization system, based on an open-ended coaxial probe, for discriminating between benign and malignant breast tissues in a clinical setting. The probe’s development involved a well-balanced compromise between physical feasibility and its combined use with a reconstruction algorithm known as the virtual transmission line model (VTLM). Immediately following the biopsy procedure, the dielectric properties of the breast tissues were reconstructed, enabling tissue discrimination based on a rule-of-thumb using the obtained dielectric parameters. A comparative analysis was then performed by analyzing the outcomes of the dielectric investigation with respect to conventional histological results. The experimental procedure took place at Complejo Hospitalario Universitario de Toledo—Hospital Virgen de la Salud, Spain, where excised breast tissues were collected and subsequently analyzed using the dielectric characterization system. A comprehensive statistical evaluation of the probe’s performance was carried out, obtaining a sensitivity, specificity, and accuracy of 81.6%, 61.5%, and 73.4%, respectively, compared to conventional histological assessment, considered as the gold standard in this investigation

Practical and accurate calculations of Askaryan radiation

An in-depth characterization of coherent radio Cherenkov pulses from particle showers in dense dielectric media, referred to as the Askaryan effect, is presented. The time-domain calculation developed in this article is based on a form factor to account for the lateral dimensions of the shower. It is computationally efficient and able to reproduce the results of detailed particle shower simulations with high fidelity in most regions of practical interest including Fresnel effects due to the longitudinal development of the shower. In addition, an intuitive interpretation of the characteristics of the Askaryan pulse is provided. We expect our approach to benefit the analysis of radio pulses in experiments exploiting the radio technique.Comment: Replaced with version published Phys. Rev.

Which blazars are neutrino loud?

Protons accelerated in the cores of active galactic nuclei can effectively produce neutrinos only if the soft radiation background in the core is sufficiently high. We find restrictions on the spectral properties and luminosity of blazars under which they can be strong neutrino sources. We analyze the possibility that neutrino flux is highly beamed along the rotation axis of the central black hole. The enhancement of neutrino flux compared to GeV gamma-ray flux from a given source makes the detection of neutrino point sources more probable. At the same time the smaller open angle reduces the number of possible neutrino-loud blazars compared to the number of gamma-ray loud ones. We present the table of 15 blazars which are the most likely candidates for the detection by future neutrino telescopes.Comment: 9 pages, 5 figures, version to be published in PR