Bacteriophage Infection of the Marine Bacterium Shewanella glacialimarina Induces Dynamic Changes in tRNA Modifications.

Viruses are obligate intracellular parasites that, throughout evolution, have adapted numerous strategies to control the translation machinery, including the modulation of post-transcriptional modifications (PTMs) on transfer RNA (tRNA). PTMs are critical translation regulators used to further host immune responses as well as the expression of viral proteins. Yet, we lack critical insight into the temporal dynamics of infection-induced changes to the tRNA modification landscape (i.e., 'modificome'). In this study, we provide the first comprehensive quantitative characterization of the tRNA modificome in the marine bacterium Shewanella glacialimarina during Shewanella phage 1/4 infection. Specifically, we show that PTMs can be grouped into distinct categories based on modification level changes at various infection stages. Furthermore, we observe a preference for the UAC codon in viral transcripts expressed at the late stage of infection, which coincides with an increase in queuosine modification. Queuosine appears exclusively on tRNAs with GUN anticodons, suggesting a correlation between phage codon usage and PTM modification. Importantly, this work provides the basis for further studies into RNA-based regulatory mechanisms employed by bacteriophages to control the prokaryotic translation machinery.

Impact of Clostridioides difficile Therapy on Nosocomial Acquisition of Vancomycin-Resistant Enterococci.

Vancomycin is frequently used for the treatment of C. difficile infections (CDI). There are concerns that this might increase the risk of selecting vancomycin resistant enterococci (VRE). Here, we evaluated whether there is an increased risk of VRE acquisition following vancomycin for CDI specific treatment. Patients with CDI, metronidazole, or oral vancomycin treatment and without preexisting VRE were monitored for VRE acquisition. VRE isolates from patients with acquired and preexisting colonization were collected and subjected to whole genome sequencing. In total, 281 patients (median age 56 years, 54% of the male sex) presented with toxin positive C. difficile. Of them, 170 patients met the inclusion criteria, comprising 37 patients treated with metronidazole and 133 treated with oral vancomycin. In total, 14 patients meeting the inclusion criteria acquired VRE (vancomycin: n = 11; metronidazole: n = 3). Statistical analysis revealed no significant differences between both VRE acquisition rates. Genetic comparison of detected VRE isolates resulted in eight clusters of closely related genotypes comprising acquired and preexisting strains. Our results suggest that vancomycin and metronidazole likewise increase the risk of VRE acquisition. Genetic comparison indicates that VRE acquisition is a result of both antibiotic selection and pathogen transmission.

Structural basis of successive adenosine modifications by the conserved ribosomal methyltransferase KsgA.

Biogenesis of ribosomal subunits involves enzymatic modifications of rRNA that fine-tune functionally important regions. The universally conserved prokaryotic dimethyltransferase KsgA sequentially modifies two universally conserved adenosine residues in helix 45 of the small ribosomal subunit rRNA, which is in proximity of the decoding site. Here we present the cryo-EM structure of Escherichia coli KsgA bound to an E. coli 30S at a resolution of 3.1 Å. The high-resolution structure reveals how KsgA recognizes immature rRNA and binds helix 45 in a conformation where one of the substrate nucleotides is flipped-out into the active site. We suggest that successive processing of two adjacent nucleotides involves base-flipping of the rRNA, which allows modification of the second substrate nucleotide without dissociation of the enzyme. Since KsgA is homologous to the essential eukaryotic methyltransferase Dim1 involved in 40S maturation, these results have also implications for understanding eukaryotic ribosome maturation.

[Trivialization of prostate cancer? : Stage shift and possible causes]. / Bagatellisierung des Prostatakarzinoms? : Stadien-Shift und mögliche Ursachen.

BACKGROUND: According to the strongly negative grade D recommendation of the U.S. Preventive Services Task Force in 2012, the prostate-specific antigen (PSA) test was not only not recommended but was also warned against. As a result in the USA there was a stage shift towards more advanced tumor stages under the newly detected prostate cancers; however, in contrast to the highly questionable American PLCO study, the European ERSPC study showed a clear reduction in prostate cancer-related mortality. OBJECTIVE: In this patient cohort it was investigated whether the tumor stage distribution in curatively treated prostate cancer has significantly changed, whether this has an influence on the perioperative results and complication rates and how these changes could have occurred. MATERIAL AND METHODS: Patients after radical prostatectomy from 2008 to 2010 were compared to those from 2017. Demographic data, intraoperative courses, perioperative and postoperative complications and histopathological results were compared. RESULTS: A total of 1276 operations were analyzed. Preoperative PSA levels showed a significant increase in 2017 (10.5 ± 13.4 ng/ml vs. 8.4 ± 9.1 ng/ml, p = 0.032). The pathological staging revealed a 20% increase in T3 tumors (49.4% versus 29.0%, p < 0.001). Correspondingly, moderately and poorly differentiated cancers and therefore those with higher aggressiveness were significantly more frequent with 11.2% (p < 0.001) and 10.4% (p < 0.001), respectively. The number of patients with lymph node metastases at prostatectomy even increased fourfold (4.5% vs. 16.9%, p < 0.001). CONCLUSION: In the radical prostatectomy group, there was a shift to unfavorable and metastatic tumor stages. This negative trend seems largely to be caused by a lower acceptance of early detection by means of PSA determination.

The Effects of Naturalistic Light on Diurnal Plasma Melatonin and Serum Cortisol Levels in Stroke Patients during Admission for Rehabilitation: A Randomized Controlled Trial.

Background: Stroke patients admitted for rehabilitation often lack sufficient daytime blue light exposure due to the absence of natural light and are often exposed to light at unnatural time points. We hypothesized that artificial light imitating daylight, termed naturalistic light, would stabilize the circadian rhythm of plasma melatonin and serum cortisol levels among long-term hospitalized stroke patients. Methods: A quasi-randomized controlled trial. Stroke patients in need of rehabilitation were randomized between May 1, 2014, and June 1, 2015 to either a rehabilitation unit equipped entirely with always on naturalistic lighting (IU), or to a rehabilitation unit with standard indoor lighting (CU). At both inclusion and discharge after a hospital stay of at least 2 weeks, plasma melatonin and serum cortisol levels were measured every 4 hours over a 24-hour period. Circadian rhythm was estimated using cosinor analysis, and variance between time-points. Results: A total of 43 were able to participate in the blood collection. Normal diurnal rhythm of melatonin was disrupted at both inclusion and discharge. In the IU group, melatonin plasma levels were increased at discharge compared to inclusion (n = 23; median diff, 2.9; IQR: -1.0 to 9.9, p = 0.030) and rhythmicity evolved (n = 23; p = 0.007). In the CU group, melatonin plasma levels were similar between discharge and inclusion and no rhythmicity evolved. Overall, both patient groups showed normal cortisol diurnal rhythms at both inclusion and discharge. Conclusions: This study is the first to demonstrate elevated melatonin plasma levels and evolved rhythmicity due to stimulation with naturalistic light.

Selective parallel integration of individual metallic single-walled carbon nanotubes from heterogeneous solutions.

The dielectrophoretic separation of individual metallic single-walled carbon nanotubes (SWNTs) from heterogeneous solutions and their simultaneous deposition between electrodes is achieved and confirmed by direct electric transport measurements. Out-of-solution guided parallel assembly of individual SWNTs was investigated for electric field frequencies between 1 and 200 MHz. At 200 MHz, 19 of the 22 deposited SWNTs (86%) displayed metallic behavior, whereas at lower frequencies the expected random growth distribution of 1/3 metallic SWNTs prevailed. A threshold separation frequency of 188 MHz is extracted from a surface-conductivity model, and a conductivity weighting factor is introduced to elucidate the separation frequency dependence. Low-frequency experiments and numerical simulations show that long-range nanotube transport is governed by hydrodynamic effects whereas local trapping is dominated by dielectrophoretic forces. The electrokinetic framework of dielectrophoresis in low-concentration solutions is thus provided and allows a deeper understanding of the underlying mechanisms in dielectrophoretic deposition processes for long and large-diameter SWNT-based low-resistance device integration.

An electrical method for the measurement of the thermal and electrical conductivity of reduced graphene oxide nanostructures.

This paper introduces an electrical four-point measurement method enabling thermal and electrical conductivity measurements of nanoscale materials. The method was applied to determine the thermal and electrical conductivity of reduced graphene oxide flakes. The dielectrophoretically deposited samples exhibited thermal conductivities in the range of 0.14-2.87 W m(-1) K(-1) and electrical conductivities in the range of 6.2 x 10(2)-6.2 x 10(3) Omega(-1) m(-1). The measured properties of each flake were found to be dependent on the duration of the thermal reduction and are in this sense controllable.

Aqueous dispersion and dielectrophoretic assembly of individual surface-synthesized single-walled carbon nanotubes.

The successful dispersion and large-scale parallel assembly of individual surface-synthesized large-diameter (1-3 nm) single-walled carbon nanotubes (SWNTs), grown by chemical vapor deposition (CVD), is demonstrated. SWNTs are removed from the growth substrate by a short, low-energy ultrasonic pulse to produce ultrapure long-term stable surfactant-stabilized solutions. Subsequent dielectrophoretic deposition bridges individual, straight, and long SWNTs between two electrodes. Electrical characterization on 223 low-resistance devices (R(average) approximately 200 kOmega) evidences the high quality of the SWNT raw material, prepared solution, and contact interface. The research reported herein provides an important framework for the large-scale industrial integration of carbon nanotube-based devices, sensors, and applications.

Antennulary sensory organs in cyprids of Octolasmis and Lepas (Crustacea: Thecostraca: Cirripedia: Thoracica): a scanning electron microscopic study.

Cypris larvae of the pedunculate barnacles Octolasmis angulata (Poecilasmatidae), Lepas australis, L. pectinata, and Dosima fascicularis (Lepadidae) were studied with scanning electron microscopy, focusing on the sensory setae and the attachment disc on the antennules. The antennules of O. angulata did not exhibit any remarkable trait, but carry the same number of setae as seen in most other thoracicans. The third segment is bell-shaped and quite distinct from the second and its attachment disc is surrounded by a skirt. We found several potential synapomorphies in antennulary morphology between cyprids of the lepadid species but none of them were shared with the cyprids of Octolasmis; the list of unique lepadid characters includes: one additional, preaxial seta on the second segment; multiple similar (up to eight) postaxial setae (PS3) on the third segment, unlike all other thoracicans, where there is only a single PS3; the third segment consists almost entirely of the attachment disc, which is distended and surrounded by two parallel rows of radial setae; on the fourth segment the terminal seta E is diminutive. We found no traits in cyprids of Octolasmis that seem to be adaptations to their attachment site within the branchial chamber of swimming crabs and, in particular, no similarities with cyprids of rhizocephalan barnacles, many of which also attach in the gill chamber. The synapomorphies between cyprids of the lepadid species may be adaptations to their life in the neuston.

Epicardial electrical activation analyzed via frequency-wavenumber spectrum estimation for the characterization of arrhythmiagenic states.

The application of a new signal processing methodology to the analysis of epicardial array ECG signals is presented as an alternative to isopotential or isochrones mapping by the use of a zero-delay wavenumber spectrum (ZDWS) estimation technique. The methodology "explains" the array data as the sum of modulated wideband (non-sinusoidal) propagating waves projected onto the array plane and provides an accurate estimate of their number and bearing. The slowness distribution of each of the waves is then obtained by estimating their temporal spectrum. In this experimental study the effects of localized noninfarcting reversible low flow ischemia, digoxin toxicity and verapamil reversal of digoxin toxicity are quantified via the ZDWS methodology and are compared with the information that can be extracted from isopotential mapping. It is demonstrated that the ZDWS methodology permits the epicardial electric activation to be decomposed into a number of quantification parameters which possess a hierarchical "tree" structure and therefore provide a means for an objective and robust characterization of the effects of agents which alter myocardial conduction and arrhythmia generation.