Dissipative control over the toehold-mediated DNA strand displacement reaction

Here we show a general approach to achieve dissipative control over toehold-mediated strand-displacement, the most widely employed reaction in the field of DNA nanotechnology. The approach relies on rationally re-engineering the classic strand displacement reaction such that the high-energy invader strand (fuel) is converted into a low-energy waste product through an energy-dissipating reaction allowing the spontaneous return to the original state over time. We show that such dissipative control over the toehold-mediated strand displacement process is reversible (up to 10 cycles), highly controllable and enables unique temporal activation of DNA systems. We show here two possible applications of this strategy: the transient labelling of DNA structures and the additional temporal control of cascade reactions

Spontaneous reorganization of DNA-based polymers in higher ordered structures fueled by RNA

We demonstrate a strategy that allows for the spontaneous reconfiguration of self-assembled DNA polymers exploiting RNA as chemical fuel. To do this, we have rationally designed orthogonally addressable DNA building blocks that can be transiently deactivated by RNA fuels and subtracted temporarily from participation in the self-assembly process. Through a fine modulation of the rate at which the building blocks are reactivated we can carefully control the final composition of the polymer and convert a disordered polymer in a higher order polymer, which is disfavored from a thermodynamic point of view. We measure the dynamic reconfiguration via fluorescent signals and confocal microscopy, and we derive a kinetic model that captures the experimental results. Our approach suggests a novel route toward the development of biomolecular materials in which engineered chemical reactions support the autonomous spatial reorganization of multiple components

Role of narrow band imaging (NBI), in the treatment of non-polypoid colorectal lesions, with endoscopic mucosal resection (EMR). A single-center experience

BACKGROUND: In this study, the authors evaluated the role of narrow band imaging endoscopy in the early detection of infiltration of the colon wall by flat and depressed lesions, highlighted during colonoscopy, to confirm the possibility of removal with Endoscopic Mucosal Resection (EMR). METHODS: 67 patients (37 males and 30 females) with non-polypoid colorectal lesions were included in this study. The location of the lesions, the size and possible infiltration of the colon wall were performed with a colonoscopy with NBI. Lesions without massive invasion were treated with an EMR. RESULTS: NBI was found to be a sensitive, specific, and accurate technique in assessing any infiltration of the colon wall. Endoscopic resection of the mucous membrane was successfully performed in 62 patients, it was not possible to perform it in 5 patients, due to the lack of dissection, and they underwent surgery. CONCLUSIONS: Non-polypoid colorectal lesions and early tumors can be treated with EMR. Certainly, early detection with Narrow Band Imaging endoscopy and subsequent endoscopic resection can reduce colorectal cancer mortality. Many studies have confirmed that these two methods have achieved important results comparable with surgical procedures. KEY WORDS: Endoscopic Mucosal Resection, Narrow Band Imaging, Therapy

Characterization of Salmonella Occurring at High Prevalence in a Population of the Land Iguana Conolophus subcristatus in Galapagos Islands, Ecuador

The aim of the study was to elucidate the association between the zoonotic pathogen Salmonella and a population of land iguana, Colonophus subcristatus, endemic to Galápagos Islands in Ecuador. We assessed the presence of Salmonella subspecies and serovars and estimated the prevalence of the pathogen in that population. Additionally, we investigated the genetic relatedness among isolates and serovars utilising pulsed field gel electrophoresis (PFGE) on XbaI-digested DNA and determined the antimicrobial susceptibility to a panel of antimicrobials. The study was carried out by sampling cloacal swabs from animals (n = 63) in their natural environment on in the island of Santa Cruz. A high prevalence (62/63, 98.4%) was observed with heterogeneity of Salmonella subspecies and serovars, all known to be associated with reptiles and with reptile-associated salomonellosis in humans. Serotyping revealed 14 different serovars among four Salmonella enterica subspecies: S. enterica subsp. enterica (n = 48), S. enterica subsp. salamae (n = 2), S. enterica subsp. diarizonae (n = 1), and S. enterica subsp. houtenae (n = 7). Four serovars were predominant: S. Poona (n = 18), S. Pomona (n = 10), S. Abaetetuba (n = 8), and S. Newport (n = 5). The S. Poona isolates revealed nine unique XbaI PFGE patterns, with 15 isolates showing a similarity of 70%. Nine S. Pomona isolates had a similarity of 84%. One main cluster with seven (88%) indistinguishable isolates of S. Abaetetuba was observed. All the Salmonella isolates were pan-susceptible to antimicrobials representative of the most relevant therapeutic classes. The high prevalence and absence of clinical signs suggest a natural interaction of the different Salmonella serovars with the host species. The interaction may have been established before any possible exposure of the iguanas and the biocenosis to direct or indirect environmental factors influenced by the use of antimicrobials in agriculture, in human medicine or in veterinary medicine

Encrusted cystitis in an immunocompromised patient: possible coinfection by Corynebacterium urealyticum and E. coli.

n/

A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI).

This work was supported by: Associazione Italiana Ricerca sul Cancro (AIRC) [Grant 5 x mille n.9980, (to M.F., F.M. and A. N.)]; AIRC I.G. [n. 14,326 (to M.F.)], [n.10136 and 16,722 (A.N.)], [n.15426 (to F.F.)]. AIRC and Fondazione CaRiCal co-financed Multi Unit Regional Grant 2014 [n.16695 (to F.M.)]. Italian Ministry of Health 5 × 1000 funds (to F.F). A.G R. was supported by Associazione Italiana contro le Leucemie-Linfomi-Mielomi (AIL) Cosenza - Fondazione Amelia Scorza (FAS). S.M. C.M., F.V., L. E., S. B., were supported by AIRC.Peer reviewedPostprin

Minimalist Design of Wireframe DNA Nanotubes: Tunable Geometry, Size, Chirality, and Dynamics

DNA nanotubes (NTs) have attracted extensive interest as artificial cytoskeletons for biomedical, synthetic biology, and materials applications. Here, we report the modular design and assembly of a minimalist yet robust DNA wireframe nanotube with tunable cross-sectional geometry, cavity size, chirality, and length, while using only four DNA strands. We introduce an h-motif structure incorporating double-crossover (DX) tile-like DNA edges to achieve structural rigidity and provide efficient self-assembly of h-motif-based DNA nanotube (H-NT) units, thus producing programmable, micrometer-long nanotubes. We demonstrate control of the H-NT nanotube length via short DNA modulators. Finally, we use an enzyme, RNase H, to take these structures out of equilibrium and trigger nanotube assembly at a physiologically relevant temperature, underlining future cellular applications. The minimalist H-NTs can assemble at near-physiological salt conditions and will serve as an easily synthesized, DNA-economical modular template for biosensors, plasmonics, or other functional materials and as cost-efficient drug-delivery vehicles for biomedical applications.A minimalist design of robust DNA nanotubes from only 4 DNA strands, with tunable geometry, chirality, length, and assembly dynamics is reported. The method leads to robust nanotubes under physiologically relevant conditions, as cost-efficient nanomaterial templates or drug-delivery vehicles.+imag

MRI index lesion radiomics and machine learning for detection of extraprostatic extension of disease: a multicenter study

Objectives: To build a machine learning (ML) model to detect extraprostatic extension (EPE) of prostate cancer (PCa), based on radiomics features extracted from prostate MRI index lesions. Methods: Consecutive MRI exams of patients undergoing radical prostatectomy for PCa were retrospectively collected from three institutions. Axial T2-weighted and apparent diffusion coefficient map images were annotated to obtain index lesion volumes of interest for radiomics feature extraction. Data from one institution was used for training, feature selection (using reproducibility, variance and pairwise correlation analyses, and a correlation-based subset evaluator), and tuning of a support vector machine (SVM) algorithm, with stratified 10-fold cross-validation. The model was tested on the two remaining institutions' data and compared with a baseline reference and expert radiologist assessment of EPE. Results: In total, 193 patients were included. From an initial dataset of 2436 features, 2287 were excluded due to either poor stability, low variance, or high collinearity. Among the remaining, 14 features were used to train the ML model, which reached an overall accuracy of 83% in the training set. In the two external test sets, the SVM achieved an accuracy of 79% and 74% respectively, not statistically different from that of the radiologist (81-83%, p = 0.39-1) and outperforming the baseline reference (p = 0.001-0.02). Conclusions: A ML model solely based on radiomics features demonstrated high accuracy for EPE detection and good generalizability in a multicenter setting. Paired to qualitative EPE assessment, this approach could aid radiologists in this challenging task

Fishing for Targets of Alien Metabolites: A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Agonist from a Marine Pest

Although the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)—a bioactive component of the green alga Caulerpa cylindracea that has invaded the entire Mediterranean basin—is an agonist of peroxisome proliferator-activated receptors (PPARs). Our interdisciplinary study started with the in silico prediction of the ligand-protein interaction, which was then validated by in vivo, ex vivo and in vitro assays. On the basis of these results, we candidate CAU as a causal factor of the metabolic and behavioural disorders observed in Diplodus sargus, a native edible fish of high ecological and commercial relevance, feeding on C. cylindracea. Moreover, given the considerable interest in PPAR activators for the treatment of relevant human diseases, our findings are also discussed in terms of a possible nutraceutical/pharmacological valorisation of the invasive algal biomasses, supporting an innovative strategy for conserving biodiversity as an alternative to unrealistic campaigns for the eradication of invasive pest