Reorganization of self-assembled DNA-based polymers using orthogonally addressable building blocks

Nature uses non-covalent interactions to achieve structural dynamic reconfiguration of biopolymers. Taking advantage of the programmability of DNA/DNA interactions we report here the rational design of orthogonal DNA-based addressable tiles that self-assemble into polymer-like structures that can be reconfigured by external inputs. The different tiles share the same sticky ends responsible for self-assembly but are rationally designed to contain a specific regulator-binding domain that can be orthogonally targeted by different DNA regulator strands. We show that by sequentially adding specific inputs it is possible to re-organize the formed structures to display well-defined distributions: homopolymers, random and block structures. The versatility of the systems presented in this study shows the ease with which DNA-based addressable monomers can be designed to create reconfigurable micron-scale DNA structures offering a new approach to the growing field of supramolecular polymers

Fuel-Responsive Allosteric DNA-Based Aptamers for the Transient Release of ATP and Cocaine

We show herein that allostery offers a key strategy for the design of out-of-equilibrium systems by engineering allosteric DNA-based nanodevices for the transient loading and release of small organic molecules. To demonstrate the generality of our approach, we used two model DNA-based aptamers that bind ATP and cocaine through a target-induced conformational change. We re-engineered these aptamers so that their affinity towards their specific target is controlled by a DNA sequence acting as an allosteric inhibitor. The use of an enzyme that specifically cleaves the inhibitor only when it is bound to the aptamer generates a transient allosteric control that leads to the release of ATP or cocaine from the aptamers. Our approach confirms that the programmability and predictability of nucleic acids make synthetic DNA/RNA the perfect candidate material to re-engineer synthetic receptors that can undergo chemical fuel-triggered release of small-molecule cargoes and to rationally design non-equilibrium systems

Fast adiabatic control of an optomechanical cavity

The development of quantum technologies present important challenges such as the need for fast and precise protocols for implementing quantum operations. Shortcuts to adiabaticity (STA) are a powerful tool for achieving these goals, as they enable us to perform an exactly adiabatic evolution in finite time. In this paper we present a shortcut to adiabaticity for the control of an optomechanical cavity with two moving mirrors. Given reference trajectories for the mirrors, we find analytical expressions that give us effective trajectories which implement a STA for the quantum field inside the cavity. We then solve these equations numerically for different reference protocols, such as expansions, contractions and rigid motions; thus confirming the successful implementation of the STA and finding some general features of these effective trajectories.Comment: 13 pages, 9 figure

One year after on Tyrrhenian coasts: The ban of cotton buds does not reduce their dominance in beach litter composition

In January 2019, Italy banned the sale of plastic cotton buds, which is one of the most abundant litter items entering the sea and then washing ashore. However, since the ban came into force, no studies have been carried out to assess whether the measure has actually led to the reduction of plastic cotton buds accumulating on Italian coasts. Here we aim at evaluating the effectiveness of the ban in reducing the amount of cotton buds reaching sandy beaches of the Tyrrhenian coast. Specifically, we monitored the accumulation of beach litter for one year since the ban came into force. By surveying eight coastal sites from winter 2019 to winter 2020, we collected a total of 52,824 items mostly constituted by plastic debris (97.6%). We found that cotton buds were the most abundant item (42.3% of total litter), followed by plastic (28.5%) and polystyrene (5.43%) fragments. Our preliminary assessment suggests that the ban has so far not led to a sensible reduction in the amount of cotton buds entering the marine ecosystem. This was to be expected since implementation strategies are still lacking (i.e. no economic sanctions can be imposed in case of non-compliance) and bans are differently implemented among countries facing the Mediterranean Sea, calling for law enforcement and implementation at the national and international levels

A Systems Biology Approach to Characterize the Regulatory Networks Leading to Trabectedin Resistance in an In Vitro Model of Myxoid Liposarcoma

Trabectedin, a new antitumor compound originally derived from a marine tunicate, is clinically effective in soft tissue sarcoma. The drug has shown a high selectivity for myxoid liposarcoma, characterized by the translocation t(12;16)(q13; p11) leading to the expression of FUS-CHOP fusion gene. Trabectedin appears to act interfering with mechanisms of transcription regulation. In particular, the transactivating activity of FUS-CHOP was found to be impaired by trabectedin treatment. Even after prolonged response resistance occurs and thus it is important to elucidate the mechanisms of resistance to trabectedin. To this end we developed and characterized a myxoid liposarcoma cell line resistant to trabectedin (402-91/ET), obtained by exposing the parental 402-91 cell line to stepwise increases in drug concentration. The aim of this study was to compare mRNAs, miRNAs and proteins profiles of 402-91 and 402-91/ET cells through a systems biology approach. We identified 3,083 genes, 47 miRNAs and 336 proteins differentially expressed between 402-91 and 402-91/ET cell lines. Interestingly three miRNAs among those differentially expressed, miR-130a, miR-21 and miR-7, harbored CHOP binding sites in their promoter region. We used computational approaches to integrate the three regulatory layers and to generate a molecular map describing the altered circuits in sensitive and resistant cell lines. By combining transcriptomic and proteomic data, we reconstructed two different networks, i.e. apoptosis and cell cycle regulation, that could play a key role in modulating trabectedin resistance. This approach highlights the central role of genes such as CCDN1, RB1, E2F4, TNF, CDKN1C and ABL1 in both pre- and post-transcriptional regulatory network. The validation of these results in in vivo models might be clinically relevant to stratify myxoid liposarcoma patients with different sensitivity to trabectedin treatment

The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector.

The development and operation of liquid-argon time-projection chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies

Real Life Clinical Management and Survival in Advanced Cutaneous Melanoma: The Italian Clinical National Melanoma Registry Experience

Background: Cutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR). Methods: Melanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. Results: The median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62). Conclusions: The nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment