Self-assembling DNA-caged particles: nanoblocks for hierarchical self-assembly

DNA is an ideal candidate to organize matter on the nanoscale, primarily due to the specificity and complexity of DNA based interactions. Recent advances in this direction include the self-assembly of colloidal crystals using DNA grafted particles. In this article we theoretically study the self-assembly of DNA-caged particles. These nanoblocks combine DNA grafted particles with more complicated purely DNA based constructs. Geometrically the nanoblock is a sphere (DNA grafted particle) inscribed inside a polyhedron (DNA cage). The faces of the DNA cage are open, and the edges are made from double stranded DNA. The cage vertices are modified DNA junctions. We calculate the equilibriuim yield of self-assembled, tetrahedrally caged particles, and discuss their stability with respect to alternative structures. The experimental feasability of the method is discussed. To conclude we indicate the usefulness of DNA-caged particles as nanoblocks in a hierarchical self-assembly strategy.Comment: v2: 21 pages, 8 figures; revised discussion in Sec. 2, replaced 2 figures, added new reference

Functional characterization of Ebola virus L-domains using VSV recombinants

AbstractVSV recombinants containing the overlapping L-domain sequences from Ebola virus VP40 (PTAPPEY) were recovered by reverse-genetics. Replication kinetics of M40-WT, M40-P24L, and M40-Y30A were indistinguishable from VSV-WT in BHK-21 cells, whereas the double mutant (M40-P2728A) was defective in budding. Insertion of the Ebola L-domain region into VSV M protein was sufficient to alter the dependence on host proteins for efficient budding. Indeed, M40 recombinants containing a functional PTAP motif specifically incorporated endogenous tsg101 into budding virions and were dependent on tsg101 expression for efficient budding. Thus, VSV represents an excellent negative-sense RNA virus model for elucidating the functional aspects and diverse host interactions associated with the L-domains of Ebola virus

Statistical Mechanics of DNA-Mediated Colloidal Aggregation

We present a statistical mechanical model of aggregation in colloidal systems with DNA mediated interactions. We obtain a general result for the two-particle binding energy in terms of the hybridization free energy $\Delta G$ of DNA and two model dependent properties: the average number of available DNA bridges \left and the effective DNA conccentration $c_{eff}$. We calculate these parameters for a particular DNA bridging scheme. The fraction of all the $n$-mers, including the infinite aggregate, are shown to be universal functions of a single parameter directly related to the two-particle binding energy. We explicitly take into account the partial ergodicity of the problem resulting from the slow DNA binding-unbinding dynamics, and introduce the concept of angular localization of DNA linkers. In this way, we obtain a direct link between DNA thermodynamics and the global aggregation and melting properties in DNA-colloidal systems. The results of the theory are shown to be in quantitative agreement with two recent experiments with particles of micron and nanometer size. PACS numbers: 81.16.Dn, 82.20.Db, 68.65.-k, 87.14.GgComment: 12 pages, 6 figures, v2: added reference, expanded conclusion, added journal re

How to build nanoblocks using DNA scaffolds

In recent years there have been a number of proposals to utilize the specificity of DNA based interactions for potential applications in nanoscience. One interesting direction is the self-assembly of micro- and nanoparticle clusters using DNA scaffolds. In this letter we consider a DNA scaffold method to self-assemble clusters of "colored" particles. Stable clusters of microspheres have recently been produced by an entirely different method. Our DNA based approach self-assembles clusters with additional degrees of freedom associated with particle permutation. We demonstrate that in the non-equilibrium regime of irreversible binding the self-assembly process is experimentally feasible. These color degrees of freedom may allow for more diverse intercluster interactions essential for hierarchical self-assembly of larger structures.Comment: 4 pages, 2 figures ; epl forma

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia as a consequence of pancreatic β cell loss and/or dysfunction, also caused by oxidative stress. The molecular mechanisms involved inβ cell dysfunction and in response to oxidative stress are also regulated by microRNAs (miRNAs). miRNAs are a class of negative gene regulators, which modulate pathologic mechanisms occurring in diabetes and its complications. Although several pharmacological therapies specifically targeting miRNAs have already been developed and brought to the clinic, most previous miRNA-based drug delivery methods were unable to target a specific miRNA in a single cell type or tissue, leading to important off-target effects. In order to overcome these issues, aptamers and nanoparticles have been described as non-cytotoxic vehicles for miRNA-based drug delivery. These approaches could represent an innovative way to specifically target and modulate miRNAs involved in oxidative stress in diabetes and its complications. Therefore, the aims of this review are: (i) to report the role of miRNAs involved in oxidative stress in diabetes as promising therapeutic targets; (ii) to shed light onto the new delivery strategies developed to modulate the expression of miRNAs in diseases

Clebsch-Gordan Coefficients for the Extended Quantum-Mechanical Poincar\'e Group and Angular Correlations of Decay Products

This paper describes Clebsch-Gordan coefficients (CGCs) for unitary irreducible representations (UIRs) of the extended quantum mechanical Poincar\'e group \pt. `Extended' refers to the extension of the 10 parameter Lie group that is the Poincar\'e group by the discrete symmetries $C$, $P$, and $T$; `quantum mechanical' refers to the fact that we consider projective representations of the group. The particular set of CGCs presented here are applicable to the problem of the reduction of the direct product of two massive, unitary irreducible representations (UIRs) of \pt with positive energy to irreducible components. Of the sixteen inequivalent representations of the discrete symmetries, the two standard representations with $U_C U_P = \pm 1$ are considered. Also included in the analysis are additive internal quantum numbers specifying the superselection sector. As an example, these CGCs are applied to the decay process of the $\Upsilon(4S)$ meson.Comment: 26 pages, double spaced. Version 2: typos corrected, introduction change

Prognostic indicators of successful endoscopic sclerotherapy for prevention of rebleeding from oesophageal varices in cirrhosis: a long-term cohort study.

BACKGROUND: Although band ligation is now recommended for prevention of rebleeding from oesophageal varices in cirrhosis, sclerotherapy is still widely used. Patients submitted to chronic sclerotherapy undergo several endoscopies and experience a large number of serious complications. However, long-term outcome is poorly defined. AIMS: To assess the clinical course and prognostic indicators of patients undergoing chronic sclerotherapy for prevention of variceal rebleeding as a basis for future evaluation of long-term band ligation outcome. METHODS: Prospective cohort study; prognostic analysis by the Cox proportional hazards model. RESULTS: A total of 218 consecutive cirrhotic patients (37 Child class A, 154 B, 27 C) were enrolled in the study Varices were obliterated in 139 (64%) patients in a mean of 5 (+/-2.6) sessions and recurred in 58/139 (41.7%) within one year. A total of 132 (60%) patients experienced 283 rebleeding episodes and 73 (33%) died. Bleeding from oesophageal ulcers was the most serious complication causing 14% of all rebleeding episodes. Significant prognostic indicators of sclerotherapy outcome were: Child-Pugh class for variceal obliteration; gastric varices and platelet count for recurrence of varices; failure to obliterate varices, variceal size and gastric varices for rebleeding; blood urea nitrogen and failure to obliterate varices for death. Presence of gastric varices was the only prognostic indicator for death in the 79 patients not achieving variceal obliteration. A mean of 10 endoscopies and of 6 hospital admissions were needed per each patient with an estimated cost of US dollars 7154 per patient during the first two years of therapy. CONCLUSIONS: Sclerotherapy is a very demanding and costly treatment, and is associated with frequent and serious side-effects. The probability of treatment failure is significantly higher in Child C patients with gastric varices. Alternative treatments should be considered for these patients

Clinical course and genetic susceptibility of primary biliary cirrhosis: Analysis of a prospective cohort

Background: Natural history of primary biliary cirrhosis (PBC) is partially characterized in patients from the Mediterranean area whose genetic background differs from that of Northern Europeans. Objectives: We aimed to describe genetic susceptibility and clinical course of PBC in patients from Southern Italy. Methods: Socio-demographic, clinical, biochemical and histological data at diagnosis as well as disease progression of 81 PBC consecutive patients were collected. All subjects were treated with Ursodeoxycholic acid at a dose of 15 mg/kg. HLA class II DRB1 alleles were compared with those of 237 healthy control subjects. IL28B genotyping for IL28B rs12979860 C/T and rs80899917 G/T was performed in a sub-group of patients. Results: HLA-DRB1*07 (RR 5.3, P = 0.0008) and HLA-DRB1*08 (RR n.c. P = 0.0005) were significantly associated with the risk of PBC development. Patients younger than 45 years had significantly higher alanine aminotransferase (P = 0.038) and alkaline phosphatase levels (P = 0.047) than older cases. In comparison to non-CC rs12979860, patients with CC rs12979860 genotype showed an early histological stage at onset (93.8% vs. 62.5%, P = 0.03). After a mean follow-up of 61 months, three patients died, one underwent liver transplantation and sixteen (21.9%) had progression of the disease. At multivariate analysis, extrahepatic autoimmune disease (P = 0.04), pruritus (P = 0.008) and advanced histological stage (P < 0.0001) were independent risk factors for disease progression. Conclusions: HLA-DRB1*07 and HLA-DRB1*08 alleles increase susceptibility to disease development. At onset, higher biochemical activity was observed in younger patients, whereas rs12979860 CC genotype was associated with milder histological stage. Pruritus and coexistence of extrahepatic autoimmune diseases were significantly associated with poorer prognosis

On the six-dimensional origin of the AGT correspondence

We argue that the six-dimensional (2,0) superconformal theory defined on M \times C, with M being a four-manifold and C a Riemann surface, can be twisted in a way that makes it topological on M and holomorphic on C. Assuming the existence of such a twisted theory, we show that its chiral algebra contains a W-algebra when M = R^4, possibly in the presence of a codimension-two defect operator supported on R^2 \times C \subset M \times C. We expect this structure to survive the \Omega-deformation.Comment: References added. 14 page

COMEPA (COVID-19 Medicina Policlinico Palermo): a study in hospitalized patients.

Coronavirus disease 2019 (COVID-19) has dramatically changed our lives. In the past months, hospitals were saturated of patients; therefore, it is still important to have simple and standardized prognostic factors and to evaluate the efficacy and safety of medications commonly used for COVID-19. We aimed to collect data of the patients hospitalized in Internal Medicine and Geriatrics Wards at the University Hospital (Policlinico) ‘P. Giaccone’ in Palermo, Italy (COMEPA, COVID-19 Medicina Policlinico Palermo), with the main purpose of finding prognostic tools that can be easily used in clinical practice in order to identify patients hospitalized for/with COVID-19 at higher risk of negative outcomes, such as mortality, transfer to Intensive Care Unit (ICU) and institutionalization, as well as evaluating the efficacy/safety of medications commonly used for COVID-19. For reaching these aims, the medical records of approximately 600 patients will be recorded, having data on several parameters and including as outcomes mortality, ICU placement, institutionalization. With the COMEPA study, we therefore plan to update current literature, giving new data on prognostic factors and on the efficacy/safety of some medications used for COVID-19