Random-Matrix Theory of Quantum Size Effects on Nuclear Magnetic Resonance in Metal Particles

The distribution function of the local density of states is computed exactly for the Wigner-Dyson ensemble of random Hamiltonians. In the absence of time-reversal symmetry, precise agreement is obtained with the "supersymmetry" theory by Efetov and Prigodin of the NMR lineshape in disordered metal particles. Upon breaking time-reversal symmetry, the variance of the Knight shift in the smallest particles is reduced by a universal factor of 2/3. ***To be published in Physical Review B.****Comment: 4 pages, REVTeX-3.0, 1 postscript figure, INLO-PUB-940819; [2017: figure included in text

Physico-chemical foundations underpinning microarray and next-generation sequencing experiments

Hybridization of nucleic acids on solid surfaces is a key process involved in high-throughput technologies such as microarrays and, in some cases, next-generation sequencing (NGS). A physical understanding of the hybridization process helps to determine the accuracy of these technologies. The goal of a widespread research program is to develop reliable transformations between the raw signals reported by the technologies and individual molecular concentrations from an ensemble of nucleic acids. This research has inputs from many areas, from bioinformatics and biostatistics, to theoretical and experimental biochemistry and biophysics, to computer simulations. A group of leading researchers met in Ploen Germany in 2011 to discuss present knowledge and limitations of our physico-chemical understanding of high-throughput nucleic acid technologies. This meeting inspired us to write this summary, which provides an overview of the state-of-the-art approaches based on physico-chemical foundation to modeling of the nucleic acids hybridization process on solid surfaces. In addition, practical application of current knowledge is emphasized

Junín Virus Infection of Human Hematopoietic Progenitors Impairs In Vitro Proplatelet Formation and Platelet Release via a Bystander Effect Involving Type I IFN Signaling

Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by Junín virus (JUNV), a member of the arenaviridae family. Although a recently introduced live attenuated vaccine has proven to be effective, AHF remains a potentially lethal infection. Like in other viral hemorrhagic fevers (VHF), AHF patients present with fever and hemorrhagic complications. Although the causes of the bleeding are poorly understood, impaired hemostasis, endothelial cell dysfunction and low platelet counts have been described. Thrombocytopenia is a common feature in VHF syndromes, and it is a major sign for its diagnosis. However, the underlying pathogenic mechanism has not yet been elucidated. We hypothesized that thrombocytopenia results from a viral-triggered alteration of the megakaryo/thrombopoiesis process. Therefore, we evaluated the impact of JUNV on megakaryopoiesis using an in vitro model of human CD34+ cells stimulated with thrombopoietin. Our results showed that CD34+ cells are infected with JUNV in a restricted fashion. Infection was transferrin receptor 1 (TfR1)-dependent and the surface expression of TfR1 was higher in infected cultures, suggesting a novel arenaviral dissemination strategy in hematopoietic progenitor cells. Although proliferation, survival, and commitment in JUNV-infected cultures were normal, viral infection impaired thrombopoiesis by decreasing in vitro proplatelet formation, platelet release, and P-selectin externalization via a bystander effect. The decrease in platelet release was also TfR1-dependent, mimicked by poly(I:C), and type I interferon (IFN α/β) was implicated as a key paracrine mediator. Among the relevant molecules studied, only the transcription factor NF-E2 showed a moderate decrease in expression in megakaryocytes from either infected cultures or after type I IFN treatment. Moreover, type I IFN-treated megakaryocytes presented ultrastructural abnormalities resembling the reported thrombocytopenic NF-E2−/− mouse phenotype. Our study introduces a potential mechanism for thrombocytopenia in VHF and other diseases associated with increased bone marrow type I IFN levels

SERS-melting: a new method for discriminating mutations in dna sequences

The reliable discrimination of mutations, single nucleotide polymorphisms (SNPs), and other differences in genomic sequence is an essential part of DNA diagnostics and forensics. It is commonly achieved using fluorescently labeled DNA probes and thermal gradients to distinguish between the matched and mismatched DNA. Here, we describe a novel method that uses surface enhanced (resonance) Raman spectroscopy (SER(R)S) to follow denaturation of dsDNA attached to a structured gold surface. This denaturation is driven either electrochemically or thermally on SERS active sphere segment void (SSV) gold substrates. Using this method, we can distinguish between wild type, a single point mutation (1653C/T), and a triple deletion (?F 508) in the CFTR gene at the 0.02 attomole level, and the method can be used to differentiate the unpurified PCR products of the wild type and ?F 508 mutation. Our method has the potential to provide small, rapid, sensitive, reproducible platforms for detecting genetic variations and sequencing genes

Free energy considerations for nucleic acids with dangling ends near a surface: a coarse grained approach

A coarse grain model for the thermodynamics of nucleic acid hybridization near surfaces has been extended and parameterized to consider unpaired dangling end contributions. The parameters of the model differ when representing a double stranded DNA section, or a single stranded DNA section. The thermodynamic effects of the possibility of different dangling end combinations were considered in the presence of different types of surfaces. Configurational sampling was achieved by Metropolis Monte Carlo. To have a more complete picture of the free energy changes, an estimation of the conformational entropy was included. We find a strong thermodynamic effect for dangling mismatches due to sequence requirements when they are nearer the surface as opposed to being held away from the surface