Circular RNAs as novel regulators of β-cell functions in normal and disease conditions.

There is strong evidence for an involvement of different classes of non-coding RNAs, including microRNAs and long non-coding RNAs, in the regulation of β-cell activities and in diabetes development. Circular RNAs were recently discovered to constitute a substantial fraction of the mammalian transcriptome but the contribution of these non-coding RNAs in physiological and disease processes remains largely unknown. The goal of this study was to identify the circular RNAs expressed in pancreatic islets and to elucidate their possible role in the control of β-cells functions. We used a microarray approach to identify circular RNAs expressed in human islets and searched their orthologues in RNA sequencing data from mouse islets. We then measured the level of four selected circular RNAs in the islets of different Type 1 and Type 2 diabetes models and analyzed the role of these circular transcripts in the regulation of insulin secretion, β-cell proliferation, and apoptosis. We identified thousands of circular RNAs expressed in human pancreatic islets, 497 of which were conserved in mouse islets. The level of two of these circular transcripts, circHIPK3 and ciRS-7/CDR1as, was found to be reduced in the islets of diabetic db/db mice. Mimicking this decrease in the islets of wild type animals resulted in impaired insulin secretion, reduced β-cell proliferation, and survival. ciRS-7/CDR1as has been previously proposed to function by blocking miR-7. Transcriptomic analysis revealed that circHIPK3 acts by sequestering a group of microRNAs, including miR-124-3p and miR-338-3p, and by regulating the expression of key β-cell genes, such as Slc2a2, Akt1, and Mtpn. Our findings point to circular RNAs as novel regulators of β-cell activities and suggest an involvement of this novel class of non-coding RNAs in β-cell dysfunction under diabetic conditions

Chitosan polyplex mediated delivery of miRNA-124 reduces activation of microglial cells in vitro and in rat models of spinal cord injury

AbstractTraumatic injury to the central nervous system (CNS) is further complicated by an increase in secondary neuronal damage imposed by activated microglia/macrophages. MicroRNA-124 (miR-124) is responsible for mouse monocyte quiescence and reduction of their inflammatory cytokine production. We describe the formulation and ex vivo transfection of chitosan/miR-124 polyplex particles into rat microglia and the resulting reduction of reactive oxygen species (ROS) and TNF-α and lower expression of MHC-II. Upon microinjection into uninjured rat spinal cords, particles formed with Cy3-labeled control sequence RNA, were specifically internalized by OX42 positive macrophages and microglia cells. Alternatively particles injected in the peritoneum were transported by macrophages to the site of spinal cord injury 72h post injection. Microinjections of chitosan/miR-124 particles significantly reduced the number of ED-1 positive macrophages in the injured spinal cord. Taken together, these data present a potential treatment technique to reduce inflammation for a multitude of CNS neurodegenerative conditions.From the Clinical EditorThe treatment of spinal cord injury remains an unresolved problem. Secondary damage is often the result of inflammation caused by activated microglia and/or macrophages. In this article, the authors developed their formulation of chitosan/miR-124 polyplex particles and investigated their use in the suppression of neuronal inflammation. This exciting data may provide a new horizon for patients who suffer from spinal cord injury

Quantum internal modes of solitons in 1d easy-plane antiferromagnet in strong magnetic field

In presence of a strong external magnetic field the dynamics of solitons in a one-dimensional easy-plane Heisenberg antiferromagnet exhibits a number of peculiarities. Dynamics of internal soliton degrees of freedom is essentially quantum, and they are strongly coupled to the "translational" mode of soliton movement. These peculiarities lead to considerable changes in the response functions of the system which can be detected experimentally.Comment: 8 pages, RevTeX, 6 figures, uses psfig.sty, submitted to PR

^{63,65}Cu NMR and NQR evidence for an unusual spin dynamics in PrCu_2 below 100 K

We report the results of a $^{63,65}$Cu NMR/NQR study probing the intermetallic compound PrCu$_2$. The previously claimed onset of magnetic order at 65 K, indicated in a $\mu$SR study, is not confirmed. Based on our data we discuss different possible reasons for this apparent discrepancy, including a non negligible influence of the implanted muons on their environment. Competing dipolar and quadrupolar interactions lead to unusual features of the magnetic-ion/conduction-electron system, different from those of common intermetallics exhibiting structural or magnetic instabilities.Comment: 8 pages, 7 figures, submitted to Phys Rev

Elastic Scattering by Deterministic and Random Fractals: Self-Affinity of the Diffraction Spectrum

The diffraction spectrum of coherent waves scattered from fractal supports is calculated exactly. The fractals considered are of the class generated iteratively by successive dilations and translations, and include generalizations of the Cantor set and Sierpinski carpet as special cases. Also randomized versions of these fractals are treated. The general result is that the diffraction intensities obey a strict recursion relation, and become self-affine in the limit of large iteration number, with a self-affinity exponent related directly to the fractal dimension of the scattering object. Applications include neutron scattering, x-rays, optical diffraction, magnetic resonance imaging, electron diffraction, and He scattering, which all display the same universal scaling.Comment: 20 pages, 11 figures. Phys. Rev. E, in press. More info available at http://www.fh.huji.ac.il/~dani

A circular RNA generated from an intron of the insulin gene controls insulin secretion.

Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling. The effect of the circular RNA is exerted at the transcriptional level and involves an interaction with the RNA-binding protein TAR DNA-binding protein 43 kDa (TDP-43). The level of this circularized intron is reduced in the islets of rodent diabetes models and of type 2 diabetic patients, possibly explaining their impaired secretory capacity. The study of this and other circular RNAs helps understanding β-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder

A circular RNA generated from an intron of the insulin gene controls insulin secretion

Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling. The effect of the circular RNA is exerted at the transcriptional level and involves an interaction with the RNA-binding protein TAR DNA-binding protein 43 kDa (TDP-43). The level of this circularized intron is reduced in the islets of rodent diabetes models and of type 2 diabetic patients, possibly explaining their impaired secretory capacity. The study of this and other circular RNAs helps understanding β-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder

Report of the Regional Co-ordination Meeting for the North Sea and Eastern Arctic (RCM NS&EA) 2014

Report of the Regional Co-ordination Meeting for the North Sea and Eastern Arctic (RCM NS&EA) 2014 Swedish University of Agriculture Sciences (SLU Aqua) Lysekil, Sweden 08-12 September 2014The RCM NS&EA met in Lysekil (Sweden) between 8-12 September 2014. The main purpose of the RCM is coordinate the National Programmes (NP) of the Member States (MS) in the North Sea region for 2015