Nuclear Receptor Rev-erb Alpha (Nr1d1) Functions in Concert with Nr2e3 to Regulate Transcriptional Networks in the Retina

The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1 has been widely studied for its role in the circadian cycle and cell metabolism, however its role in the retina is unknown. In order to understand the role of Rev-erb alpha/Nr1d1 in the retina, we evaluated the effects of loss of Nr1d1 to the developing retina and its co-regulation with the photoreceptor-specific nuclear receptor gene Nr2e3 in the developing and mature retina. Knock-down of Nr1d1 expression in the developing retina results in pan-retinal spotting and reduced retinal function by electroretinogram. Our studies show that NR1D1 protein is co-expressed with NR2E3 in the outer neuroblastic layer of the developing mouse retina. In the adult retina, NR1D1 is expressed in the ganglion cell layer and is co-expressed with NR2E3 in the outer nuclear layer, within rods and cones. Several genes co-targeted by NR2E3 and NR1D1 were identified that include: Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1. We examined the cyclic expression of Nr1d1 and Nr2e3 over a twenty-four hour period and observed that both nuclear receptors cycle in a similar manner. Taken together, these studies reveal a novel role for Nr1d1, in conjunction with its cofactor Nr2e3, in regulating transcriptional networks critical for photoreceptor development and function

Heavy Ion Carcinogenesis and Human Space Exploration

Prior to the human exploration of Mars or long duration stays on the Earth s moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated. Space radiation, comprised of energetic protons and heavy nuclei, has been show to produce distinct biological damage compared to radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, while obscuring evaluation of the effectiveness of possible countermeasures. Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets

Strategies Based on Nitride Materials Chemistry to Stabilize Li Metal Anode

Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.Lithium metal battery is a promising candidate for high-energy-density energy storage. Unfortunately, the strongly reducing nature of lithium metal has been an outstanding challenge causing poor stability and low coulombic efficiency in lithium batteries. For decades, there are significant research efforts to stabilize lithium metal anode. However, such efforts are greatly impeded by the lack of knowledge about lithium-stable materials chemistry. So far, only a few materials are known to be stable against Li metal. To resolve this outstanding challenge, lithium-stable materials have been uncovered out of chemistry across the periodic table using first-principles calculations based on large materials database. It is found that most oxides, sulfides, and halides, commonly studied as protection materials, are reduced by lithium metal due to the reduction of metal cations. It is discovered that nitride anion chemistry exhibits unique stability against Li metal, which is either thermodynamically intrinsic or a result of stable passivation. The results here establish essential guidelines for selecting, designing, and discovering materials for lithium metal protection, and propose multiple novel strategies of using nitride materials and high nitrogen doping to form stable solid-electrolyte-interphase for lithium metal anode, paving the way for high-energy rechargeable lithium batteries