Non-long terminal repeat (non-LTR) retrotransposons: mechanisms, recent developments, and unanswered questions

Non-long terminal repeat (non-LTR) retrotransposons are present in most eukaryotic genomes. In some species, such as humans, these elements are the most abundant genome sequence and continue to replicate to this day, creating a source of endogenous mutations and potential genotoxic stress. This review will provide a general outline of the replicative cycle of non-LTR retrotransposons. Recent findings regarding the host regulation of non-LTR retrotransposons will be summarized. Finally, future directions of interest will be discussed

A Method of Limited Replication for the Efficient In Vivo Delivery of Adenovirus to Cancer Cells

Overview summary Replication-defective viral vectors are limited in their ability to diffuse through tissue. This poses a problem for treating tumors in vivo using gene transfer. This article demonstrates that limited replication of adenovirus leads to greater gene transfer efficiency in vitro and in vivo without introducing additional safety concerns beyond traditional adenovirus administration. This has implications for the improvement of current gene transfer methods for treating cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63280/1/hum.1998.9.8-1209.pd

Belowground competition among invading detritivores

Author Posting. © Ecological Society of America, 2016. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Ecology 97 (2016): 160–170, doi:10.1890/15-0551.1.The factors regulating soil animal communities are poorly understood. Current theory favors niche complementarity and facilitation over competition as the primary forms of non-trophic interspecific interaction in soil fauna; however, competition has frequently been suggested as an important community-structuring factor in earthworms, ecosystem engineers that influence belowground processes. To date, direct evidence of competition in earthworms is lacking due to the difficulty inherent in identifying a limiting resource for saprophagous animals. In the present study, we offer the first direct evidence of interspecific competition for food in this dominant soil detritivore group by combining field observations with laboratory mesocosm experiments using 13C and 15N double-enriched leaf litter to track consumption patterns. In our experiments, the Asian invasive species Amynthas hilgendorfi was a dominant competitor for leaf litter against two European species currently invading the temperate deciduous forests in North America. This competitive advantage may account for recent invasion success of A. hilgendorfi in forests with established populations of European species, and we hypothesize that specific phenological differences play an important role in determining the outcome of the belowground competition. In contrast, Eisenoides lonnbergi, a common native species in the Eastern United States, occupied a unique trophic position with limited interactions with other species, which may contribute to its persistence in habitats dominated by invasive species. Furthermore, our results supported neither the hypothesis that facilitation occurs between species of different functional groups nor the hypothesis that species in the same group exhibit functional equivalency in C and N translocation in the soil. We propose that species identity is a more powerful approach to understand earthworm invasion and its impacts on belowground processes.EPS Field Funds; National Science Foundation Grant Numbers: EEC-0540832, ACI 1244820, EAR-0748574; Microsoft Researc

MR diffusion changes in the perimeter of the lateral ventricles demonstrate periventricular injury in post-hemorrhagic hydrocephalus of prematurity

OBJECTIVES: Injury to the preterm lateral ventricular perimeter (LVP), which contains the neural stem cells responsible for brain development, may contribute to the neurological sequelae of intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus of prematurity (PHH). This study utilizes diffusion MRI (dMRI) to characterize the microstructural effects of IVH/PHH on the LVP and segmented frontal-occipital horn perimeters (FOHP). STUDY DESIGN: Prospective study of 56 full-term infants, 72 very preterm infants without brain injury (VPT), 17 VPT infants with high-grade IVH without hydrocephalus (HG-IVH), and 13 VPT infants with PHH who underwent dMRI at term equivalent. LVP and FOHP dMRI measures and ventricular size-dMRI correlations were assessed. RESULTS: In the LVP, PHH had consistently lower FA and higher MD and RD than FT and VPT (p\u3c.050). However, while PHH FA was lower, and PHH RD was higher than their respective HG-IVH measures (p\u3c.050), the MD and AD values did not differ. In the FOHP, PHH infants had lower FA and higher RD than FT and VPT (p\u3c.010), and a lower FA than the HG-IVH group (p\u3c.001). While the magnitude of AD in both the LVP and FOHP were consistently less in the PHH group on pairwise comparisons to the other groups, the differences were not significant (p\u3e.050). Ventricular size correlated negatively with FA, and positively with MD and RD (p\u3c.001) in both the LVP and FOHP. In the PHH group, FA was lower in the FOHP than in the LVP, which was contrary to the observed findings in the healthy infants (p\u3c.001). Nevertheless, there were no regional differences in AD, MD, and RD in the PHH group. CONCLUSION: HG-IVH and PHH results in aberrant LVP/FOHP microstructure, with prominent abnormalities among the PHH group, most notably in the FOHP. Larger ventricular size was associated with greater magnitude of abnormality. LVP/FOHP dMRI measures may provide valuable biomarkers for future studies directed at improving the management and neurological outcomes of IVH/PHH

Adaptation and Re-Use of Spacecraft Power System Models for the Constellation Program

NASA's Constellation Program is embarking on a new era of space exploration, returning to the Moon and beyond. The Constellation architecture will consist of a number of new spacecraft elements, including the Orion crew exploration vehicle, the Altair lunar lander, and the Ares family of launch vehicles. Each of these new spacecraft elements will need an electric power system, and those power systems will need to be designed to fulfill unique mission objectives and to survive the unique environments encountered on a lunar exploration mission. As with any new spacecraft power system development, preliminary design work will rely heavily on analysis to select the proper power technologies, size the power system components, and predict the system performance throughout the required mission profile. Constellation projects have the advantage of leveraging power system modeling developments from other recent programs such as the International Space Station (ISS) and the Mars Exploration Program. These programs have developed mature power system modeling tools, which can be quickly modified to meet the unique needs of Constellation, and thus provide a rapid capability for detailed power system modeling that otherwise would not exist

Long-term spatial and temporal variation of CO2 partial pressure in the Yellow River, China

10.5194/bg-12-921-2015Biogeosciences124921-93

Lunar In-Situ Aluminum Production through Molten Salt Electrolysis (LISAP-MSE)

The goal of Artemis is to establish a sustained presence on the Moon. To achieve so, numerous resources are necessary. The Moon contains several essential elements needed to sustain human presence. Most of those elements are trapped in the form of minerals. To refine those minerals into useful materials, reduction methods are needed. Most reduction methods on Earth require large amounts of mass and power which is unrealistic for early stages of building a lunar base. To solve this problem, we are developing a concept of Lunar In-Situ Aluminum Production through Molten Salt Electrolysis (LISAP-MSE). The LISAP-MSE project, if successful, will demonstrate the use of the Fray-Farthing-Chen (FFC) Cambridge process to reduce aluminum oxide (i.e., alumina) into aluminum and oxygen gas via electrolysis in a molten salt bath for the production of aluminum on the Moon. It will be shown that with a steady supply of hydrogen chloride, this in-situ resource utilization (ISRU) method can supply almost all of the necessary materials consumed in the FFC Cambridge process (except hydrogen chloride) to produce aluminum metal, oxygen, water, and silica from anorthite. This project is designed to answer the call from the BIG Ideas Challenge 2023 (Lunar Forge), and will leverage an ongoing Lunar Surface Technology Research (LuSTR) project titled “Regolith Beneficiation System for Production of Lunar Calcium and Aluminum” underway at Missouri S&T, which is developing systems to beneficiate anorthite from lunar regolith particles with the promising potential to provide enriched anorthite to the LISAP-MSE process. Once sourced and constructed, the LISAP-MSE apparatus will be characterized and calibrated in an atmospheric pressure setting before being tested inside vacuum chambers. These testing conditions include under atmospheric pressure to be conducted at a foundry laboratory, and under vacuum conditions inside two vacuum chambers, one induction chamber and one thermal chamber, all located on site at Missouri S&T. Once testing is completed, the end product will be characterized using a handheld X-ray fluorescence (XRF) analyzer along with density tests to verify the elemental composition. Following the XRF analysis is a set of density tests that will be compared to the densities of pure aluminum and pure alumina. This will help determine the amount of aluminum produced, and thus assess the efficiency of conversion. Mainly driven by chemical reactions, the LISAP-MSE process is massively scalable allowing for a smooth transition from testing phase to batch production. This aluminum can be used to construct habitats and infrastructure for a lunar base which can potentially support a sustained human presence on the Moon

Characterization of a synthetic human LINE-1 retrotransposon ORFeus-Hs

Long interspersed elements, type 1(LINE-1, L1) are the most abundant and only active autonomous retrotransposons in the human genome. Native L1 elements are inefficiently expressed because of a transcription elongation defect thought to be caused by high adenosine content in L1 sequences. Previously, we constructed a highly active synthetic mouse L1 element (ORFeus-Mm), partially by reducing the nucleotide composition bias. As a result, the transcript abundance of ORFeus-Mm was greatly increased, and its retrotransposition frequency was > 200-fold higher than its native counterpart. In this paper, we report a synthetic human L1 element (ORFeus-Hs) synthesized using a similar strategy. The adenosine content of the L1 open reading frames (ORFs) was reduced from 40% to 27% by changing 25% of the bases in the ORFs, without altering the amino acid sequence. By studying a series of native/synthetic chimeric elements, we observed increased levels of full-length L1 RNA and ORF1 protein and retrotransposition frequency, mostly proportional to increased fraction of synthetic sequence. Overall, the fully synthetic ORFeus-Hs has > 40-fold more RNA but is at most only ~threefold more active than its native counterpart (L1RP); however, its absolute retrotransposition activity is similar to ORFeus-Mm. Owing to the elevated expression of the L1 RNA/protein and its high retrotransposition ability, ORFeus-Hs and its chimeric derivatives will be useful tools for mechanistic L1 studies and mammalian genome manipulation

Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene.

BackgroundPreserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.MethodsData from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.ResultsThe prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter's syndrome (47XXY) was observed (p-value < 0.001). Subgroups identified through k-means clustering include a putative "COPD-subtype", "Restrictive-subtype", and a highly symptomatic "Metabolic-subtype".ConclusionsPRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.Trial registrationClinicaltrials.gov Identifier: NCT000608764