Candidate cryovolcanic regions on Ganymede: a target priority for JUICE

Jupiter’s largest moon, Ganymede, is the main target of the upcoming ESA mission JUpiter ICy moons Explorer (JUICE), which is planned to launch in 2023. One of the top priorities of the JUICE mission is investigation of past and/or recent cryovolcanic and tectonic activity and the exchange processes with the subsurface and possibly with the ocean (Grasset et al., 2013). Following that objective, the science team has defined ‘potential cryovolcanic regions’ as a category of high interest for observation by JUICE (Stephan et al. 2021). Hence, for preparation of the scientific return of the mission, it is important to study in detail the regions that are considered to be good candidates for past or present activity

A Vision for Ice Giant Exploration

From Voyager to a Vision for 2050: NASA and ESA have just completed a study of candidate missionsto Uranus and Neptune, the so-called ice giant planets. It is a Pre-Decadal Survey Study, meant to inform the next Planetary Science Decadal Survey about opportunities for missions launching in the 2020's and early 2030's. There have been no space flight missions to the ice giants since the Voyager 2 flybys of Uranus in 1986 and Neptune in 1989. This paper presents some conclusions of that study (hereafter referred to as The Study), and how the results feed into a vision for where planetary science can be in 2050. Reaching that vision will require investments in technology andground-based science in the 2020's, flight during the 2030's along with continued technological development of both ground- and space-based capabilities, and data analysis and additional flights in the 2040's. We first discuss why exploring the ice giants is important. We then summarize the science objectives identified by The Study, and our vision of the science goals for 2050. We then review some of the technologies needed to make this vision a reality

Ganymede paterae: a priority target for JUICE

The JUpiter ICy moons Explorer (JUICE), the first large-class of the European Space Agency (ESA), is planned to launch in 2023, and one of its main goals is to make detailed observations of Jupiter’s moon Ganymede. The mission will investigate the past and/or recent cryovolcanic and tectonic activity of the moon and the exchange processes with the subsurface and possibly with the ocean. Recently, the science team defined “potential cryovolcanic regions” as a category of high interest for observation by JUICE (Stephan et al., 2021). For preparation of the scientific return of the mission, it is important to study in detail the regions that are considered to be good candidates for past/present activity. Light material areas on Ganymede imaged by Voyager have been suggested to represent dark terrain resurfaced by cryovolcanic flows (e.g., Parmentier et al., 1982), while the dark terrain’s speculated cryovolcanic origin was later disputed based on higher-resolution images of the Galileo mission. Additional Galileo data showed the significant role of tectonism in the formation of the light material areas, while the role of cryovolcanism remained inconclusive. Currently, small, isolated depressions called ‘paterae’, are the best candidate regions for cryovolcanic activity on Ganymede and suggested to be potential caldera-like cryovolcanic source vents (e.g., Spaun et al., 2001). Their nature has been interpreted as “possible cryovolcanic source vents for extrusion of clean icy material to form light material units” (Collins et al., 2013), and their small size is consistent with a cryovolcanic origin that operates on a local scale. The high-resolution JUICE camera, JANUS, in combination with other remote sensing instruments, is expected to resolve many of the mysteries concerning cryovolcanism on Ganymede and the origin of the moon’s varied geologic features. The “potential cryovolcanic regions” identified by the JUICE team includes 19 out of 30 paterae mapped by Collins et al., (2013) using Voyager and Galileo images. In this study, with the aim to enhance the preparation of the JUICE mission and its science return, we present: a thorough view of all 19 paterae regions; a detailed geomorphological characterization and comparison between the Ganymede paterae with paterae from other planetary bodies; and a spectral assessment using Galileo NIMS data

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers

Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important

Analysis of adenovirus VA RNAI structure and stability using compensatory base pair modifications

Adenovirus VA RNAs are short non-coding transcripts that assist in maintaining viral protein expression in infected cells. Six sets of mismatch and compensatory base pair mutants of VA RNAI were examined by gel mobility and RNA UV melting to assess the contribution of each structural domain to its overall structure and stability. Each domain of VA RNAI was first assigned to one of two apparent unfolding transitions in the wild-type melting profile. The Terminal Stem and Central Domain unfold in a single cooperative apparent transition with an apparent Tm of ∼60°C. In contrast, the Apical Stem unfolds independently and with much higher apparent Tm of ∼83°C. Remarkably, this domain appears to behave as an almost entirely autonomous unit within the RNA, mirroring the functional division within the RNA between PKR binding and inhibition. The effects of mismatch and compensatory mutations at five of the six sites on the RNA melting profile are consistent with proposed base pairing and provide further validation of the current secondary structure model. Mutations in the Central Domain were tested in PKR inhibition assays and a component of the VA RNAI Central Domain structure essential for PKR inhibitory activity was identified

West-Nile virus replicon particles infect 293T cells expressing DC-SIGNR

West-Nile virus (WNV) is an arbovirus usually transmitted to humans via a mosquito vector. Infections commonly result in febrile symptoms while rare severe neuroinvasive cases may result in encephalitis or meningitis. Studies have shown that WNV infection efficiency is enhanced by expression of DC-SIGNR on target cells, which normally do not express DC-SIGNR. To investigate WNV tropism, we established 293T kidney epithelial cell lines that stably express vector, DC-SIGNR and mutants of DC-SIGNR that lack the entire carbohydrate-recognition domain (CRD) or lack the C-terminal half of the CRD. We demonstrate successful surface expression of DC-SIGNR and its mutants from stablytransfected 293T cells, but not vector-transfected 293T cells. Further, we show that monoclonal antibody 120604 which binds specifically to the DC-SIGNR CRD binds to DCSIGNR expressing 293T cells, but not to vector nor any of the DC-SIGNR mutants expressing cells. Virus replicon particles (VRPs), replication-incompetent viral particles containing necessary structural proteins for infection and a viral plasmid including a GFP reporter are used to safely and conveniently study viral entry. Entry assays using WNV (NY99) VRPs as well as a variant of WNV (NY99) which contains the beta-lactamase enzyme show significant entry into DC-SIGNR expressing cell lines, but not in controls that do not express DC-SIGNR. Additionally, we show that WNV VRPs do not enter DC-SIGNR expressing cells that lack the CRD or the C-terminal half of the CRD suggesting that the Cterminal half of the CRD is required for successful entry of WNV via DC-SIGNR. Future experiments may be able to shed light on which amino acids are required for entryhttps://openriver.winona.edu/urc2018/1057/thumbnail.jp

The 1501 Ma Kuonamka Large Igneous Province of northern Siberia: U-Pb geochronology, geochemistry, and links with coeval magmatism on other crustal blocks

© 2015.A new large igneous province (LIP), the 1501 ± 3 Ma Kuonamka LIP, extends across 700 km of northern Siberia and is linked with coeval dikes and sills in the formerly attached Sao Francisco craton (SFC)-Congo craton to yield a short-duration event 2000 km across. The age of the Kuonamka LIP can be summarized as 1501 ± 3 Ma (95% confidence), based on 7 U-Pb ID-TIMS ages (6 new herein) from dolerite dikes and sills across the Anabar shield and within western Riphean cover rocks for a distance of 270 km. An additional sill yielded a SIMS (CAMECA) age of 1483 ± 17 Ma and sill in the Olenek uplift several hundred kilometers farther east, a previous SIMS (SHRIMP) age of ca. 1473 Ma was obtained on a sill; both SIMS ages are within the age uncertainty of the ID-TIMS ages. Geochemical data indicate a tholeiitic basalt composition with low MgO (4-7 wt%) within-plate character based on trace element classification diagrams and source between E-MORB and OIB with only minor contamination from crust or metasomatized lithospheric mantle. Two subgroups are distinguished: Group 1 has gently sloping LREE ((La/Sm)PM = 1.9) and HREE ((Gd/Yb)PM = 1.8) patterns, slightly negative Sr and moderate TiO2 (2.2 wt%), and Group 2 has steeper LREE ((La/Sm)PM = 2.3) and HREE ((Gd/Yb)PM = 2.3), strong negative Sr anomaly, is higher in TiO2 (2.7 wt%), and is transitional from tholeiitic to weakly alkaline in composition. The slight differences in REE slopes are consistent with Group 2 on average melting at deeper levels. Proposed reconstructions of the Kuonamka LIP with 1500 Ma magmatism of the SFC-Congo craton are supported by a geochemical comparison. Specifically, the chemistry of the Chapada Diamantina and Curaga dikes of the SFC can be linked to that of Groups 1 and 2, respectively, of the Kuonamka LIP and are consistent with a common mantle source between EMORB and OIB and subsequent differentiation history. However, the coeval Humpata sills and dikes of the Angola block of the Congo craton represent a different magma batch

Methylation-sensitive linking libraries enhance gene-enriched sequencing of complex genomes and map DNA methylation domains

<p>Abstract</p> <p>Background</p> <p>Many plant genomes are resistant to whole-genome assembly due to an abundance of repetitive sequence, leading to the development of gene-rich sequencing techniques. Two such techniques are hypomethylated partial restriction (HMPR) and methylation spanning linker libraries (MSLL). These libraries differ from other gene-rich datasets in having larger insert sizes, and the MSLL clones are designed to provide reads localized to "epigenetic boundaries" where methylation begins or ends.</p> <p>Results</p> <p>A large-scale study in maize generated 40,299 HMPR sequences and 80,723 MSLL sequences, including MSLL clones exceeding 100 kb. The paired end reads of MSLL and HMPR clones were shown to be effective in linking existing gene-rich sequences into scaffolds. In addition, it was shown that the MSLL clones can be used for anchoring these scaffolds to a BAC-based physical map. The MSLL end reads effectively identified epigenetic boundaries, as indicated by their preferential alignment to regions upstream and downstream from annotated genes. The ability to precisely map long stretches of fully methylated DNA sequence is a unique outcome of MSLL analysis, and was also shown to provide evidence for errors in gene identification. MSLL clones were observed to be significantly more repeat-rich in their interiors than in their end reads, confirming the correlation between methylation and retroelement content. Both MSLL and HMPR reads were found to be substantially gene-enriched, with the <it>Sal</it>I MSLL libraries being the most highly enriched (31% align to an EST contig), while the HMPR clones exhibited exceptional depletion of repetitive DNA (to ~11%). These two techniques were compared with other gene-enrichment methods, and shown to be complementary.</p> <p>Conclusion</p> <p>MSLL technology provides an unparalleled approach for mapping the epigenetic status of repetitive blocks and for identifying sequences mis-identified as genes. Although the types and natures of epigenetic boundaries are barely understood at this time, MSLL technology flags both approximate boundaries and methylated genes that deserve additional investigation. MSLL and HMPR sequences provide a valuable resource for maize genome annotation, and are a uniquely valuable complement to any plant genome sequencing project. In order to make these results fully accessible to the community, a web display was developed that shows the alignment of MSLL, HMPR, and other gene-rich sequences to the BACs; this display is continually updated with the latest ESTs and BAC sequences.</p