Integrated Genomic Analysis Implicates Haploinsufficiency of Multiple Chromosome 5q31.2 Genes in De Novo Myelodysplastic Syndromes Pathogenesis

Deletions spanning chromosome 5q31.2 are among the most common recurring cytogenetic abnormalities detectable in myelodysplastic syndromes (MDS). Prior genomic studies have suggested that haploinsufficiency of multiple 5q31.2 genes may contribute to MDS pathogenesis. However, this hypothesis has never been formally tested. Therefore, we designed this study to systematically and comprehensively evaluate all 28 chromosome 5q31.2 genes and directly test whether haploinsufficiency of a single 5q31.2 gene may result from a heterozygous nucleotide mutation or microdeletion. We selected paired tumor (bone marrow) and germline (skin) DNA samples from 46 de novo MDS patients (37 without a cytogenetic 5q31.2 deletion) and performed total exonic gene resequencing (479 amplicons) and array comparative genomic hybridization (CGH). We found no somatic nucleotide changes in the 46 MDS samples, and no cytogenetically silent 5q31.2 deletions in 20/20 samples analyzed by array CGH. Twelve novel single nucleotide polymorphisms were discovered. The mRNA levels of 7 genes in the commonly deleted interval were reduced by 50% in CD34+ cells from del(5q) MDS samples, and no gene showed complete loss of expression. Taken together, these data show that small deletions and/or point mutations in individual 5q31.2 genes are not common events in MDS, and implicate haploinsufficiency of multiple genes as the relevant genetic consequence of this common deletion

Relative sea-level rise around East Antarctica during Oligocene glaciation

During the middle and late Eocene (∼48-34 Myr ago), the Earth's climate cooled and an ice sheet built up on Antarctica. The stepwise expansion of ice on Antarcticainduced crustal deformation and gravitational perturbations around the continent. Close to the ice sheet, sea level rosedespite an overall reduction in the mass of the ocean caused by the transfer of water to the ice sheet. Here we identify the crustal response to ice-sheet growth by forcing a glacial-hydro isostatic adjustment model with an Antarctic ice-sheet model. We find that the shelf areas around East Antarctica first shoaled as upper mantle material upwelled and a peripheral forebulge developed. The inner shelf subsequently subsided as lithosphere flexure extended outwards from the ice-sheet margins. Consequently the coasts experienced a progressive relative sea-level rise. Our analysis of sediment cores from the vicinity of the Antarctic ice sheet are in agreement with the spatial patterns of relative sea-level change indicated by our simulations. Our results are consistent with the suggestion that near-field processes such as local sea-level change influence the equilibrium state obtained by an icesheet grounding line

Eocene cooling linked to early flow across the Tasmanian Gateway

The warmest global temperatures of the past 85 million years occurred during a prolonged greenhouse episode known as the Early Eocene Climatic Optimum (52–50 Ma). The Early Eocene Climatic Optimum terminated with a long-term cooling trend that culminated in continental-scale glaciation of Antarctica from 34 Ma onward. Whereas early studies attributed the Eocene transition from greenhouse to icehouse climates to the tectonic opening of Southern Ocean gateways, more recent investigations invoked a dominant role of declining atmospheric greenhouse gas concentrations (e.g., CO(2)). However, the scarcity of field data has prevented empirical evaluation of these hypotheses. We present marine microfossil and organic geochemical records spanning the early-to-middle Eocene transition from the Wilkes Land Margin, East Antarctica. Dinoflagellate biogeography and sea surface temperature paleothermometry reveal that the earliest throughflow of a westbound Antarctic Counter Current began ∼49–50 Ma through a southern opening of the Tasmanian Gateway. This early opening occurs in conjunction with the simultaneous onset of regional surface water and continental cooling (2–4 °C), evidenced by biomarker- and pollen-based paleothermometry. We interpret that the westbound flowing current flow across the Tasmanian Gateway resulted in cooling of Antarctic surface waters and coasts, which was conveyed to global intermediate waters through invigorated deep convection in southern high latitudes. Although atmospheric CO(2) forcing alone would provide a more uniform middle Eocene cooling, the opening of the Tasmanian Gateway better explains Southern Ocean surface water and global deep ocean cooling in the apparent absence of (sub-) equatorial cooling

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Creania lacyae gen. nov et sp nov and Synedropsis cheethamii sp nov., fossil indicators of Antarctic sea ice?

A new fossil araphid genus and species, Creania lacyae, and a new fossil araphid species, Synedropsis cheethamii are described from Oligocene to lower Miocene sediments recovered from the Victoria Land Basin, Antarctica. The new genus Creania possesses round, uniseriate areolae, a central sternum and apical fields composed of a row of short rectangular openings. Presence of two distinctive rimoportulae per valve, and the shape and number of apical field openings are the primary features that distinguish the genus. The genus is (at present) monospecific. The new species Synedropsis cheethamii is closely related to the modern species Synedropsis lata and S. lato var. angustata but is distinguished by its less dense stria, the shape and position of the rimoportula and the shape and structure of the apical slit field. The presence of Synedropsis in upper Oligocene sediments marks the earliest Occurrence of this genus which is commonly associated with sea-ice. We Postulate that both Synedropsis cheethamii and Creania lacyae may be utilized as paleo sea-ice indicators. New taxa formally proposed here are: Synedropsis cheethamii Olney sp. nov., Creania Olney gen. nov. and Creania lacyae Olney sp. nov

Oligocene–early Miocene Antarctic nearshore diatom biostratigraphy

Lower Oligocene (ca. 31 Ma) to lower Miocene (ca. 18.5 Ma) biosiliceous microfossils recovered from the Cape Roberts Project (CRP-2/2A) drill cores provide both paleoenvironmental and biostratigraphic information, enhancing our understanding of the geological history of the Victoria Land Basin, Antarctica. The biochronostratigraphic record obtained provides key data with which time–space–facies models may be developed. Assemblages of neritic and pelagic microfossils such as those from the CRP-2/2A drill cores provide links between the primarily pelagic microfossil-derived chronostratigraphy of the Southern Ocean and the facies models of the neritic zone.The CRP-2/2A holes drilled in the Victoria Land Basin, Antarctica during 1998 [Barrett, P.J., et al. (Eds.), 2001. Studies from the Cape Roberts Project, Ross Sea, Antarctica, Scientific Results of CRP-2/2A, Parts I and II: Terra Antarctica, vol. 7(4/5), 665pp] include several sections that contain well-preserved and relatively abundant biosiliceous microfossils. Scherer et al. [2001. Oligocene and Lower Miocene Siliceous Microfossil Biostratigraphy of Cape Roberts Project Core CRP-2/2A, Victoria Land Basin, Antarctica. In: Barrett, P.J., Ricci, C.A. (Eds.) Studies from the Cape Roberts Project, Ross Sea, Antarctica, Scientific Report of CRP-2/2A, Terra Antarctica, vol. 7(4), pp. 417–442] produced a biostratigraphic zonal framework consisting of 10 biozones; two of the zonal boundaries were correlated with the magnetostratigraphically calibrated Southern Ocean diatom biozonation. Many of the taxa observed and utilized in the above framework could not be assigned categorically to existing taxa, leading to use of informal nomenclature. We present an updated biostratigraphy and zonation scheme based on the latest taxonomic concepts and on new quantitative and qualitative siliceous microfossil data from the CRP-2/2A drill core, including formal description of four new diatom taxa used in the definition of Antarctic nearshore diatom zonal boundaries. New taxa formally proposed are Fragilariopsis truncata, Cymatosira palpebraforma, Rhizosolenia fidicularis, and Hemiaulus angustobrachiatus

Regionally specific TSC1 and TSC2 gene expression in tuberous sclerosis complex

Tuberous sclerosis complex (TSC), a heritable neurodevelopmental disorder, is caused by mutations in the TSC1 or TSC2 genes. To date, there has been little work to elucidate regional TSC1 and TSC2 gene expression within the human brain, how it changes with age, and how it may influence disease. Using a publicly available microarray dataset, we found that TSC1 and TSC2 gene expression was highest within the adult neo-cerebellum and that this pattern of increased cerebellar expression was maintained throughout postnatal development. During mid-gestational fetal development, however, TSC1 and TSC2 expression was highest in the cortical plate. Using a bioinformatics approach to explore protein and genetic interactions, we confirmed extensive connections between TSC1/TSC2 and the other genes that comprise the mammalian target of rapamycin (mTOR) pathway, and show that the mTOR pathway genes with the highest connectivity are also selectively expressed within the cerebellum. Finally, compared to age-matched controls, we found increased cerebellar volumes in pediatric TSC patients without current exposure to antiepileptic drugs. Considered together, these findings suggest that the cerebellum may play a central role in TSC pathogenesis and may contribute to the cognitive impairment, including the high incidence of autism spectrum disorder, observed in the TSC population

Selective loss of NMDA receptor NR1 subunit isoforms in Alzheimer's disease

Previous work had shown that the ratio of NMDA receptor NR1 subunit mRNA transcripts containing an N-terminal splice cassette to those that do not is markedly lower in regions of the Alzheimer's disease (AD) brain that are susceptible to pathological damage, compared with spared regions in the same cases or homotropic regions in controls. To elucidate the origins of this difference in proportionate expression, we measured the absolute levels of each of the eight NR1 transcripts by quantitative internally standardized RT-PCR assay. Expression of transcripts with the cassette was strongly attenuated in susceptible regions of Alzheimer's brain, whereas expression of non-cassette transcripts differed little from that in controls. The expression of other NR1 splice variants was not associated with pathology relevant to disease status, although some combinations of splice cassettes were well maintained in AD cases. The population profile of NR1 transcripts in occipital cortex differed from the profiles in other brain regions studied. Western analysis confirmed that the expression of protein isoforms containing the N-terminal peptide was very low in susceptible areas of the Alzheimer's brain. Cells that express NR1 subunits with the N-terminal cassette may be selectively vulnerable to toxicity in AD