Description: Atmospheric CO2 and global climate are closely coupled. Since 800 ka CO2 concentrations have been up to 50% higher during interglacial compared to glacial periods. Because of its dependence on temperature, humidity, and erosion rates, chemical weathering of exposed silicate minerals was suggested to have dampened these cyclic variations of atmospheric composition. Cooler and drier conditions and lower non-glacial erosion rates suppressed in situ chemical weathering rates during glacial periods. However, using systematic variations in major element geochemistry, Sr–Nd isotopes and clay mineral records from Ocean Drilling Program Sites 1143 and 1144 in the South China Sea spanning the last 1.1 Ma, we show that sediment deposited during glacial periods was more weathered than sediment delivered during interglacials. We attribute this to subaerial exposure and weathering of unconsolidated shelf sediments during glacial sealevel lowstands. Our estimates suggest that enhanced silicate weathering of tropical shelf sediments exposed during glacial lowstands can account for ∼9% of the carbon dioxide removed from the atmosphere during the glacial and thus represent a significant part of the observed glacial–interglacial variation of ∼80 ppmv. As a result, if similar magnitudes can be identified in other tropical shelf-slope systems, the effects of increased sediment exposure and subsequent silicate weathering during lowstands could have potentially enhanced the drawdown of atmospheric CO2 during cold stages of the Quaternary. This in turn would have caused an intensification of glacial cycles.

Description: Long non-coding RNAs (lncRNAs) perform a diversity of functions in numerous important biological processes and are implicated in many human diseases. In this report we present lncRNAWiki ( http://lncrna.big.ac.cn ), a wiki-based platform that is open-content and publicly editable and aimed at community-based curation and collection of information on human lncRNAs. Current related databases are dependent primarily on curation by experts, making it laborious to annotate the exponentially accumulated information on lncRNAs, which inevitably requires collective efforts in community-based curation of lncRNAs. Unlike existing databases, lncRNAWiki features comprehensive integration of information on human lncRNAs obtained from multiple different resources and allows not only existing lncRNAs to be edited, updated and curated by different users but also the addition of newly identified lncRNAs by any user. It harnesses community collective knowledge in collecting, editing and annotating human lncRNAs and rewards community-curated efforts by providing explicit authorship based on quantified contributions. LncRNAWiki relies on the underling knowledge of scientific community for collective and collaborative curation of human lncRNAs and thus has the potential to serve as an up-to-date and comprehensive knowledgebase for human lncRNAs.

Description: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that was first reported in China in 2009. Phylogenetic analysis of the viral genome showed that SFTS virus represents a new lineage within the Phlebovirus genus, distinct from the existing sandfly fever and Uukuniemi virus groups, in the family Bunyaviridae . SFTS disease is characterized by gastrointestinal symptoms, chills, joint pain, myalgia, thrombocytopenia, leukocytopenia, and some hemorrhagic manifestations with a case fatality rate of about 2 to 15%. Here we report the development of reverse genetics systems to study STFSV replication and pathogenesis. We developed and optimized functional T7 polymerase-based M- and S-segment minigenome assays, which revealed errors in the published terminal sequences of the S segment of the Hubei 29 strain of SFTSV. We then generated recombinant viruses from cloned cDNAs prepared to the antigenomic RNAs both of the minimally passaged virus (HB29) and of a cell culture-adapted strain designated HB29pp. The growth properties, pattern of viral protein synthesis, and subcellular localization of viral N and NSs proteins of wild-type HB29pp (wtHB29pp) and recombinant HB29pp viruses were indistinguishable. We also show that the viruses fail to shut off host cell polypeptide production. The robust reverse genetics system described will be a valuable tool for the design of therapeutics and the development of killed and attenuated vaccines against this important emerging pathogen. IMPORTANCE SFTSV and related tick-borne phleboviruses such as Heartland virus are emerging viruses shown to cause severe disease in humans in the Far East and the United States, respectively. Study of these novel pathogens would be facilitated by technology to manipulate these viruses in a laboratory setting using reverse genetics. Here, we report the generation of infectious SFTSV from cDNA clones and demonstrate that the behavior of recombinant viruses is similar to that of the wild type. This advance will allow for further dissection of the roles of each of the viral proteins in the context of virus infection, as well as help in the development of antiviral drugs and protective vaccines.

Description: Platinum and PARP inhibitor (PARPi) sensitivity commonly coexist in epithelial ovarian cancer (EOC) due to the high prevalence of alterations in the homologous recombination (HR) DNA repair pathway that confer sensitivity to both drugs. In this report, we describe a unique subset of EOC with alterations in another DNA repair pathway, the nucleotide excision repair (NER) pathway, which may exhibit a discordance in sensitivities to these drugs. Specifically, 8% of high-grade serous EOC from The Cancer Genome Atlas dataset exhibited NER alterations, including nonsynonymous or splice site mutations and homozygous deletions of NER genes. Tumors with NER alterations were associated with improved overall survival (OS) and progression-free survival (PFS), compared with patients without NER alterations or BRCA1/2 mutations. Furthermore, patients with tumors with NER alterations had similar OS and PFS as BRCA1/2-mutated patients, suggesting that NER pathway inactivation in EOC conferred enhanced platinum sensitivity, similar to BRCA1/2-mutated tumors. Moreover, two NER mutations (ERCC6-Q524* and ERCC4-A583T), identified in the two most platinum-sensitive tumors, were functionally associated with platinum sensitivity in vitro. Importantly, neither NER alteration affected HR or conferred sensitivity to PARPi or other double-strand break–inducing agents. Overall, our findings reveal a new mechanism of platinum sensitivity in EOC that, unlike defective HR, may lead to a discordance in sensitivity to platinum and PARPi, with potential implications for previously reported and ongoing PARPi trials in this disease. Cancer Res; 75(4); 628–34. ©2015 AACR.

Description: Intratumoral heterogeneity of ADAM23 promotes tumor growth and metastasis through LGI4 and nitric oxide signals Oncogene 34, 1270 (05 March 2015). doi:10.1038/onc.2014.70 Authors: E T Costa, G F Barnabé, M Li, A A M Dias, T R Machado, P F Asprino, F P Cavalher, E N Ferreira, M del Mar Inda, M H Nagai, B Malnic, M L Duarte, K R M Leite, A C S D de Barros, D M Carraro, R Chammas, H A Armelin, W Cavenee, F Furnari & A A Camargo

Description: From a survey of the first nightside season of NASA's Van Allen Probes mission (Dec/2012 – Sep/2013), 47 energetic (10s to 100s of keV) electron injection events were found at L-shells ≤ 4, all of which are deeper than any previously reported substorm-related injections. Preliminary details from these events are presented, including how: all occurred shortly after dipolarization signatures and injections were observed at higher L-shells; the deepest observed injection was at L~2.5; and, surprisingly, L≤4 injections are limited in energy to ≤250 keV. We present a detailed case study of one example event revealing that the injection of electrons down to L~3.5 was different from injections observed at higher L and likely resulted from drift resonance with a fast magnetosonic wave in the Pi 2 frequency range inside the plasmasphere. These observations demonstrate that injections occur at very low L-shells and may play an important role for inner zone electrons.

Description: Plasmodium vivax merozoites only invade reticulocytes, a minor though heterogeneous population of red blood cell precursors that can be graded by levels of transferrin receptor (CD71) expression. The development of a protocol that allows sorting reticulocytes into defined developmental stages and a robust ex vivo P vivax invasion assay has made it possible for the first time to investigate the fine-scale invasion preference of P vivax merozoites. Surprisingly, it was the immature reticulocytes (CD71 + ) that are generally restricted to the bone marrow that were preferentially invaded, whereas older reticulocytes (CD71 – ), principally found in the peripheral blood, were rarely invaded. Invasion assays based on the CD71 + reticulocyte fraction revealed substantial postinvasion modification. Thus, 3 to 6 hours after invasion, the initially biomechanically rigid CD71 + reticulocytes convert into a highly deformable CD71 – infected red blood cell devoid of host reticular matter, a process that normally spans 24 hours for uninfected reticulocytes. Concurrent with these changes, clathrin pits disappear by 3 hours postinvasion, replaced by distinctive caveolae nanostructures. These 2 hitherto unsuspected features of P vivax invasion, a narrow preference for immature reticulocytes and a rapid remodeling of the host cell, provide important insights pertinent to the pathobiology of the P vivax infection.

Description: An epidemiologic risk prediction model for ovarian cancer in Europe: the EPIC study British Journal of Cancer 112, 1257 (31 March 2015). doi:10.1038/bjc.2015.22 Authors: K Li, A Hüsing, R T Fortner, A Tjønneland, L Hansen, L Dossus, J Chang-Claude, M Bergmann, A Steffen, C Bamia, D Trichopoulos, A Trichopoulou, D Palli, A Mattiello, C Agnoli, R Tumino, N C Onland-Moret, P H Peeters, H B(as) Bueno-de-Mesquita, I T Gram, E Weiderpass, E Sánchez-Cantalejo, M-D Chirlaque, E J Duell, E Ardanaz, A Idahl, E Lundin, K-T Khaw, R C Travis, M A Merritt, M J Gunter, E Riboli, P Ferrari, K Terry, D Cramer & R Kaaks

Description: We report on the implementation of 5 THz quantum well photodetector exploiting a patch antenna cavity array. The benefit of our plasmonic architecture on the detector performance is assessed by comparing it with detectors made using the same quantum well absorbing region, but processed into a standard 45° polished facet mesa. Our results demonstrate a clear improvement in responsivity, polarization insensitivity, and background limited performance. Peak detectivities in excess of 5 × 10 12 cmHz 1/2 /W have been obtained, a value comparable with that of the best cryogenic cooled bolometers.

Description: During the Holocene there has been a gradual increase in the influence of humans on Earth systems. High-resolution sedimentary records can help us to assess how erosion and weathering have evolved in response to recent climatic and anthropogenic disturbances. Here we present data from a high-resolution (~75 cm/k.y.) sedimentary archive from the South China Sea. Provenance data indicate that the sediment was derived from the Red River, and can be used to reconstruct the erosion and/or weathering history in this river basin. Accelerator mass spectrometry 14 C dating provides direct age control and reveals coherent variations in clay mineralogy, geochemistry, and terrigenous flux, indicative of strong chemical weathering and physical erosion during the mid-Holocene warm period (6400–4000 cal [calibrated] yr B.P.), followed by weakening from ca. 4000–1800 cal yr B.P., and renewed intensification since 1800 cal yr B.P.. Comparison with climatic records from China indicates that precipitation and temperature controlled both physical erosion and chemical weathering intensity before 1800 cal yr B.P.. However, weathering proxies in the offshore sediment indicate recent increased soil erosion. We suggest that enhanced human activity (deforestation, cultivation, and mining) since the end of the Chinese Han Dynasty (220 CE) has overwhelmed the natural climatic controls on erosion in the Red River.