Single cell cortical bone transcriptomics define novel osteolineage gene sets altered in chronic kidney disease

IntroductionDue to a lack of spatial-temporal resolution at the single cell level, the etiologies of the bone dysfunction caused by diseases such as normal aging, osteoporosis, and the metabolic bone disease associated with chronic kidney disease (CKD) remain largely unknown.MethodsTo this end, flow cytometry and scRNAseq were performed on long bone cells from Sost-cre/Ai9+ mice, and pure osteolineage transcriptomes were identified, including novel osteocyte-specific gene sets.ResultsClustering analysis isolated osteoblast precursors that expressed Tnc, Mmp13, and Spp1, and a mature osteoblast population defined by Smpd3, Col1a1, and Col11a1. Osteocytes were demarcated by Cd109, Ptprz1, Ramp1, Bambi, Adamts14, Spns2, Bmp2, WasI, and Phex. We validated our in vivo scRNAseq using integrative in vitro promoter occupancy via ATACseq coupled with transcriptomic analyses of a conditional, temporally differentiated MSC cell line. Further, trajectory analyses predicted osteoblast-to-osteocyte transitions via defined pathways associated with a distinct metabolic shift as determined by single-cell flux estimation analysis (scFEA). Using the adenine mouse model of CKD, at a time point prior to major skeletal alterations, we found that gene expression within all stages of the osteolineage was disturbed.ConclusionIn sum, distinct populations of osteoblasts/osteocytes were defined at the single cell level. Using this roadmap of gene assembly, we demonstrated unrealized molecular defects across multiple bone cell populations in a mouse model of CKD, and our collective results suggest a potentially earlier and more broad bone pathology in this disease than previously recognized

Climate Science Special Report: Fourth National Climate Assessment (NCA4), Volume I

New observations and new research have increased our understanding of past, current, and future climate change since the Third U.S. National Climate Assessment (NCA3) was published in May 2014. This Climate Science Special Report (CSSR) is designed to capture that new information and build on the existing body of science in order to summarize the current state of knowledge and provide the scientific foundation for the Fourth National Climate Assessment (NCA4)

\u3ci\u3eSchizaphis minuta\u3c/i\u3e (van der Goot) (Homoptera: Aphididae), new to the United States

Schizaphis minuta (van der Goot) (Fig. 1) was found for the first time in the Western Hemisphere in suction trap samples in Florida. The first specimen was collected in a trap at Quincy (Gadsden County) for the period 16 - 23 November 1998. The record subsequently was verified by collections on several species of Cyperus in the Ft. Pierce area. The aphid is specific to Cyperus and is unlikely to pose any threat to agriculture. Schizaphis minuta probably is native to Asia and has been recorded previously in Africa and Australia. It is not known to be a pest

Palaeomagnetism of the ca. 440 Ma Cape St Mary's sills of the Avalon Peninsula of Newfoundland: implications for Iapetus Ocean closure

We report on the palaeomagnetism of the gabbroic Cape St Mary’s sills of the Avalon Peninsula of Newfoundland, which have previously yielded a 441±2 Ma U–Pb baddeleyite age (latest Ordovician or earliest Silurian). At 12 of 19 sites, stepwise alternating-field or thermal demagnetization isolated a stable characteristic remanence carried by magnetite. This remanence is shown to pre-date Early Devonian folding of the sills. Although a baked-contact test was inconclusive, the positive fold test and the low grade of metamorphism of the sills (prehnite–pumpellyite facies) make it likely that the characteristic remanence is primary. The tilt-corrected site-mean characteristic remanence has a declination of 343° and an inclination of −51° (k=25, a95=9°), yielding a ~440 Ma palaeopole at 10°N, 140°E (dm=12°, dp=8°) for West (North American) Avalonia. The corresponding ~440 Ma palaeolatitude for the Avalon Peninsula is 32°S±8°. The only other West Avalonian palaeolatitude determination from rocks that could be of similar age is from the Dunn Point volcanics of Nova Scotia; their more southerly palaeolatitude of 41°S±5° suggests that they are significantly older than 440 Ma, a possibility that we recommend testing with U–Pb dating. Although no ~440 Ma palaeolatitude determinations are available for East Avalonia (parts of southern Britain and Ireland), interpolating between mid-Ordovician and mid-Silurian determinations gives an estimate of ~25°S. This is consistent with our Cape St Mary’s result and, if the Iapetus Ocean closed orthogonally, with a narrow (~1000 km) Iapetus Ocean of approximately east–west orientation between Avalonia and Laurentia by 440 Ma