Bighorn Basin Coring Project (BBCP): a continental perspective on early Paleogene hyperthermals

During the summer of 2011, the Bighorn Basin Coring Project (BBCP) recovered over 900m of overlapping core from 3 different sites in late Paleocene to early Eocene fluvial deposits of northwestern Wyoming. BBCP cores are being used to develop high-resolution proxy records of the Paleocene–Eocene Thermal Maximum (PETM) and Eocene Thermal Maximum 2 (ETM2) hyperthermal events. These events are short-term, large magnitude global warming events associated with extreme perturbations to the earth’s carbon cycle. Although the PETM and ETM2 occurred ~55–52 million years ago, they are analogous in many ways to modern anthropogenic changes to the carbon cycle. By applying various sedimentological, geochemical, and palynological methods to the cores, we hope to better understand what caused these events, study the biogeochemical and ecological feedbacks that operated during them, and reveal precisely how they impacted continental environments. Core recovery was > 98% in all holes and most drilling was carried out without fluid additives, showing that continuous coring of continental smectitic deposits like these can be achieved with minimal risk of contamination to molecular biomarkers. Cores were processed in the Bremen Core Repository where the science team convened for 17 days to carry out data collection and sampling protocols similar to IODP projects. Initial results show that the weathered horizon extends to as much as ~30m below the surface and variations in magnetic susceptibility within the cores record an interplay between grain size and pedogenesis. Previous investigations of outcrops near the BBCP drill sites allow detailed evaluation of the effects of weathering on common proxy methods. Studies of lithofacies, organic geochemistry, stable isotope geochemistry, calibrated XRF core scanning, paleomagnetics, and palynology are underway and will represent the highest resolution and most integrated proxy records of the PETM from a continental setting yet known. An extensive outreach program is in place to capitalize on the educational value associated with the Bighorn Basin’s unusually complete record of Phanerozoic earth history

Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies

Loss of nuclear TDP-43 is a hallmark of neurodegeneration in TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 mislocalization results in cryptic splicing and polyadenylation of pre–messenger RNAs (pre-mRNAs) encoding stathmin-2 (also known as SCG10), a protein that is required for axonal regeneration. We found that TDP-43 binding to a GU-rich region sterically blocked recognition of the cryptic 3′ splice site in STMN2 pre-mRNA. Targeting dCasRx or antisense oligonucleotides (ASOs) suppressed cryptic splicing, which restored axonal regeneration and stathmin-2–dependent lysosome trafficking in TDP-43–deficient human motor neurons. In mice that were gene-edited to contain human STMN2 cryptic splice-polyadenylation sequences, ASO injection into cerebral spinal fluid successfully corrected Stmn2 pre-mRNA misprocessing and restored stathmin-2 expression levels independently of TDP-43 binding