Incomplete penetrance for isolated congenital asplenia in humans with mutations in translated and untranslated RPSA exons.

Isolated congenital asplenia (ICA) is the only known human developmental defect exclusively affecting a lymphoid organ. In 2013, we showed that private deleterious mutations in the protein-coding region of RPSA, encoding ribosomal protein SA, caused ICA by haploinsufficiency with complete penetrance. We reported seven heterozygous protein-coding mutations in 8 of the 23 kindreds studied, including 6 of the 8 multiplex kindreds. We have since enrolled 33 new kindreds, 5 of which are multiplex. We describe here 11 new heterozygous ICA-causing RPSA protein-coding mutations, and the first two mutations in the 5'-UTR of this gene, which disrupt mRNA splicing. Overall, 40 of the 73 ICA patients (55%) and 23 of the 56 kindreds (41%) carry mutations located in translated or untranslated exons of RPSA. Eleven of the 43 kindreds affected by sporadic disease (26%) carry RPSA mutations, whereas 12 of the 13 multiplex kindreds (92%) carry RPSA mutations. We also report that 6 of 18 (33%) protein-coding mutations and the two (100%) 5'-UTR mutations display incomplete penetrance. Three mutations were identified in two independent kindreds, due to a hotspot or a founder effect. Finally, RPSA ICA-causing mutations were demonstrated to be de novo in 7 of the 23 probands. Mutations in RPSA exons can affect the translated or untranslated regions and can underlie ICA with complete or incomplete penetrance.

Pliocene-Pleistocene evolution of sea surface and intermediate water temperatures from the southwest Pacific.

Over the last 5 million years, the global climate system has evolved toward a colder mean state, marked by large-amplitude oscillations in continental ice volume. Equatorward expansion of polar waters and strengthening temperature gradients have been detected. However, the response of the mid latitudes and high latitudes of the Southern Hemisphere is not well documented, despite the potential importance for climate feedbacks including sea ice distribution and low-high latitude heat transport. Here we reconstruct the Pliocene-Pleistocene history of both sea surface and Antarctic Intermediate Water (AAIW) temperatures on orbital time scales from Deep Sea Drilling Project Site 593 in the Tasman Sea, southwest Pacific. We confirm overall Pliocene-Pleistocene cooling trends in both the surface ocean and AAIW, although the patterns are complex. The Pliocene is warmer than modern, but our data suggest an equatorward displacement of the subtropical front relative to present and a poleward displacement of the subantarctic front of the Antarctic Circumpolar Current (ACC). Two main intervals of cooling, from ~3 Ma and ~1.5 Ma, are coeval with cooling and ice sheet expansion noted elsewhere and suggest that equatorward expansion of polar water masses also characterized the southwest Pacific through the Pliocene-Pleistocene. However, the observed trends in sea surface temperature and AAIW temperature are not identical despite an underlying link to the ACC, and intervals of unusual surface ocean warmth (~2 Ma) and large-amplitude variability in AAIW temperatures (from ~1 Ma) highlight complex interactions between equatorward displacements of fronts associated with the ACC and/or varying poleward heat transport from the subtropics.

Estimating biodiversity across the tree of life on Mount Everest's southern flank with environmental DNA.

Species composition in high-alpine ecosystems is a useful indicator for monitoring climatic and environmental changes at the upper limits of habitable environments. We used environmental DNA (eDNA) analysis to document the breadth of high-alpine biodiversity present on Earth's highest mountain, Mt. Everest (8,849 m a.s.l.) in Nepal's Khumbu region. In April-May 2019, we collected eDNA from ten ponds and streams between 4,500 m and 5,500 m. Using multiple sequencing and bioinformatic approaches, we identified taxa from 36 phyla and 187 potential orders across the Tree of Life in Mt. Everest's high-alpine and aeolian ecosystem. These organisms, all recorded above 4,500 m-an elevational belt comprising <3% of Earth's land surface-represents ∼16% of global taxonomic order estimates. Our eDNA inventory will aid future high-Himalayan biomonitoring and retrospective molecular studies to assess changes over time as climate-driven warming, glacial melt, and anthropogenic influences reshape this rapidly transforming world-renowned ecosystem.

Climatic and tectonic significance of Taboche Lake, Khumbu Region, Nepal.

The Everest region is characterized by its alpine glacial environment. In an effort to understand environmental change and tectonic activity, our team cored Taboche Lake, situated at 4,712 m along the western margin of the Ngozumpa Glacier. This research catalogs past earthquakes using geological records of the lake core that are important for the assessment of future earthquake hazards in the region and provides information for tectonic risk of glacial lake floods. Core grain size characteristics and internal sedimentary structures from computed tomographic scan were coupled with radiocarbon dating of organic matter preserved in the core to reconstruct the environmental history of the area. The 58-cm-long core consists of laminated silty sands and sandy silts with particle diameters <2 mm. The core records a syn-sedimentary deformational structure, folded sediments, rhythmically alternating dark- and light-colored laminations, and turbidites, which indicate coeval climatic and tectonic variations over the past ∼1,600 years.

A case study using 2019 pre-monsoon snow and stream chemistry in the Khumbu region, Nepal.

This case study provides a framework for future monitoring and evidence for human source pollution in the Khumbu region, Nepal. We analyzed the chemical composition (major ions, major/trace elements, black carbon, and stable water isotopes) of pre-monsoon stream water (4300-5250 m) and snow (5200-6665 m) samples collected from Mt. Everest, Mt. Lobuche, and the Imja Valley during the 2019 pre-monsoon season, in addition to a shallow ice core recovered from the Khumbu Glacier (5300 m). In agreement with previous work, pre-monsoon aerosol deposition is dominated by dust originating from western sources and less frequently by transport from southerly air mass sources as demonstrated by evidence of one of the strongest recorded pre-monsoon events emanating from the Bay of Bengal, Cyclone Fani. Elevated concentrations of human-sourced metals (e.g., Pb, Bi, As) are found in surface snow and stream chemistry collected in the Khumbu region. As the most comprehensive case study of environmental chemistry in the Khumbu region, this research offers sufficient evidence for increased monitoring in this watershed and surrounding areas.

Into Thick(er) Air? Oxygen Availability at Humans' Physiological Frontier on Mount Everest.

Global audiences are captivated by climbers pushing themselves to the limits in the hypoxic environment of Mount Everest. However, air pressure sets oxygen abundance, meaning it varies with the weather and climate warming. This presents safety issues for mountaineers but also an opportunity for public engagement around climate change. Here we blend new observations from Everest with ERA5 reanalysis (1979-2019) and climate model results to address both perspectives. We find that plausible warming could generate subtle but physiologically relevant changes in summit oxygen availability, including an almost 5% increase in annual minimum VO2 max for 2°C warming since pre-industrial. In the current climate we find evidence of swings in pressure sufficient to change Everest's apparent elevation by almost 750 m. Winter pressures can also plunge lower than previously reported, highlighting the importance of air pressure forecasts for the safety of those trying to push the physiological frontier on Mt. Everest.

Mid Pleistocene foraminiferal mass extinction coupled with phytoplankton evolution.

Understanding the interaction between climate and biotic evolution is crucial for deciphering the sensitivity of life. An enigmatic mass extinction occurred in the deep oceans during the Mid Pleistocene, with a loss of over 100 species (20%) of sea floor calcareous foraminifera. An evolutionarily conservative group, benthic foraminifera often comprise >50% of eukaryote biomass on the deep-ocean floor. Here we test extinction hypotheses (temperature, corrosiveness and productivity) in the Tasman Sea, using geochemistry and micropalaeontology, and find evidence from several globally distributed sites that the extinction was caused by a change in phytoplankton food source. Coccolithophore evolution may have enhanced the seasonal 'bloom' nature of primary productivity and fundamentally shifted it towards a more intra-annually variable state at ∼0.8 Ma. Our results highlight intra-annual variability as a potential new consideration for Mid Pleistocene global biogeochemical climate models, and imply that deep-sea biota may be sensitive to future changes in productivity.