Abnormal Properties of Milk from Transgenic Mice Expressing Bovine β-Casein under Control of the Bovine α-lactalbumin 5\u27 Flanking Region

Transgenic mice produced in this investigation contained the proximal promoter elements, the genomic coding sequence and the 3\u27 flanking region of bovine β-casein and the 5\u27 regulatory elements of bovine α-lactalbumin. Specifically, the gene construct included the TATAA box, CAAT box and polyadenylation signal of bovine β-casein in addition to the 5\u27 regulatory elements of the bovine α-lactalbumin gene. Four lines of transgenic mice were generated; they expressed bovine β-casein in their milk at concentrations of up to 10 mg mL-1. The milk from the transgenic mice tended to be very viscous and a proportion of these mice stopped lactating before the normal onset of involution. The time at which the abrupt involution occurred was directly correlated to the amount of β-casein produced. Mice secreting approximately 10 mg mL-1 of β-casein in their milk stopped lactating approximately 1-3 days after parturition while mice expressing 1-3 mg mL-1 stopped lactating around days 10-18. The high expressing mice appeared to lactate normally on day 1 of lactation, but on day 3 the mammary gland morphology revealed alveoli and ducts which were very distended and contained milk components. However, the viscous milk solution could not be removed from the gland at this stage of lactation. There were also a number of alveoli that appeared to have gone through the process of involution by day 3 of lactation

Genetic Modification of Bovine β-Casein and Its Expression in the Milk of Transgenic Mice

Genomic vectors containing mutant bovine β-casein with putative glycosylation sites were constructed to study the functional properties of glycosylated β-casein and its possible effects in milk. The mutation was performed by PCR-based site-directed mutagenesis. The tripeptide sequence, Asn-X-Ser, was generated between Asn68 and Asn73 in mature β-casein. The resulting β-casein mutants were designated pCJB68 and pCJB6873. pCJB68 carries a substitution of Ser70 for Leu70 (Asn68-Ser69-Ser70-Pro71), and pCJB6873 carries a substitution of Ser70-Ser71 for Leu70-Pro71 (Asn68-Ser69-Ser70-Ser71). The two mutated genomic constructs were placed under control of the bovine α-lactalbumin promoter, and lines of mice expressing the pCJB68 and pCJB6873 have been established. The milk from transgenic mice contained bovine β-casein at levels up to 2-3 mg/mL. N-Linked glycosylation of bovine β-casein in the pCJB6873 line was confirmed by peptide-N-glycosidase F treatment, but glycosylation of bovine β-casein did not occur in pCJB68 mice. In addition, mouse casein micelles containing glycosylated bovine β-casein showed the largest median diameter and rough outer surface, compared to normal mouse casein micelles and micelles from transgenic milk containing bovine β-casein

GISS-E2.1: Configurations and Climatology

This paper describes the GISS-E2.1 contribution to the Coupled Model Intercomparison Project, Phase 6 (CMIP6). This model version differs from the predecessor model (GISS-E2) chiefly due to parameterization improvements to the atmospheric and ocean model components, while keeping atmospheric resolution the same. Model skill when compared to modern era climatologies is significantly higher than in previous versions. Additionally, updates in forcings have a material impact on the results. In particular, there have been specific improvements in representations of modes of variability (such as the Madden-Julian Oscillation and other modes in the Pacific) and significant improvements in the simulation of the climate of the Southern Oceans, including sea ice. The effective climate sensitivity to 2 × CO2 is slightly higher than previously at 2.7–3.1°C (depending on version) and is a result of lower CO2 radiative forcing and stronger positive feedbacks.Y

Future Climate Change Under SSP Emission Scenarios With GISS-E2.1

This paper presents the response to anthropogenic forcing in the GISS-E2.1 climate models for the 21st century Shared Socioeconomic Pathways emission scenarios within the Coupled Model Intercomparison Project Phase 6 (CMIP6). The experiments were performed using an updated and improved version of the NASA Goddard Institute for Space Studies (GISS) coupled general circulation model that includes two different versions for atmospheric composition: A non-interactive version (NINT) with prescribed composition and a tuned aerosol indirect effect and the One-Moment Aerosol model (OMA) version with fully interactive aerosols which includes a parameterized first indirect aerosol effect on clouds. The effective climate sensitivities are 3.0°C and 2.9°C for the NINT and OMA models, respectively. Each atmospheric version is coupled to two different ocean general circulation models: The GISS ocean model (E2.1-G) and HYCOM (E2.1-H). We describe the global mean responses for all future scenarios and spatial patterns of change for surface air temperature and precipitation for four of the marker scenarios: SSP1-2.6, SSP2-4.5, SSP4-6.0, and SSP5-8.5. By 2100, global mean warming ranges from 1.5°C to 5.2°C relative to 1,850–1,880 mean temperature. Two high-mitigation scenarios SSP1-1.9 and SSP1-2.6 limit the surface warming to below 2°C by the end of the 21st century, except for the NINT E2.1-H model that simulates 2.2°C of surface warming. For the high emission scenario SSP5-8.5, the range is 4.6–5.2°C at 2100. Due to about 15% larger effective climate sensitivity and stronger transient climate response in both NINT and OMA CMIP6 models compared to CMIP5 versions, there is a stronger warming by 2100 in the SSP emission scenarios than in the comparable Representative Concentration Pathway (RCP) scenarios in CMIP5. Changes in sea ice area are highly correlated to global mean surface air temperature anomalies and show steep declines in both hemispheres, with the largest sea ice area decreases occurring during September in the Northern Hemisphere in both E2.1-G (−1.21 × 106 km2/°C) and E2.1-H models (−0.94 × 106 km2/°C). Both coupled models project decreases in the Atlantic overturning stream function by 2100. The largest decrease of 56%–65% in the 21st century overturning stream function is produced in the warmest scenario SSP5-8.5 in the E2.1-G model, comparable to the reduction in the corresponding CMIP5 GISS-E2 RCP8.5 simulation. Both low-end scenarios SSP1-1.9 and SSP1-2.6 also simulate substantial reductions of the overturning (9%–37%) with slow recovery of about 10% by the end of the 21st century (relative to the maximum decrease at the middle of the 21st century).Y

CMIP6 Historical Simulations (1850–2014) With GISS-E2.1

Simulations of the CMIP6 historical period 1850–2014, characterized by the emergence of anthropogenic climate drivers like greenhouse gases, are presented for different configurations of the NASA Goddard Institute for Space Studies (GISS) Earth System ModelE2.1. The GISS-E2.1 ensembles are more sensitive to greenhouse gas forcing than their CMIP5 predecessors (GISS-E2) but warm less during recent decades due to a forcing reduction that is attributed to greater longwave opacity in the GISS-E2.1 pre-industrial simulations. This results in an atmosphere less sensitive to increases in opacity from rising greenhouse gas concentrations, demonstrating the importance of the base climatology to forcing and forced climate trends. Most model versions match observed temperature trends since 1979 from the ocean to the stratosphere. The choice of ocean model is important to the transient climate response, as found previously in CMIP5 GISS-E2: the model that more efficiently exports heat to the deep ocean shows a smaller rise in tropospheric temperature. Model sea level rise over the historical period is traced to excessive drawdown of aquifers to meet irrigation demand with a smaller contribution from thermal expansion. This shows how fully coupled models can provide indirect observational constraints upon forcing, in this case, constraining irrigation rates with observed sea level changes. The overall agreement of GISS-E2.1 with observed trends is familiar from evaluation of its predecessors, as is the conclusion that these trends are almost entirely anthropogenic in origin.Y

GISS‐E2.1: Configurations and Climatology

Abstract This paper describes the GISS‐E2.1 contribution to the Coupled Model Intercomparison Project, Phase 6 (CMIP6). This model version differs from the predecessor model (GISS‐E2) chiefly due to parameterization improvements to the atmospheric and ocean model components, while keeping atmospheric resolution the same. Model skill when compared to modern era climatologies is significantly higher than in previous versions. Additionally, updates in forcings have a material impact on the results. In particular, there have been specific improvements in representations of modes of variability (such as the Madden‐Julian Oscillation and other modes in the Pacific) and significant improvements in the simulation of the climate of the Southern Oceans, including sea ice. The effective climate sensitivity to 2 × CO2 is slightly higher than previously at 2.7–3.1°C (depending on version) and is a result of lower CO2 radiative forcing and stronger positive feedbacks