A pause in Southern Hemisphere circulation trends due to the Montreal Protocol.

Observations show robust near-surface trends in Southern Hemisphere tropospheric circulation towards the end of the twentieth century, including a poleward shift in the mid-latitude jet1,2, a positive trend in the Southern Annular Mode1,3-6 and an expansion of the Hadley cell7,8. It has been established that these trends were driven by ozone depletion in the Antarctic stratosphere due to emissions of ozone-depleting substances9-11. Here we show that these widely reported circulation trends paused, or slightly reversed, around the year 2000. Using a pattern-based detection and attribution analysis of atmospheric zonal wind, we show that the pause in circulation trends is forced by human activities, and has not occurred owing only to internal or natural variability of the climate system. Furthermore, we demonstrate that stratospheric ozone recovery, resulting from the Montreal Protocol, is the key driver of the pause. Because pre-2000 circulation trends have affected precipitation12-14, and potentially ocean circulation and salinity15-17, we anticipate that a pause in these trends will have wider impacts on the Earth system. Signatures of the effects of the Montreal Protocol and the associated stratospheric ozone recovery might therefore manifest, or have already manifested, in other aspects of the Earth system.

Significant impact of forcing uncertainty in a large ensemble of climate model simulations.

Forcing due to solar and volcanic variability, on the natural side, and greenhouse gas and aerosol emissions, on the anthropogenic side, are the main inputs to climate models. Reliable climate model simulations of past and future climate change depend crucially upon them. Here we analyze large ensembles of simulations using a comprehensive Earth System Model to quantify uncertainties in global climate change attributable to differences in prescribed forcings. The different forcings considered here are those used in the two most recent phases of the Coupled Model Intercomparison Project (CMIP), namely CMIP5 and CMIP6. We show significant differences in simulated global surface air temperature due to volcanic aerosol forcing in the second half of the 19th century and in the early 21st century. The latter arise from small-to-moderate eruptions incorporated in CMIP6 simulations but not in CMIP5 simulations. We also find significant differences in global surface air temperature and Arctic sea ice area due to anthropogenic aerosol forcing in the second half of the 20th century and early 21st century. These differences are as large as those obtained in different versions of an Earth System Model employing identical forcings. In simulations from 2015 to 2100, we find significant differences in the rates of projected global warming arising from CMIP5 and CMIP6 concentration pathways that differ slightly but are equivalent in terms of their nominal radiative forcing levels in 2100. Our results highlight the influence of assumptions about natural and anthropogenic aerosol loadings on carbon budgets, the likelihood of meeting Paris targets, and the equivalence of future forcing scenarios.

Societal shifts due to COVID-19 reveal large-scale complexities and feedbacks between atmospheric chemistry and climate change.

The COVID-19 global pandemic and associated government lockdowns dramatically altered human activity, providing a window into how changes in individual behavior, enacted en masse, impact atmospheric composition. The resulting reductions in anthropogenic activity represent an unprecedented event that yields a glimpse into a future where emissions to the atmosphere are reduced. Furthermore, the abrupt reduction in emissions during the lockdown periods led to clearly observable changes in atmospheric composition, which provide direct insight into feedbacks between the Earth system and human activity. While air pollutants and greenhouse gases share many common anthropogenic sources, there is a sharp difference in the response of their atmospheric concentrations to COVID-19 emissions changes, due in large part to their different lifetimes. Here, we discuss several key takeaways from modeling and observational studies. First, despite dramatic declines in mobility and associated vehicular emissions, the atmospheric growth rates of greenhouse gases were not slowed, in part due to decreased ocean uptake of CO2 and a likely increase in CH4 lifetime from reduced NO x emissions. Second, the response of O3 to decreased NO x emissions showed significant spatial and temporal variability, due to differing chemical regimes around the world. Finally, the overall response of atmospheric composition to emissions changes is heavily modulated by factors including carbon-cycle feedbacks to CH4 and CO2, background pollutant levels, the timing and location of emissions changes, and climate feedbacks on air quality, such as wildfires and the ozone climate penalty.

Quantifying stochastic uncertainty in detection time of human-caused climate signals.

Large initial condition ensembles of a climate model simulation provide many different realizations of internal variability noise superimposed on an externally forced signal. They have been used to estimate signal emergence time at individual grid points, but are rarely employed to identify global fingerprints of human influence. Here we analyze 50- and 40-member ensembles performed with 2 climate models; each was run with combined human and natural forcings. We apply a pattern-based method to determine signal detection time [Formula: see text] in individual ensemble members. Distributions of [Formula: see text] are characterized by the median [Formula: see text] and range [Formula: see text], computed for tropospheric and stratospheric temperatures over 1979 to 2018. Lower stratospheric cooling-primarily caused by ozone depletion-yields [Formula: see text] values between 1994 and 1996, depending on model ensemble, domain (global or hemispheric), and type of noise data. For greenhouse-gas-driven tropospheric warming, larger noise and slower recovery from the 1991 Pinatubo eruption lead to later signal detection (between 1997 and 2003). The stochastic uncertainty [Formula: see text] is greater for tropospheric warming (8 to 15 y) than for stratospheric cooling (1 to 3 y). In the ensemble generated by a high climate sensitivity model with low anthropogenic aerosol forcing, simulated tropospheric warming is larger than observed; detection times for tropospheric warming signals in satellite data are within [Formula: see text] ranges in 60% of all cases. The corresponding number is 88% for the second ensemble, which was produced by a model with even higher climate sensitivity but with large aerosol-induced cooling. Whether the latter result is physically plausible will require concerted efforts to reduce significant uncertainties in aerosol forcing.

On the Detection of COVID-Driven Changes in Atmospheric Carbon Dioxide.

We assess the detectability of COVID-like emissions reductions in global atmospheric CO2 concentrations using a suite of large ensembles conducted with an Earth system model. We find a unique fingerprint of COVID in the simulated growth rate of CO2 sampled at the locations of surface measurement sites. Negative anomalies in growth rates persist from January 2020 through December 2021, reaching a maximum in February 2021. However, this fingerprint is not formally detectable unless we force the model with unrealistically large emissions reductions (2 or 4 times the observed reductions). Internal variability and carbon-concentration feedbacks obscure the detectability of short-term emission reductions in atmospheric CO2. COVID-driven changes in the simulated, column-averaged dry air mole fractions of CO2 are eclipsed by large internal variability. Carbon-concentration feedbacks begin to operate almost immediately after the emissions reduction; these feedbacks reduce the emissions-driven signal in the atmosphere carbon reservoir and further confound signal detection.

The Ocean Carbon Response to COVID-Related Emissions Reductions.

The decline in global emissions of carbon dioxide due to the COVID-19 pandemic provides a unique opportunity to investigate the sensitivity of the global carbon cycle and climate system to emissions reductions. Recent efforts to study the response to these emissions declines has not addressed their impact on the ocean, yet ocean carbon absorption is particularly susceptible to changing atmospheric carbon concentrations. Here, we use ensembles of simulations conducted with an Earth system model to explore the potential detection of COVID-related emissions reductions in the partial pressure difference in carbon dioxide between the surface ocean and overlying atmosphere (ΔpCO2), a quantity that is regularly measured. We find a unique fingerprint in global-scale ΔpCO2 that is attributable to COVID, though the fingerprint is difficult to detect in individual model realizations unless we force the model with a scenario that has four times the observed emissions reduction.

The Climate Response to Emissions Reductions Due to COVID-19: Initial Results From CovidMIP.

Many nations responded to the corona virus disease-2019 (COVID-19) pandemic by restricting travel and other activities during 2020, resulting in temporarily reduced emissions of CO2, other greenhouse gases and ozone and aerosol precursors. We present the initial results from a coordinated Intercomparison, CovidMIP, of Earth system model simulations which assess the impact on climate of these emissions reductions. 12 models performed multiple initial-condition ensembles to produce over 300 simulations spanning both initial condition and model structural uncertainty. We find model consensus on reduced aerosol amounts (particularly over southern and eastern Asia) and associated increases in surface shortwave radiation levels. However, any impact on near-surface temperature or rainfall during 2020-2024 is extremely small and is not detectable in this initial analysis. Regional analyses on a finer scale, and closer attention to extremes (especially linked to changes in atmospheric composition and air quality) are required to test the impact of COVID-19-related emission reductions on near-term climate.

Secondary Palate Development in the Dog (Canis lupus familiaris).

OBJECTIVE: To investigate the gestational timing of morphologic events in normal canine secondary palate development as a baseline for studies in dog models of isolated cleft palate (CP). METHODS: Beagle and beagle/cocker spaniel-hybrid fetal dogs were obtained by cesarean-section on various days of gestation, timed from the initial rise of serum progesterone concentration. Morphology of fetal heads was determined by examining serial coronal sections. RESULTS: On gestational day 35 (d35), the palatal shelves pointed ventrally alongside the tongue. On d36, palatal shelves were elongated and elevated to a horizontal position above the tongue but were not touching. On d37, palatine shelves and vomer were touching, but the medial epithelial seam (MES) between the apposed shelves remained. Immunostaining with epithelial protein markers showed that the MES gradually dissolved and was replaced by mesenchyme during d37-d44, and palate fusion was complete by d44. Examination of remnant MES suggested that fusion of palatal shelves began in mid-palate and moved rostrally and caudally. CONCLUSION: Palate development occurs in dogs in the steps described in humans and mice, but palate closure occurs at an intermediate time in gestation. These normative data will form the basis of future studies to determine pathophysiologic mechanisms in dog models of CP. Added clinical significance is the enhancement of dogs as a large animal model to test new approaches for palate repair, with the obvious advantage of achieving full maturity within 2 years rather than 2 decades.

PRESUMPTIVE CONGENITAL HYPOTHYROIDISM IN RED PANDAS (AILURUS FULGENS FULGENS) FROM FOUR SUCCESSIVE LITTERS.

High neonatal mortality among red pandas (Ailurus fulgens) challenges the long-term sustainability of the Species Survival Plan population. Congenital hypothyroidism (CH) is a rare condition in domestic animals, typically due to an inherited genetic defect. Nongoitrous CH was presumptively diagnosed in 75% (n = 6/8) of red panda neonates from four successive litters, with a common sire and two closely related dams. Antemortem diagnosis of CH was made in three cubs (n = 3/6) based on elevated thyroid stimulating hormone and decreased free thyroxine and total thyroxine levels. Affected cubs also had suggestive clinical signs, which included delayed growth with cretinous dwarf appearance, atonic bladder, delayed gastrointestinal motility, hypercholesterolemia, and hypocalcemia. With sodium levothyroxine therapy, two of the three cubs developed into normal adult red pandas in terms of body size, appearance, and behavior. On necropsy cubs (n = 4) were small with varying degrees of cretin dwarf appearance and hypoplastic thyroids with reduced to no colloid in follicles. These cases demonstrate the importance of collecting thyroid tissue, (or proximal trachea/larynx if gross visualization not possible), in neonates for histopathology. Further investigation into the role of thyroid disease in neonatal red panda mortality is warranted.

Inherited selective cobalamin malabsorption in Komondor dogs associated with a CUBN splice site variant.

BACKGROUND: Three Komondor dogs in a small family and 3 sporadic cases exhibited a constellation of signs that included juvenile-onset of failure-to-thrive, inappetence, vomiting and/or diarrhea, and weakness. In each we documented dyshematopoiesis, increased anion gap, methylmalonic acidemia/-uria, and serum cobalamin deficiency. Urine protein electrophoresis demonstrated excretion of cubam ligands. All clinical signs and metabolic abnormalities, except proteinuria, were reversed by regular parenteral cobalamin administration. The pattern of occurrence and findings in the disorder suggested an autosomal recessive inheritance of cobalamin malabsorption with proteinuria, a condition in humans called Imerslund-Gräsbeck syndrome. The purpose of this study was to determine the molecular cause of this disorder in Komondors. RESULTS: Whole genome sequencing of two affected Komondor dogs of unknown relatedness and one parent and a clinically-normal littermate of an affected dog revealed a pathogenic single-base change in the CUBN intron 55 splice donor consensus sequence (NM_001003148.1: c.8746 + 1G > A) that was homozygous in affected dogs and heterozygous in the unaffected parents. Alleles of the variant co-segregated with alleles of the disease locus in the entire family and all more distantly-related sporadic cases. A population study using a simple allele-specific DNA test indicated mutant allele frequencies of 8.3 and 4.5% among North American and Hungarian Komondors, respectively. CONCLUSIONS: DNA testing can be used diagnostically in Komondors when clinical signs are suggestive of cobalamin deficiency or to inform Komondor breeders prospectively and prevent occurrence of future affected dogs. This represents the third cubilin variant causing inherited selective cobalamin malabsorption in a large animal ortholog of human Imerslund-Gräsbeck syndrome.

Failure to thrive and life-threatening complications due to inherited selective cobalamin malabsorption effectively managed in a juvenile Australian shepherd dog.

A juvenile Australian shepherd dog exhibited failure to grow, inappetence, weakness, nonregenerative anemia, neutropenia, and cobalamin deficiency. DNA testing confirmed homozygosity of an amnionless mutation (AMN c.3G > A). Clinical signs resolved with supportive care and parenteral cobalamin supplementation. Inherited selective intestinal cobalamin malabsorption requiring lifelong parenteral supplementation should be considered in Australian shepherds, giant schnauzers, border collies, and beagles that fail to thrive.

Gestion efficace d'un retard de croissance et de complications potentiellement mortelles attribuables à une malabsorption de cobalamine sélective héréditaire chez un jeune chien Berger australien. Un jeune chien Berger australien a manifesté une absence de croissance, de l'inappétence, de la faiblesse, une anémie non régénérative, de la neutropénie et une déficience de cobalamine. Des tests d'ADN ont confirmé l'homozygotisme d'une mutation des récepteurs amnionless (AMN c.3G > A). Les signes cliniques se sont résorbés avec des soins de soutien et des suppléments de cobalamine parentéraux. Une malabsorption intestinale sélective héréditaire de cobalamine exigeant des suppléments parentéraux à vie devrait être considérée chez les Bergers australiens, les Schnauzers géants, les Border-Collies et les Beagles qui manifestent des problèmes de croissance.(Traduit par Isabelle Vallières).

A thyroid peroxidase (TPO) mutation in dogs reveals a canid-specific gene structure.

Congenital hypothyroidism with goiter (CHG) occurring as an autosomal recessive disorder is typically due to a defect of thyroid hormone synthesis (aka dyshormonogenesis). Thyroid peroxidase (TPO) is a multifunctional, heme-containing enzyme whose activity is required, and several inactivating TPO mutations causing CHG in humans and dogs have been described. Recently, two half-sib Spanish water dog (SWD) pups were diagnosed with CHG based on clinical signs, endocrine testing, and thyroid histology. TPO enzyme activity was absent, and immuno-cross-reactive TPO was undetectable in affected-dog thyroid tissue. A single guanosine insertion was observed in the first exon of the affected-dog TPO cDNA at a site not previously thought to be within the coding sequence. The insertion allele segregated with the deduced disease allele in the SWD breed and was not observed in unrelated dogs of various breeds. Comparison of the insertion site (an 8-nt poly-G tract) with the orthologous sequences of other mammalian reference genomes revealed that the octa-G tract obliterated the intron 1 splice acceptor site and the exon 2 translation initiation codon found at that position in other species. An in-frame ATG in strong Kozak consensus context was observed in the normal dog sequence 12 codons 5' of the usual mammalian start site, suggesting that dogs have lost the noncoding exon 1 demonstrated in human and mouse. A survey of TPO sequences in other carnivore species indicates that the poly-G tract necessitating an alternative translation initiation site is a canid-specific feature.

An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs.

Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome.

Climate models fail to capture strengthening wintertime North Atlantic jet and impacts on Europe.

Projections of wintertime surface climate over Europe depend on reliable simulations of the North Atlantic atmospheric circulation from climate models. However, it is unclear whether these models capture the long-term observed trends in the North Atlantic circulation. Here, we show that over the period from 1951 to 2020, the wintertime North Atlantic jet has strengthened, while model trends are, on average, only very weakly positive. The observed strengthening is greater than in any one of the 303 simulations from 44 climate models considered in our study. This divergence between models and observations is now much more apparent because of a very strong jet observed over the past decade. The models similarly have difficulty capturing the observed precipitation trends over Europe. Our results suggest that projections of winter atmospheric circulation and associated precipitation over Europe may be unreliable because they fail to capture the response to human emissions or underestimate the magnitude of multidecadal-to-centennial time scale internal variability.

A novel mitofusin 2 mutation causes canine fetal-onset neuroaxonal dystrophy.

We recently reported autosomal recessive fetal-onset neuroaxonal dystrophy (FNAD) in a large family of dogs that is not caused by mutation in the PLA2G6 locus (Fyfe et al., J Comp Neurol 518:3771-3784, 2010). Here, we report a genome-wide linkage analysis using 333 microsatellite markers to map canine FNAD to the telomeric end of chromosome 2. The interval of zero recombination was refined by single-nucleotide polymorphism (SNP) haplotype analysis to ~200 kb, and the included genes were sequenced. We found a homozygous 3-nucleotide deletion in exon 14 of mitofusin 2 (MFN2), predicting loss of a glutamate residue at position 539 in the protein of affected dogs. RT-PCR demonstrated near normal expression of the mutant mRNA, but MFN2 expression was undetectable to very low on western blots of affected dog brainstem, cerebrum, kidney, and cultured fibroblasts and by immunohistochemistry on brainstem sections. MFN2 is a multifunctional, membrane-bound GTPase of mitochondria and endoplasmic reticulum most commonly associated with human Charcot-Marie-Tooth disease type 2A2. The canine disorder extends the range of MFN2-associated phenotypes and suggests MFN2 as a candidate gene for rare cases of human FNAD.

Lix1 knockout mouse does not exhibit spinal muscular atrophy phenotype.

Feline spinal muscular atrophy (SMA) is an autosomal recessive juvenile onset lower motor neuron disease caused by an ∼ 140 kb deletion that disrupts expression of 2 genes, limb expression 1 (LIX1) and leucyl/cystinyl aminopeptidase (LNPEP). A previously generated Lnpep knockout (KO) mouse did not demonstrate a neuromuscular phenotype. Little is known about LIX1, except that it is evolutionarily conserved and highly expressed in spinal cord motor neurons. To determine whether loss of LIX1 alone is responsible for the feline SMA phenotype, a Lix1 intron 1 gene trap KO mouse line was obtained from Lexicon Genetics, Inc. Mating of F(1) heterozygotes produced offspring in the expected Mendelian ratios. KO and normal littermates were studied through 2 years of age by hanging latency, rotarod, inked footprint analysis, and histological methods. Disruption of Lix1 expression did not affect survival nor result in any neuromuscular phenotype. Reverse transcriptase-PCR amplification of spinal cord RNA identified a Lix1 alternative transcript beginning in intron 4 and containing exons 5 and 6. The alternative transcript appeared to be rodent specific, and its expression was not disrupted in Lix1 KO mice. Expression of the alternative transcript may have compensated for the loss of Lix1 in the KO mice and thus protected against motor neuron degeneration.

Blood and bone marrow findings in two pups with mucopolysaccharidosis type VII.

Routine blood smear findings in two of four 11-day-old mixed-breed dog littermates were suggestive of a lysosomal storage disease (LSD) that was documented to be mucopolysaccharidosis type VII (MPS VII) by molecular testing. In this condition, a functional ß-glucuronidase deficiency results in the accumulation of glycosaminoglycans (GAGs) in cells and tissues where ß-glucuronidase is important in GAG degradation. Most neutrophils and a moderate number of lymphocytes within the blood had atypical cytoplasmic magenta inclusions. The bone marrow assessment from one of the two affected pups at 24 days of age revealed similar magenta granulation in myeloid precursor cells that was most prominent in promyelocytes and myelocytes. Moreover, atypical magenta material was present within vacuoles as well as extracellularly in some osteoblasts and macrophages. Histologic bone marrow sections revealed prominent vacuolation of osteoblasts, and some osteoclasts appeared separated from the bone by layers of osteoblasts or hematopoietic cells. At 2 months of age, the second affected dog showed moderate growth retardation and had similar but more prominent hematologic findings that extended to monocytes, eosinophils, and eosinophil precursors. It had an increased number of bone marrow macrophages with many vacuoles that could be seen cytologically to contain magenta material, and there was mild nonselective phagocytosis of hemic cells. Of the hematologic cells, inclusions were most prominent in promyelocytes, myelocytes, and macrophages, cells with relatively high ß-glucuronidase activity, and GAG exposure within lysosomes or lysosome-like primary granules of granulocyte precursors.

Glycogen storage disease type IIIa in curly-coated retrievers.

BACKGROUND: Inborn errors of metabolism impose a significant genetic burden on purebred dogs and cats. The glycogen storage diseases are a category of such disorders that are typed by enzyme analysis, but deoxyribonucleic acid (DNA) based carrier tests are needed for definitive, noninvasive diagnosis and to prevent at-risk matings. HYPOTHESIS: Glycogen storage disease type IIIa (GSD IIIa) is caused by a mutation of the glycogen debranching enzyme gene (AGL) in Curly-Coated Retrievers (CCR). ANIMALS: Two CCR exhibiting episodic exercise intolerance, collapse, and lethargy, and related dogs were studied. METHODS: Structure and amount of glycogen isolated from tissue biopsy specimens was determined by enzymatic digestion, and activities of enzymes of glycogen metabolism were measured. The 33 AGL coding exons and flanking splice sites of an affected dog were amplified by polymerase chain reaction and sequenced. RESULTS: Debranching enzyme activity was undetectable in liver and skeletal muscle of affected dogs, and accumulated glycogen had absent or short outer chains of alpha1, 4-linked glucose. A single adenosine (A) deletion in AGL exon 32 of affected dog genomic DNA predicted a frame-shift and truncation of the protein product by 126 amino acid residues. The mutation was homozygous in affected dogs and heterozygous in both parents. In addition, the deletion mutation was heterozygous in 16 or not detected at all in 31 related but clinically normal CCR. CONCLUSIONS AND CLINICAL IMPORTANCE: GSD IIIa in CCR is an autosomal recessive trait caused by mutation of AGL. A DNA sequence-based carrier test was developed, and carriers were identified in the United States, New Zealand, Australia, and Finland.

Large near-term projected snowpack loss over the western United States.

Peak runoff in streams and rivers of the western United States is strongly influenced by melting of accumulated mountain snowpack. A significant decline in this resource has a direct connection to streamflow, with substantial economic and societal impacts. Observations and reanalyses indicate that between the 1980s and 2000s, there was a 10-20% loss in the annual maximum amount of water contained in the region's snowpack. Here we show that this loss is consistent with results from a large ensemble of climate simulations forced with natural and anthropogenic changes, but is inconsistent with simulations forced by natural changes alone. A further loss of up to 60% is projected within the next 30 years. Uncertainties in loss estimates depend on the size and the rate of response to continued anthropogenic forcing and the magnitude and phasing of internal decadal variability. The projected losses have serious implications for the hydropower, municipal and agricultural sectors in the region.