ALBERT

Description: Strong upwelling events inshore of the Agulhas Current close to 33.5°S are investigated. These events are important to the exchange of shelf and slope waters, potentially enhancing primary productivity and advecting larvae offshore. Using hydrographic observations, this study shows that a wind-driven upwelling event and a current-driven upwelling event can each advect central waters more than 130 m upward, resulting in a maximum 9°C cooling at 50-m depth over the continental shelf and surface cooling greater than 4°C. The authors use satellite data to assess the frequency and forcing mechanisms of similar cold events from January 2003 through December 2011, defining cold events as days when the sea surface temperature (SST) anomaly is significantly correlated with a local current or wind forcing. The authors identify 47 events with an average length of 2.2 days and SST anomaly of −1.6°C, corresponding to an average 13 days of surface cold events along the Agulhas Current front per year. This study uses combined EOF analysis to characterize these cold events based on four highly correlated forcing mechanisms: alongshore wind speed, wind stress curl, current meandering, and current speed over the slope. The authors find that meanders act in combination with upwelling-favorable winds to force the strongest cold events, while upwelling-favorable winds alone, possibly primed by Ekman veering, force weaker cold events. Most significantly, it is found that the frontal curvature of warm Agulhas Current meanders couples with the atmosphere to drive local wind stress curl anomalies that reinforce upwelling.

Description: Of the interannual variance of the Agulhas Current transport, 29% can be linearly related to six modes of Southern Hemisphere atmospheric variability. Agulhas Current transport is quantified by a 24-yr proxy constructed using satellite altimetry and in situ data, while atmospheric variability is represented by two reanalysis products. The two leading modes of atmospheric variability, each explaining 5% of the variance of the Agulhas Current, can be described as a tropical Indo-Pacific mode, strongly correlated to ENSO, and a subtropical–subpolar mode, strongly correlated with the SAM. ENSO alone can explain 11.5% of Agulhas transport variance, yet SAM alone has no significant correlation. The remaining four atmospheric modes are not related to common climate indices and together they explain 19% of Agulhas variance, describing decadal oscillations. In previous studies using reanalyses and climate models it has been suggested that the Agulhas Current is intensifying in response to a strengthening and poleward shift of the westerlies, expressed by a positive trend in the SAM. Here, the authors find that, given its apparent weak sensitivity to the SAM, the increase in SAM over the past 24 years does not lead to a detectable trend in Agulhas Current transport.

Description: Thank you to those who reviewed in 2017 for Geophysical Research Letters. ©2018. American Geophysical Union. All Rights Reserved.

Description: The Agulhas leakage transports warm and saline water from the Indian Ocean into the South Atlantic Ocean, forming part of the upper returning arm of the meridional overturning circulation, which can influence climate. Ocean–atmosphere interactions and the strength of Agulhas leakage control sea surface temperature (SST) in the Agulhas leakage corridor, which may in turn affect regional climate variability. In a high-resolution run of the Community Climate System Model (version 3.5; CCSM3.5), it is found that the interannual variability of Agulhas leakage SST is linked to El Niño–Southern Oscillation (ENSO). Anomalous wind stress curl over the south Indian Ocean associated with ENSO excites westward-propagating oceanic Rossby waves that initiate southwestward-propagating anomalies along the coast of Africa. It takes approximately 2 years for this signal to reach the southern tip of South Africa and enter the South Atlantic, where it accounts for 20%–30% of the interannual SSH variability in the Agulhas leakage region. The authors find a similar propagation of anomalies with satellite observations. A similar ENSO cycle along with Rossby wave adjustment is detected in an analogous low-resolution CCSM3.5 run. However, the signal does not propagate all the way along the boundary to affect Agulhas leakage SST. Hence, it is found that high-resolution coupled climate models are necessary to resolve the tropical–subtropical oceanic teleconnection between ENSO and Agulhas leakage SST.

Description: The leakage of warm and salty water from the Indian Ocean via the Agulhas system into the South Atlantic may play a critical role in climate variability by modulating the buoyancy fluxes associated with the meridional overturning circulation (MOC). New climate models, such as the Community Climate System Model, version 3.5 (CCSM3.5), are now able to resolve the Agulhas retroflection and constrain the inertially choked Agulhas leakage to more realistic values. These ocean-eddy-resolving climate models are poised to bolster understanding of the sensitivity and influence of Agulhas leakage in the coupled climate system. Here, a strategy is devised to quantify Agulhas leakage in CCSM3.5 by applying an offline Lagrangian particle-tracking approach, finding a mean interbasin transport of 11.2 Sv (1 Sv ≡ 106 m3 s−1). It is shown that monthly mean outputs can be used to produce a reliable time series of Agulhas leakage variability on longer-than-seasonal time scales (correlation coefficient r = 0.88; p 〈 0.01) by comparing to a parallel simulation that archives daily mean fields every 5 days. The results show that Agulhas leakage variability at longer-than-seasonal time scales is less sensitive to the temporal resolution of the velocity fields than is the mean leakage transport.

Description: The seasonal variability in volume transport of the South Indian Ocean subtropical gyre is characterized for the first time. Only three complete hydrographic crossings of the gyre have been conducted over a 22-year period, with an upcoming repeat in 2019. Changes to geostrophic transport and thermocline properties imply a strengthening of the gyre from 1987 to 2002. However, some of this strengthening could result from aliasing of seasonal variability. We use data from Argo, satellite altimetry, and an Agulhas Current transport proxy at 34∘S to quantify the seasonal variability of the upper 2,000-m volume transport. A semiannual cycle is revealed, with peak-to-peak amplitude of 6.4 ± 3.1 Sv(1Sv = 106 m3 s−1) and dominated by annual anomalies in quadrature near the eastern and western boundaries. Seasonal aliasing does not account for the observed gyre strengthening. ©2018. American Geophysical Union. All Rights Reserved.

Description: Insulator elements are found at the boundary between euchromatin and heterochromatin, and are responsible for maintaining the correct chromatin configuration for a locus. The best characterized vertebrate insulator element, 5′ Hypersensitive Site (HS) 4 from the chicken β-globin locus (ch5′HS4), has two separable activities: enhancer blocking, which requires binding of the transcription factor CTCF, and barrier, which prevents transgene silencing. We have previously reported that transgenic mice carrying a wild-type erythrocyte ankyrin promoter (ANK-1E)/γ-globin gene showed uniform (γ-globin in 100% of red cells), position-independent (32/32 lines express), copy number-dependent (p=0.0005) expression of γ-globin mRNA and protein. Mutations in the ANK-1E promoter at positions −108 and −153 cause ankyrin-deficient Hereditary Spherocytosis. Transgenic mice with the −108/−153 ANK-1E/γ-globin transgene showed variegated (γ-globin in 0–80% of red cells), position-dependent (8/14 lines express), copy number-independent (p=0.27) expression of γ-globin. Flanking the −108/−153 ANK-1E/γ-globin transgene with the ch5′HS4 insulator restored uniform, position-independent (9/9 lines), copy number-dependent expression (p=0.003) at levels identical to the wild-type ANK-1E promoter. We hypothesized that we could test sequences for barrier activity by assaying their ability to restore normal expression to the −108/−153 ANK-1E/γ-globin gene in transgenic mice. In mammalian β-globin loci, human 5′HS5 and mouse 3′HS1 have been proposed to be insulator elements, similar to chicken 5′HS4, based on their ability to block enhancer element function. To test barrier function, we generated transgenic mice containing the −108/−153 ANK-1E/γ-globin transgene flanked by human 5′HS5, mouse wild-type 3′HS1, or mouse 3′HS1 with mutations that disrupt the binding of CTCF (×CTCF). A total of 5 lines of transgenic mice were generated containing the 5′HS5/−108/−153 ANK-1E/γ-globin transgene. γ-globin mRNA and protein were undetectable in 3/5 lines, indicating that expression was position-dependent, and in the two positive lines, mRNA levels did not correlate with copy number. A total of 9 lines of 3′HS1-flanked transgenic mice were generated, 3 of which did not express γ-globin mRNA and protein, demonstrating position-dependent expression. Among the 6 expressing lines, two lines showed variegated expression and the correlation between γ-globin mRNA level and copy number was significant (p=0.0117). In contrast, 3′HS1×CTCF transgenic mice expressed γ-globin in a uniform, position-independent (7/7 lines express), copy number-dependent (p=0.0005) manner. The levels of γ-globin mRNA in both the 3′HS1 and 3′HS1×CTCF transgenic mice were 2-fold greater than the levels measured in transgenic mice with the wild-type ANK-1E promoter (p=0.019; 0.0003 respectively), suggesting that 3′HS1 may contain an enhancer element. Our results indicate that while human 5′HS5 and mouse 3′HS1 block the effects of enhancer elements, neither are barrier elements as defined by the ability to prevent gene silencing. We hypothesize that the mutation of the CTCF binding sites allows the ANK-1E promoter to take greater advantage of the 3′HS1 enhancer, leading to a more uniform, position-independent, and copy number-dependent pattern of expression, as has been described for other enhancer elements in the β-globin Locus Control Region.

Description: Chromosome 16 inversion, inv(16)(p13q22), is one of the most frequent chromosome abnormalities in human acute myeloid leukemia (AML), comprising almost 100% of subtype M4Eo and up to 15% of all AML. This inv(16) leads to an in-frame fusion of CBFB and MYH11 genes. CBFB-MYH11 encodes a fusion protein between CBFβ, which is an obligate partner of RUNX1 or AML1, and smooth muscle myosin heavy chain (SMMHC). Using knock-in mouse models we have previously demonstrated that Cbfb-MYH11 dominantly blocks Runx1/Cbfb function in hematopoiesis and predisposes mice to AML (requiring a second hit from ENU or retroviral mutagenesis). However, the molecular mechanism underlying these findings remains unclear. Current hypotheses, which are based on previous in vitro studies, focus on the ability of CBFβ-SMMHC to dominantly inhibit RUNX1/CBFβ and include CBFβ-SMMHC binding RUNX1 with higher affinity than CBFβ; CBFβ-SMMHC sequestration of RUNX1 in the cytoplasm; CBFβ-SMMHC stabilization of RUNX1 by decreasing RUNX1 ubiquitination; and CBFβ-SMMHC repression of RUNX1 transactivation, which is dependent on SMMHC multimerization and repressor recruitment. To test these hypotheses in vivo, we generated knock in chimeric and F1 heterozygous mice expressing CBFβ-SMMHC with C-terminal and internal deletions. One of the deletions removes only the domain responsible for high affinity binding of RUNX1 (HABD). The CBFβ-SMMHC protein with HABD deletion did not bind RUNX1 with higher affinity than CBFβ and was hypothesized to be unable to dominantly repress RUNX1. Consistent with this hypothesis, the HABD-deleted protein was less efficient in sequestering RUNX1 and caused less severe hematopoietic defects in F1 embryos than full length CBFβ-SMMHC. In contrast to mice expressing full length CBFβ-SMMHC, which develop AML only after ENU or retroviral mutagenesis, most HABD-deleted chimeric and all HABD-deleted F1 mice developed AML spontaneously shortly after birth. A larger deletion removed both the HABD and the RUNX1 stabilization domain (RSD). CBFβ-SMMHC with the HABD-RSD double deletion did not bind RUNX1 with high affinity and could not sequester RUNX1 in the cytoplasm. Mice expressing HABD-RSD double deleted CBFβ-SMMHC had normal hematopoiesis, did not develop leukemia spontaneously and developed T cell (not myeloid) malignancies after ENU treatment. These data suggest that HABD and RSD are important for CBFβ-SMMHC to block RUNX1 function and to dominantly impair hematopoiesis. The accelerated leukemogenesis associated with HABD deletion and induction of T cell malignancies in mice expressing HABD-RSD double deleted CBFβ-SMMHC strongly support the hypothesis that CBFβ-SMMHC can induce leukemia through RUNX1-inhibition-independent pathways.