Deletion of \u3cem\u3eULS1\u3c/em\u3e Confers Damage Tolerance in \u3c/em\u3esgs1\u3c/em\u3e Mutants Through a Top3-dependent D-loop Mediated Fork Restart Pathway

Homologous recombination (HR)-based repair during DNA replication can apparently utilize several partially overlapping repair pathways in response to any given lesion. A key player in HR repair is the Sgs1-Top3-Rmi1 (STR) complex, which is critical for resolving X-shaped recombination intermediates formed following bypass of methyl methanesulfonate (MMS)-induced damage. STR mutants are also sensitive to the ribonucleotide reductase inhibitor, hydroxyurea (HU), but unlike MMS treatment, HU treatment is not accompanied by X-structure accumulation, and it is thus unclear how STR functions in this context. Here we provide evidence that HU-induced fork stalling enlists Top3 prior to recombination intermediate formation. The resistance of sgs1Δ mutants to HU is enhanced by the absence of the putative SUMO (Small Ubiquitin MOdifier)-targeted ubiquitin ligase, Uls1, and we demonstrate that Top3 is required for this enhanced resistance and for coordinated breaks and subsequent d-loop formation at forks stalled at the ribosomal DNA (rDNA) replication fork block (RFB). We also find that HU resistance depends on the catalytic activity of the E3 SUMO ligase, Mms21, and includes a rapid Rad51-dependent restart mechanism that is different from the slow Rad51-independent HR fork restart mechanism operative in sgs1Δ ULS1+ mutants. These data support a model in which repair of HU-induced damage in sgs1Δ mutants involves an error-prone break-induced replication pathway but, in the absence of Uls1, shifts to one that is higher-fidelity and involves the formation of Rad51-dependent d-loops

The lipid droplet protein DHRS3 is a regulator of melanoma cell state

Lipid droplets are fat storage organelles composed of a protein envelope and lipid rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role. To address this, we performed proteomic analysis of the lipid droplet envelope in melanoma. We found that lipid droplet proteins were differentially enriched in distinct melanoma states; from melanocytic to undifferentiated. DHRS3, which converts all-trans-retinal to all-trans-retinol, is upregulated in the MITFLO/undifferentiated/neural crest-like melanoma cell state and reduced in the MITFHI/melanocytic state. Increased DHRS3 expression is sufficient to drive MITFHI/melanocytic cells to a more undifferentiated/invasive state. These changes are due to retinoic acid mediated regulation of melanocytic genes. Our data demonstrate that melanoma cell state can be regulated by expression of lipid droplet proteins which affect downstream retinoid signaling

Structure and variability of the Antilles current at 26.5°N

Observations from five different systems provide a robust picture of the structure and variability of the Antilles Current, an important contributor to the oceanic flux budget, at 26.5°N during 2005–2015. The analysis includes three direct measurement technologies (current meters, shipboard acoustic Doppler current profilers, and lowered acoustic Doppler current profilers) and two geostrophy‐based measurement technologies (conductivity‐temperature‐depth profilers and pressure‐equipped inverted echo sounders). The direct systems are shown to produce weaker, and less variable, Antilles Current transport estimates than the geostrophy‐based systems. The record‐length‐mean geostrophic estimate for the Antilles Current is 4.7 Sverdrups (Sv; 1 Sv = 106 m3/s), and the daily temporal standard deviation is 7.5 Sv. The variations of the Antilles Current transport exceed those of the entire basin‐wide meridional overturning circulation, illustrating the impact of this unusual current. Seasonal variability shows a maximum northward transport in August–September; however, the seasonal component of the variability is weak, and aliasing of higher frequencies is still a problem even with 10.5 years of data. The dominant time scales of variability in the spectra are at 70 and 180 days, and there is indication of westward propagation of Rossby Wave‐like features into the region at a speed of 9 cm/s. There is no significant correlation between the Antilles Current transport variations and those of the Florida Current at 27°N, in phase or at lags/leads of up to 5 years, likely reflecting the varying coastal wave/wall jet time scales for information to pass from the basin interior through the Bahamas Islands

Pending recovery in the strength of the meridional overturning circulation at 26° N

The strength of the Atlantic meridional overturning circulation (AMOC) at 26∘ N has now been continuously measured by the RAPID array over the period April 2004–September 2018. This record provides unique insight into the variability of the large-scale ocean circulation, previously only measured by sporadic snapshots of basin-wide transport from hydrographic sections. The continuous measurements have unveiled striking variability on timescales of days to a decade, driven largely by wind forcing, contrasting with previous expectations about a slowly varying buoyancy-forced large-scale ocean circulation. However, these measurements were primarily observed during a warm state of the Atlantic multidecadal variability (AMV) which has been steadily declining since a peak in 2008–2010. In 2013–2015, a period of strong buoyancy forcing by the atmosphere drove intense water-mass transformation in the subpolar North Atlantic and provides a unique opportunity to investigate the response of the large-scale ocean circulation to buoyancy forcing. Modelling studies suggest that the AMOC in the subtropics responds to such events with an increase in overturning transport, after a lag of 3–9 years. At 45∘ N, observations suggest that the AMOC may already be increasing. Examining 26∘ N, we find that the AMOC is no longer weakening, though the recent transport is not above the long-term mean. Extending the record backwards in time at 26∘ N with ocean reanalysis from GloSea5, the transport fluctuations at 26∘ N are consistent with a 0- to 2-year lag from those at 45∘ N, albeit with lower magnitude. Given the short span of time and anticipated delays in the signal from the subpolar to subtropical gyres, it is not yet possible to determine whether the subtropical AMOC strength is recovering nor how the AMOC at 26∘ N responds to intense buoyancy forcing

Do early warning indicators consistently predict nonlinear change in long-term ecological data?

1. Anthropogenic pressures, including climate change, are causing nonlinear changes in ecosystems globally. The development of reliable early warning indicators (EWIs) to predict these changes is vital for the adaptive management of ecosystems and the protection of biodiversity, natural capital and ecosystem services. Increased variance and autocorrelation are potential early warning indicators and can be readily estimated from ecological time series. Here, we undertook a comprehensive test of the consistency between early warning indicators and nonlinear abundance change across species, trophic levels and ecosystem types. 2. We tested whether long-term abundance time series of 55 taxa (126 data sets) across multiple trophic levels in marine and freshwater ecosystems showed (i) significant nonlinear change in abundance ‘turning points’ and (ii) significant increases in variance and autocorrelation (‘early warning indicators’). For each data set, we then quantified the prevalence of three cases: true positives (early warning indicators and associated turning point), false negatives (turning point but no associated early warning indicators) and false positives (early warning indicators but no turning point). 3. True positives were rare, representing only 9% (16 of 170) of cases using variance, and 13% (19 of 152) of cases using autocorrelation. False positives were more prevalent than false negatives (53% vs. 38% for variance; 47% vs. 40% for autocorrelation). False results were found in every decade and across all trophic levels and ecosystems. 4. Time series that contained true positives were uncommon (8% for variance; 6% for autocorrelation), with all but one time series also containing false classifications. Coherence between the types of early warning indicators was generally low with 43% of time series categorized differently based on variance compared to autocorrelation. 5. Synthesis and applications. Conservation management requires effective early warnings of ecosystem change using readily available data, and variance and autocorrelation in abundance data have been suggested as candidates. However, our study shows that they consistently fail to predict nonlinear change. For early warning indicators to be effective tools for preventative management of ecosystem change, we recommend that multivariate approaches of a suite of potential indicators are adopted, incorporating analyses of anthropogenic drivers and process-based understanding

The North Atlantic Ocean is in a state of reduced overturning

The Atlantic Meridional Overturning Circulation (AMOC) is responsible for a variable and climatically important northward transport of heat. Using data from an array of instruments that span the Atlantic at 26°N, we show that the AMOC has been in a state of reduced overturning since 2008 as compared to 2004-2008. This change of AMOC state is concurrent with other changes in the North Atlantic such as a northward shift and broadening of the Gulf Stream, and altered patterns of heat content and sea-surface temperature. These changes resemble the response to a declining AMOC predicted by coupled climate models. Concurrent changes in air-sea fluxes close to the western boundary reveal that the changes in ocean heat transport and SST have altered the pattern of ocean-atmosphere heat exchange over the North Atlantic. These results provide strong observational evidence that the AMOC is a major factor in decadal scale variability of North Atlantic climate

The North Atlantic Ocean is in a state of reduced overturning

The Atlantic Meridional Overturning Circulation (AMOC) is responsible for a variable and climatically important northward transport of heat. Using data from an array of instruments that span the Atlantic at 26°N, we show that the AMOC has been in a state of reduced overturning since 2008 as compared to 2004-2008. This change of AMOC state is concurrent with other changes in the North Atlantic such as a northward shift and broadening of the Gulf Stream, and altered patterns of heat content and sea-surface temperature. These changes resemble the response to a declining AMOC predicted by coupled climate models. Concurrent changes in air-sea fluxes close to the western boundary reveal that the changes in ocean heat transport and SST have altered the pattern of ocean-atmosphere heat exchange over the North Atlantic. These results provide strong observational evidence that the AMOC is a major factor in decadal scale variability of North Atlantic climate