Nonequilibrium mechanism of transcription termination from observations of single RNA polymerase molecules

Cessation of transcription at specific terminator DNA sequences is used by viruses, bacteria, and eukaryotes to regulate the expression of downstream genes, but the mechanisms of transcription termination are poorly characterized. To elucidate the kinetic mechanism of termination at the intrinsic terminators of enteric bacteria, we observed, by using single-molecule light microscopy techniques, the behavior of surface-immobilized Escherichia coli RNA polymerase (RNAP) molecules in vitro. An RNAP molecule remains at a canonical intrinsic terminator for ≈64 s before releasing DNA, implying the formation of an elongation-incompetent (paused) intermediate by transcription complexes that terminate but not by those that read through the terminator. Analysis of pause lifetimes establishes a complete minimal mechanism of termination in which paused intermediate formation is both necessary and sufficient to induce release of RNAP at the terminator. The data suggest that intrinsic terminators function by a nonequilibrium process in which terminator effectiveness is determined by the relative rates of nucleotide addition and paused state entry by the transcription complex.

Termination of signaling by protease-activated receptor-1 is linked to lysosomal sorting

The irreversible proteolytic mechanism by which protease-activated receptor-1 (PAR1), the G protein-coupled receptor (GPCR) for thrombin, is activated raises the question of how it is shut off. Like classic GPCRs, activated PAR1 is rapidly phosphorylated and internalized, but unlike classic GPCRs, which recycle, internalized PAR1 is sorted to lysosomes. A chimeric PAR1 bearing the substance P receptor’s cytoplasmic carboxyl tail sequestered and recycled like wild-type substance P receptor. In cells expressing this chimera, signaling in response to the PAR1-activating peptide SFLLRN ceased as expected upon removal of this agonist. Strikingly, however, when the chimera was activated proteolytically by thrombin, signaling persisted even after thrombin was removed. This persistent signaling was apparently due to “resignaling” by previously activated receptors that had internalized and recycled back to the cell surface. Thus the cytoplasmic carboxyl tail of PAR1 specifies an intracellular sorting pattern that is linked to its signaling properties. In striking contrast to most GPCRs, sorting of activated PAR1 to lysosomes rather than recycling is critical for terminating PAR1 signaling—a trafficking solution to a signaling problem.

Sea-surface temperature reconstruction for sediment core GeoB1023-5

Sediment core GeoB 1023-5 from the eastern South Atlantic was investigated at high temporal resolution for variations of sea-surface temperature (SST) during the past 22 kyr, using the alkenone (UK'37) method. SSTs increased by 3.5°C from about 18°C during the Last Ice Age (21±2 cal kyr BP) to about 21.5°C at 14.5 cal kyr BP. This warming trend associated with the deglaciation phase was followed by a cooling event with lowest SSTs near 20°C, persisting for about 1000 years between 13 and 12 cal kyr BP. The SSTs then continued to increase to about 22.5°C at the Holocene climatic optimum at 7 cal kyr BP, and decreased again during the Late Holocene to a core-top value of 19.8°C that is comparable to modern annual mean SST values. When compared with alkenone SST records from the eastern North Atlantic, our SST record indicates continuous warming throughout the deglaciation phase in the Benguela Current, while its northern counterpart, the Canary Current, experienced prominent cooling during 'Heinrich Event 1' (H1). On the other hand, for the time period corresponding to the 'Younger Dryas' (YD) cooling event, the Benguela SST record exhibits a cold-temperature interval that corresponds to that observed in the eastern North Atlantic SST records. This observation suggests that interhemispheric climate response in Atlantic eastern boundary current systems was different with respect to the two abrupt climate events associated with Termination I. For the H1, the eastern South Atlantic SST record strongly supports the hypothesis that an 'anti-phase' thermal behavior in South Atlantic surface waters was forced by the slowdown of the North Atlantic Deep Water formation during cold spells in the North Atlantic. In contrast, the abrupt cooling in the eastern South Atlantic coincident with the YD period was probably induced by more vigorous global atmospheric circulation, enhancing the upwelling intensity in both eastern boundary current systems. This atmospheric control may have overridden any effect caused by changes in thermohaline circulation on the South Atlantic SSTs during the YD, which leads to the assumption that the thermohaline circulation was already much closer to its interglacial mode during the YD than during the H1.

Planktonic foraminifer abundance and estimated sea surface temperatures and salinities of DSDP Leg 74 holes

Two hydraulic piston cores containing the total Quaternary suite were analyzed quantitatively in their planktonic foraminiferal contents. For the Early Pleistocene, the Caribbean standard zonation (BOLLI & PREMOLI-SILVA) can be adopted and refined by the introduction of an additional subzone at its base (the Globorotalia triangula subzone). Local substages are proposed for the Late Pleistocene because index fossils are missing. The use of the transfer-function technique resulted in paleotemperature and paleosalinity curves with a time resolution of cycles of about 4-68,000 years duration. The Early Pleistocene paleoenvironment is characterized by low oscillations of the surface water temperatures, followed by a distinct cooling trend during the Globorotalia viola subzone, a period of smoothed cycles during the Globorotalia hessi subzone and distinctly developed cycles during the late Pleistocene since the oxygen isotope termination III. Grainsize distribution and several dissolution indices gave evidence for current activities on the top of the Walvis Ridge, where the amount of fine grained components in the sediment is reduced in comparison with that of the flanks.

The record of stable isotope composition of surface and thermocline planktic foraminifera from sediment core 64PE-174P13 for the last 460,000 years

The upper branch of the Atlantic Meridional Overturning Circulation predominantly enters the Atlantic Ocean through the southeast, where the subtropical gyre is exposed to the influence of the Agulhas leakage (AL). To understand how the transfer of Indian Ocean waters via the AL affected the upper water column of this region, we have generated new proxy records of planktic foraminifera from a core on the central Walvis Ridge, on the eastern flank of the South Atlantic Gyre (SAG). We analyzed the isotopic composition of subsurface dweller Globigerinoides ruber sensu lato, and thermocline Globorotalia truncatulinoides sinistral, spanning the last five Pleistocene glacial-interglacial (G-IG) cycles. The former displays a response to obliquity, suggesting connection with high latitude forcing, and a warming tendency during each glacial termination, in response to the interhemispheric seesaw. The d18O difference between the two species, interpreted as a proxy for upper ocean stratification, reveals a remarkably regular sawtooth pattern, bound to G-IG cyclicity. It rises from interglacials until glacial terminations, with fast subsequent decrease, appearing to promptly respond to deglacial peaks of AL. Stratification, however, bears a different structure during the last cycle, being minimal at Last Glacial Maximum, and peaking at Termination I. We suggest this to be the result of the intensified glacial wind field over the SAG and/or of the invasion of the South Atlantic thermocline by Glacial North Atlantic Intermediate Waters. The d13C time series of the two species have similar G-IG pattern, whereas their difference is higher during interglacials. We propose that this may be the result of the alternation of intermediate water masses in different circulation modes, and of a regionally more efficient biological pump at times of high pCO2.

Stable isotop record of sediments across MIS 5 and Termination II

New surface water records from two high sedimentation rate sites, located in the western subtropical North Atlantic near the axis of the Gulf Stream, provide clear evidence of suborbital climate variations through marine isotope stage (MIS) 5 persisting even into the warm peak of the interglaciation (substage 5e). We found that the amplitude of suborbital climate oscillations did not vary significantly for the whole of MIS 5, implying that ice volume has little or no influence on the amplitude of suborbital climate variability in this region. Although some records suggest that longer suborbital variations (4-10 kyr) during MIS 5 are linked to deepwater changes, none of the existing records is of sufficient resolution to assess if a linkage occurred for oscillations shorter than 4 kyr. However, when examined in conjunction with published data from the Norwegian Sea, new evidence from the subpolar North Atlantic suggests that coupled surface-deepwater oscillations occurred during the penultimate deglaciation. This supports the hypothesis that during glacial and deglacial times, ocean-ice interactions and deepwater variability amplify suborbital climate change at higher latitudes. We suggest that during the penultimate deglaciation the North Atlantic deepwater source varied between Nordic Sea and open North Atlantic locations, in parallel with surface temperature oscillations.

Integration of ice-core, marine and terrestrial records for the Australian Last Glacial Maximum and Termination: a contribution from the OZ INTIMATE group

The degree to which Southern Hemisphere climatic changes during the end of the last glacial period and early Holocene (30-8 ka) were influenced or initiated by events occurring in the high latitudes of the Northern Hemisphere is a complex issue. There is conflicting evidence for the degree of hemispheric 'teleconnection' and an unresolved debate as to the principle forcing mechanism(s). The available hypotheses are difficult to test robustly, however, because the few detailed palaeoclimatic records in the Southern Hemisphere are widely dispersed and lack duplication. Here we present climatic and environmental reconstructions from across Australia, a key region of the Southern Hemisphere because of the range of environments it covers and the potentially important role regional atmospheric and oceanic controls play in global climate change. We identify a general scheme of events for the end of the last glacial period and early Holocene but a detailed reconstruction proved problematic. Significant progress in climate quantification and geochronological control is now urgently required to robustly investigate change through this period. Copyright (c) 2006 John Wiley & Sons, Ltd.

Climatic variability in the southwest Pacific during the Last Termination (20-10 kyr BP)

The degree to which palaeoclimatic changes in the Southern Hemisphere co-varied with events in the high latitude Northern Hemisphere during the Last Termination is a contentious issue, with conflicting evidence for the degree of 'teleconnection' between different regions of the Southern Hemisphere. The available hypotheses are difficult to test robustly, however, because there are few detailed palaeoclimatic records in the Southern Hemisphere. Here we present climatic reconstructions from the southwestern Pacific, a key region in the Southern Hemisphere because of the potentially important role it plays in global climate change. The reconstructions for the period 20-10 kyr BP were obtained from five sites along a transect from southern New Zealand, through Australia to Indonesia, supported by 125 calibrated C-14 ages. Two periods of significant climatic change can be identified across the region at around 17 and 14.2 cal kyr BP, most probably associated with the onset of warming in the West Pacific Warm Pool and the collapse of Antarctic ice during Meltwater Pulse-1A, respectively. The severe geochronological constraints that inherently afflict age models based on radiocarbon dating and the lack of quantified climatic parameters make more detailed interpretations problematic, however. There is an urgent need to address the geochronological limitations, and to develop more precise and quantified estimates of the pronounced climate variations that clearly affected this region during the Last Termination. (c) 2005 Elsevier Ltd. All rights reserved.

Water temperature reconstructions based on paired Uk'37 and Tex86 records, and paired surface and subsurface Mg/Ca records

This dataset contains the collection of available published paired Uk'37 and Tex86 records spanning multi-millennial to multi-million year time scales, as well as a collection of Mg/Ca-derived temperatures measured in parallel on surface and subsurface dwelling foraminifera, both used in the analyses of Ho and Laepple, Nature Geoscience 2016. As the signal-to-noise ratios of proxy-derived Holocene temperatures are relatively low, we selected records that contain at least the last deglaciation (oldest sample >18kyr BP).