Number of active transcription factor binding sites is essential for the Hes7 oscillator

BACKGROUND: It is commonly accepted that embryonic segmentation of vertebrates is regulated by a segmentation clock, which is induced by the cycling genes Hes1 and Hes7. Their products form dimers that bind to the regulatory regions and thereby repress the transcription of their own encoding genes. An increase of the half-life of Hes7 protein causes irregular somite formation. This was shown in recent experiments by Hirata et al. In the same work, numerical simulations from a delay differential equations model, originally invented by Lewis, gave additional support. For a longer half-life of the Hes7 protein, these simulations exhibited strongly damped oscillations with, after few periods, severely attenuated the amplitudes. In these simulations, the Hill coefficient, a crucial model parameter, was set to 2 indicating that Hes7 has only one binding site in its promoter. On the other hand, Bessho et al. established three regulatory elements in the promoter region. RESULTS: We show that – with the same half life – the delay system is highly sensitive to changes in the Hill coefficient. A small increase changes the qualitative behaviour of the solutions drastically. There is sustained oscillation and hence the model can no longer explain the disruption of the segmentation clock. On the other hand, the Hill coefficient is correlated with the number of active binding sites, and with the way in which dimers bind to them. In this paper, we adopt response functions in order to estimate Hill coefficients for a variable number of active binding sites. It turns out that three active transcription factor binding sites increase the Hill coefficient by at least 20% as compared to one single active site. CONCLUSION: Our findings lead to the following crucial dichotomy: either Hirata's model is correct for the Hes7 oscillator, in which case at most two binding sites are active in its promoter region; or at least three binding sites are active, in which case Hirata's delay system does not explain the experimental results. Recent experiments by Chen et al. seem to support the former hypothesis, but the discussion is still open

Atlantic Deep-water Response to the Early Pliocene Shoaling of the Central American Seaway

The early Pliocene shoaling of the Central American Seaway (CAS), ~4.7–4.2 million years ago (mega annum-Ma), is thought to have strengthened Atlantic Meridional Overturning Circulation (AMOC). The associated increase in northward flux of heat and moisture may have significantly influenced the evolution of Pliocene climate. While some evidence for the predicted increase in North Atlantic Deep Water (NADW) formation exists in the Caribbean and Western Atlantic, similar evidence is missing in the wider Atlantic. Here, we present stable carbon (δ13C) and oxygen (δ18O) isotope records from the Southeast Atlantic-a key region for monitoring the southern extent of NADW. Using these data, together with other δ13C and δ18O records from the Atlantic, we assess the impact of the early Pliocene CAS shoaling phase on deep-water circulation. We find that NADW formation was vigorous prior to 4.7 Ma and showed limited subsequent change. Hence, the overall structure of the deep Atlantic was largely unaffected by the early Pliocene CAS shoaling, corroborating other evidence that indicates larger changes in NADW resulted from earlier and deeper shoaling phases. This finding implies that the early Pliocene shoaling of the CAS had no profound impact on the evolution of climate

(Table 1) Content of sand fraction components in sediments of the interglacial MIS 7 optimum from Core LV28-42-4

Distribution of diatoms, radiolarians, planktonic and benthic foraminifers, and sediment components in fraction >0.125 mm was analyzed in a core obtained from the central Sea of Okhotsk within frameworks of the Russian-German KOMEX Project. The core section characterizes the period 190-350 ka, which corresponds to marine-isotopic stages (MIS) 7 to 10. During glacial MIS 10 and MIS 8, the basin accumulated terrigenous material lacking microfossils or containing them in low abundance, which reflects, along with their composition, heavy sea-ice conditions, suppressed bioproductivity, and bottom environment aggressive toward calcium carbonate. Interglacial MIS 9 was characterized by elevated bioproductivity with accumulation of diatomaceous ooze during the climatic optimum (328 to 320 ka). Water exchange with the Pacific was maximal from 328 to 324 ka ago. Environment became moderate and close to the present-day one at the end of the optimum exhibiting possible existence of a dichothermal layer with substantial amounts of surface Pacific water still flowing into the basin. Similar to interglacial MIS 5e and MIS 1, ''old'' Pacific water determined near-bottom environment in the central Sea of Okhotsk during that period, although influx of terrigenous material was higher, probably reflecting more humid climate of the region. Slight warming marked the terminal MIS 8 (approximately 260 ka ago). Paleoceanographic situation during the interglacial MIS 7 was highly variable: from warm-water to almost glacial. The main climatic optimum of MIS 7 occurred within 220-210 ka, when subsurface stratification increased and the dichothermal layer developed. Bottom environment during the studied time interval, except for the optimum of interglacial MIS 9, resembled those characteristic of glacial periods: actively formed ''young'' Okhotsk water displaced ''old'' Pacific deep water

Paleoceanography of the Central Sea of Okhotsk during the Middle Pleistocene (350-190 ka) as inferred from micropaleontological data

The distribution of diatoms, radiolarians, planktonic and benthic foraminifers, and sediment components in the fraction >0.125 mm was analyzed in the core obtained from the central Sea of Okhotsk within the frameworks of the Russian-German KOMEX project. The core section characterizes the period 190–350 ka, which corresponds to marine-isotopic stages (MIS) 7 to 10. During glacial MIS 10 and MIS 8, the basin accumulated terrigenous material lacking microfossils or containing them in low abundance, which reflects, along with their composition, heavy sea-ice conditions, suppressed bioproductivity, and bottom environments aggressive toward calcium carbonate. Interglacial MIS 9 was characterized by elevated bioproductivity with accumulation of diatomaceous ooze during the climatic optimum (328 to 320 ka). The water exchange with the Pacific was maximal from 328 to 324 ka ago. Environments became moderate and close to the present-day ones at the end of the optimum exhibiting the possible existence of a dichothermal layer with substantial amounts of the surface Pacific water still flowing into the basin. Similar to interglacial MIS 5e and MIS 1, the “old” Pacific water determined near-bottom environments in the central Sea of Okhotsk during that period, although the influx of terrigenous material was higher, probably reflecting a more humid climate of the region. Slight warming marked the terminal MIS 8 (approximately 260 ka ago). The paleoceanographic situation during interglacial MIS 7 was highly variable: from warm-water to almost glacial. The main climatic optimum of MIS 7 occurred within 220–210 ka, when the subsurface stratification increased and the dichothermal layer developed. Bottom environments during the studied time interval, except for the optimum of interglacial MIS 9, resembled those characteristic of glacial periods: the actively formed “young” Okhotsk water displaced the “old” Pacific deep water

Stratigraphy and major paleoenvironmental changes in the Sea of Okhotsk during the last million years inferred from radiolarian data

The radiolarian distribution is studied in Core IMAGES MD01-2415(46-m-long) from the central Sea of Okhotsk. The obtained data made it possible to refine the regional biostratigraphy and document the major paleoenvironmental changes in the basin in the last million years. In total, 17 radiolarian datum planes are defined with 12 of them being new. Their number exceeds that previously established for different fossil groups in the Subarctic Pacific for this period. Radiolarian datum planes are usually confined to the main boundaries and Quaternary climatic events. The analysis of the radiolaria distribution reveals several major paleoenvironmental shifts in the sea that occurred 950, 700, and 420-280 ka ago and are correlative with regional and global phases of the Middle Pleistocene climatic revolution