The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a critical role in the pathogenesis of many cancers. The structure of intact forms of this receptor has yet to be ...determined, but intense investigations of fragments of the receptor have provided a detailed view of its activation mechanism, which we review here. Ligand binding converts the receptor to a dimeric form, in which contacts are restricted to the receptor itself, allowing heterodimerization of the four EGFR family members without direct ligand involvement. Activation of the receptor depends on the formation of an asymmetric dimer of kinase domains, in which one kinase domain allosterically activates the other. Coupling between the extracellular and intracellular domains may involve a switch between alternative crossings of the transmembrane helices, which form dimeric structures. We also discuss how receptor regulation is compromised by oncogenic mutations and the structural basis for negative cooperativity in ligand binding.
Cantu syndrome is a hyperhairy osteochondroplasia syndrome caused by abnormal function of ATP-dependent potassium ion channel, involving multiple systems, mainly manifested as hyperhairy body, ...skeletal muscle abnormalities and heart disease, etc. In this article, clinical data and gene sequencing results of a 10-month-old boy with Cantu syndrome were reported. He mainly presented with special facial features, and with congenital heart disease and recurrent respiratory tract infections. The results of whole exon gene sequencing showed that the child had missense mutation in exon 9 of ABCC9 gene, c.1138G > A (p.Gly380Ser). This mutation has not been previously reported. Genetic testing is helpful to early diagnosis of Cantu syndrome and guide the eugenics.
As a paradigm of greenhouse climate in Earth's history, the Cretaceous provides significant rock records of global climate changes under conditions of greenhouse climate. The Songliao Basin, among ...the longest duration (85–90m.y.) of continental sedimentary basins, provides an excellent opportunity to recover a nearly complete Cretaceous terrestrial sedimentary record. Extensive lake deposits, ten-kilometers deep and covering an area of 260,000km2 of the Songliao Basin, provide unique, detailed records that can be tied to the global stratigraphic time scale, thereby improving our understanding of the continental paleoclimate and ecological system. The two coreholes at SKIs and SKIn sites were drilled into this basin and completed with a total length of 2485.89m of recovered core that spanned the complete middle-to-Upper Cretaceous strata in the basin. The unique geological setting of long-term continuous subsidence within the largest Cretaceous landmass in the world — makes the Cretaceous Songliao Basin of northeastern China an ideal place to study Cretaceous climate change on the continent. This paper reviews the literature on the paleogeography and paleoclimate of the northern East Asia and the Songliao Basin during the Cretaceous. Based on the climatologically sensitive deposits, oxygen isotope studies, and paleontology, the climate during the Cretaceous in the Songliao Basin was temperate and humid with relatively abundant rainfall. During the period, significant changes – four cooling, three warming, and three semiarid events – are generally consistent with the oxygen isotope data from East Asia, and the four cooling events, in Berriasian–Valanginian, Aptian–Albian, early Santonian, and Campanian–Maastrichtian, may be related to potential glaciations in Cretaceous.
► We analyze the Cretaceous paleogeography and paleoclimate in the Songliao Basin. ► The basin located in the Northern Hemisphere middle latitude spans up to 85–90m.y. ► Tectonic activity and water supply controlled the character of sediment facies. ► The climate of the basin was temperate and humid with relatively abundant rainfall. ► There were four cooling, three warming and three semiarid events in the Cretaceous.
The Songliao Basin (SLB) in Northeast China has a succession of terrestrial sedimentary deposits that span much of the Cretaceous. The sedimentary records recovered from SLB allow us to investigate ...the relationship between astronomically forced climate and clastic sediment accumulation in a terrestrial setting from the mid to high latitudes. Here, we compiled high-resolution X-Ray Fluorescence (XRF) datasets (K/Ti, Rb/Sr, Ca/Ti), and gamma ray (GR) logging data from Member 2 of the Nenjiang Formation in the SK-1n borehole. Power spectral analysis of the GR data revealed that sedimentary cycles had wavelengths of 27.4 m, 6.56 m, 2.60 m, and 1.27 m. These wavelengths are interpreted as the orbital cycles of long-eccentricity, short-eccentricity, obliquity, and precession, respectively. We established an astronomical time scale by assuming that the 27.4 m cycles represent ~405 kyr eccentricity. We also applied correlation coefficient (COCO) analysis to identify the astronomical forcing periods. The chemical weathering history was classified by the relative changes of Rb/Sr and K/Ti ratios. The lower Rb/Sr and higher K/Ti values correspond to weak weathering, interpreted as arid periods, and vice versa. Ca/Ti ratios correlate with the humid periods and we attribute this correspondence to a salinity control on Ca/Ti. Furthermore, the unconventional 173-kyr obliquity cycle associated with the secular frequency interference of orbital inclinations between Earth and Saturn was recognized and manifested by humid/arid cliamtic oscillations, suggesting that high obliquity contributed to strengthening the hydrological cycles in SLB and bringing more precipitation and runoff towards the basin. The unique paleogeographic location and the existing paleoclimate simulations of SLB further demonstrated the existence of paleomonsoon variations in East Asia during the Late Cretaceous.
•Sedimentation rate from 5.1 to 8.3 cm/kyr was simulated by three proxies.•The chemical weathering suggested humid-arid changes related to the paleomonsoon.•The ~173 kyr cycle was recognized and associated with the humid-arid changes.•High obliquity contributes to strengthening the hydrological cycles in Songliao Basin.
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•Milankovitch cycles were recorded in Rb/Sr series from Member 1 (K2n1) and Member 2 (K2n2) of the Nenjiang Formation.•K2n1 experienced a longer humid period and more pronounced ...climatic fluctuation than K2n2.•The mean sedimentation rates of 6.577 and 8.369 cm/ka for K2n1 and K2n2 were provided by ASM method.•The collectively regulation of obliquity and precession amplified the paleomonsoon effect during humid periods in K2n1 and K2n2.
Cretaceous terrestrial sedimentary records are crucial for our understanding of geological systems’ responses to past climate change under greenhouse condition. Numerous publications have documented that Milankovitch cycles were a dominant climate driver over multi-millennial timescales. However, most of these orbital signals were derived from marine records obtained during the Cenozoic geological period, whereas knowledge of Milankovitch cycles preserved in lacustrine sediments prior to the Cenozoic is limited due to the lack of a precise chronological framework, poor preservation rate of terrestrial sediments, limited records, and fewer experts in this research area. This paper reports high-resolution X-ray fluorescence (XRF) elemental records of K, Ti, Rb, Sr, Zr, Zr/Rb, Rb/Sr, and K/Ti from Member 1 (k2n1) and Member 2 (k2n2) of the Nenjiang Formation, which were obtained from a near-continuous SK-2 East (SK-2e) borehole drilled in the Songliao Basin (SB) of northeastern (NE) China. Variations of the elemental records reveal a humid-arid-humid-semiarid climatic evolution throughout the deposition of k2n1 and a humid-arid-humid-arid climatic variation throughout the deposition of k2n2. In this context, K2n1 experienced a relatively longer humid period and more pronounced climatic fluctuation than K2n2. A method of average spectral misfit (ASM) was adopted to successfully identify two optimal sedimentation rates of 6.577 and 8.369 cm/ka for K2n1 and K2n2, respectively. Based on these two sedimentation rates, nearly all significant Milankovitch cycles preserved in the Rb/Sr record were recognized. It is suggested that westerly wind was the main climatic driving factor of climate evolution in the SB under the forcing of Milankovitch cycles. The collectively regulation of obliquity and precession increased the seasonal contrasts during humid periods in the Nenjiang Formation and thereby amplified the paleomonsoon effect, thus bringing more moisture towards the SB and lead to enhanced rainfall.
The mechanisms of short-term (105–106 years) and high-magnitude (>20 m) sea-level oscillations have long been debated involving glacio- and aquifer-eustasy, largely owing to the sparse robust ...evidence for the presence and significance of aquifer-eustasy, and lack of knowledge about the hydrological dynamics behind it. Non-marine/continental greenhouse archives (e.g., lake level) and their temporal correlation to marine successions (e.g., sea level) could provide clues to aquifer-eustasy. The Songliao Basin (SLB) in Northeast China is one of the largest Mesozoic terrestrial inland basins and provides a terrestrial archive of nearly all Cretaceous successions. The greenhouse late Santonian–early Campanian lower Nenjiang Formation (K2n1+2), recovered from three boreholes in the SLB, provides a unique opportunity for validating and decoding aquifer-eustasy. Initially, the cyclostratigraphy of logging gamma ray (GR) and thorium (Th) series from three boreholes was implemented, which in conjunction with precise geochronological (U/Pb zircon) ages renewed the chronology framework of the SLB. Using the astronomically tuned GR and Th datasets, the lake level of the SLB, which was recovered from sedimentary noise modeling and presented as a proxy for the water table of the groundwater reservoir, showed a clear out-of-phase relationship with the coeval sea level, validating the aquifer-eustasy hypothesis. The lake level of SLB shows prominent ∼1.2 Myr cycles and a well-coupled relationship with sea level and obliquity modulation, indicating that orbital obliquity drove the lake level and modulated water exchange between ocean and continent during the Cretaceous greenhouse period. Strong precipitation events indicated by negative excursions of ostracod δ18O correlate well with high lake levels, high obliquity, and low sea level, suggesting that more moisture was precipitated into the high-latitude continents during obliquity modulation maxima, consequently recharging the aquifer and raising the lake level while drawing down the sea level and vice versa. The close correlation between the reported marine incursion layers and the lowstand of sea level casts a doubt on the marine incursion hypothesis in the SLB; thus, more work is needed to reconcile this paradox. Overall, this study provides the first robust geological evidence for aquifer-eustasy and decodes its role in Cretaceous short-term eustasy.
•Rebuilt the chronological framework for the Songliao Basin.•First gave robust Cretaceous geological evidence for aquifer-eustasy hypothesis.•Illustrated the driving role of obliquity on aquifer-eustasy water exchange.•Tested the practicability of sedimentary noise modeling on recovering lake level.
Cretaceous climate data of the long-lived Cretaceous Songliao Basin (SB) in eastern Asia is correlated and compared with the Western Interior Seaway (WIS) on the northern American plate, in order to ...understand better the dynamics of the Earth's past ‘greenhouse’ climates. Nearly continuous Late Cretaceous terrestrial deposition in the Songliao Basin is represented by two cores totaling 2431m in length. The Turonian–Maastrichtian age of the section is based on integrated stratigraphy, and is comparable in age with Upper Cretaceous strata in the WIS. Being consistent with global trends, the dynamic Late Cretaceous climates of both the SB and WIS gradually cooled from the warmest Albian–Cenomanian time to the end of the Maastrichtian with several intervening warm periods as did the global climate. However regional differences existed, the Songliao Basin climate was humid to semi-humid, warm temperate–subtropical and the Western Interior Seaway was in the humid, warm temperate zone and experienced only moderate climatic changes. The shifts of oxygen isotope data in the Songliao Basin were frequent and abrupt, whereas WIS records more gradual change affected mainly by fresh-water runoff mixing with southern Tethyan and northern Arctic waters. Sedimentary cycles of eccentricity, obliquity and precession bands are recorded in both the SB and WIS basins. The sedimentary cycles in the WIS and SB are interpreted to be related to variations of the wet/dry runoff cycles, which indicate that orbital forcing played an important role in global climate change in Late Cretaceous. The most favorable condition for organic carbon burial in both the SB and WIS basin was bottom water anoxia regardless of the cause of the anoxia. But the organic carbon burial rate was usually much higher in the Songliao Lake than in the WI epeiric sea suggesting that giant lakes may serve as important sinks of atmospheric CO2. In both basins organic-rich deposits formed during a rise in water level and incursion of saline waters. The integration of paleoclimate data from Cretaceous marine deposits and terrestrial sedimentary record will promote our understanding of the Cretaceous ‘greenhouse’ climate change and may provide insights for a future greenhouse world.
The study of sedimentary pyrite morphological characteristics provides useful information on depositional environments and early diagenic processes and can be used as an indicator of redox conditions ...in ancient lake bottom waters. The results of this study in the Songliao basin in northeastern China show that euhedral crystals and framboids are the dominant pyrite forms in the mudstones of the first member of the Qingshankou Formation (K2qn1). The framboidal size distribution indicates that during the deposition of K2qn1, redox conditions in the bottom water fluctuated from oxic–dysoxic to euxinic–anoxic to oxic–dysoxic. The presence of euxinic–anoxic bottom water suggests that an anoxic event developed in the Songliao ancient-lake and continued for 196ka. The development of an anoxic bottom environment was the most important factor in hydrocarbon source rock formation in the Songliao Basin.
Relationships between different pyrite forms from K2qn1 mudstone and lake bottom water. 1 — framboid; 2 — euhedral crystal; 3 — dumbbell-shaped and irregular framboidal aggregate; 4 — lentoid framboidal aggregate; 5 — ostracoda-shaped enhedral crystal aggregate; 6 — bubble-shaped enhedral crystal aggregate; 7 — ribbon enhedral crystal aggregate; 8 — phytoclasts-shaped enhedral crystal aggregate. Display omitted
► Different pyrite forms were found in mudstones of K2qn1 in the Songliao basin. ► The framboid size distribution indicates lake anoxic events during K2qn1. ► During K2qn1 the anoxic lake event continuing for about 196ka. ► The different S:Fe ratios may represent different stages of pyrite formation.
Fischer plots are widely used in paleoenvironmental research as graphic representations of sea- and lake-level changes through mapping linearly corrected variation of accumulative cycle thickness ...over cycle number or stratum depth. Some kinds of paleoenvironmental proxy data (especially subsurface data, such as natural gamma-ray logging data), which preserve continuous cyclic signals and have been largely collected, are potential materials for constructing Fischer Plots. However, it is laborious to count the cycles preserved in these proxy data manually and map Fischer plots with these cycles. In this paper, we introduce an original open-source Python code "PyFISCHERPLOT" for constructing Fischer Plots in batches utilizing paleoenvironmental proxy data series. The principle of constructing Fischer plots based on proxy data, the data processing and usage of the PyFISCHERPLOT code and the application cases of the code are presented. The code is compared with existing methods for constructing Fischer plots.
The International Continental Scientific Drilling Project of Cretaceous Songliao Basin has recovered a complete Cretaceous terrestrial sedimentary record in northeastern China, providing a unique ...opportunity to understand the terrestrial climate change during the Cretaceous period. In this study, we present high-resolution geochemical records from Members 3 and 4 of the Quantou Formation in the SK-1 South borehole. The findings show that samples from Members 3 and 4 of the Quantou Formation originated from a source area of a homogeneous composition. Most of the samples were sediments that underwent the first round of weathering. The geochemical proxies (Th, CIA, CIW, τNa) and average value of the CIA proxy indicate that the strata have been subjected to moderate chemical weathering. The weathering intensity trend was divided into four evolutionary stages based on the CIA proxy: the steady lower part (1915–1878 m), the slowly rising lower and middle part (1878–1815 m), the middle and upper part (1815–1800 m) showing the highest values, and the gently fluctuating upper part (1800–1783 m). Precession, obliquity, and short-eccentricity signals were recognized in the proxies of Th, τNa, corrected CIA, and corrected CIW from Members 3 and 4 of the Quantou Formation, including about seven short-eccentricity cycle periods with a duration of ∼700 ka. The high peaks in short-eccentricity correspond to the high values of Th, corrected CIA, and corrected CIW proxies, and are consistent with the amplitudes of precession signals preserved in τNa during humid periods. During strong precession, the enhanced seasonal contrasts increased humidity, which intensified chemical weathering. The paleoclimatic pattern of interaction between the monsoon-like system and westerlies in the Cretaceous Songliao Basin may be the underlying interpretation that causes cyclic variation in the chemical weathering proxies in Members 3 and 4 of the Quantou Formation.
•Reconstruction of historical chemical weathering using multiple weathering proxies.•Humid climate derived from a non-linear response of the climate system to precession.•Interaction between the monsoon-like system and westerlies may be the interpretation causing cyclic variation.
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