Substantial evidence now exists to support that formation of DNA G-quadruplexes (G4s) is coupled to altered gene expression. However, approaches that allow us to probe G4s in living cells without ...perturbing their folding dynamics are required to understand their biological roles in greater detail. Herein, we report a G4-specific fluorescent probe (SiR-PyPDS) that enables single-molecule and real-time detection of individual G4 structures in living cells. Live-cell single-molecule fluorescence imaging of G4s was carried out under conditions that use low concentrations of SiR-PyPDS (20 nM) to provide informative measurements representative of the population of G4s in living cells, without globally perturbing G4 formation and dynamics. Single-molecule fluorescence imaging and time-dependent chemical trapping of unfolded G4s in living cells reveal that G4s fluctuate between folded and unfolded states. We also demonstrate that G4 formation in live cells is cell-cycle-dependent and disrupted by chemical inhibition of transcription and replication. Our observations provide robust evidence in support of dynamic G4 formation in living cells.
Characterizing drug-target engagement is essential to understand how small molecules influence cellular functions. Here we present Chem-map for in situ mapping of small molecules that interact with ...DNA or chromatin-associated proteins, utilizing small-molecule-directed transposase Tn5 tagmentation. We demonstrate Chem-map for three distinct drug-binding modalities as follows: molecules that target a chromatin protein, a DNA secondary structure or that intercalate in DNA. We map the BET bromodomain protein-binding inhibitor JQ1 and provide interaction maps for DNA G-quadruplex structure-binding molecules PDS and PhenDC3. Moreover, we determine the binding sites of the widely used anticancer drug doxorubicin in human leukemia cells; using the Chem-map of doxorubicin in cells exposed to the histone deacetylase inhibitor tucidinostat reveals the potential clinical advantages of this combination therapy. In situ mapping with Chem-map of small-molecule interactions with DNA and chromatin proteins provides insights that will enhance understanding of genome and chromatin function and therapeutic interventions.
The Ireviken event was one of the most intense extinction episodes that occurred during the mid-Paleozoic era. It had a strong global effect on a range of clades, with conodonts, graptolites and ...chitinozoans affected most. Using geophysical proxies and conodont species parameters of their temporal abundance structure we investigate how they affected the selectivity of conodont species survival during this calamity. After performing bivariate logistic analyses on 34 species of conodonts, we find three variables that were statistically significantly associated with their odds of survival. These namely include spectral exponents that describe degrees of autocorrelation in a time series, the skewness of species abundance distribution, and average environmental preferences, which are mostly determined by ancient water depths at sampling sites. Model selection of multivariate logistic models found the best model includes species local abundance skewness and substrate preference. A similar pattern is revealed through the regression tree analysis. The apparent extinction selectivity points to a possible causes of environmental deterioration during the Ireviken event. The significant positive relationship between extinction risk and preferential existence in deeper environments suggests the open ocean causal mechanisms of biotic stress that occurred during the Ireviken event. Marine regressions, which were previously suggested as a causal factor in this extinction episode, on theoretical grounds should have had higher impact on species living in near-shore environments, through the processes of habitat loss which are associated with decreases of shelfal areas. In addition, the significant positive correlations found between skewness of abundance distributions and spectral exponent values and the probability of species survival suggest that community and ecosystem processes (which controlled species abundance fluctuation patterns) were significantly related to selectivity processes of this smaller mass extinction event.
The Silurian period, and the Wenlock epoch in particular, experienced a series of powerful bioevents, among which was the Mulde event (upper Homerian). Here, the results of a study of the mid- to ...late Wenlock conodont paleocommunities in the shallow platform environments of the Lithuanian part of the Silurian Baltic Basin are presented. The analyses are based on a detailed quantitative description of the abundance and diversity patterns of the conodonts, as well as the geochemical and geophysical environmental proxies in the Ledai-179 core (central Lithuania). A model selection analysis of the conodont rank abundance distributions revealed episodic and progressive change from the complex communities of the early Jaagarahu time (lower Homerian), to the simple and much more even communities of the early Gėluva time (lower part of the upper Homerian). Spectral and cross-spectral analyses of the conodont species' apparent richness, evenness and abundance, as well as the δ13C and natural gamma ray trends, revealed transient episodes of 5th order periodic fluctuations. It is shown that the transitions in the community states and the transient episodes of the oscillations approximately coincided with the onset of the Mulde event (latest Jaagarahu and early Gėluva time).
•Conodont RADs experienced simplification and increase in evenness during the Mulde event•During the onset of the Mulde event conodont abundance, diversity, and evenness experienced strong 5th order fluctuations•Upper Homerian conodont community change was modulated by periodic climatic fluctuations
In recent years it has become commonplace to formalize chemostratigraphic units and identify isotopic zones (chemostratigraphic units) from excursions. Stable carbon isotopes have been used in ...solving stratigraphic problems in the Silurian for more than 30 years. delta.sup.13C data supplement other stratigraphic proxies, allowing the subdivision of geological sections and more precise correlation. In this paper we give new delta.sup.13C data from the Silurian section of the Jocionys-299 borehole, which is located in eastern Lithuania, crossing shallow marine and lagunal deposits. Based on delta.sup.13C variability, the Ireviken carbon isotope excursion (CIE), the Slilale CIE, and probably the Valgu CIE have been identified in the investigated section. The Valgu CIE is linked to the lower part of the Svencionys Formation. The Ireviken CIE is linked to the upper parts of the Svencionys Formation and the Paprieniai Formation (rise in delta.sup.13C values), the Jocionys Formation (moderately stable delta.sup.13C.sub.carb values) and the Verkne Formation (fall in delta.sup.13C values).A small negative delta.sup.13C shift is documented in the Pabrade Formation. Chemostratigraphy together with biostratigraphic data allow us to correlate eastern Lithuanian lithostratigraphic units (shallow marine environment) with the global Silurian Geochronological Scale more accurately. Keywords: carbon isotopes, chemostratigraphy, Silurian, Lithuania.
The Homerian to Ludfordian interval of the mid to late Silurian Period was a time of significant changes in conodont communities, global climate, oceanographic patterns and biogeochemical cycles. The ...Mulde and the Lau events are preeminent examples of globally recognized conodont extinction episodes from this interval in Earth's history. The Silurian Baltic Basin is the most suitable locality, globally, for studying these perturbations to the ocean-atmosphere system, since there is an extensive record of conodont taxa occurrences, their communities, and their environments spanning across shore-face to open-ocean settings. In this study, we present new conodont and δ13C data from the upper Homerian to Ludlow interval from two core sections – Gėluva-99 and Gėluva-118, representing shelfal environments, and the numerical conodont data from the Viduklė-61 section, from deep-water settings, and compare them with patterns of conodont diversity change, as revealed in the data-rich Milaičiai-103 core section. For this purpose, we explored the stratigraphically tied time series of conodont diversity changes employing recurrence and cross-recurrence plots – the binary similarity matrices that are used for deciphering complex spatial and temporal dynamic patterns. The cross-recurrence plots were used as a means of synchronizing the geological sections by applying dynamic time warping and the newly described moving window median recurrence point search algorithms. The results revealed that the conodont community compositional data are sufficiently temporally and spatially coherent to be reasonably used for synchronizing geological records. Moreover, the sudden state transitions detected in the cross-recurrence plots suggest that the Lau Event was of great importance for conodont community evolution in the studied time slice.
•Integrated stratigraphical model implies existence of a significant regression in the late Ludlow.•The Lau Event represented the only significant shift in conodont communities of the Ludlow.•Spatiotemporal conodont community coherence enables high resolution eco-correlation.
In recent years it has become commonplace to formalize chemostratigraphic units and identify isotopic zones (chemostratigraphic units) from excursions. Stable carbon isotopes have been used in ...solving stratigraphic problems in the Silurian for more than 30 years. 513C data supplement other stratigraphic proxies, allowing the subdivision of geological sections and more precise correlation. In this paper we give new 513C data from the Silurian section of the Jocionys-299 borehole, which is located in eastern Lithuania, crossing shallow marine and lagunal deposits. Based on 513C variability, the Ireviken carbon isotope excursion (CIE), the Šlilale CIE, and probably the Valgu CIE have been identified in the investigated section. The Valgu CIE is linked to the lower part of the Švencionys Formation. The Ireviken CIE is linked to the upper parts of the Švencionys Formation and the Paprieniai Formation (rise in 513C values), the Jocionys Formation (moderately stable 513Ccarb values) and the Verkne Formation (fall in 513C values). A small negative 513C shift is documented in the Pabrade Formation. Chemostratigraphy together with biostratigraphic data allow us to correlate eastern Lithuanian lithostratigraphic units (shallow marine environment) with the global Silurian Geochronological Scale more accurately.
The upper Silurian, and especially Pridoli epoch is a critical interval for the understanding the evolution of Earth's biota, since it witnessed series of powerful extinction events, global ...reorganizations of paleocommunities, and expansion of new clades, which assumed dominance in the subsequent Devonian period. The stratigraphic record of the eastern part of the Silurian Baltic Basin represents an excellent candidate for the fine scale analysis of paleoecological and paleoceanographic dynamics. Therefore we presenting here stratigraphic record of the Milaičiai-103 core (south western Lithuania) of conodonts, brachiopods, δ13Ccarb, δ18Ocarb and a series of various geochemical and geophysical proxies, most of which were sampled at a very high resolution (~11 Ka), spanning uppermost Ludlow, Pridoli, and the lowermost Devonian. The analysis revealed that the Pridoli was characterized by four distinct long-term dynamic states here named: i) Normal Pridoli I, ii) Šilalė negative carbon isotopic excursion and extinction event, iii) Normal Pridoli II, and iv) Klonk positive stable carbon isotopic event and excursion. The most significant change in most variables is detected approximately in the middle of the Pridoli, at the beginning of the Delotaxis detorta Zone, at the recovery after Šilalė event of conodonts, and at the onset of collapse of brachiopod communities. The analysis of dynamic complexity revealed the strong evidence for the presence of ~405 Ka metronome Milankovitch cycles in the record of δ13Ccarb, which constrains the duration of the Pridoli epoch to 4.3 ± 0.2 Ma. The recurrence plot analyses revealed deterministic coordination between δ13Ccarb and conodont paleocommunity dynamics at all scales. Finally lead-lag analysis, using conditional joint recurrence, revealed that conodont dynamics, as a rule, were driven by perturbations in the carbon cycle, although Šilalė event interval shown opposite pattern, thus confirming the unusual nature of this previously unrecognized coordinated climatic and biotic event.
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•The biogeochemical and paleoecological record of the Pridoli is characterized by four dynamic states.•Šilalė event of coordinated conodont extinctions and negative carbon isotopic excursion is distinguished in the lower Pridoli.•Pronounced ~405 Ka cycles in the time series of dynamic complexity of δ13Ccarb enable accurate estimation of the duration of Pridoli.•Conodont communities and stable carbon isotopic ratios show joint coordination at a range of time scales.
This paper discusses rapid flow and stage fluctuations in a large lowland river downstream from a large hydropower plant (HPP) in Lithuania. The main problem arises when the HPP is operating in peak ...mode. Such operation of HPP causes rapid flow and stage fluctuations, which can have a certain impact on river ecosystems. The study analyzes general abiotic indicators such as upramping and downramping rates and stage fluctuations downstream of the HPP. The main idea was to assess recorded stage upramping and downramping rates along the river downstream of large HPP. To assess stage fluctuation statistics, COSH software was used. A maximum upramping rate of 1.04 m/h and maximum downramping rate of 0.88 m/h were identified using data from temporary and permanent gauging stations. Obtained results revealed that stage fluctuations exceed ecologically acceptable rates up to 20 km downstream of HPP. The effect of hydropeaking fades out only at a chainage of 45 km downstream of HPP. In mountainous regions, ecologically acceptable rates are reached at much smaller distances. The study shows that the traditional coefficient of variation of stage fluctuation data can be used to describe hydropeaking indicators. The main results of this study can be used for environmental impact assessment downstream from HPPs.
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