Crinoid columnals are major faunal components of interbedded shales and carbonates of the Upper Ordovician Kope to Fairview formations (Edenian-Maysvillian) of the Cincinnati Arch region. Six species ...can be identified on the basis of distinctive morphological characters of the columnals. Crinoid distribution was plotted from point-counted carbonate samples taken through a 68-m thick composite section of the Kope to Fairview formations in Campbell County, Kentucky. This section spans a shallowing-upward, third-order depositional sequence (C1), part of C2, and the Edenian-Maysvillian Stage boundary. The slender cladid crinoid Merocrinus occurs in the lowermost Kope below the base of this section. The slender disparids Cincinnaticrinus and Ectenocrinus occur throughout the section but are most abundant in the lower 25 m where the shale percentage is 60–90 percent. The larger, more robust disparid Iocrinus appears within the carbonate-rich Grand Avenue member of the Kope at 40–50 m, and the large, plated camerate Glyptocrinus first appears just above the Grand Avenue and becomes the dominant crinoid above the C1–C2 sequence boundary that lies just above the Kope-Fairview contact. The largest and most robust crinoid in this sequence, Anomalocrinus, occurs at the top of the Grand Avenue Member. Siliciclastic ratio and biofacies composition indicate that the occurrence of larger, more robust crinoid taxa is correlated with shallowing depth. Crinoid trophic niche differentiation is also correlated with decreasing depth and the concomitant increase in water movement caused by waves and currents. The deeper water disparids have a nonpinnulate filtration fan with low branch density and wider ambulacral grooves. The shallower water camerate Glyptocrinus has a pinnulate filtration fan with high branch density and narrower ambulacral grooves. These relationships are consistent with the predictions of aerosol filtration theory.
Vaccination against COVID-19 with the recently approved mRNA vaccines BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) is currently underway in a large number of countries. However, high incidence ...rates and rapidly spreading SARS-CoV-2 variants are concerning. In combination with acute supply deficits in Europe in early 2021, the question arises of whether stretching the vaccine, for instance by delaying the second dose, can make a significant contribution to preventing deaths, despite associated risks such as lower vaccine efficacy, the potential emergence of escape mutants, enhancement, waning immunity, reduced social acceptance of off-label vaccination, and liability shifts. A quantitative epidemiological assessment of risks and benefits of non-standard vaccination protocols remains elusive. To clarify the situation and to provide a quantitative epidemiological foundation we develop a stochastic epidemiological model that integrates specific vaccine rollout protocols into a risk-group structured infectious disease dynamical model. Using the situation and conditions in Germany as a reference system, we show that delaying the second vaccine dose is expected to prevent deaths in the four to five digit range, should the incidence resurge. We show that this considerable public health benefit relies on the fact that both mRNA vaccines provide substantial protection against severe COVID-19 and death beginning 12 to 14 days after the first dose. The benefits of protocol change are attenuated should vaccine compliance decrease substantially. To quantify the impact of protocol change on vaccination adherence we performed a large-scale online survey. We find that, in Germany, changing vaccination protocols may lead to small reductions in vaccination intention. In sum, we therefore expect the benefits of a strategy change to remain substantial and stable.
Although parasequence and sequence are scale‐independent terms, they are frequently applied only to specific scales of cycles. For example, meter‐scale cycles are commonly assumed to be parasequences ...or PACs. In the Upper Ordovi‐cian Kope and Fairview Formations of northern Kentucky, we examined a succession of 50 meter‐scale cycles that have been variously interpreted as deepening‐upward, shallowing‐upward, or showing no relationship with water depth. Our analysis shows that these cycles, characterized by shifts in storm‐bed proximality, are highly variable in their thickness and internal construction. Most cycles are best considered high‐frequency sequences, because deepening‐upward intervals are common, and many cycles contain evidence of abrupt basinward shifts in facies as expected at sequence boundaries. A minority fit the parasequence model of shallowing‐upward cycles bounded by flooding surfaces. Larger, 20 m scale cycles are defined by systematic thickening and thinning trends of meter‐scale cycles. However, meter‐scale cycles do not display any systematic trends in cycle anatomy as a function of position within the 20 m cycles or position within the Kope and Fairview Formations. The high cycle variability and the lack of systematic stratigraphic organization with respect to longer‐term cyclicity reflect either the irregularity of relative sea‐level changes, the poor recording of sea‐level changes in this deep‐water setting, or the generation of these cycles by climate‐induced cyclicity in storm intensity. These three mechanisms would generate similar patterns at the outcrop scale, so it is not possible at the present to distinguish between them.
Environmental controls on the distribution of fossils most commonly are found by recognizing that certain distinctive fossil assemblages are associated with particular lithofacies. Lack of change in ...lithofacies commonly is used as indicating a lack of significant environmental effects on the stratigraphic distribution of fossils. The results presented here challenge that view. The Upper Ordovician Kope Formation of the Cincinnati, Ohio, area has long been considered a single unit, both lithostratigraphically and in terms of depositional environment. Gradient analysis of over 1000 fossil assemblages reveals subtle environmental control on the distribution of fossils, in the absence of obvious lithologic change. This gradient analysis is used to construct an ecological model of the Kope fauna, with values of preferred depth, depth tolerance, and peak abundance estimated for the most common fossils. This method, conducted within a single lithofacies, offers the potential for reconstructing sequence architecture because faunas can be more sensitive recorders of environment than lithofacies. In addition, the presence of subtle facies control as in the Kope raises the prospect that environmental controls on paleobiologic and biostratigraphic patterns may be more pervasive than generally acknowledged.
N-glycosylation of proteins is one of the most prevalent posttranslational modifications in nature. Accordingly, a pathway with shared commonalities is found in all three domains of life. While ...excellent model systems have been developed for studying N-glycosylation in both Eukarya and Bacteria, an understanding of this process in Archaea was hampered until recently by a lack of effective molecular tools. However, within the last decade, impressive advances in the study of the archaeal version of this important pathway have been made for halophiles, methanogens, and thermoacidophiles, combining glycan structural information obtained by mass spectrometry with bioinformatic, genetic, biochemical, and enzymatic data. These studies reveal both features shared with the eukaryal and bacterial domains and novel archaeon-specific aspects. Unique features of N-glycosylation in Archaea include the presence of unusual dolichol lipid carriers, the use of a variety of linking sugars that connect the glycan to proteins, the presence of novel sugars as glycan constituents, the presence of two very different N-linked glycans attached to the same protein, and the ability to vary the N-glycan composition under different growth conditions. These advances are the focus of this review, with an emphasis on N-glycosylation pathways in Haloferax, Methanococcus, and Sulfolobus.
In-situ resource utilization (ISRU) is increasingly acknowledged as an essential requirement for the construction of sustainable extra-terrestrial colonies. Even with decreasing launch costs, the ...ultimate goal of establishing colonies must be the usage of resources found at the destination of interest. Typical approaches towards ISRU are often constrained by the mass and energy requirements of transporting processing machineries, such as rovers and massive reactors, and the vast amount of consumables needed. Application of self-reproducing bacteria for the extraction of resources is a promising approach to reduce these pitfalls. In this work, the bacterium Shewanella oneidensis was used to reduce three different types of Lunar and Martian regolith simulants, allowing for the magnetic extraction of iron-rich materials. The combination of bacterial treatment and magnetic extraction resulted in a 5.8-times higher quantity of iron and 43.6% higher iron concentration compared to solely magnetic extraction. The materials were 3D printed into cylinders and the mechanical properties were tested, resulting in a 400% improvement in compressive strength in the bacterially treated samples. This work demonstrates a proof of concept for the on-demand production of construction and replacement parts in space exploration.
The epithelial lining of the fallopian tube is of critical importance for human reproduction and has been implicated as a site of origin of high-grade serous ovarian cancer. Here we report on the ...establishment of long-term, stable 3D organoid cultures from human fallopian tubes, indicative of the presence of adult stem cells. We show that single epithelial stem cells in vitro can give rise to differentiated organoids containing ciliated and secretory cells. Continuous growth and differentiation of organoids depend on both Wnt and Notch paracrine signalling. Microarray analysis reveals that inhibition of Notch signalling causes downregulation of stem cell-associated genes in parallel with decreased proliferation and increased numbers of ciliated cells and that organoids also respond to oestradiol and progesterone treatment in a physiological manner. Thus, our organoid model provides a much-needed basis for future investigations of signalling routes involved in health and disease of the fallopian tube.
Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Here, we combined FACS-based genome-wide CRISPR screens ...with a data-mining approach to identify drugs that can upregulate MHC-I without inducing PD-L1. CRISPR screening identified TRAF3, a suppressor of the NFκB pathway, as a negative regulator of MHC-I but not PD-L1. The
-knockout gene expression signature is associated with better survival in ICB-naïve patients with cancer and better ICB response. We then screened for drugs with similar transcriptional effects as this signature and identified Second Mitochondria-derived Activator of Caspase (SMAC) mimetics. We experimentally validated that the SMAC mimetic birinapant upregulates MHC-I, sensitizes cancer cells to T cell-dependent killing, and adds to ICB efficacy. Our findings provide preclinical rationale for treating tumors expressing low MHC-I expression with SMAC mimetics to enhance sensitivity to immunotherapy. The approach used in this study can be generalized to identify other drugs that enhance immunotherapy efficacy. SIGNIFICANCE: MHC-I loss or downregulation in cancer cells is a major mechanism of resistance to T cell-based immunotherapies. Our study reveals that birinapant may be used for patients with low baseline MHC-I to enhance ICB response. This represents promising immunotherapy opportunities given the biosafety profile of birinapant from multiple clinical trials.
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Filamentous fungi are confronted with changes and limitations of their carbon source during growth in their natural habitats and during industrial applications. To survive life-threatening starvation ...conditions, carbon from endogenous resources becomes mobilized to fuel maintenance and self-propagation. Key to understand the underlying cellular processes is the system-wide analysis of fungal starvation responses in a temporal and spatial resolution. The knowledge deduced is important for the development of optimized industrial production processes.
This study describes the physiological, morphological and genome-wide transcriptional changes caused by prolonged carbon starvation during submerged batch cultivation of the filamentous fungus Aspergillus niger. Bioreactor cultivation supported highly reproducible growth conditions and monitoring of physiological parameters. Changes in hyphal growth and morphology were analyzed at distinct cultivation phases using automated image analysis. The Affymetrix GeneChip platform was used to establish genome-wide transcriptional profiles for three selected time points during prolonged carbon starvation. Compared to the exponential growth transcriptome, about 50% (7,292) of all genes displayed differential gene expression during at least one of the starvation time points. Enrichment analysis of Gene Ontology, Pfam domain and KEGG pathway annotations uncovered autophagy and asexual reproduction as major global transcriptional trends. Induced transcription of genes encoding hydrolytic enzymes was accompanied by increased secretion of hydrolases including chitinases, glucanases, proteases and phospholipases as identified by mass spectrometry.
This study is the first system-wide analysis of the carbon starvation response in a filamentous fungus. Morphological, transcriptomic and secretomic analyses identified key events important for fungal survival and their chronology. The dataset obtained forms a comprehensive framework for further elucidation of the interrelation and interplay of the individual cellular events involved.
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