Defining bounding surfaces within and between eolian and non-eolian deposits, Lower Jurassic Navajo Sandstone, Moab Area, Utah, U.S.A.: Implications for subdividing erg system strata

ABSTRACT A model-independent, sequence stratigraphic approach is used to define bounding surfaces in the Navajo Sandstone in order to identify an architectural hierarchy of genetically related sedimentary packages and the surfaces that bound them across multiple scales of both eolian and non-eolian components of an erg system. Seven bounding surfaces and eight depositional units are defined, from small to large scale. A lamina-deviation surface bounds wedge- and tabular-shaped sets of laminae and/or laminasets, separating those that have different angle orientations on the dune slipface. A bed-deviation surface bounds a succession of beds (crossbeds) that lie at different angles or orientations to bedding above, below, or adjacent to it. A bedset-deviation surface is curved, inclined, and/or wavy and irregular that bounds bedsets and their internal stratification patterns; that is, bed-deviation surfaces, and lamina-deviation surfaces. A simple surface is gently inclined with or without small, concave or convex segments that bound beds and bedsets. A composite surface is horizontal with or without concave, curved, or irregular portions of that surface. A complex surface is laterally extensive (∼ 1–10+ km) that regionally bounds and truncates underlying conterminous and interfingered eolian and non-eolian strata. An amalgamated surface is a regionally extensive (∼ 10 to 100s km) mappable unconformity, merged unconformities, and their laterally equivalent conformable surface that can exhibit local to regional pedogenic modification, lags, and significant (meters to 10s m) paleotopographic relief. The genetically related sedimentary packages typically bounded by like or higher-rank surfaces are defined as laminae, laminasets, bed, bedsets, and simple, composite, complex, and amalgamated units. Field relationships of strata and surfaces are key to reconstructing the interactions between eolian and non-eolian deposits and the processes they represent at the local, regional, and basin scale. This classification scheme can be applied to erg-system strata to fully integrate changes in diverse facies within and between contiguous deposits.

Deciphering the Taxonomic Delimitation of Ottelia acuminata (Hydrocharitaceae) Using Complete Plastomes as Super-Barcodes

Accurate species delimitation and identification, which is a challenging task in traditional morphology-based taxonomy, is crucial to species conservation. Ottelia acuminata (Hydrocharitaceae) is a severely threatened submerged macrophyte endemic to southwestern China. The taxonomy of O. acuminata, which has long been in dispute, remains unresolved, impeding effective conservation and management practices. Here, we aim to address the long-standing issues concerning species boundary and intraspecific subdivision of O. acuminata using complete plastome sequences as super-barcodes. The taxonomic delimitation of O. acuminata was explored using phylogenetic inference and two independent sequence-based species delimitation schemes: automatic barcode gap discovery (ABGD) and multi-rate Poisson tree processes (mPTP). The reciprocally reinforcing results support the reduction of the closely related congeneric species, O. balansae and O. guanyangensis, as two conspecific varieties of O. acuminata. Within the newly defined O. acuminata, accurate varietal identification can be achieved using plastome super-barcodes. These findings will help inform future decisions regarding conservation, management and restoration of O. acuminata. This case study suggests that the use of plastome super-barcodes can provide a solution for species delimitation and identification in taxonomically difficult plant taxa, thus providing great potential to lessen the challenges of inventorying biodiversity, as well as biologically monitoring and assessing threatened species.

Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene

Multiple independent sequence variants of the hTERT locus have been associated with telomere length and cancer risks in genome-wide association studies. Here, we identified an intronic variable number tandem repeat, VNTR2-1, as an enhancer-like element, which activated hTERT transcription in a cell in a chromatin-dependent manner. VNTR2-1, consisting of 42-bp repeats with an array of enhancer boxes, cooperated with the proximal promoter in the regulation of hTERT transcription by basic helix–loop–helix transcription factors and maintained hTERT expression during embryonic stem-cell differentiation. Genomic deletion of VNTR2-1 in MelJuSo melanoma cells markedly reduced hTERT transcription, leading to telomere shortening, cellular senescence, and impairment of xenograft tumor growth. Interestingly, VNTR2-1 lengths varied widely in human populations; hTERT alleles with shorter VNTR2-1 were underrepresented in African American centenarians, indicating its role in human aging. Therefore, this polymorphic element is likely a missing link in the telomerase regulatory network and a molecular basis for genetic diversities of telomere homeostasis and age-related disease susceptibilities.

Evolution of Ribosomal Protein S14 Demonstrated by the Reconstruction of Chimeric Ribosomes in Bacillus subtilis

ABSTRACT Ribosomal protein S14 can be classified into three types. The first, the C+ type has a Zn2+ binding motif and is ancestral. The second and third are the C− short and C− long types, neither of which contain a Zn2+ binding motif and which are ca. 90 residues and 100 residues in length, respectively. In the present study, the C+ type S14 from Bacillus subtilis ribosomes (S14BsC+) were completely replaced by the heterologous C− long type of S14 from Escherichia coli (S14Ec) or Synechococcus elongatus (S14Se). Surprisingly, S14Ec and S14Se were incorporated fully into 70S ribosomes in B. subtilis. However, the growth rates as well as the sporulation efficiency of the mutants harboring heterologous S14 were significantly decreased. In these mutants, the polysome fraction was decreased and the 30S and 50S subunits accumulated unusually, indicating that cellular translational activity of these mutants was decreased. In vitro analysis showed a reduction in the translational activity of the 70S ribosome fraction purified from these mutants. The abundance of ribosomal proteins S2 and S3 in the 30S fraction in these mutants was reduced while that of S14 was not significantly decreased. It seems likely that binding of heterologous S14 changes the structure of the 30S subunit, which causes a decrease in the assembly efficiency of S2 and S3, which are located near the binding site of S14. Moreover, we found that S3 from S. elongatus cannot function in B. subtilis unless S14Se is present. IMPORTANCE S14, an essential ribosomal protein, may have evolved to adapt bacteria to zinc-limited environments by replacement of a zinc-binding motif with a zinc-independent sequence. It was expected that the bacterial ribosome would be tolerant to replacement of S14 because of the previous prediction that the spread of C− type S14 involved horizontal gene transfer. In this study, we completely replaced the C+ type of S14 in B. subtilis ribosome with the heterologous C− long type of S14 and characterized the resulting chimeric ribosomes. Our results suggest that the B. subtilis ribosome is permissive for the replacement of S14, but coevolution of S3 might be required to utilize the C− long type of S14 more effectively.

A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.

APPLICABILITY OF HAUNTOLOGY TO THE STUDY OF THE ORIGINS OF SCREEN ARTS

The article discusses the possibility of making hauntology one of the methods of studying screen arts at the stage of their formation, which might make it possible to correctly interpret the use of early screen arts techniques in later cinema and television broadcasts. Hauntology is a method backed by a program of research into social life and the role of associations in maintaining stable communicative structures, which program is based on the assumption of “ghosts” as cultural actors inherently belonging to the cultural order. Based on the ideas of Jacques Derrida and Mark Fischer, going back to Sigmund Freud’s methods of studying the “uncanny” and “effect of reality”, hauntology claims that ghosts determine the modes of nostalgia and user orientation of a number of screen and visual arts, in particular, the visual principles of modern musical culture. Although hauntology researchers focus extensively on the world of ghosts in the culture of the 19th century, they limit themselves to private remarks and often optimistically presume the fact that the plot rationality ultimately triumphs over the power of ghosts. However, this contradicts both the actual history of the culture then, and the basic principles of hauntology, which asserts that ghosts cannot be fully rationalized. Therefore, the article proposes a visual-critical hauntology, which allows us to explain how visualization techniques contributed to the rationalization of ghostly existence, and how, to create the effect of reality, a screen was required as the basic method of this visualization. Vladimir Toporov’s work on the mystical prose of Turgenev provides the main source of visual-critical hauntology thus proving the need for screen projection to express the author’s position in the era under consideration. The article establishes a connection between the ghostly statuses and the need for a screen reflection mode, which provides a consistent description of psychological reality. It is pointed out that a number of literary experiments of the Victorian era require a screen medium as a basis for understanding the independent sequence of events, from the plot of internal psychological transformation in Dickens’s A Christmas Carol to the “unreliable storyteller” technique in Henry James’s The Turn of the Screw. Visual-critical hauntology, referring to the history of psychology, the decisions of directors, especially Hitchcock, indisputably proves that it is possible to cope with ghosts and rationalize them not with the help of everyday life staging, as it is usually considered, but with the help of its adaptation, which allows to apply emerging technology for creation long-term effect of reality.

A homology independent sequence replacement strategy in human cells using a CRISPR nuclease

Precision genomic alterations largely rely on homology directed repair (HDR), but targeting without homology using the non-homologous end-joining (NHEJ) pathway has gained attention as a promising alternative. Previous studies demonstrated precise insertions formed by the ligation of donor DNA into a targeted genomic double-strand break in both dividing and non-dividing cells. Here, we demonstrate the use of NHEJ repair to replace genomic segments with donor sequences; we name this method ‘Replace’ editing ( R ational e nd-joining p rotocol de l ivering a targeted sequen c e e xchange). Using CRISPR/Cas9, we create two genomic breaks and ligate a donor sequence in-between. This exchange of a genomic for a donor sequence uses neither microhomology nor homology arms. We target four loci in cell lines and show successful exchange of exons in 16–54% of human cells. Using linear amplification methods and deep sequencing, we quantify the diversity of outcomes following Replace editing and profile the ligated interfaces. The ability to replace exons or other genomic sequences in cells not efficiently modified by HDR holds promise for both basic research and medicine.

Whole-genome sequencing analysis of the cardiometabolic proteome

The human proteome is a crucial intermediate between complex diseases and their genetic and environmental components, and an important source of drug development targets and biomarkers. Here, we comprehensively assess the genetic architecture of 257 circulating protein biomarkers of cardiometabolic relevance through high-depth (22.5×) whole-genome sequencing (WGS) in 1328 individuals. We discover 131 independent sequence variant associations (P < 7.45 × 10−11) across the allele frequency spectrum, all of which replicate in an independent cohort (n = 1605, 18.4x WGS). We identify for the first time replicating evidence for rare-variant cis-acting protein quantitative trait loci for five genes, involving both coding and noncoding variation. We construct and validate polygenic scores that explain up to 45% of protein level variation. We find causal links between protein levels and disease risk, identifying high-value biomarkers and drug development targets.

ADEPT: a domain independent sequence alignment strategy for gpu architectures

Background Bioinformatic workflows frequently make use of automated genome assembly and protein clustering tools. At the core of most of these tools, a significant portion of execution time is spent in determining optimal local alignment between two sequences. This task is performed with the Smith-Waterman algorithm, which is a dynamic programming based method. With the advent of modern sequencing technologies and increasing size of both genome and protein databases, a need for faster Smith-Waterman implementations has emerged. Multiple SIMD strategies for the Smith-Waterman algorithm are available for CPUs. However, with the move of HPC facilities towards accelerator based architectures, a need for an efficient GPU accelerated strategy has emerged. Existing GPU based strategies have either been optimized for a specific type of characters (Nucleotides or Amino Acids) or for only a handful of application use-cases. Results In this paper, we present ADEPT, a new sequence alignment strategy for GPU architectures that is domain independent, supporting alignment of sequences from both genomes and proteins. Our proposed strategy uses GPU specific optimizations that do not rely on the nature of sequence. We demonstrate the feasibility of this strategy by implementing the Smith-Waterman algorithm and comparing it to similar CPU strategies as well as the fastest known GPU methods for each domain. ADEPT’s driver enables it to scale across multiple GPUs and allows easy integration into software pipelines which utilize large scale computational systems. We have shown that the ADEPT based Smith-Waterman algorithm demonstrates a peak performance of 360 GCUPS and 497 GCUPs for protein based and DNA based datasets respectively on a single GPU node (8 GPUs) of the Cori Supercomputer. Overall ADEPT shows 10x faster performance in a node-to-node comparison against a corresponding SIMD CPU implementation. Conclusions ADEPT demonstrates a performance that is either comparable or better than existing GPU strategies. We demonstrated the efficacy of ADEPT in supporting existing bionformatics software pipelines by integrating ADEPT in MetaHipMer a high-performance denovo metagenome assembler and PASTIS a high-performance protein similarity graph construction pipeline. Our results show 10% and 30% boost of performance in MetaHipMer and PASTIS respectively.