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At least 109 records · Page 6

Life on Mars? 1: The chemical environment

The origin of life at its abiotic evolutionary stage, requires a combination of constituents and environmental conditions that enable the synthesis of complex replicating macromolecules from simpler monomeric molecules. It is very likely that the early stages of this evolutionary process have been spontaneous, rapid and widespread on the surface of the primitive Earth, resulting in the formation of quite sophisticated living organisms within less than a billion years. To what extend did such conditions prevail on Mars? Two companion-papers will review and discuss the available information related to the chemical, physical and environmental conditions on Mars and assess it from the perspective of potential exobiological evolution.

Banin, A.↗

Influenza A Virus Multicycle Replication Yields Comparable Viral Population Emergence in Human Respiratory and Ocular Cell Types

While primarily considered a respiratory pathogen, influenza A virus (IAV) is nonetheless capable of spreading to, and replicating in, numerous extrapulmonary tissues in humans. However, within-host assessments of genetic diversity during multicycle replication have been largely limited to respiratory tract tissues and specimens. As selective pressures can vary greatly between anatomical sites, there is a need to examine how measures of viral diversity may vary between influenza viruses exhibiting different tropisms in humans, as well as following influenza virus infection of cells derived from different organ systems. Here, we employed human primary tissue constructs emulative of the human airway or corneal surface, and we infected both with a panel of human- and avian-origin IAV, inclusive of H1 and H3 subtype human viruses and highly pathogenic H5 and H7 subtype viruses, which are associated with both respiratory disease and conjunctivitis following human infection. While both cell types supported productive replication of all viruses, airway-derived tissue constructs elicited greater induction of genes associated with antiviral responses than did corneal-derived constructs. We used next-generation sequencing to examine viral mutations and population diversity, utilizing several metrics. With few exceptions, generally comparable measures of viral diversity and mutational frequency were detected following homologous virus infection of both respiratory-origin and ocular-origin tissue constructs. Expansion of within-host assessments of genetic diversity to include IAV with atypical clinical presentations in humans or in extrapulmonary cell types can provide greater insight into understanding those features most prone to modulation in the context of viral tropism.

59 BASIC BIOLOGICAL SCIENCES↗

The origin of polynucleotide-directed protein synthesis

If protein synthesis evolved in an RNA world it was probably preceded by simpler processes by means of which interaction with amino acids conferred selective advantage on replicating RNA molecules. It is suggested that at first the simple attachment of amino acids to the 2'(3') termini of RNA templates favored initiation of replication at the end of the template rather than at internal positions. The second stage in the evolution of protein synthesis would probably have been the association of pairs of charged RNA adaptors in such a way as to favor noncoded formation of peptides. Only after this process had become efficient could coded synthesis have begun.

Orgel, Leslie E.↗

Cell and molecular biology of simian virus 40: implications for human infections and disease

Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

Review↗

Lower temperature optimum of a smaller, fragmented triphosphorylation ribozyme

The RNA world hypothesis describes a stage in the early evolution of life in which catalytic RNAs mediated the replication of RNA world organisms. One challenge to this hypothesis is that most existing ribozymes are much longer than what may be expected to originate from prebiotically plausible methods, or from the polymerization by currently existing polymerase ribozymes. We previously developed a 96-nucleotide long ribozyme, which generates a chemically activated 5'-phosphate (a 5'-triphosphate) from a prebiotically plausible molecule, trimetaphosphate, and an RNA 5'-hydroxyl group. Analogous ribozymes may have been important in the RNA world to access an energy source for the earliest life forms. Here we reduce the length of this ribozyme by fragmenting the ribozyme into multiple RNA strands, and by successively removing its longest double strand. The resulting ribozyme is composed of RNA fragments with none longer than 34 nucleotides. The temperature optimum was ~20°C, compared to ~40°C for the parent ribozyme. This shift in temperature dependence may be a more general phenomenon for fragmented ribozymes, and may have helped RNA world organisms to emerge at low temperature.

Arvin Akoopie↗

Adaptive Laboratory Evolution for algal strain improvement: methodologies and applications

Originally developed in bacterial and fungal models, Adaptive Laboratory Evolution (ALE) experimentally selects for targeted phenotypes by allowing cells containing beneficial random genetic mutations to replicate more quickly in the presence of environmental stress. When applied to microalgae, this technique has been used to increase growth rate, stress tolerance, substrate utilization, and product yield. This review discusses ALE experimental design parameters, and summarizes key results and lessons learned from recent microalgal ALE studies. By documenting the current state of the field, we provide insight on the ways microalgal ALE might be used to develop commercially viable biotechnology strains.

09 BIOMASS FUELS↗

Direct numerical simulation of laminar breakdown in high-speed, axisymmetric boundary layers

The compressible Navier-Stokes equations are solved using spectral collocation and high-order compact-difference techniques to simulate the laminar breakdown in high-speed, axisymmetric boundary-layer flow. Mach 4.5 flow along a hollow cylinder and Mach 6.8 flow along a sharp cone are considered. Data obtained replicate two previously unexplained phenomena, namely, the appearance of so-called 'rope-like waves' and 'the precursor transition effect', in which transitional flow originates near the critical layer well upstream of the transition location at the wall. The numerical data also reveal that neither of these effects can be explained, even qualitatively, by linear stability theory alone. It is shown that rope-like appearance arises from secondary instability. Certain features of the precursor transition effect also emerge from secondary instability but its nature is revealed to be fundamentally nonlinear.

Pruett, C. D.↗

Novel mutation leading to splice donor loss in a conserved site of DMD gene causes Duchenne muscular dystrophy with cryptorchidism

Background As one of the most common congenital abnormalities in male births, cryptorchidism has been found to have a polygenic aetiology according to previous studies of common variants. However, little is known about genetic predisposition of rare variants for cryptorchidism, since rare variants have larger effective size on diseases than common variants. Methods In this study, a cohort of 115 Chinese probands with cryptorchidism was analysed using whole-genome sequencing, alongside 19 parental controls and 2136 unaffected men. Additionally, CRISPR-Cas9 editing of a conserved variant was performed in a mouse model, with MRI screening used to observe the phenotype. Results In 30 of 115 patients (26.1%), we identified four novel genes ( ARSH , DMD , MAGEA4 and SHROOM2 ) affecting at least five unrelated patients and four known genes ( USP9Y , UBA1 , BCORL1 and KDM6A ) with the candidate rare pathogenic variants affecting at least two cases. Burden tests of rare variants revealed the genome-wide significances for newly identified genes (p<2.5×10 −6 ) under the Bonferroni correction. Surprisingly, novel and known genes were mainly found on X chromosome (seven on X and one on Y) and all rare X-chromosomal segregating variants exhibited a maternal inheritance rather than de novo origin. CRISPR-Cas9 mouse modelling of a splice donor loss variant in DMD (NC_000023.11:g.32454661C>G), which resides in a conserved site across vertebrates, replicated bilateral cryptorchidism phenotypes, confirmed by MRI at 4 and 10 weeks. The movement tests further revealed symptoms of Duchenne muscular dystrophy (DMD) in transgenic mice. Conclusion Our results revealed the role of the DMD gene mutation in causing cryptorchidism. The results also suggest that maternal-X inheritance of pathogenic defects could have a predominant role in the development of cryptorchidism.

Chen, Jianhai (ORCID:0000000300932003)↗

Continental and oceanic magnetic anomalies: Enhancement through GRM

In contrast to the POGO and MAGSAT satellites, the Geopotential Research Mission (GRM) satellite system will orbit at a minimum elevation to provide significantly better resolved lithospheric magnetic anomalies for more detailed and improved geologic analysis. In addition, GRM will measure corresponding gravity anomalies to enhance our understanding of the gravity field for vast regions of the Earth which are largely inaccessible to more conventional surface mapping. Crustal studies will greatly benefit from the dual data sets as modeling has shown that lithospheric sources of long-wavelength magnetic anomalies frequently involve density variations which may produce detectable gravity anomalies at satellite elevations. Furthermore, GRM will provide an important replication of lithospheric magnetic anomalies as an aid to identifying and extracting these anomalies from satellite magnetic measurements. The potential benefits to the study of the origin and characterization of the continents and oceans, that may result from the increased GRM resolution are examined.

Vonfrese, R. R. B.↗

Continental and oceanic magnetic anomalies: Enhancement through GRM

In contrast to the POGO and MAGSAT satellites, the Geopotential Research Mission (GRM) satellite system will orbit at a minimum elevation to provide significantly better resolved lithospheric magnetic anomalies for more detailed and improved geologic analysis. In addition, GRM will measure corresponding gravity anomalies to enhance our understanding of the gravity field for vast regions of the Earth which are largely inaccessible to more conventional surface mapping. Crustal studies will greatly benefit from the dual data sets as modeling has shown that lithospheric sources of long wavelength magnetic anomalies frequently involve density variations which may produce detectable gravity anomalies at satellite elevations. Furthermore, GRM will provide an important replication of lithospheric magnetic anomalies as an aid to identifying and extracting these anomalies from satellite magnetic measurements. The potential benefits to the study of the origin and characterization of the continents and oceans, that may result from the increased GRM resolution are examined.

Vonfrese, R. R. B.↗

Ames interactive molecular model building system - A 3-D computer modelling system applied to the study of the origin of life

The investigation of specific interactions among biological molecules must take into consideration the stereochemistry of the structures. Thus, models of the molecules are essential for describing the spatial organization of potentially interacting groups, and estimations of conformation are required for a description of spatial organization. Both the function of visualizing molecules, and that of estimating conformation through calculations of energy, are part of the molecular modeling system described in the present paper. The potential uses of the system in investigating some aspects of the origin of life rest on the assumption that translation of conformation from genetic elements to catalytic elements would have been required for the development of the first replicating systems subject to the process of biological evolution.

Coeckelenbergh, Y.↗

Role of the likelihood for elastic scattering uncertainty quantification

In the last decade, uncertainty quantification (UQ) for optical model potentials (OMPs) has become a focal point for nuclear reaction theory, and several competing approaches for OMP UQ have recently been developed. Here, we clarify recent efforts to compare frequentist and Bayesian approaches in the context of OMP UQ [G. B. King et al., Phys. Rev. Lett. 122, 232502 (2019)]. We replicate a portion of that OMP UQ study but use independent statistical tools. Specifically, we compare two methods for OMP parameter inference from elastic scattering data: the Levenberg-Marquardt algorithm for χ 2 minimization on one hand and Markov chain Monte Carlo (MCMC) sampling on the other. Separately, we assess the common practice of using a renormalized likelihood (χ 2 /N), N being the number of data points, instead of the canonical weighted-least-squares likelihood (χ 2 ), as a way of accounting for unknown data correlations. Here, we show that for a generic linear model and for a five-parameter OMP analysis, frequentist and uniform-prior Bayesian approaches recover the same optimum and uncertainty estimates—not systematically larger uncertainties for the Bayesian approach, as was concluded in G. B. King et al., Phys. Rev. Lett. 122, 232502 (2019). Further, we show that if an additional, near-degenerate parameter is introduced into the same OMP analysis such that the parameter posterior becomes non-Gaussian, then covariance-based estimates of uncertainty become unreliable. Finally, we show that regardless of optimization approach, if χ 2 /N is used for the likelihood, the resulting parametric uncertainties increase by $\sqrt{N}$, and that this is responsible for the conclusions drawn in the revisited study. Based on our replication results, we find that a fortuitous cancellation of unreported errors and the renormalization factor can lead to improvement in empirical coverages, as was the case in the original comparative study. We emphasize that developing and applying a realistic likelihood function is an essential task in a UQ analysis, and that several recent UQ studies that employed a renormalized likelihood (i.e., including a 1/N factor) may have yielded unrealistically large uncertainties for elastic-scattering observables. If the parameter posterior deviates from multivariate-normal, a sampling-based approach like MCMC has a clear advantage over methods that assume the Laplace approximation holds. We note that empirical coverage can serve as an important internal check for the analyst whose model or data may have additional, unaccounted-for uncertainties.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

De Novo Synthesis and Functional Study of Primitive Polypeptides in the Prebiotic Protein World

DNA, RNA and proteins within a lipid-bound membrane are the core components of life, but the order of their appearance during the origin of life is still under debate. The widely accepted RNA World hypothesis states that RNA likely emerged prior to proteins and DNA since RNA can serve both replicative and catalytic roles. While biochemists have reproduced the synthesis, polymerization, and replication of nucleotides and RNA under controlled prebiotic conditions, it is clear that such complex organic molecules were are not present in significant amounts in the the starting prebiotic material on Earth either from endogenous production or meteoritic input. In contrast, amino acids are naturally abundant in various prebiotic contexts such as carbonaceous chondrites and Urey-Miller type experiments, and many studies have demonstrated that under plausible prebiotic conditions amino acids could condense or polymerize to give rise to short peptides. These findings support the basis of a Protein World hypothesis for life, however little has been done to study the functions of such primitive peptides. Here we present our novel synthetic biology-based approach to the de novo synthesis of billions of primitive peptidesproteins derived from a limited set of naturally abundant proteinogenic amino acids such as glycine, alanine, aspartic acid, glutamic acid, valine and serine. Of these peptides, the ones with divalent metal-binding capability are of particular interest and will be screened and identified. Certain divalent metals were likely present in prebiotic environments. Not only do they coordinate well with amino acids, but they also catalyze reactions, which are difficult to achieve in organic chemistry. Since D-chiral and non-proteinogenic amino acids are also abundant in the universe and may provide insight into the pathway by which life developed, we will also discuss methods to analyze primitive peptides consisting of these amino acids and D-chiral and non-proteinogenic amino acids. By understanding this naturalistic pathway, we will be able to better understand how life developed here on Earth. Since these amino acids are abundant in universe, this work provide insight into pathways by which life developed on Earth and, by extension, the probability of life arising elsewhere.

Fujishima, Kosuke↗

Original images, ground truth annotations, and precited masks from U-NET for a fungal species x nitrogen experiment

This document describes the “MicroVision-MV003” dataset. This folder contains three subfolders: “originals”, “predicted_masks”, and “gt_masks”. The “originals” folder contains 720 original images acquired using two imaging modalities: 360 images from overhead imaging and 360 images from transmission (raw) imaging. Naming scheme:YYYY-MM-dd__plate_strain_nitrogen-level_replication_experiment_imaging-modalityYYYY-MM-dd: 2024-12-20, 2024-12-21, 2024-12-22,2024-12-23,2024-12-24,2024-12-25,2024-12-26,2024-12-27,2024-12-28,2024-12-29,2024-12-30,2024-12-31.plate: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30.strain: FG, LE.nitrogen-level: N-1, N-10, N-100.replication: 1, 2, 3, 4, 5.experiment: MV.003.imaging-modality: overhead, transmission (raw). For example, the image2024-12-20__1_FG_N-10_3_MV.003_overheadwas taken on 2024-12-20. The plate number is 1, the fungal strain is FG, the nitrogen treatment is N-10, and the replication number is 3 for experiment MV.003, acquired using the overhead imaging modality. The “predicted_masks” folder contains masks generated by a trained U-Net model for the transmission imaging modality.The “gt_masks” folder contains 326 human hand-traced masks that serve as ground truth.

09 BIOMASS FUELS↗

Potential absence of observed π2 linear-chain structures in 14O via 10C(α,α) resonances scattering

Background: The preference for light nuclear systems to coagulate into -particle clusters has been well-studied. The possibility of a linear chain configuration of -particles would allow for a new way to study this phenomenon. Purpose: A rotational band of states in C has been claimed showing a linear chain structure. The mirror system, O, has been studied here to examine how this linear chain structure is affected by replacing the valence neutrons with protons. Method: A beam of C was incident into a chamber filled with He:CO gas with the tracks recorded inside the TexAT Time Projection Chamber and the recoil -particles detected by a silicon detector array to measure the cross section. Results: The experimental cross section was compared with previous studies and fit using R-Matrix theory with the previously-observed O states being transformed to the C using mirror symmetry. The measured cross section does not replicate the claimed states, with the predicted cross section exceeding that observed at several energies and angles. Conclusion: A series of possibilities are highlighted with the most likely being that the originally-seen C states did not constitute a rotational band with a potentially incorrect spin assignment due to the limitations of the angular correlation method with non-zero spin particles. The work highlights the difficulties in measuring broad resonances corresponding to a linear chain state in a high level density.

Bishop, J.↗

Image Discrimination Models Predict Object Detection in Natural Backgrounds

Object detection involves looking for one of a large set of object sub-images in a large set of background images. Image discrimination models only predict the probability that an observer will detect a difference between two images. In a recent study based on only six different images, we found that discrimination models can predict the relative detectability of objects in those images, suggesting that these simpler models may be useful in some object detection applications. Here we replicate this result using a new, larger set of images. Fifteen images of a vehicle in an other-wise natural setting were altered to remove the vehicle and mixed with the original image in a proportion chosen to make the target neither perfectly recognizable nor unrecognizable. The target was also rotated about a vertical axis through its center and mixed with the background. Sixteen observers rated these 30 target images and the 15 background-only images for the presence of a vehicle. The likelihoods of the observer responses were computed from a Thurstone scaling model with the assumption that the detectabilities are proportional to the predictions of an image discrimination model. Three image discrimination models were used: a cortex transform model, a single channel model with a contrast sensitivity function filter, and the Root-Mean-Square (RMS) difference of the digital target and background-only images. As in the previous study, the cortex transform model performed best; the RMS difference predictor was second best; and last, but still a reasonable predictor, was the single channel model. Image discrimination models can predict the relative detectabilities of objects in natural backgrounds.

Ahumada, Albert J., Jr.↗

Life's origin: the cosmic, planetary and biological processes

From elements formed in interstellar furnaces to humans peering back at the stars, the evolution of life has been a long, intricate and perhaps inevitable process. Life as we know it requires a planet orbiting a star at just the right distance so that water can exist in liquid form. It needs a rich supply of chemicals and energy sources. On Earth, the combination of chemistry and energy generated molecules that evolved ways of replicating themselves and of passing information from one generation to the next. Thus, the thread of life began. This chart traces the thread, maintained by DNA molecules for much of its history, as it weaves its way through the primitive oceans, gaining strength and diversity along the way. Organisms eventually moved onto the land, where advanced forms, including humans, ultimately arose. Finally, assisted by a technology of its own making, life has reached back out into space to understand its own origins, to expand into new realms, and to seek other living threads in the cosmos.

NASA Center ARC↗