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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3

A Fast Algorithm for Computing Zigzag Representatives

Zigzag filtrations of simplicial complexes generalize the usual filtrations by allowing simplex deletions in addition to simplex insertions. The barcodes computed from zigzag filtrations encode the evolution of homological features. Although one can locate a particular feature at any index in the filtration using existing algorithms, the resulting representatives may not be compatible with the zigzag: a representative cycle at one index may not map into a representative cycle at its neighbor. For this, one needs to compute compatible representative cycles along each bar in the barcode. It is known that the barcode for a zigzag filtration with m insertions and deletions can be computed $O(m^ω)$ in time, where $ω < 2.373$ is the matrix multiplication exponent. However, it is not known how to compute the compatible representatives so efficiently. For a non-zigzag filtration, the classical matrix-based algorithm provides representatives in $O(m^3)$ time, which can be improved to $O(m^ω)$. However, no known algorithm for zigzag filtrations computes the representatives with the $O(m^3)$ time bound. We present an $O(m^3 n)$ time algorithm for this problem, where $n ≤ m$ is the size of the largest complex in the filtration.

Persistent homology↗

Local Versus Global Distances for Zigzag and Multi-Parameter Persistence Modules

In this paper, we establish explicit and broadly applicable relationships between persistence-based distances computed locally and globally. In particular, we show that the bottleneck distance and the Wasserstein distance between two zigzag persistence modules restricted to an interval is always bounded above by the distance between the unrestricted versions. While this result is not surprising, it could have potential practical implications. We give two related applications for metric graph distances, as well as an extension for the matching distance between multi-parameter persistence modules.

persistent homology, metric graph, inequality↗

Tracking the topology of neural manifolds across populations

Neural manifolds summarize the intrinsic structure of the information encoded by a population of neurons. Advances in experimental techniques have made simultaneous recordings from multiple brain regions increasingly commonplace, raising the possibility of studying how these manifolds relate across populations. However, when the manifolds are nonlinear and possibly code for multiple unknown variables, it is challenging to extract robust and falsifiable information about their relationships. We introduce a framework, called the method of analogous cycles, for matching topological features of neural manifolds using only observed dissimilarity matrices within and between neural populations. We demonstrate via analysis of simulations and in vivo experimental data that this method can be used to correctly identify multiple shared circular coordinate systems across both stimuli and inferred neural manifolds. Conversely, the method rejects matching features that are not intrinsic to one of the systems. Further, as this method is deterministic and does not rely on dimensionality reduction or optimization methods, it is amenable to direct mathematical investigation and interpretation in terms of the underlying neural activity. We thus propose the method of analogous cycles as a suitable foundation for a theory of cross-population analysis via neural manifolds.

97 MATHEMATICS AND COMPUTING↗

Cadmus v1.0

This software package is for distributed computation of persistent (co)homology. It is primarily intended for Topological Data Analysis (TDA) audience and scientists who use TDA methods and apply them to datasets that are too big to handle on a single machine. There are very few codes available for this; Cadmus outperforms DIPHA, if the user is interested in cohomology. The accompanying paper explaining the algorithm was accepted to ALENEX 26.

Nigmetov, Arnur [Lawrence Berkeley National Labora↗

Microbial species and intraspecies units exist and are maintained by ecological cohesiveness coupled to high homologous recombination

Abstract Recent genomic analyses have revealed that microbial communities are predominantly composed of persistent, sequence-discrete species and intraspecies units (genomovars), but the mechanisms that create and maintain these units remain unclear. By analyzing closely-related isolate genomes from the same or related samples and identifying recent recombination events using a novel bioinformatics methodology, we show that high ecological cohesiveness coupled to frequent-enough and unbiased (i.e., not selection-driven) horizontal gene flow, mediated by homologous recombination, often underlie these diversity patterns. Ecological cohesiveness was inferred based on greater similarity in temporal abundance patterns of genomes of the same vs. different units, and recombination was shown to affect all sizable segments of the genome (i.e., be genome-wide) and have two times or greater impact on sequence evolution than point mutations. These results were observed in bothSalinibacter ruber, an environmental halophilic organism, andEscherichia coli, the model gut-associated organism and an opportunistic pathogen, indicating that they may be more broadly applicable to the microbial world. Therefore, our results represent a departure compared to previous models of microbial speciation that invoke either ecology or recombination, but not necessarily their synergistic effect, and answer an important question for microbiology: what a species and a subspecies are.

Science & Technology - Other Topics↗

A crucial role for dynamic expression of components encoding the negative arm of the circadian clock

In the Neurospora circadian system, the White Collar Complex (WCC) drives expression of the principal circadian negative arm component frequency ( frq ). FRQ interacts with FRH (FRQ-interacting RNA helicase) and CKI, forming a stable complex that represses its own expression by inhibiting WCC. In this study, a genetic screen identified a gene, designated as brd-8 , that encodes a conserved auxiliary subunit of the NuA4 histone acetylation complex. Loss of brd-8 reduces H4 acetylation and RNA polymerase (Pol) II occupancy at frq and other known circadian genes, and leads to a long circadian period, delayed phase, and defective overt circadian output at some temperatures. In addition to strongly associating with the NuA4 histone acetyltransferase complex, BRD-8 is also found complexed with the transcription elongation regulator BYE-1. Expression of brd-8, bye-1, histone h2a.z , and several NuA4 subunits is controlled by the circadian clock, indicating that the molecular clock both regulates the basic chromatin status and is regulated by changes in chromatin. Taken together, our data identify auxiliary elements of the fungal NuA4 complex having homology to mammalian components, which along with conventional NuA4 subunits, are required for timely and dynamic frq expression and thereby a normal and persistent circadian rhythm.

59 BASIC BIOLOGICAL SCIENCES↗

Expression of the ctenophore Brain Factor 1 forkhead gene ortholog (ctenoBF-1) mRNA is restricted to the presumptive mouth and feeding apparatus: implications for axial organization in the Metazoa

Ctenophores are thoroughly modern animals whose ancestors are derived from a separate evolutionary branch than that of other eumetazoans. Their major longitudinal body axis is the oral-aboral axis. An apical sense organ, called the apical organ, is located at the aboral pole and contains a highly innervated statocyst and photodetecting cells. The apical organ integrates sensory information and controls the locomotory apparatus of ctenophores, the eight longitudinal rows of ctene/comb plates. In an effort to understand the developmental and evolutionary organization of axial properties of ctenophores we have isolated a forkhead gene from the Brain Factor 1 (BF-1) family. This gene, ctenoBF-1, is the first full-length nuclear gene reported from ctenophores. This makes ctenophores the most basal metazoan (to date) known to express definitive forkhead class transcription factors. Orthologs of BF-1 in vertebrates, Drosophila, and Caenorhabditis elegans are expressed in anterior neural structures. Surprisingly, in situ hybridizations with ctenoBF-1 antisense riboprobes show that this gene is not expressed in the apical organ of ctenophores. CtenoBF-1 is expressed prior to first cleavage. Transcripts become localized to the aboral pole by the 8-cell stage and are inherited by ectodermal micromeres generated from this region at the 16- and 32-cell stages. Expression in subsets of these cells persists and is seen around the edge of the blastopore (presumptive mouth) and in distinct ectodermal regions along the tentacular poles. Following gastrulation, stomodeal expression begins to fade and intense staining becomes restricted to two distinct domains in each tentacular feeding apparatus. We suggest that the apical organ is not homologous to the brain of bilaterians but that the oral pole of ctenophores corresponds to the anterior pole of bilaterian animals.

Non-NASA Center↗

Reactive oxygen species control protein degradation at the mitochondrial import gate

While reactive oxygen species (ROS) have long been known to drive aging and neurodegeneration, their persistent depletion below basal levels also disrupts organismal function. Cells counteract loss of basal ROS via the reductive stress response, but the identity and biochemical activity of ROS sensed by this pathway remain unknown. Here, we show that the central enzyme of the reductive stress response, the E3 ligase Cullin 2-FEM1 homolog B (CUL2 FEM1B ), specifically acts at mitochondrial TOM complexes, where it senses ROS produced by complex III of the electron transport chain (ETC). ROS depletion during times of low ETC activity triggers the localized degradation of CUL2 FEM1B substrates, which sustains mitochondrial import and ensures the biogenesis of the rate-limiting ETC complex IV. As complex III yields most ROS when the ETC outpaces metabolic demands or oxygen availability, basal ROS are sentinels of mitochondrial activity that help cells adjust their ETC to changing environments, as required for cell differentiation and survival.

FEM1B↗

Involvement of DNA-PK(sub cs) in DSB Repair Following Fe-56 Ion Irradiation

When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with <5% of M059K cells indicating that persistent DSBs or those formed at stalled replication forks recruit RAD51 in DNA-PK(sub cs) deficient cells. Following 1 Gy gamma-radiation the induction of gamma-H2AX foci is similar in M059J and M059K cells. However, the repair rate of DSBs is slower in M059J cells than in M059K as shown previously but faster than seen with DSB induced by 56Fe ions. Vanillin, an inhibitor of DNA-PK(sub cs), reduces significantly the rate of DSB repair in HF19 cells following 1 Gy gamma-radiation but at 0.25 Gy gamma-irradiation the rate of DSB repair is similar in the presence or absence vanillin, thus suggesting the repair of a sub-set of DSBs induced by low dose, low-LET radiation does not require DNA-PK(sub cs). This sub-set of DSBs is formed in lower yield with high LET radiation. T he complexity of DNA DSBs induced by HZE radiation will be discussed in terms of reduced repair efficiency and provide scope to model different sub-classes of DSBs as precursors that may lead to the detrimental health effects of HZE radiation.

O'Neill, Peter↗

Dermatitis During Spaceflight Associated With HSV-1 Reactivation- A Case Study

Human alpha herpesviruses herpes simplex virus (HSV-1 or -2) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia, and often reactivate in response to stress-associated immune system dysregulation. Reactivation of Epstein Barr Virus (EBV), VZV, HSV-1 and Cytomegalovirus (CMV) is typically asymptomatic during spaceflight, though live/infectious virus has been recovered and the shedding rate increases with mission duration. The risk of clinical disease, therefore, may increase for astronauts assigned to extended missions (>180 days). Here, we report for the first time, a case of HSV-1 skin rash (dermatitis) occurring during a long duration spaceflight. The astronaut reported persistent dermatitis during flight, which was treated onboard with oral antihistamines and topical/oral steroids. No HSV-1 DNA was detected in 6-month pre-mission saliva samples, but on flight day 82, a saliva and rash swab both yielded 4.8 copies/ng DNA and 5.3×104 copies/ng DNA, respectively. Post-mission saliva samples continued to have high infectious HSV-1 load (1.67×107 copies/ng DNA). HSV-1 from both rash and saliva samples had 99.4% genotype homology. Additional physiological monitoring, including stress biomarkers (cortisol, dehydroepiandrosterone (DHEA), and salivary amylase), immune markers (adaptive regulatory and inflammatory plasma cytokines) and biochemical profile markers including vitamin/mineral status and bone metabolism are also presented for this case. These data highlight an atypical presentation of HSV-1 during spaceflight and underscore the importance of viral screening during clinical evaluations of in-flight dermatitis, to determine viral etiology and guide treatment.

Herpes, Viral Reactivation, Spaceflight, Dermatiti↗

Dermatitis during Spaceflight Associated with HSV-1 Reactivation

Human alpha herpesviruses herpes simplex virus (HSV-1) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia and often reactivate in response to stress-associated immune system dysregulation. Reactivation of Epstein Barr virus (EBV), VZV, HSV-1, and cytomegalovirus (CMV) is typically asymptomatic during spaceflight, though live/infectious virus has been recovered and the shedding rate increases with mission duration. The risk of clinical disease, therefore, may increase for astronauts assigned to extended missions (>180 days). Here, we report, for the first time, a case of HSV-1 skin rash (dermatitis) occurring during long-duration spaceflight. The astronaut reported persistent dermatitis during flight, which was treated onboard with oral antihistamines and topical/oral steroids. No HSV-1 DNA was detected in 6-month pre-mission saliva samples, but on flight day 82, a saliva and rash swab both yielded 4.8 copies/ng DNA and 5.3 × 104 copies/ng DNA, respectively. Post-mission saliva samples continued to have a high infectious HSV-1 load (1.67 × 107 copies/ng DNA). HSV-1 from both rash and saliva samples had 99.9% genotype homology. Additional physiological monitoring, including stress biomarkers (cortisol, dehydroepiandrosterone (DHEA), and salivary amylase), immune markers (adaptive regulatory and inflammatory plasma cytokines), and biochemical profile markers, including vitamin/mineral status and bone metabolism, are also presented for this case. These data highlight an atypical presentation of HSV-1 during spaceflight and underscore the importance of viral screening during clinical evaluations of in-flight dermatitis to determine viral etiology and guide treatment.

Satish K. Mehta↗

Anaerobic benzene oxidation in Geotalea daltonii involves activation by methylation and is regulated by the transition state regulator AbrB

ABSTRACT Benzene is a widespread groundwater contaminant that persists under anoxic conditions. The aim of this study was to more accurately investigate anaerobic microbial degradation pathways to predict benzene fate and transport. Preliminary genomic analysis of Geotalea daltonii strain FRC-32, isolated from contaminated groundwater, revealed the presence of putative aromatic-degrading genes. G. daltonii was subsequently shown to conserve energy for growth on benzene as the sole electron donor and fumarate or nitrate as the electron acceptor. The hbs gene, encoding for 3-hydroxybenzylsuccinate synthase (Hbs), a homolog of the radical-forming, toluene-activating benzylsuccinate synthase (Bss), was upregulated during benzene oxidation in G. daltonii , while the bss gene was upregulated during toluene oxidation. Addition of benzene to the G. daltonii whole-cell lysate resulted in toluene formation, indicating that methylation of benzene was occurring. Complementation of σ 54 - (deficient) E. coli transformed with the bss operon restored its ability to grow in the presence of toluene, revealing bss to be regulated by σ 54 . Binding sites for σ 70 and the transition state regulator AbrB were identified in the promoter region of the σ 54 -encoding gene rpoN, and binding was confirmed. Induced expression of abrB during benzene and toluene degradation caused G. daltonii cultures to transition to the death phase. Our results suggested that G. daltonii can anaerobically oxidize benzene by methylation, which is regulated by σ 54 and AbrB. Our findings further indicated that the benzene, toluene, and benzoate degradation pathways converge into a single metabolic pathway, representing a uniquely efficient approach to anaerobic aromatic degradation in G. daltonii . IMPORTANCE The contamination of anaerobic subsurface environments including groundwater with toxic aromatic hydrocarbons, specifically benzene, toluene, ethylbenzene, and xylene, has become a global issue. Subsurface groundwater is largely anoxic, and further study is needed to understand the natural attenuation of these compounds. This study elucidated a metabolic pathway utilized by the bacterium Geotalea daltonii capable of anaerobically degrading the recalcitrant molecule benzene using a unique activation mechanism involving methylation. The identification of aromatic-degrading genes and AbrB as a regulator of the anaerobic benzene and toluene degradation pathways provides insights into the mechanisms employed by G. daltonii to modulate metabolic pathways as necessary to thrive in anoxic contaminated groundwater. Our findings contribute to the understanding of novel anaerobic benzene degradation pathways that could potentially be harnessed to develop improved strategies for bioremediation of groundwater contaminants.

Bullows, James E.↗

Investigating Biological Responses to Space-like Radiation using the yeast Saccharomyces cerevisiae

As we plan crewed missions to the Moon, Mars, and beyond, it is essential to understand how persistent exposure to space radiation affects biology. Unlike on the International Space Station, where crew support and sample return are possible, experiments for long-duration missions require autonomous systems with no sample return. Human cells would be ideal biosensors, but limitations in culture methods, extended prelaunch storage, and long flight durations make it very difficult to keep human cells alive. Unlike other model systems, yeast can survive the constraints of long-duration spaceflight. Despite a billion years of evolution separating yeast from humans, we share homology in hundreds of genes important for basic cell function, including responses to DNA damage. Thus, yeast are excellent biosensors for detecting types/extent of damage induced by space radiation. BioSentinel is NASA’s latest biological CubeSat, and first interplanetary space bioscience mission. BioSentinel is manifested on Artemis 1, the first test flight of NASA’s Space Launch System, in the coming year. The BioSensor payload within BioSentinel contains two yeast strains. The wild type serves as a control for health and “normal” DNA damage repair (DDR). The rad51 deletion mutant is defective for DDR and will undergo alterations to growth and metabolism as it accumulates radiation damage. Changes in growth and metabolic activity will be measured using a 3-color LED detection system and the metabolic redox dye alamarBlue®. Preliminary tests indicate a significant change in alamarBlue response to space-like, low-dose ionizing radiation. We will discuss these findings in four parts – Introduction to biological CubeSats and the BioSentinel mission (presented by Sergio Santa Maria), preliminary responses to space-like ionizing radiation (presented here), a deeper dive into tracking metabolic changes after exposure to ionizing radiation (presented by Diana Gentry), and a look into methods for correcting flight optical data (presented by Abbey Kim). This work is funded by NASA’s Advanced Exploration Systems.

CubeSat↗

Investigating Molecular Responses to Space Radiation for Biological Missions Beyond Low Earth Orbit

As we plan crewed missions to the Moon, Mars, and beyond, it is essential to understand how persistent exposure to deep space radiation affects biology. Unlike on the International Space Station (ISS), where crew support and sample return are possible, experiments for long-duration missions require autonomous systems with no sample return. Human cells would be ideal biosensors, but limitations in culture methods, extended prelaunch storage, and long flight durations make it difficult to keep human cells alive. Unlike other model systems, yeast can survive the constraints of long-duration spaceflight. Despite a billion years of evolution separating yeast from humans, we share homology in hundreds of genes important for basic cell function, including responses to DNA damage. Thus, yeast are excellent biosensors for detecting types/extent of damage induced by space radiation. BioSentinel is NASA’s latest biological CubeSat, and first interplanetary space bioscience mission. BioSentinel is launching on Artemis 1, the first flight of NASA’s Space Launch System, in 2022. The BioSensor payload within BioSentinel contains two yeast strains. The wild type serves as a control for health and normal DNA damage repair (DDR). The rad51 deletion mutant is defective for DDR and will undergo alterations to growth and metabolism as it accumulates radiation damage. Changes in growth and metabolic activity will be measured using a 3-color LED detection system and the metabolic redox dye alamarBlue®. Preliminary tests indicate a significant change in alamarBlue responses to space-like, low-dose ionizing radiation. We will discuss these findings in five parts – Introduction to NASA’s biological CubeSats and BioSentinel (presented by Sergio Santa Maria), analysis of flight data from the ISS mission (presented by Kylie Akiyama), preliminary molecular responses to space radiation (presented here), a deeper dive into those pathways (presented by Kyra Keenan), and characterizing stress response through redox potential data (presented by Diana Gentry).

Lauren Courtney Liddell↗

Kaposi's sarcoma herpesvirus exploits the DNA damage response to circularize its genome

Abstract To establish lifelong, latent infection, herpesviruses circularize their linear, double-stranded, DNA genomes through an unknown mechanism. Kaposi's sarcoma (KS) herpesvirus (KSHV), a gamma herpesvirus, is tightly linked with KS, primary effusion lymphoma, and multicentric Castleman's disease. KSHV persists in latently infected cells as a multi-copy, extrachromosomal episome. Here, we show the KSHV genome rapidly circularizes following infection, and viral protein expression is unnecessary for this process. The DNA damage response (DDR) kinases, ATM and DNA-PKcs, each exert roles, and absence of both severely compromises circularization and latency. These deficiencies were rescued by expression of ATM and DNA-PKcs, but not catalytically inactive mutants. In contrast, γH2AX did not function in KSHV circularization. The linear viral genomic ends resemble a DNA double strand break, and non-homologous DNA end joining (NHEJ) and homologous recombination (HR) reporters indicate both NHEJ and HR contribute to KSHV circularization. Last, we show, similar to KSHV, ATM and DNA-PKcs have roles in circularization of the alpha herpesvirus, herpes simplex virus-1 (HSV-1), while γH2AX does not. Therefore, the DDR mediates KSHV and HSV-1 circularization. This strategy may serve as a general herpesvirus mechanism to initiate latency, and its disruption may provide new opportunities for prevention of herpesvirus disease.

Li, Shijun↗

Mini‐synplastomes for plastid genetic engineering

Summary In the age of synthetic biology, plastid engineering requires a nimble platform to introduce novel synthetic circuits in plants. While effective for integrating relatively small constructs into the plastome, plastid engineering via homologous recombination of transgenes is over 30 years old. Here we show the design–build–test of a novel synthetic genome structure that does not disturb the native plastome: the ‘mini‐synplastome’. The mini‐synplastome was inspired by dinoflagellate plastome organization, which is comprised of numerous minicircles residing in the plastid instead of a single organellar genome molecule. The first mini‐synplastome in plants was developed in vitro to meet the following criteria: (i) episomal replication in plastids; (ii) facile cloning; (iii) predictable transgene expression in plastids; (iv) non‐integration of vector sequences into the endogenous plastome; and (v) autonomous persistence in the plant over generations in the absence of exogenous selection pressure. Mini‐synplastomes are anticipated to revolutionize chloroplast biotechnology, enable facile marker‐free plastid engineering, and provide an unparalleled platform for one‐step metabolic engineering in plants.

Occhialini, Alessandro↗

Structure and Function of REP34 Implicates Carboxypeptidase Activity in Francisella tularensis Host Cell Invasion

Francisella tularensis is the etiological agent of tularemia, or rabbit fever. Although F. tularensis is a recognized biothreat agent with broad and expanding geographical range, its mechanism of infection and environmental persistence remain poorly understood. Previously, we identified seven F. tularensis proteins that induce a rapid encystment phenotype (REP) in the free-living amoeba, Acanthamoeba castellanii. Encystment is essential to the pathogen's long term intracellular survival in the amoeba. Here, we characterize the cellular and molecular function of REP34, a REP protein with a mass of 34 kDa. A REP34 knock-out strain of F. tularensis has a reduced ability to both induce encystment in A. castellanii and invade human macrophages. We determined the crystal structure of REP34 to 2.05-Å resolution and demonstrate robust carboxypeptidase B-like activity for the enzyme. REP34 is a zinc-containing monomeric protein with close structural homology to the metallocarboxypeptidase family of peptidases. REP34 possesses a novel topology and substrate binding pocket that deviates from the canonical funnelin structure of carboxypeptidases, putatively resulting in a catalytic role for a conserved tyrosine and distinct S1' recognition site. Taken together, these results identify REP34 as an active carboxypeptidase, implicate the enzyme as a potential key F. tularensis effector protein, and may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells.

59 BASIC BIOLOGICAL SCIENCES↗