Deep tissue profiling of Populus stem at single nucleus level reveals uncharacterized cell types and cell-specific gene regulatory networks
Not provided.
Biotechnology & Applied Microbiology↗
SEARCH · Engineering Papers
Results for “SPECIFICATIONS”
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.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Co‑cultivation of the anaerobic fungus Caecomyces churrovis with Methanobacterium bryantii enhances transcription of carbohydrate binding modules, dockerins, and pyruvate formate lyases on specific substrates
Abstract Anaerobic fungi and methanogenic archaea are two classes of microorganisms found in the rumen microbiome that metabolically interact during lignocellulose breakdown. Here, stable synthetic co-cultures of the anaerobic fungus Caecomyces churrovis and the methanogen Methanobacterium bryantii (not native to the rumen) were formed, demonstrating that microbes from different environments can be paired based on metabolic ties. Transcriptional and metabolic changes induced by methanogen co-culture were evaluated in C. churrovis across a variety of substrates to identify mechanisms that impact biomass breakdown and sugar uptake. A high-quality genome of C. churrovis was obtained and annotated, which is the first sequenced genome of a non-rhizoid-forming anaerobic fungus. C. churrovis possess an abundance of CAZymes and carbohydrate binding modules and, in agreement with previous studies of early-diverging fungal lineages, N6-methyldeoxyadenine (6mA) was associated with transcriptionally active genes. Co-culture with the methanogen increased overall transcription of CAZymes, carbohydrate binding modules, and dockerin domains in co-cultures grown on both lignocellulose and cellulose and caused upregulation of genes coding associated enzymatic machinery including carbohydrate binding modules in family 18 and dockerin domains across multiple growth substrates relative to C. churrovis monoculture. Two other fungal strains grown on a reed canary grass substrate in co-culture with the same methanogen also exhibited high log2-fold change values for upregulation of genes encoding carbohydrate binding modules in families 1 and 18. Transcriptional upregulation indicated that co-culture of the C. churrovis strain with a methanogen may enhance pyruvate formate lyase (PFL) function for growth on xylan and fructose and production of bottleneck enzymes in sugar utilization pathways, further supporting the hypothesis that co-culture with a methanogen may enhance certain fungal metabolic functions. Upregulation of CBM18 may play a role in fungal–methanogen physical associations and fungal cell wall development and remodeling.
09 BIOMASS FUELS↗
Exposing new taxonomic variation with inflammation — a murine model-specific genome database for gut microbiome researchers
The murine CBA/J mouse model widely supports immunology and enteric pathogen research. This model has illuminated Salmonella interactions with the gut microbiome since pathogen proliferation does not require disruptive pretreatment of the native microbiota, nor does it become systemic, thereby representing an analog to gastroenteritis disease progression in humans. Despite the value to broad research communities, microbiota in CBA/J mice are not represented in current murine microbiome genome catalogs. Here we present the first microbial and viral genomic catalog of the CBA/J murine gut microbiome. Using fecal microbial communities from untreated and Salmonella-infected, highly inflamed mice, we performed genomic reconstruction to determine the impacts on gut microbiome membership and functional potential. From high depth whole community sequencing (~ 42.4 Gbps/sample), we reconstructed 2281 bacterial and 4516 viral draft genomes. Salmonella challenge significantly altered gut membership in CBA/J mice, revealing 30 genera and 98 species that were conditionally rare and unsampled in non-inflamed mice. Additionally, inflamed communities were depleted in microbial genes that modulate host anti-inflammatory pathways and enriched in genes for respiratory energy generation. Our findings suggest decreases in butyrate concentrations during Salmonella infection corresponded to reductions in the relative abundance in members of the Alistipes. Strain-level comparison of CBA/J microbial genomes to prominent murine gut microbiome databases identified newly sampled lineages in this resource, while comparisons to human gut microbiomes extended the host relevance of dominant CBA/J inflammation-resistant strains. This CBA/J microbiome database provides the first genomic sampling of relevant, uncultivated microorganisms within the gut from this widely used laboratory model. Using this resource, we curated a functional, strain-resolved view on how Salmonella remodels intact murine gut communities, advancing pathobiome understanding beyond inferences from prior amplicon-based approaches. Salmonella-induced inflammation suppressed Alistipes and other dominant members, while rarer commensals like Lactobacillus and Enterococcus endure. The rare and novel species sampled across this inflammation gradient advance the utility of this microbiome resource to benefit the broad research needs of the CBA/J scientific community, and those using murine models for understanding the impact of inflammation on the gut microbiome more generally.
59 BASIC BIOLOGICAL SCIENCES↗
Optimizing Patient-Specific Medication Regimen Policies Using Wearable Sensors in Parkinson’s Disease
Effective treatment of Parkinson’s disease (PD) is a continual challenge for healthcare providers, and providers can benefit from leveraging emerging technologies to supplement traditional clinic care. We develop a data-driven reinforcement learning (RL) framework to optimize PD medication regimens through wearable sensors. We leverage a data set of n = 26 PD patients who wore wrist-mounted movement trackers for two separate six-day periods. Using these data, we first build and validate a simulation model of how individual patients’ movement symptoms respond to medication administration. We then pair this simulation model with an on-policy RL algorithm that recommends optimal medication types, timing, and dosages during the day while incorporating human-in-the-loop considerations on medication administration. The results show that the RL-prescribed medication regimens outperform physicians’ medication regimens, despite physicians having access to the same data as the RL agent. To validate our results, we assess our wearable-based RL medication regimens using n = 399 PD patients from the Parkinson’s Progression Markers Initiative data set. We show that the wearable-based RL medication regimens would lead to significant symptom improvement for these patients, even more so than training RL policies directly from this data set. In doing so, we show that RL models from even small data sets of wearable data can offer novel, generalizable clinical insights and medication strategies, which may outperform those derived from larger data sets without wearable data.
60 APPLIED LIFE SCIENCES↗
Flux balance analysis of the ammonia-oxidizing bacterium Nitrosomonas europaea ATCC19718 unravels specific metabolic activities while degrading toxic compounds
The ammonia-oxidizing bacterium Nitrosomonas europaea has been widely recognized as an important player in the nitrogen cycle as well as one of the most abundant members in microbial communities for the treatment of industrial or sewage wastewater. Its natural metabolic versatility and extraordinary ability to degrade environmental pollutants (e.g., aromatic hydrocarbons such as benzene and toluene) enable it to thrive under various harsh environmental conditions. Constraint-based metabolic models constructed from genome sequences enable quantitative insight into the central and specialized metabolism within a target organism. These genome-scale models have been utilized to understand, optimize, and design new strategies for improved bioprocesses. Reduced modeling approaches have been used to elucidate Nitrosomonas europaea metabolism at a pathway level. However, genome-scale knowledge about the simultaneous oxidation of ammonia and pollutant metabolism of N . europaea remains limited. Here, we describe the reconstruction, manual curation, and validation of the genome-scale metabolic model for N . europaea , i GC535. This reconstruction is the most accurate metabolic model for a nitrifying organism to date, reaching an average prediction accuracy of over 90% under several growth conditions. The manually curated model can predict phenotypes under chemolithotrophic and chemolithoorganotrophic conditions while oxidating methane and wastewater pollutants. Calculated flux distributions under different trophic conditions show that several key pathways are affected by the type of carbon source available, including central carbon metabolism and energy production.
59 BASIC BIOLOGICAL SCIENCES↗
Diverse modes of galacto-specific carbohydrate recognition by a family 31 glycoside hydrolase from Clostridium perfringens
Explore the source record for details and available documents.
99 GENERAL AND MISCELLANEOUS↗
Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases
Explore the source record for details and available documents.
99 GENERAL AND MISCELLANEOUS↗
Characterization of a broadly specific cadaverine N-hydroxylase involved in desferrioxamine B biosynthesis in Streptomyces sviceus
N-hydroxylating flavin-dependent monooxygenases (FMOs) are involved in the biosynthesis of hydroxamate siderophores, playing a key role in microbial virulence. Herein, we report the first structural and kinetic characterization of a novel alkyl diamine N-hydroxylase DesB from Streptomyces sviceus (SsDesB). This enzyme catalyzes the first committed step in the biosynthesis of desferrioxamine B, a clinical drug used to treat iron overload disorders. X-ray crystal structures of the SsDesB holoenzyme with FAD and the ternary complex with bound NADP + were solved at 2.86 Å and 2.37 Å resolution, respectively, providing a structural view of the active site environment. SsDesB crystallized as a tetramer and the structure of the individual protomers closely resembles the structures of homologous N-hydroxylating FMOs from Erwinia amylovora (DfoA), Pseudomonas aeruginosa (PvdA), and Aspergillus fumigatus (SidA). Using NADPH oxidation, oxygen consumption, and product formation assays, kinetic parameters were determined for various substrates with SsDesB. SsDesB exhibited typical saturation kinetics with substrate inhibition at high concentrations of NAD(P)H as well as cadaverine. The apparent k cat values for NADPH in steady-state NADPH oxidation and oxygen consumption assays were 0.28 ± 0.01 s -1 and 0.24 ± 0.01 s -1 , respectively. However, in product formation assays used to measure the rate of N-hydroxylation, the apparent k cat for NADPH (0.034 ± 0.008 s -1 ) was almost 10-fold lower under saturating FAD and cadaverine concentrations, reflecting an uncoupled reaction, and the apparent NADPH K M was 33 ± 24 μM. Under saturating FAD and NADPH concentrations, the apparent k cat and K M for cadaverine in Csaky assays were 0.048 ± 0.004 s -1 and 19 ± 9 μM, respectively. SsDesB also N-hydroxylated putrescine, spermidine, and L-lysine substrates but not alkyl (di)amines that were branched or had fewer than four methylene units in an alkyl chain. These data demonstrate that SsDesB has wider substrate scope compared to other well-studied ornithine and lysine N-hydroxylases, making it an amenable biocatalyst for the production of desferrioxamine B, derivatives, and other N-substituted products.
59 BASIC BIOLOGICAL SCIENCES↗
Potent, specific MEPicides for treatment of zoonotic staphylococci
Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) of isoprenoid biosynthesis represent potential targets for treating zoonotic staphylococci. Here we demonstrate that fosmidomycin (FSM) inhibits the first step of the isoprenoid biosynthetic pathway catalyzed by deoxyxylulose phosphate reductoisomerase (DXR) in staphylococci. In addition, we have both enzymatically and structurally determined the mechanism by which FSM elicits its effect. Using a forward genetic screen, the glycerol-3-phosphate transporter GlpT that facilitates FSM uptake was identified in two zoonotic staphylococci, Staphylococcus schleiferi and Staphylococcus pseudintermedius . A series of lipophilic ester prodrugs (termed MEPicides) structurally related to FSM were synthesized, and data indicate that the presence of the prodrug moiety not only substantially increased potency of the inhibitors against staphylococci but also bypassed the need for GlpT-mediated cellular transport. Collectively, our data indicate that the prodrug MEPicides selectively and robustly inhibit DXR in zoonotic staphylococci, and further, that DXR represents a promising, druggable target for future development.
59 BASIC BIOLOGICAL SCIENCES↗
ToF-SIMS imaging reveals that p -hydroxybenzoate groups specifically decorate the lignin of fibres in the xylem of poplar and willow
Esterified phenolics occur as γ-linked lignin acylations in many plant taxa but little is known about the distribution or function of such groups. In the family Salicaceae, p-hydroxybenzoate groups are present in the lignin of poplars (Populus spp.) and willows (Salix spp.). In this study, the distribution of cell wall-bound p-hydroxybenzoate was examined in different tissue and cell types of poplar and willow trees. This analysis showed that p-hydroxybenzoate groups were most prevalent in juvenile stems, and were elevated in tension wood and following nitrogen fertilisation. Closer examination of stem cross-sections using time-of-flight secondary-ion mass spectrometry (ToF-SIMS) directly showed that p-hydroxybenzoate groups occur predominantly in the cell walls of fibres and are largely absent from vessel elements. Furthermore, these results point to a role for ester-linked groups in modifying the syringyl-rich lignin of fibres, perhaps to strengthen the cell walls of these structural elements or to increase lignification rates.
59 BASIC BIOLOGICAL SCIENCES↗
Recognition of centromere‐specific histone Cse4 by the inner kinetochore Okp1‐Ame1 complex
Abstract Successful mitosis depends on the timely establishment of correct chromosomal attachments to microtubules. The kinetochore, a modular multiprotein complex, mediates this connection by recognizing specialized chromatin containing a histone H3 variant called Cse4 in budding yeast and CENP‐A in vertebrates. Structural features of the kinetochore that enable discrimination between Cse4/CENP‐A and H3 have been identified in several species. How and when these contribute to centromere recognition and how they relate to the overall structure of the inner kinetochore are unsettled questions. More generally, this molecular recognition ensures that only one kinetochore is built on each chromatid and that this happens at the right place on the chromatin fiber. We have determined the crystal structure of a Cse4 peptide bound to the essential inner kinetochore Okp1‐Ame1 heterodimer from budding yeast. The structure and related experiments show in detail an essential point of Cse4 contact and provide information about the arrangement of the inner kinetochore.
59 BASIC BIOLOGICAL SCIENCES↗
The Effect of Prostate-Specific Antigen (PSA) Test on Radiation Risk Estimate for Prostate Cancer Incidence among Atomic-Bomb Survivors
Following our previous report on the radiation doseresponse for prostate cancer incidence rates in the Life Span Study (LSS) cohort of atomic bomb survivors, we reevaluated the radiation-related risk adjusting for differences in baseline cancer incidence rates among three subsets of the LSS cohort defined by the timing of their first participation in biennial health examinations offered to the Adult Health Study (AHS) sub-cohort members and prostate-specificantigen (PSA) testing status for AHS participants: 1. nonAHS participants, 2. AHS participants before receiving PSA test, and 3. AHS participants after receiving PSA test. We found a 2.9-fold increase in the baseline incidence rates among AHS participants after receiving PSA test. After adjusting for the PSA-testing-status effects on the baseline rates the estimated excess relative risk (ERR) per Gy was 0.54 (95% CI: 0.15, 1.05), which was almost identical to the previously reported unadjusted ERR estimate (0.57, 95% CI: 0.21, 1.00). The current results confirmed that, while the PSA testing among AHS participants increased the baseline incidence rates, it did not impact the radiation risk estimate, strengthening the previously reported dose-response relationship for prostate cancer incidence in the LSS. As the use of PSA tests continue in screening and medical settings, analyses of possible effects of PSA testing should be an important aspect of future epidemiological studies of the association between radiation exposure and prostate cancer.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Tundra SGS – Critical Importance of Site-Specific Injectivity Testing for Carbon Dioxide Injection Well Simulation Calibration
Paper presented at 16th International Conference on Greenhouse Gas Control Technologies (GHGT-16), October 23–27, 2022, Lyon, France. Brine injectivity tests were conducted on both the Broom Creek (BC) and Deadwood (DW) storage formations in one of the cored stratigraphic test wells prior to finalized simulations. The injectivity tests entailed injection of brine into the formations, followed by shutting in the wells. The shut-in duration represents the fall-off period which was used to carry out pressure transient analyses of the tests. The analysis of injectivity tests indicated that core-indicated and modeled permeability distributions should be conservatively multiplied by 2.5× and 5× in the BC and DW geologic models, respectively, prior to numerical simulations of CO 2 injection using Computer Modelling Group’s (CMG’s) GEM equation-of-state reservoir simulator. The scaler permeability multipliers allowed the fluid flow simulations to fully represent well test-measured injection well rates in the respective formations.
20 FOSSIL-FUELED POWER PLANTS↗
1st MPEX Users Research Forum (MURF) summary report: specifications for the Surface Analysis Station (SAS)
The Material Plasma Exposure eXperiment (MPEX) Team has reached out to the community of potential users of the MPEX facility to assess the high-priority capabilities which should be considered for inclusion in the design of the MPEX Surface Analysis Station (SAS). This activity is being carried out during the “advanced conceptual design” period of MPEX, i.e. post Conceptual Design Review (CDR) but prior to Preliminary Design (PD), to respond to a recommendation by the U.S. D.O.E. following the CDR. The MPEX Team will summarize the community recommendations into a guidance document (i.e. this report), which will influence the Surface Analysis Station during the Preliminary Design phase of the project.
70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
Digital Application Specific Integrated Circuit Design
Single radiation effects can be transient and static. The charge collected from radiation has a prompt (drift) and a slow (diffusion) component. This current spike causes disparate results: SEU, SET, SEB, MBU, and more. A system level SEE mitigation technique, used to overcome, is the triple module redundancy (TMR). TMR for system Verilog (TMR4SV), written in Python, is the first step towards design IP triplication. It allows various triplication methods for flip flops, clocks, and logic.
46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
Multi-Axis Resonant Plate Shock Testing Evaluation and Test Specification Development
Resonant plate testing is a shock test method that is frequently used to simulate pyroshock events in the laboratory. Recently, it was discovered that if the unit under test is installed at an off-center location, a tri-axial accelerometer would record a shock response in three directions and the resulting shock response spectra implied that the test may have qualified the component in three directions simultaneously. The purpose of this research project was to evaluate this idea of multi-axis shock testing to determine if it was truly a multi-axis shock environment and if such a test could be used as an equivalent component qualification test. A study was conducted using generic, additively manufactured components tested on a resonant plate, along with an investigation of plate motion to evaluate the component response to off- center plate excitation. The data obtained here along with the analytical simulations performed indicate that off-center resonant plate tests are actually not three-axis shock tests, but rather single axis shocks at an arbitrary angle dictated by the location of the unit under test on the plate. This conclusion is supported by the fact that only one vectored shock input is provided to the component in a resonant plate test. Thus, the output response is a coupled response of the transverse plate vibration and the rotational motion of the component on the plate. Additionally, a multi-axis shock test defined by three single axis test environments always results in a significant component over-test in one direction.
42 ENGINEERING↗
Application-Specific Implementations: Self-Consistent Analysis, Uncertainty Estimation, Instrumentation Effects
When UF 6 is located on the bottom of a cylindrical container lying flat, the Hage-Cifarelli formalism can be used to reconstruct the multiplication of the UF 6 and the strength of the 234 U (a,n) source, from which the 235 U can be inferred. However, when the UF 6 sticks to the ends or to the sides of the container, the reconstruction is no longer predictive in terms of source strength. The same conclusions were reached, whether one uses 3 He tubes or scintillators to detect the neutrons. Feynman’s point theory underlying the reconstruction would need to be improved to address the differences in source strenghts observed.
11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
UPC++ v1.0 Specification, Revision 2020.10.0
UPC++ is a C++11 library providing classes and functions that support Partitioned Global Address Space (PGAS) programming. The key communication facilities in UPC++ are one-sided Remote Memory Access (RMA) and Remote Procedure Call (RPC). All communication operations are syntactically explicit and default to non-blocking; asynchrony is managed through the use of futures, promises and continuation callbacks, enabling the programmer to construct a graph of operations to execute asynchronously as high-latency dependencies are satisfied. A global pointer abstraction provides system-wide addressability of shared memory, including host and accelerator memories. The parallelism model is primarily process-based, but the interface is thread-safe and designed to allow efficient and expressive use in multi-threaded applications. The interface is designed for extreme scalability throughout, and deliberately avoids design features that could inhibit scalability.
97 MATHEMATICS AND COMPUTING↗