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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 415 records · Page 23

The thioreduction component CcmG confers efficiency and the heme ligation component CcmH ensures stereo-specificity during cytochrome c maturation

In many Gram-negative bacteria, including Rhodobacter capsulatus, cytochrome c maturation (Ccm) is carried out by a membrane-integral machinery composed of nine proteins (CcmA to I). During this process, the periplasmic thiol-disulfide oxidoreductase DsbA is thought to catalyze the formation of a disulfide bond between the Cys residues at the apocytochrome c heme binding site (CXXCH). Subsequently, a Ccm-specific thioreductive pathway involving CcmG and CcmH reduces this disulfide bond to allow covalent heme ligation. Currently, the sequence of thioredox reactions occurring between these components and apocytochrome c, and the identity of their active Cys residues are unknown. In this work, we first investigated protein-protein interactions among the apocytochrome c, CcmG, and the heme ligation components CcmF, CcmH, and CcmI. We found that they all interact with each other, forming a CcmFGHI-apocytochrome c complex. Using purified wild-type CcmG, CcmH, and apocytochrome c, as well as their respective Cys mutant variants we determined the rates of thiol-disulfide exchange reactions between selected pairs of Cys residues from these proteins. We established that CcmG can efficiently reduce the disulfide bond of apocytochrome c and also resolve a mixed disulfide bond formed between apocytochrome c and CcmH. We further show that C45 of CcmH and C34 of apocytochrome c are most likely to form this mixed disulfide bond, which is consistent with the stereo-specificity of the heme-apocytochrome c ligation reaction. We conclude that CcmG confers efficiency, and CcmH ensures stereo-specificity during Ccm, and present a comprehensive model for thioreduction reactions that lead to heme-apocytochrome c ligation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Previous exposure to Spike-providing parental strains confers neutralizing immunity to XBB lineage and other SARS-CoV-2 recombinants in the context of vaccination

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as “Deltacron.” We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.

59 BASIC BIOLOGICAL SCIENCES↗

Conference report on the 1st US–Japan workshop on power and particle control by liquid metal plasma-facing components in a steady state magnetic fusion DEMO reactor

As part of the US–Japan bilateral collaboration program, a new series of workshops have been inaugurated on the subject of 'Power and Particle Control by Liquid Metal Plasma-Facing Components in a Steady State Magnetic Fusion DEMO Reactor'. The first workshop of this series was held at Princeton Plasma Physics Laboratory on 11–13 March 2019. This conference report is intended to share 24 technical presentations, discussion and the planning of future workshops with the world magnetic fusion community.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

ALD1 accumulation in Arabidopsis epidermal plastids confers local and non-autonomous disease resistance

The Arabidopsis plastid-localized ALD1 protein acts in the lysine catabolic pathway that produces infection-induced pipecolic acid (Pip), Pip derivatives, and basal non-Pip metabolite(s). ALD1 is indispensable for disease resistance associated with Pseudomonas syringae infections of naïve plants as well as those previously immunized by a local infection, a phenomenon called systemic acquired resistance (SAR). Pseudomonas syringae is known to associate with mesophyll as well as epidermal cells. To probe the importance of epidermal cells in conferring bacterial disease resistance, we studied plants in which ALD1 was only detectable in the epidermal cells of specific leaves. Local disease resistance and many features of SAR were restored when ALD1 preferentially accumulated in the epidermal plastids at immunization sites. Interestingly, SAR restoration occurred without appreciable accumulation of Pip or known Pip derivatives in secondary distal leaves. Our findings establish that ALD1 has a non-autonomous effect on pathogen growth and defense activation. We propose that ALD1 is sufficient in the epidermis of the immunized leaves to activate SAR, but basal ALD1 and possibly a non-Pip metabolite(s) are also needed at all infection sites to fully suppress bacterial growth. Thus, epidermal plastids that contain ALD1 play a key role in local and whole-plant immune signaling.

59 BASIC BIOLOGICAL SCIENCES↗

The role of emerging scientists in restoration ecology: insights from a SER2023 conference workshop

Emerging professionals are crucial in advancing ecological restoration by connecting newcomers with established leaders and blending new ideas with traditional practices. This paper highlights the vital role emerging scientists play in restoration ecology and the Society for Ecological Restoration (SER). A survey conducted during the SER2023 conference workshop, organized by the Students and Emerging Professionals committee, showed that emerging professionals contribute significantly to every stage of scientific work, from planning to publication. However, participants emphasized the scarcity of funding opportunities for non‐senior scientists, which limits academic growth. The workshop underscored the importance of nurturing emerging professionals to develop future leaders for SER and ensure continuity. Fostering non‐hierarchical and inclusive networking is key to engaging and empowering these professionals, ultimately contributing to the long‐term success of ecological restoration efforts.

Weidlich, Emanuela W. A.↗

Trivalent rare earth metal cofactors confer rapid NP-DNA polymerase activity

Here, a DNA polymerase with a single mutation and a divalent calcium cofactor catalyzes the synthesis of unnatural N3'→P5' phosphoramidate (NP) bonds to form NP-DNA. However, this template-directed phosphoryl transfer activity remains orders of magnitude slower than native phosphodiester synthesis. Here, we used time-resolved x-ray crystallography to show that NP-DNA synthesis proceeds with a single detectable calcium ion in the active site. Using insights from isotopic and elemental effects, we propose that one-metal-ion electrophilic substrate activation is inferior to the native two-metal-ion mechanism. We found that this deficiency in divalent activation could be ameliorated by trivalent rare earth and post–transition metal cations, substantially enhancing NP-DNA synthesis. Scandium(III), in particular, confers highly specific NP activity with kinetics enhanced by more than 100-fold over calcium(II), yielding NP-DNA strands up to 100 nucleotides in length.

59 BASIC BIOLOGICAL SCIENCES↗

A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been responsible for a global pandemic. Monoclonal antibodies (mAbs) have been used as antiviral therapeutics; however, these therapeutics have been limited in efficacy by viral sequence variability in emerging variants of concern (VOCs) and in deployment by the need for high doses. In this study, we leveraged the multi-specific, multi-affinity antibody (Multabody, MB) platform, derived from the human apoferritin protomer, to enable the multimerization of antibody fragments. MBs were shown to be highly potent, neutralizing SARS-CoV-2 at lower concentrations than their corresponding mAb counterparts. In mice infected with SARS-CoV-2, a tri-specific MB targeting three regions within the SARS-CoV-2 receptor binding domain was protective at a 30-fold lower dose than a cocktail of the corresponding mAbs. Furthermore, we showed in vitro that mono-specific MBs potently neutralize SARS-CoV-2 VOCs by leveraging augmented avidity, even when corresponding mAbs lose their ability to neutralize potently, and that tri-specific MBs expanded the neutralization breadth beyond SARS-CoV-2 to other sarbecoviruses. Our work demonstrates how avidity and multi-specificity combined can be leveraged to confer protection and resilience against viral diversity that exceeds that of traditional monoclonal antibody therapies.

60 APPLIED LIFE SCIENCES↗

Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance

HIV-1 reverse transcriptase (RT) is targeted by multiple drugs. RT mutations that confer resistance to nucleoside RT inhibitors (NRTIs) emerge during clinical use. Q151M and four associated mutations, A62V, V75I, F77L, and F116Y, were detected in patients failing therapies with dideoxynucleosides (didanosine [ddI], zalcitabine [ddC]) and/or zidovudine (AZT). The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs. To understand the structural basis for Q151M and Q151Mc resistance, we systematically determined the crystal structures of the wild-type RT/double-stranded DNA (dsDNA)/dATP (complex I), wild-type RT/dsDNA/ddATP (complex II), Q151M RT/dsDNA/dATP (complex III), Q151Mc RT/dsDNA/dATP (complex IV), and Q151Mc RT/dsDNA/ddATP (complex V) ternary complexes. The structures revealed that the deoxyribose rings of dATP and ddATP have 3'-endo and 3'-exo conformations, respectively. The single mutation Q151M introduces conformational perturbation at the deoxynucleoside triphosphate (dNTP)-binding pocket, and the mutated pocket may exist in multiple conformations. The compensatory set of mutations in Q151Mc, particularly F116Y, restricts the side chain flexibility of M151 and helps restore the DNA polymerization efficiency of the enzyme. The altered dNTP-binding pocket in Q151Mc RT has the Q151-R72 hydrogen bond removed and has a switched conformation for the key conserved residue R72 compared to that in wild-type RT. On the basis of a modeled structure of hepatitis B virus (HBV) polymerase, the residues R72, Y116, M151, and M184 in Q151Mc HIV-1 RT are conserved in wild-type HBV polymerase as residues R41, Y89, M171, and M204, respectively; functionally, both Q151Mc HIV-1 and wild-type HBV are resistant to dideoxynucleoside analogs.

59 BASIC BIOLOGICAL SCIENCES↗

Designing, Constructing, and Operating an IPv6 Network at SC23: A case study in implementing the IPv6 protocol on a heterogenous network that supports the SC23 conference

IPv6 is the current version of IP, the protocol that is used to route traffic across internet connections. This standard was originally developed as a new approach to mitigate concerns about address exhaustion and allow for near infinite scalability. While this protocol has gained significant support in mobile and broadband networks, as well as being the default for networks in emerging economies, it has yet to be fully adopted as a standard deployment model. Complications include legacy devices unable to support the proposed changes, as well as potential challenges that exist between devices that may not be able to fully implement current standards or configuration norms. The SCinet volunteers who deliver advanced networking to support the SC Conference set an ambitious goal of deploying an IPv6-only network at SC23. While the necessary technology is widely available and understood, the implications of deployment to support more than 15,000 users, each with multiple devices of different operating environments and ages, presents a unique technology and policy challenge. This paper will highlight the effort put into designing, implementing, and operating this innovative IPv6-only environment.

Robinson, Kate↗

A single, improbable B cell receptor mutation confers potent neutralization against cytomegalovirus

Cytomegalovirus (CMV) is a leading cause of infant hearing loss and neurodevelopmental delay, but there are no clinically licensed vaccines to prevent infection, in part due to challenges eliciting neutralizing antibodies. One of the most well-studied targets for CMV vaccines is the viral fusogen glycoprotein B (gB), which is required for viral entry into host cells. Within gB, antigenic domain 2 site 1 (AD-2S1) is a target of potently neutralizing antibodies, but gB-based candidate vaccines have yet to elicit robust responses against this region. We mapped the genealogy of B cells encoding potently neutralizing anti-gB AD-2S1 antibodies from their inferred unmutated common ancestor (UCA) and characterized the binding and function of early lineage ancestors. Surprisingly, we found that a single amino acid heavy chain mutation A33N, which was an improbable mutation rarely generated by somatic hypermutation machinery, conferred broad CMV neutralization to the non-neutralizing UCA antibody. Structural studies revealed that this mutation mediated key contacts with the gB AD-2S1 epitope. Collectively, these results provide insight into potently neutralizing gB-directed antibody evolution in a single donor and lay a foundation for using this B cell-lineage directed approach for the design of next-generation CMV vaccines.

59 BASIC BIOLOGICAL SCIENCES↗

6th Annual Earth System Grid Federation Face to Face Conference Report

The Sixth Annual Face-to-Face (F2F) Conference of the Earth System Grid Federation (ESGF), a global consortium of international government agencies, institutions, and companies dedicated to the creation, management, analysis, and distribution of extreme-scale scientific data, was held December 5–9, 2016, in Washington, D.C.

54 ENVIRONMENTAL SCIENCES↗

Biannual Conference on Molybdenum- and Tungsten-Containing Enzymes (Final Technical Support)

This award supported a biannual conference on molybdenum- and tungsten-containing enzymes, specifically providing travel support for graduate students and post-doctoral scholars, as well as new, under-represented minority investigators. The meeting was held June 18-23 in Santa Fe, NM and was extremely successful. No publications were forthcoming from the meeting, no intellectual property was generated and there were no residual funds.

59 BASIC BIOLOGICAL SCIENCES↗

6th Annual Earth System Grid Federation Face-to-Face Conference Report, December 5–9, 2016, Washington, D.C.

Since its inception in the late 1990s, the Earth System Grid Federation (ESGF) has evolved significantly as a system. As technology changed and its user base grew larger and more diverse, ESGF gradually developed into the state-of-the-art federated system it is today. Due to the enormity of its scope and the urgency of community needs, many features had to be tested in the real world during the expansion process. The rollout of Version 2.4 in 2016 culminated a series of releases and user feedback initiatives that began in 2013. During this 3-year period, ESGF hosted user group meetings to better understand how the system was being used; this information was then leveraged to begin Version 3.0 planning and preparations. The user meetings were collectively led and organized by the U.S. Department of Energy (DOE), the Infrastructure for the European Network for Earth System Modelling (IS-ENES), the U.S. National Aeronautics and Space Administration (NASA), the Australian National Computational Infrastructure (NCI), the U.S. National Oceanic and Atmospheric Administration (NOAA), and the U.S. National Science Foundation (NSF). The information emerging from the user group meetings influenced requirements, development, and operations. In 2015, representatives from a significant fraction of projects that use ESGF to disseminate and analyze data attended the Fifth Annual ESGF Face-to-Face (F2F) Conference (DOI: 10.2172/1253685). Attendees provided important feedback regarding current and future community data use cases. Discussions focused on maintaining essential operations while developing new and improved software to handle ever-increasing data variety, complexity, velocity, and volume—a task accomplished by the entire consortium.

97 MATHEMATICS AND COMPUTING↗

Transmittal of Draft Consultation Letter to the New Mexico State Historic Preservation Officer Regarding the Proposed Loading Dock to Conference Room Conversion Building 303 at Technical Area 16

The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), Los Alamos Field Office (NA-LA) proposes to enclose the existing loading dock to create a conference room at building 303, located within Technical Area (TA) 16, Los Alamos National Laboratory (LANL). TA-16-303 has been determined eligible for listing in the National Register of Historic Places in correspondence with the New Mexico State Historic Preservation Division dated June 22, 2003. Eligibility status is based on its historical significance during the Cold War at Los Alamos and its representative architectural style, which is associated with high explosives research and development in support of the nation’s nuclear weapons program. As shown in the enclosed photograph, key architectural elements include a flat roof with overhangs, unpainted reinforced-concrete construction, green painted doors and trim.

99 GENERAL AND MISCELLANEOUS↗

8th Annual Earth System Grid Federation Face-to-Face Conference Report

Members of the Earth System Grid Federation (ESGF) gathered in Washington, DC, on December 3–7, 2018, for the 8th Annual ESGF Face-to-Face (F2F) Conference. The event packed 40 presentations, several plenary sessions, a poster session, guest speakers, an awards ceremony, and an Executive Committee (XC) meeting into the week. ESGF working teams (WTs) conduct daily operations remotely all over the world. Although most teams meet online regularly, in-person interaction is incredibly important for cementing relationships and evaluating progress.

54 ENVIRONMENTAL SCIENCES↗

Travel Support for Western Photosynthesis Conference

This award was issued to the University of Tennessee at Knoxville. The conference was a great success we with the support provided by registration and 11 private sponsors we were able to cover all expenses. The funds were depleted by providing travels support to the selected participants.

59 BASIC BIOLOGICAL SCIENCES↗