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At least 91 records · Page 5

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↗

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↗

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↗

Molecular Magnetism in North America Conference

The report provides information on the Molecular Magnetism in North America (MAGNA) conference that the DOE funding supported. It was held 2/21/2020 - 2/24/2020 at the King and Prince Hotel on St. Simon’s Island in southern Georgia. It brought together workers from academic institutions and government laboratories working in the field of molecular magnetism, including synthetic chemistry of molecular and 1D-3D molecule-based materials, and the various physical and spectroscopic methods for their study. The oral program spanned 3½ days and comprised 32 talks (30 mins each) by faculty and government scientists, and 12 talks (15 mins each) by junior people (graduate students and postdoctorals). The poster session took place at 6 pm on Saturday, Feb 22nd, and comprised 21 posters. Total registrations for the meeting were 68.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

America Resilient Climate Conference

On April 14, 2021, scientists, policymakers, and other interested parties from research institutes, academia, and other organizations gathered together virtually at the America Resilient Climate Conference to discuss one of the most pressing challenges of the 21st century: building resilience to climate change. Climate change affects the security and health of all Americans. Coastal areas are enduring more frequent and severe flooding due to sea level rise and storm surge; western states and Alaska have experienced increasingly devastating wildfires, driven in part by hotter, drier, and longer fire seasons; and communities across the nation have suffered through extreme precipitation events and heat waves. Even if emissions are reduced aggressively in the near future, the world—and the United States—will continue to feel the impacts of climate change for decades to come, due to the continued accumulation of greenhouse gasses in the atmosphere. Consequently, it is essential to act now to protect natural and human assets from the gradual—as well as extreme—impacts of a changing climate. To build resilient communities, leaders and community members need science-based information about the potential impacts climate change will have decades into the future and for specific regions. Therefore, it is essential to develop high-resolution climate models that can project both various climate impacts and the interactions between earth system variables and humans down to regional and local scales. Collecting and curating data for such models and their computational requirements poses large challenges. In the future, artificial intelligence will be needed to increase their accuracy and reduce associated uncertainties. The investments in Earth system science and artificial intelligence made by the U.S. Department of Energy and other federal entities will be essential in addressing these challenges.

54 ENVIRONMENTAL SCIENCES↗

Developing and Integrating the Plant Phenomics Community: Support for the 2022 Conference of the North American Plant Phenotyping Network (Final Report)

The North American Plant Phenotyping Network (NAPPN) hosted our NAPPN2022 Annual Conference as a hybrid event from February 22-25, 2022, at the Classic Center in Athens, GA in cooperation with the University of Georgia. We had over 300 attendees with approximately half attending in person and half attending through our online platform. During the 4 day event, there were 92 scientific talks (33 of which were fast-forward presentations by early career researchers), eleven hands-on workshops, two in-person facility tours, a career and mentoring fair and a panel on international partnerships and perspectives.

59 BASIC BIOLOGICAL SCIENCES↗

Mach Conference, 2022.

There has been considerable interest in chemical vapor infiltration (CVI) manufactured silicon carbide fiber and silicon carbide matrix (SiC/SiC) composite tubes due to their superior mechanical properties. The SiC/SiC tubes are known to remain stable even after prolonged exposure to radiation. However, there are many variables in the manufacturing of SiC/SiC composite tubes such as elastic constants of constituent SiC fiber and SiC matrix, braiding angle, porosity, and others whose values vary over a range. The intention is to identify the distribution of elastic constants of SiC/SiC tubes which would help model the performance of the novel cladding material. To do so, a sensitivity analysis will be carried out to determine the dominant variables that influence the elastic constants of SiC/SiC tubes. A chosen number of combinations of dominant variables will be sampled through the Latin hypercube sampling (LHS) method. The elastic constants of composite tube namely Young's moduli in the circumferential and longitudinal direction, Poisson's ratio, and shear modulus will be calculated at sampled points through finite element (FE) analysis. A polynomial response surface (PRS) will be built for each of the elastic constants to be used as a surrogate to FE analysis. Once the predictive accuracy of PRS is verified at the validation set of data points, the PRS will be invoked 105 times in Monte Carlo simulations (MCS). The uncertainty can be quantified by calculating the coefficient of variation (CV) based on MCS-generated data which will be presented at the conference.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗