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At least 55 records · Page 3

A high-dimensional neural network potential for molecular dynamics simulations of condensed phase nickel and phase transitions

A high-dimensional neural network interatomic potential was developed and used in molecular dynamics simulations of condensed phase Ni and Ni systems with liquid–solid phase coexistence. The reference data set was generated by sampling the potential energy surface over a broad temperature-pressure domain using ab initio MD simulations to train a unified potential. Excellent agreement was achieved between bulk face-centered cubic nickel thermal expansion simulations and relevant experimental data. The same potential also yields accurate structures and diffusivities in the liquid state. The phase transition between liquid and solid phases was simulated using the two-phase interface method. The predicted melting point temperature is within a few kelvins of the literature value. Here, the general methodology could be applied to describe crystals with much more complex phase behaviors.

74 ATOMIC AND MOLECULAR PHYSICS↗

Highly Tunable Thiol-Ene Photoresins for Volumetric Additive Manufacturing

Volumetric additive manufacturing (VAM) forms complete 3D objects in a single photocuring operation without layering defects, enabling 3D printed polymer parts with mechanical properties similar to their bulk material counterparts. This study presents the first report of VAM-printed thiol-ene resins. With well-ordered molecular networks, thiol-ene chemistry accesses polymer materials with a wide range of mechanical properties, moving VAM beyond the limitations of commonly used acrylate formulations. Since free-radical thiol-ene polymerization is not inhibited by oxygen, the nonlinear threshold response required in VAM is introduced by incorporating 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as a radical scavenger. Tuning of the reaction kinetics is accomplished by balancing inhibitor and initiator content. Coupling this with quantitative measurements of the absorbed volumetric optical dose allows control of polymer conversion and gelation during printing. Importantly, this work thereby establishes the first comprehensive framework for spatial–temporal control over volumetric energy distribution, demonstrating structures 3D printed in thiol-ene resin by means of tomographic volumetric VAM. Mechanical characterization of this thiol-ene system, with varied ratios of isocyanurate and triethylene glycol monomers, reveals highly tunable mechanical response far more versatile than identical acrylate-based resins. This broadens the range of materials and properties available for VAM, taking another step toward high-performance printed polymers.

36 MATERIALS SCIENCE↗

Multi‐Omics Analyses Reveal Divergent Molecular Mechanisms Underlying Plant Biomass Conversion by Five Fungi

Fungal plant biomass conversion (FPBC) is of great importance to the global carbon cycle and has been increasingly applied for the production of biofuel and biochemicals from lignocellulose. However, the comprehensive understanding of relevant molecular mechanisms in different fungi remains challenging. Here, we comparatively analyzed the transcriptome, proteome and metabolome profile of four ascomycetes and one basidiomycete fungi during their growth on two common agricultural feedstocks (soybean hulls and corn stover). We revealed strong time‐, substrate‐ and species‐specific responses at multi‐omics levels for the tested fungi, highlighting species‐specific carbon utilization approaches and evolutionary adaptation to environmental niches. Notably, a remarkable expressional diversity of lignocellulose degrading enzymes, sugar transporter and metabolic genes, as well as industrially relevant metabolites were identified across different fungi and cultivation conditions. The findings improves our understanding of complex molecular networks underlying FPBC and fungal ecological roles, offering novel insights that can guide future genetic engineering of fungi for valorization of agriculture waste into value‐added bioproducts.

CAZy↗

Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis

Abstract Identification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular‐like “rosette” state. Therefore, they are compelling models for the study of early multicellularity. Comparative studies revealed that a number of putative human orthologs are present in choanoflagellate genomes, suggesting that a subset of these genes were necessary for the emergence of multicellularity. However, previous work is largely based on sequence alignments alone, which does not confirm structural nor functional similarity. Here, we focus on the PDZ domain, a peptide‐binding domain which plays critical roles in myriad cellular signaling networks and which underwent a gene family expansion in metazoan lineages. Using a customized sequence similarity search algorithm, we identified 178 PDZ domains in the Monosiga brevicollis proteome. This includes 11 previously unidentified sequences, which we analyzed using Rosetta and homology modeling. To assess conservation of protein structure, we solved high‐resolution crystal structures of representative M. brevicollis PDZ domains that are homologous to human Dlg1 PDZ2, Dlg1 PDZ3, GIPC, and SHANK1 PDZ domains. To assess functional conservation, we calculated binding affinities for mbGIPC, mbSHANK1, mbSNX27, and mbDLG‐3 PDZ domains from M. brevicollis . Overall, we find that peptide selectivity is generally conserved between these two disparate organisms, with one possible exception, mbDLG‐3. Overall, our results provide novel insight into signaling pathways in a choanoflagellate model of primitive multicellularity.

Gao, Melody↗

Comparability of Liquid Chromatography Tandem Mass Spectrometry Analysis of Dissolved Organic Matter across Laboratories

Non-targeted liquid chromatography tandem highresolution mass spectrometry (LC−MS/MS) is increasingly applied for the structure-resolved chemical analysis of dissolved organic matter (DOM). With new developments in MS instrumentation and analysis software, the approach has gained substantial momentum over the past decade. However, achieving high-quality analytical data that is reproducible and comparable across laboratories can be a bottleneck in non-targeted metabolomics and organic matter chemical analysis, especially for data reuse in repository-scale analyses. Understanding the capabilities as well as challenges of comparing LC−MS/MS data from different laboratories is necessary for inferring global trends from public data sets. To illuminate instrumentation factors that drive differences and variability, we used a standardized data analysis pipeline, including classical (CMN) and featurebased molecular networking (FBMN), to analyze data from a ring trial by 24 laboratories on identical sample sets of algal and DOM extracts that were mixed in predefined concentrations and spiked with standards. Our results showed that data sets from similar mass spectrometer types with unified instrument parameters were qualitatively comparable, resolving the same general trends and shared mass spectral features. Interlaboratory comparability was best for high-intensity features, while low-intensity features showed greater detection variability. Our analysis also highlights challenges when comparing data from instruments with different acquisition rates or operating with less standardized methods. Lastly, we provide recommendations for data integration, public data sharing, standardization, and best practices for standardized LC−MS/MS data acquisition, which will be critical for long-term time series and intercomparability of DOM chemical analyses.

DOM↗

Mass Spectrometry Adduct Calculator

We describe the Mass Spectrometry Adduct Calculator (MSAC), an automated Python tool to calculate the adduct ion masses of a parent molecule. Here, adduct refers to a version of a parent molecule [M] that is charged due to addition or loss of atoms and electrons resulting in a charged ion, e.g. [M+H] + . MSAC includes a database of 2,341 potential ions and their mass-to-charge ratios (m/z) as extracted from the NIST/EPA/NIH Mass Spectral Library (NIST17), the Global Natural Products Social Molecular Networking Public Spectral Libraries (GNPS), and MassBank of North America (MoNA). The calculator relies on user-selected subsets of the combined database to calculate expected m/z for adducts of molecules supplied as formulas This tool is intended to help researchers create identification libraries to collect evidence for the presence of molecules in mass spectrometry data. While the included adduct database focuses on adducts typically detected during liquid chromatography-mass spectrometry analyses, users may supply their own lists of adducts and charge states for calculating expected m/z. We also analyzed statistics on adducts from spectra contained in the three selected mass spectral libraries. MSAC is freely available at https://github.com/pnnl/MSAC.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

MolDiscovery: learning mass spectrometry fragmentation of small molecules

Identification of small molecules is a critical task in various areas of life science. Recent advances in mass spectrometry have enabled the collection of tandem mass spectra of small molecules from hundreds of thousands of environments. To identify which molecules are present in a sample, one can search mass spectra collected from the sample against millions of molecular structures in small molecule databases. The existing approaches are based on chemistry domain knowledge, and they fail to explain many of the peaks in mass spectra of small molecules. Here, we present molDiscovery, a mass spectral database search method that improves both efficiency and accuracy of small molecule identification by learning a probabilistic model to match small molecules with their mass spectra. A search of over 8 million spectra from the Global Natural Product Social molecular networking infrastructure shows that molDiscovery correctly identify six times more unique small molecules than previous methods.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics

Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of MS/MS spectra originating from published untargeted metabolomics experiments. Entries in this library, or “suspects,” were derived from unannotated spectra that could be linked in a molecular network to an annotated spectrum. Annotations were propagated to unknowns based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer’s brain phenotype. The nearest neighbor suspect spectral library is openly available for download or for data analysis through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.

59 BASIC BIOLOGICAL SCIENCES↗

Fast mass spectrometry search and clustering of untargeted metabolomics data

The throughput of mass spectrometers and the amount of publicly available metabolomics data are growing rapidly, but analysis tools such as molecular networking and Mass Spectrometry Search Tool do not scale to searching and clustering billions of mass spectral data in metabolomics repositories. To address this limitation, we designed MASST+ and Networking+, which can process datasets that are up to three orders of magnitude larger than those processed by state-of-the-art tools.

59 BASIC BIOLOGICAL SCIENCES↗

Quantitative relationships between film morphology, charge carrier dynamics, and photovoltaic performance in bulk-heterojunction binary vs. ternary acceptor blends

Addressing pertinent and perplexing questions regarding why nonfullerene acceptors (NFAs) promote higher power conversion efficiencies (PCEs) than traditional fullerenes and how photoactive bulk heterojunction (BHJ) film morphology, charge photogeneration, and recombination dynamics dictate solar cell performance have stimulated many studies of polymer solar cells (PSCs), yet quantitative relationships remain limited. Better understanding in these areas offers the potential to advance materials design and device engineering, afford higher PCEs, and ultimate commercialization. Here we probe quantitative relationships between BHJ film morphology, charge carrier dynamics, and photovoltaic performance in model binary and ternary blend systems having a wide bandgap donor polymer, a fullerene, and a promising NFA. We show that optimal PC 71 BM incorporation in a PBDB-TF:ITIC-Th binary system matrix retains the original π-face-on orientation, ITIC-Th crystallinity and BHJ film crystallite dimensions, and reduces film upper surface ITIC-Th segregation. Such morphology changes together simultaneously increase hole (μ h ) and electron (μ e ) mobilities, facilitate light-activated ITIC-Th to PC 71 BM domain electron delocalization, reduce free charge carrier (FC) bimolecular recombination (BR) within PBDB-TF:ITIC-Th mixed regions, and increase FC extraction pathways viaPBDB-TF:PC 71 BM pairs. The interplay of these effects yields significantly enhanced inverted cell short-circuit current density (J SC ), fill factor (FF), and PCE. Unexpectedly, we also find that excessive PC 71 BM in the PBDB-TF:ITIC-Th binary system alters the PBDB-TF orientation to π-edge-on, increases large scale PC 71 BM-rich aggregations and BHJ upper surface PC 71 BM composition. Further, these morphology changes increase parasitic decay processes such as intersystem crossing from photoexcited PC 71 BM, compromising the J SC , FF, and PCE metrics. ITIC-Th X-ray diffraction reveals a unique sidechain-dominated molecular network with previously unknown sidechain-end group stacking, rationalizing the STEM and GIWAXS results, photophysics, and the high μ e . DFT computation reveals charge transfer networks within ITIC-Th crystallites, supporting excited-state electron delocalization from ITIC-Th to PC 71 BM. This structure–property understanding leads to a newly reported NFA blend with PCE near 17%.

14 SOLAR ENERGY↗

Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ~70%–75% VO 2 max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1–2 wk and improvements in maximum run speed and maximal oxygen uptake by 4–8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

60 APPLIED LIFE SCIENCES↗

Synthesis and characterization of low-dimensional N-heterocyclic carbene lattices

The covalent interaction of N-heterocyclic carbenes (NHCs) with transition metal atoms gives rise to distinctive frontier molecular orbitals (FMOs). These emergent electronic states have spurred the widespread adoption of NHC ligands in chemical catalysis and functional materials. Although formation of carbene-metal complexes in self-assembled monolayers on surfaces has been explored, design and electronic structure characterization of extended low-dimensional NHC-metal lattices remains elusive. Here, in this work, we demonstrate a modular approach to engineering one-dimensional (1D) metal-organic chains and two-dimensional (2D) Kagome lattices using the FMOs of NHC–Au–NHC junctions to create low-dimensional molecular networks exhibiting intrinsic metallicity. Scanning tunneling spectroscopy and first-principles density functional theory reveal the contribution of C–Au–C π-bonding states to dispersive bands that imbue 1D- and 2D-NHC lattices with exceptionally small work functions.

Qie, Boyu↗

Identification of Effector Metabolites Using Exometabolite Profiling of Diverse Microalgae

Dissolved exometabolites mediate algal interactions in aquatic ecosystems, but microalgal exometabolomes remain understudied. We conducted an untargeted metabolomic analysis of nonpolar exometabolites exuded from four phylogenetically and ecologically diverse eukaryotic microalgal strains grown in the laboratory, freshwater Chlamydomonas reinhardtii, brackish Desmodesmus sp., marine Phaeodactylum tricornutum, and marine Microchloropsis salina, to identify released metabolites based on relative enrichment in the exometabolomes compared to cell pellet metabolomes. Exudates from the different taxa were distinct, but we did not observe clear phylogenetic patterns. We used feature-based molecular networking to explore the identities of these metabolites, revealing several distinct di- and tripeptides secreted by each of the algae, lumichrome, a compound that is known to be involved in plant growth and bacterial quorum sensing, and novel prostaglandin-like compounds. We further investigated the impacts of exogenous additions of eight compounds selected based on exometabolome enrichment on algal growth. Of these compounds, five (lumichrome, 5'-S-methyl-5'-thioadenosine, 17-phenyl trinor prostaglandin A2, dodecanedioic acid, and aleuritic acid) impacted growth in at least one of the algal cultures. Two of these compounds (dodecanedioic acid and aleuritic acid) produced contrasting results, increasing growth in some algae and decreasing growth in others. Together, our results reveal new groups of microalgal exometabolites, some of which could alter algal growth when provided exogenously, suggesting potential roles in allelopathy and algal interactions.

59 BASIC BIOLOGICAL SCIENCES↗

Seed coat transcriptomic profiling of 5-593, a genotype important for genetic studies of seed coat color and patterning in common bean ( Phaseolus vulgaris L.)

Common bean (Phaseolus vulgaris L.) market classes have distinct seed coat colors, which are directly related to the diverse flavonoids found in the mature seed coat. To understand and elucidate the molecular mechanisms underlying the regulation of seed coat color, RNA-Seq data was collected from the black bean 5-593 and used for a differential gene expression and enrichment analysis from four different seed coat color development stages. 5-593 carries dominant alleles for 10 of the 11 major genes that control seed coat color and expression and has historically been used to develop introgression lines used for seed coat genetic analysis. Pairwise comparison among the four stages identified 6,294 differentially expressed genes (DEGs) varying from 508 to 5,780 DEGs depending on the compared stages. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction comprised the principal pathways expressed during bean seed coat pigment development. Transcriptome analysis suggested that most structural genes for flavonoid biosynthesis and some potential regulatory genes were significantly differentially expressed. Further studies detected 29 DEGs as important candidate genes governing the key enzymatic flavonoid biosynthetic pathways for common bean seed coat color development. Additionally, four gene models, Pv5-593.02G016100, 593.02G078700, Pv5-593.02G090900, and Pv5-593.06G121300, encode MYB-like transcription factor family protein were identified as strong candidate regulatory genes in anthocyanin biosynthesis which could regulate the expression levels of some important structural genes in flavonoid biosynthesis pathway. These findings provide a framework to draw new insights into the molecular networks underlying common bean seed coat pigment development.

60 APPLIED LIFE SCIENCES↗

Holo-omics for deciphering plant-microbiome interactions

Host-microbiome interactions are recognized for their importance to host health. An improved understanding of the molecular underpinnings of host-microbiome relationships will advance our capacity to accurately predict host fitness and manipulate interaction outcomes. Within the plant microbiome research field, unlocking the functional relationships between plants and their microbial partners is the next step to effectively using the microbiome to improve plant fitness. We propose that strategies that pair host and microbial datasets—referred to here as holo-omics—provide a powerful approach for hypothesis development and advancement in this area. We discuss several experimental design considerations and present a case study to highlight the potential for holo-omics to generate a more holistic perspective of molecular networks within the plant microbiome system. In addition, we discuss the biggest challenges for conducting holo-omics studies; specifically, the lack of vetted analytical frameworks, publicly available tools, and required technical expertise to process and integrate heterogeneous data. Finally, we conclude with a perspective on appropriate use-cases for holo-omics studies, the need for downstream validation, and new experimental techniques that hold promise for the plant microbiome research field. We argue that utilizing a holo-omics approach to characterize host-microbiome interactions can provide important opportunities for broadening system-level understandings and significantly inform microbial approaches to improving host health and fitness.

59 BASIC BIOLOGICAL SCIENCES↗

Studies of surface adsorbate electronic structure and femtochemistry at the fundamental length and time scales. Final report

The electronic structure and ultrafast (10-15 s-femtosecond timescale) electron dynamics were investigated for clean and atom/molecule covered metal surfaces. The studies were performed by scanning tunneling microscopy (STM) to measure the structure of adsorbed atoms and molecules on metal surfaces, and to investigate their electronic properties. The electronic structure of the observed molecular networks was calculated by electronic structure theory in collaboration with Prof. Jin Zhao, who is a long-time collaborator, a Professor at the University of Science and Technology of China, and holds an Adjunct Professorship at the University of Pittsburgh. We also investigated the electronic properties of C60 molecules when they are templated by corrugated black phosphorous surfaces. We found unexpected charge delocalization that is enabled by the templating. This research was done in collaboration with Professor Min Feng at the Wuhan University, and who also holds an Adjunct Professorship at the University of Pittsburgh. Moreover, the electronic structure and electron dynamics in metal surfaces were investigated by time-resolved photoemission electron spectroscopy. The focus of ultrafast spectroscopy has been on the plasmonic response of silver surfaces. One direction has been to develop multidimensional (energy, momentum, and time) photoelectron spectroscopy of the coherent response of solid surfaces. This method was applied to study the collective electron excitations known generally as plasmons, which screen optical fields from penetration into metals. Although this collective response has been known for more than 60 years and is used extensively to deposit optical energy into metals, how this happens is poorly known. We investigated the plasmonic response of silver at the point where the dielectric response passes through zero and bulk plasmon is excited by light. We discovered that the plasmon excitation decays by exciting electrons from the Fermi level of a metal, which is contrary to what is believed in the plasmonic science community. This research has been performed in collaboration with Dr. Marcel Reutzel, who was a postdoctoral fellow working on this research at the University of Pittsburgh, and now has a faculty position at the University of Göttingen in Germany. Prof. Branko Gumhalter from the Institute of Physics in Zagreb contributed on the theory of plasmonic decay processes. Furthermore, we investigated the Floquet engineering of electronic bands in metals leading to multiphoton photoemission and above threshold photoemission. Finally, we demonstrated that it is possible to change the electronic structure of metals by application of optical fields. Our studies indicated that this happens on subfemtosecond time scale and could potentially be used in ultrafast information processing and quantum computation. Related document information

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Parallel Multi-Omics in High-Risk Subjects for the Identification of Integrated Biomarker Signatures of Type 1 Diabetes

Background: Biomarkers are crucial for detecting early type-1 diabetes (T1D) and preventing significant β-cell loss before the onset of clinical symptoms. Here, we present proof-of-concept studies to demonstrate the potential for identifying integrated biomarker signature(s) of T1D using parallel multi-omics. Methods: Blood from human subjects at high risk for T1D (and healthy controls; n = 4 + 4) was subjected to parallel unlabeled proteomics, metabolomics, lipidomics, and transcriptomics. The integrated dataset was analyzed using Ingenuity Pathway Analysis (IPA) software for disturbances in the at-risk subjects compared to controls. Results: The final quadra-omics dataset contained 2292 proteins, 328 miRNAs, 75 metabolites, and 41 lipids that were detected in all samples without exception. Disease/function enrichment analyses consistently indicated increased activation, proliferation, and migration of CD4 T-lymphocytes and macrophages. Integrated molecular network predictions highlighted central involvement and activation of NF-κB, TGF-β, VEGF, arachidonic acid, and arginase, and inhibition of miRNA Let-7a-5p. IPA-predicted candidate biomarkers were used to construct a putative integrated signature containing several miRNAs and metabolite/lipid features in the at-risk subjects. Conclusions: Preliminary parallel quadra-omics provided a comprehensive picture of disturbances in high-risk T1D subjects and highlighted the potential for identifying associated integrated biomarker signatures. With further development and validation in larger cohorts, parallel multi-omics could ultimately facilitate the classification of T1D progressors from non-progressors.

60 APPLIED LIFE SCIENCES↗

Shaping Symmetry and Molding Morphology of Triply-Periodic Network Assemblies via Molecular Design and Processing of Block Copolymers

This project aimed to uncover molecular design rules for block copolymer (BCP) assemblies of triply-periodic network (TPN) phases, which are highly sought after, yet elusive, nanostructures for many functional material applications that rely on their combination of symmetry and polycontinuous domain connectivity [R1, R2], such as topological-photonics, supercapacitors and ultrafiltration media. While they have been a target of “bottom up” approaches to nanostructured, hybrid materials, the ability to manipulate the tubular network morphology of TPN assemblies beyond the cubic double-gyroid (DG) phase has advanced relatively little.

36 MATERIALS SCIENCE↗