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At least 91 records · Page 5

A multi-ancestry GWAS of Fuchs corneal dystrophy highlights the contributions of laminins, collagen, and endothelial cell regulation

Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, and COL18A1. We further confirm the TCF4 locus in GWAS for admixed African and Hispanic/Latino ancestries and show an enrichment of European-ancestry haplotypes at TCF4 in FECD cases. Among the novel associations are low frequency missense variants in laminin genes LAMA5 and LAMB1 which, together with previously reported LAMC1, form laminin-511 (LM511). AlphaFold 2 protein modeling, validated through homology, suggests that mutations at LAMA5 and LAMB1 may destabilize LM511 by altering inter-domain interactions or extracellular matrix binding. Finally, phenome-wide association scans and colocalization analyses suggest that the TCF4 CTG18.1 trinucleotide repeat expansion leads to dysregulation of ion transport in the corneal endothelium and has pleiotropic effects on renal function.

59 BASIC BIOLOGICAL SCIENCES↗

Photochemistry and in vitro anticancer activity of Pt(IV)Re(I) conjugates

The photophysical and photochemical properties of two Pt(IV)Re(I) conjugates were studied via both experimental and computational methods. Additionally, both conjugates exhibit modest photocytotoxicity against ovarian cancer cells. X-ray fluorescence microscopy showed that Pt and Re colocalize in cells whether they had been irradiated or not. This work demonstrates the potential of photoactivated multilimetallic agents for combating cancer.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

ServiceX A Distributed, Caching, Columnar Data Delivery Service

We will describe a component of the Intelligent Data Delivery Service being developed in collaboration with IRIS-HEP and the LHC experiments. ServiceX is an experiment-agnostic service to enable on-demand data delivery specifically tailored for nearly-interactive vectorized analysis. This work is motivated by the data engineering challenges posed by HL-LHC data volumes and the increasing popularity of python and Spark-based analysis workflows.ServiceX gives analyzers the ability to query events by dataset metadata. It uses containerized transformations to extract just the data required for the analysis. This operation is colocated with the data to avoid transferring unnecessary branches over the WAN. Simple filtering operations are supported to further reduce the amount of data transferred.Transformed events are cached in a columnar datastore to accelerate delivery of subsequent similar requests. ServiceX will learn commonly related columns and automatically include them in the transformation to increase the potential for cache hits by other users.Selected events are streamed to the analysis system using an efficient wire protocol that can be readily consumed by a variety of computational frameworks. This reduces time-to-insight for physics analysis by delegating to ServiceX the complexity of event selection, slimming, reformatting, and streaming.

Galewsky, B.↗

Employing Technology to Enable Remote Research Charrettes as a Method for Engaging Industry and Uncovering Best Practices: A Novel Approach for a Post-COVID-19 World

Methods to collect data in construction engineering and management (CEM) research are evolving, informed by recent technological advancements. One such method is research charrettes that allow effective interactions and knowledge sharing between expert industry practitioners and academic researchers, all colocated in a single venue, enabling rich data collection and live communication. A pivot point in technological evolution occurred with the COVID-19 pandemic, forcing a global shift to remote work. Hence, planned in-person research charrettes had to shift to remote sessions, relying on virtual conferencing platforms and online data collection mechanisms. Technology-enabled charrettes have allowed the authors to collect significantly richer data sets and ensure a more diverse representation of participants, while saving tremendous amounts of time. With the continuing emergence of technological applications, the world might not go back to functioning fully in person. The authors believe remote research charrettes (RRCs) will still be used in a post-COVID-19 world because of their superior performance. This paper builds on a previous publication that described traditional research charrettes as a method to enhance CEM research a decade ago; it offers a significantly updated and improved RRC method based on the knowledge gained from transitioning a dozen in-person charrettes into RRCs. It also presents performance comparisons between RRCs and traditional charrettes by quantifying metrics indicating how RRCs are more time-efficient and cost-saving, harness more participants from more diverse locations, and enable the collection of richer data sets and four times more industry comments and expert feedback. This paper also provides guidance on the integration of technology with traditional research charrettes, hence contributing to the CEM body of knowledge.

42 ENGINEERING↗

Direct visualization of degradation microcompartments at the ER membrane

To promote the biochemical reactions of life, cells can compartmentalize molecular interaction partners together within separated non–membrane-bound regions. It is unknown whether this strategy is used to facilitate protein degradation at specific locations within the cell. Leveraging in situ cryo-electron tomography to image the native molecular landscape of the unicellular alga Chlamydomonas reinhardtii , we discovered that the cytosolic protein degradation machinery is concentrated within ∼200-nm foci that contact specialized patches of endoplasmic reticulum (ER) membrane away from the ER–Golgi interface. These non–membrane-bound microcompartments exclude ribosomes and consist of a core of densely clustered 26S proteasomes surrounded by a loose cloud of Cdc48. Active proteasomes in the microcompartments directly engage with putative substrate at the ER membrane, a function canonically assigned to Cdc48. Live-cell fluorescence microscopy revealed that the proteasome clusters are dynamic, with frequent assembly and fusion events. We propose that the microcompartments perform ER-associated degradation, colocalizing the degradation machinery at specific ER hot spots to enable efficient protein quality control.

Science & Technology - Other Topics↗

COST1 regulates autophagy to control plant drought tolerance

Plants balance their competing requirements for growth and stress tolerance via a sophisticated regulatory circuitry that controls responses to the external environments. We have identified a plant-specific gene, COST1 (constitutively stressed 1), that is required for normal plant growth but negatively regulates drought resistance by influencing the autophagy pathway. An Arabidopsis thaliana cost1 mutant has decreased growth and increased drought tolerance, together with constitutive autophagy and increased expression of drought-response genes, while overexpression of COST1 confers drought hypersensitivity and reduced autophagy. The COST1 protein is degraded upon plant dehydration, and this degradation is reduced upon treatment with inhibitors of the 26S proteasome or autophagy pathways. The drought resistance of a cost1 mutant is dependent on an active autophagy pathway, but independent of other known drought signaling pathways, indicating that COST1 acts through regulation of autophagy. In addition, COST1 colocalizes to autophagosomes with the autophagosome marker ATG8e and the autophagy adaptor NBR1, and affects the level of ATG8e protein through physical interaction with ATG8e, indicating a pivotal role in direct regulation of autophagy. We propose a model in which COST1 represses autophagy under optimal conditions, thus allowing plant growth. Under drought, COST1 is degraded, enabling activation of autophagy and suppression of growth to enhance drought tolerance. Our research places COST1 as an important regulator controlling the balance between growth and stress responses via the direct regulation of autophagy.

59 BASIC BIOLOGICAL SCIENCES↗

Lipid sponge droplets as programmable synthetic organelles

Living cells segregate molecules and reactions in various subcellular compartments known as organelles. Spatial organization is likely essential for expanding the biochemical functions of synthetic reaction systems, including artificial cells. Many studies have attempted to mimic organelle functions using lamellar membrane-bound vesicles. However, vesicles typically suffer from highly limited transport across the membranes and an inability to mimic the dense membrane networks typically found in organelles such as the endoplasmic reticulum. Here, we describe programmable synthetic organelles based on highly stable nonlamellar sponge phase droplets that spontaneously assemble from a single-chain galactolipid and nonionic detergents. Due to their nanoporous structure, lipid sponge droplets readily exchange materials with the surrounding environment. In addition, the sponge phase contains a dense network of lipid bilayers and nanometric aqueous channels, which allows different classes of molecules to partition based on their size, polarity, and specific binding motifs. The sequestration of biologically relevant macromolecules can be programmed by the addition of suitably functionalized amphiphiles to the droplets. We demonstrate that droplets can harbor functional soluble and transmembrane proteins, allowing for the colocalization and concentration of enzymes and substrates to enhance reaction rates. Droplets protect bound proteins from proteases, and these interactions can be engineered to be reversible and optically controlled. Our results show that lipid sponge droplets permit the facile integration of membrane-rich environments and self-assembling spatial organization with biochemical reaction systems.

59 BASIC BIOLOGICAL SCIENCES↗

Structural basis for autophagy inhibition by the human Rubicon–Rab7 complex

Rubicon is a potent negative regulator of autophagy and a potential target for autophagy-inducing therapeutics. Rubicon-mediated inhibition of autophagy requires the interaction of the C-terminal Rubicon homology (RH) domain of Rubicon with Rab7–GTP. Here we report the 2.8-Å crystal structure of the Rubicon RH domain in complex with Rab7–GTP. Our structure reveals a fold for the RH domain built around four zinc clusters. The switch regions of Rab7 insert into pockets on the surface of the RH domain in a mode that is distinct from those of other Rab–effector complexes. Rubicon residues at the dimer interface are required for Rubicon and Rab7 to colocalize in living cells. Mutation of Rubicon RH residues in the Rab7-binding site restores efficient autophagic flux in the presence of overexpressed Rubicon, validating the Rubicon RH domain as a promising therapeutic target.

60 APPLIED LIFE SCIENCES↗

Climate-Driven Divergence in Biophysical and Economic Impacts of Agrivoltaics

Increasing global demands for food and energy necessitate innovative land-use solutions. Agrivoltaics, colocating solar photovoltaics with agriculture, shows promise, but its widespread adoption faces complex biophysical and economic trade-offs in a changing climate. Here, we develop an integrated biophysical-economic modeling framework to quantify how agrivoltaics affect biophysical and economic impacts across the Midwestern United States under both current and project climate conditions. We find strong regional divergences driven by climate gradients. In the humid eastern Midwest, solar panel shading limits photosynthesis, leading to reduced yields (maize -24%; soybean -16%) and lower farmers' profitability (maize -16%; soybean -2%) compared to conventional agriculture. Conversely, in the semiarid western region, shading alleviates heat and water stress, moderating yield reductions for maize (-12%) and even boosting soybean yields (+6%), resulting in improved economic returns (-6% for maize; +9% for soybean), for a scenario with 33% photovoltaic ground coverage ratio. Although agrivoltaics generate substantial electrical energy across all regions, high upfront installation costs challenge solar developers compared to standalone solar photovoltaics. However, our analysis identifies “win-win” opportunities where soybean-based agrivoltaics in the semiarid region produce economic benefits for both farmers and solar developers, highlighting the necessity for region-specific designs tailored to local climate conditions. Critically, future climate projections indicate eastward expansion of semiarid conditions, broadening areas where agrivoltaics can mitigate crop yield penalties (even boosting yield) and improve overall profitability, especially under high-emission scenarios. The results provide a mechanistic and economically integrated understanding essential for developing evidence-based and region-specific strategies to scale agrivoltaics in a changing climate.

14 SOLAR ENERGY↗

QTL × environment interactions underlie ionome divergence in switchgrass

Abstract Ionomics measures elemental concentrations in biological organisms and provides a snapshot of physiology under different conditions. In this study, we evaluate genetic variation of the ionome in outbred, perennial switchgrass in three environments across the species’ native range, and explore patterns of genotype-by-environment interactions. We grew 725 clonally replicated genotypes of a large full sib family from a four-way linkage mapping population, created from deeply diverged upland and lowland switchgrass ecotypes, at three common gardens. Concentrations of 18 mineral elements were determined in whole post-anthesis tillers using ion coupled plasma mass spectrometry (ICP-MS). These measurements were used to identify quantitative trait loci (QTL) with and without QTL-by-environment interactions (QTLxE) using a multi-environment QTL mapping approach. We found that element concentrations varied significantly both within and between switchgrass ecotypes, and GxE was present at both the trait and QTL level. Concentrations of 14 of the 18 elements were under some genetic control, and 77 QTL were detected for these elements. Seventy-four percent of QTL colocalized multiple elements, half of QTL exhibited significant QTLxE, and roughly equal numbers of QTL had significant differences in magnitude and sign of their effects across environments. The switchgrass ionome is under moderate genetic control and by loci with highly variable effects across environments.

59 BASIC BIOLOGICAL SCIENCES↗

Whole-Genome Comparisons of Ergot Fungi Reveals the Divergence and Evolution of Species within the Genus Claviceps Are the Result of Varying Mechanisms Driving Genome Evolution and Host Range Expansion

The genus Claviceps has been known for centuries as an economically important fungal genus for pharmacology and agricultural research. Only recently have researchers begun to unravel the evolutionary history of the genus, with origins in South America and classification of four distinct sections through ecological, morphological, and metabolic features (Claviceps sects. Citrinae, Paspalorum, Pusillae, and Claviceps). The first three sections are additionally characterized by narrow host range, whereas section Claviceps is considered evolutionarily more successful and adaptable as it has the largest host range and biogeographical distribution. However, the reasons for this success and adaptability remain unclear. Our study elucidates factors influencing adaptability by sequencing and annotating 50 Claviceps genomes, representing 21 species, for a comprehensive comparison of genome architecture and plasticity in relation to host range potential. Our results show the trajectory from specialized genomes (sects. Citrinae and Paspalorum) toward adaptive genomes (sects. Pusillae and Claviceps) through colocalization of transposable elements around predicted effectors and a putative loss of repeat-induced point mutation resulting in unconstrained tandem gene duplication coinciding with increased host range potential and speciation. Alterations of genomic architecture and plasticity can substantially influence and shape the evolutionary trajectory of fungal pathogens and their adaptability. Furthermore, our study provides a large increase in available genomic resources to propel future studies of Claviceps in pharmacology and agricultural research, as well as, research into deeper understanding of the evolution of adaptable plant pathogens.

59 BASIC BIOLOGICAL SCIENCES↗

Sensor-Assisted Fault Mitigation in Quantum Computation

We propose a method for assisting fault mitigation in quantum computation through the use of sensors, co-located near physical qubits. Specifically, we consider using transition edge sensors co-located on silicon substrates hosting superconducting qubits to monitor for energy injection from ionizing radiation that has been demonstrated to increase decoherence in transmon qubits. We generalize from these two physical device concepts and explore the potential advantages of co-located sensors to assist fault mitigation in quantum computation. In the simplest scheme, co-located sensors beneficially assist rejection of calculations potentially affected by environmental disturbances. Investigating the potential computational advantage further required development of an extension to the standard formulation of quantum error correction. In a specific case the standard three-qubit, bit flip quantum correction code, we show that given a 20% overall error probability per qubit, approximately 90% of repeated calculation attempts are correctable. However, when sensor-detectable errors account for 45% of overall error probability, the use of colocated sensors uniquely associated with independent qubits, boosts the fraction of correct final-state calculations to 96% at the cost of rejecting 7% of repeated calculation attempts.

Orrell, John L.↗

Interferometric Constraints on Spacelike Coherent Rotational Fluctuations

Precision measurements are reported of the cross-spectrum of rotationally induced differential position displacements in a pair of colocated 39 m long, high-power Michelson interferometers. One arm of each interferometer is bent 90° near its midpoint to obtain sensitivity to rotations about an axis normal to the plane of the instrument. The instrument achieves quantum-limited sensing of spatially correlated signals in a broad frequency band extending beyond the 3.9-MHz inverse light travel time of the apparatus. For stationary signals with bandwidth Δf>10 kHz, the sensitivity to rotation-induced strain h of classical or exotic origin surpasses CSDδh

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Signature of Collective Plasma Effects in Beam-Driven QED Cascades

QED cascades play an important role in extreme astrophysical environments like magnetars. Furthermore, they can also be produced by passing a relativistic electron beam through an intense laser field. Signatures of collective pair plasma effects in these QED cascades are shown to appear, in exquisite detail, through plasma-induced frequency upshifts in the laser spectrum. Remarkably, these signatures can be detected even in small plasma volumes moving at relativistic speeds. Strong-field quantum and collective pair plasma effects can thus be explored with existing technology, provided that ultradense electron beams are colocated with multipetawatt lasers.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Kensor: Coordinated Intelligence from Co-Located Sensors

Internet of Things (IoT) is becoming more pervasive in many installations, including homes, manufacturing plants, and industrial facilities of all kinds. The data that IoT produces is a reflection of usual behavior such as daily routines and scheduled tasks, but also from unexpected behavior due to unintentional or undesirable abnormalities. Here, we focus on achieving coordinated intelligence about normal and abnormal phenomena from multiple sensors that are geographically colocated in close proximity, monitoring and controlling a set of co-located devices. Given a set of co-located sensors, we seek an intelligent approach that would automatically determine the “normal” patterns of behaviors among the correlated sensors. After normal behavior is extracted, later monitoring should detect any deviant variations over time. An example application is an entry monitoring and alert system for facilities such as nuclear reactors, where badge readers, door locks, lights, weight trackers and other co-located sensors at the entry point are collectively tracked. To address this problem, we identify the possible solution approach that can be used to solve its different variants. The implemented model is developed as a combination of rules and Markov Chain methods.

Kotevska, Olivera↗

Bounds on Optimal Revisit Times in Persistent Monitoring Missions With a Distinct and Remote Service Station</strong

We report persistent monitoring missions require an up-to-date knowledge of the changing state of the underlying environment. Unmannned aerial vehicles (UAVs) can be gainfully employed to continually visit a set of targets representing tasks (and locations) in the environment and collect data therein for long time periods. The enduring nature of these missions requires the UAV to be regularly recharged at a service station. In this article, we consider the case in which the service station is not colocated with any of the targets. An efficient monitoring requires the revisit time, defined as the maximum of the time elapsed between successive revisits to targets, to be minimized. Here, we consider the problem of determining UAV routes that lead to the minimum revisit time. The problem is NP-hard, and its computational difficulty increases with the fuel capacity of the UAV. We develop an algorithm to construct near-optimal solutions to the problem quickly when the fuel capacity exceeds a threshold. We also develop lower bounds to the optimal revisit time and use these bounds to demonstrate (through numerical simulations) that the constructed solutions are, on an average, at most 0.01% away from the optimum.

42 ENGINEERING↗

BUZZ : an essential gene for postinitiation root hair growth and a mediator of root architecture in Brachypodium distachyon

Here, we discover a player in root development. Recovered from a forward-genetic screen in Brachypodium distachyon, the buzz mutant initiates root hairs but they fail to elongate. In addition, buzz roots grow twice as fast as wild-type roots. Also, lateral roots show increased sensitivity to nitrate, whereas primary roots are less sensitive to nitrate. Using whole-genome resequencing, we identified the causal single nucleotide polymorphism as occurring in a conserved but previously uncharacterized cyclin-dependent kinase (CDK)-like gene. The buzz mutant phenotypes are rescued by the wild-type B. distachyon BUZZ coding sequence and by an apparent homolog in Arabidopsis thaliana. Moreover, T-DNA mutants in A. thaliana BUZZ have shorter root hairs. BUZZ mRNA localizes to epidermal cells and develops root hairs and, in the latter, partially colocalizes with the NRT1.1A nitrate transporter. Based on qPCR and RNA-Seq, buzz overexpresses ROOT HAIRLESS LIKE SIX-1 and -2 and misregulates genes related to hormone signaling, RNA processing, cytoskeletal, and cell wall organization, and to the assimilation of nitrate. Overall, these data demonstrate that BUZZ is required for tip growth after root hair initiation and root architectural responses to nitrate.

59 BASIC BIOLOGICAL SCIENCES↗

QTL analysis of salt tolerance in Sorghum bicolor during whole‐plant growth stages

Abstract To study the salt tolerance genetics of sorghum, 181 recombinant inbred lines (RILs) were used to locate quantitative trait loci (QTLs) underlying salt stress adaptability. Six traits, namely, plant height (PH), stem diameter (SD), total biomass (TB), stem fresh weight (SFW), juice weight (JW) and Brix, were investigated under normal and salt stress conditions in two years. A total of 53 QTLs for the six traits under both conditions and their corresponding salt tolerance index (STI) were detected and phenotypic variation explained (PVE) ranged from 4.16% to 20.42%. Six of the QTLs, qTB6 , qSFW9 , qJW9 , qBrix2 , qBrix10 and qSTI‐Brix9, were the main effect QTLs controlling salt tolerance and had a PVE more than 10%. qSFW9 and qJW9 colocalized in the same marker interval as SB5069‐UGSM18 and had PVEs of 17.70% and 14.20%, respectively, with positive effects from L‐Tian. QTL clusters controlling PH, TB, STI‐TB, SFW and JW were consistently mapped in the marker interval of Xcup19‐SB4177 on chromosome 7. These locations might serve as target sites for marker‐assisted selection (MAS) in improving salt tolerance of sorghum.

Wang, Hailian↗