bluuebunny/crossref_metadata_2025 huggingface dataset:
Decision-making in balancing fire safety hazards against security threats within the built environment
Authors: Kathage Richard , Brooks David J. , Coole Michael
Published: June 2024

The built environment faces challenges from fire hazards and threats by malicious actors. Risks presented from these hazards and threats are managed through the practices of fire safety and physical security. Whilst distinct disciplines, both impact the built environment systems, resulting in potential conflict. To manage this conflict, a complex process is required. Through the framework of Governmentality, using a mixed methods approach, the study explored the process which fire safety engineers and security practitioners undertake to manage this conflict. The study produced a conceptual model that explains how practitioners operate and manage risk associated with fire safety hazards and security threats. The model indicates that the process for resolving conflicts is a dichotomy between physical security and fire safety, with fire safety being the most dominate and influential. Nevertheless, both fire safety and physical security are subservient to building regulations in this process; however unlike security, fire safety is codified through building regulations. Risk assessment and the design process are core processes, but only used in decision-making when there is conflict between the fire safety and physical security. Findings demonstrated that context remains static for greater threats, whereas context is dynamic for fire safety.
MTM1-mediated production of phosphatidylinositol 5-phosphate fuels the formation of podosome-like protrusions regulating myoblast fusion
Authors: Mansat Mélanie , Kpotor Afi Oportune , Chicanne Gaëtan , Picot Mélanie , Mazars Anne , Flores-Flores Rémy , Payrastre Bernard , Hnia Karim , Viaud Julien
Published: June 2024

Myogenesis is a multistep process that requires a spatiotemporal regulation of cell events resulting finally in myoblast fusion into multinucleated myotubes. Most major insights into the mechanisms underlying fusion seem to be conserved from insects to mammals and include the formation of podosome-like protrusions (PLPs) that exert a driving force toward the founder cell. However, the machinery that governs this process remains poorly understood. In this study, we demonstrate that MTM1 is the main enzyme responsible for the production of phosphatidylinositol 5-phosphate, which in turn fuels PI5P 4-kinase α to produce a minor and functional pool of phosphatidylinositol 4,5-bisphosphate that concentrates in PLPs containing the scaffolding protein Tks5, Dynamin-2, and the fusogenic protein Myomaker. Collectively, our data reveal a functional crosstalk between a PI-phosphatase and a PI-kinase in the regulation of PLP formation.
Compositions of iron-meteorite parent bodies constrain the structure of the protoplanetary disk
Authors: Zhang Bidong , Chabot Nancy L. , Rubin Alan E.
Published: June 2024

Magmatic iron-meteorite parent bodies are the earliest planetesimals in the Solar System, and they preserve information about conditions and planet-forming processes in the solar nebula. In this study, we include comprehensive elemental compositions and fractional-crystallization modeling for iron meteorites from the cores of five differentiated asteroids from the inner Solar System. Together with previous results of metallic cores from the outer Solar System, we conclude that asteroidal cores from the outer Solar System have smaller sizes, elevated siderophile-element abundances, and simpler crystallization processes than those from the inner Solar System. These differences are related to the formation locations of the parent asteroids because the solar protoplanetary disk varied in redox conditions, elemental distributions, and dynamics at different heliocentric distances. Using highly siderophile-element data from iron meteorites, we reconstruct the distribution of calcium-aluminum-rich inclusions (CAIs) across the protoplanetary disk within the first million years of Solar-System history. CAIs, the first solids to condense in the Solar System, formed close to the Sun. They were, however, concentrated within the outer disk and depleted within the inner disk. Future models of the structure and evolution of the protoplanetary disk should account for this distribution pattern of CAIs.
The physical and cellular mechanism of structural color change in zebrafish
Authors: Gur Dvir , Moore Andrew S. , Deis Rachael , Pang Song , Wu Xufeng , Pinkas Iddo , Deo Claire , Iyer Nirmala , Hess Harald F. , Hammer John A. , Lippincott-Schwartz Jennifer
Published: June 2024

Many animals exhibit remarkable colors that are produced by the constructive interference of light reflected from arrays of intracellular guanine crystals. These animals can fine-tune their crystal-based structural colors to communicate with each other, regulate body temperature, and create camouflage. While it is known that these changes in color are caused by changes in the angle of the crystal arrays relative to incident light, the cellular machinery that drives color change is not understood. Here, using a combination of 3D focused ion beam scanning electron microscopy (FIB-SEM), micro-focused X-ray diffraction, superresolution fluorescence light microscopy, and pharmacological perturbations, we characterized the dynamics and 3D cellular reorganization of crystal arrays within zebrafish iridophores during norepinephrine (NE)-induced color change. We found that color change results from a coordinated 20° tilting of the intracellular crystals, which alters both crystal packing and the angle at which impinging light hits the crystals. Importantly, addition of the dynein inhibitor dynapyrazole-a completely blocked this NE-induced red shift by hindering crystal dynamics upon NE addition. FIB-SEM and microtubule organizing center (MTOC) mapping showed that microtubules arise from two MTOCs located near the poles of the iridophore and run parallel to, and in between, individual crystals. This suggests that dynein drives crystal angle change in response to NE by binding to the limiting membrane surrounding individual crystals and walking toward microtubule minus ends. Finally, we found that intracellular cAMP regulates the color change process. Together, our results provide mechanistic insight into the cellular machinery that drives structural color change.
Climate mismatches with ectomycorrhizal fungi contribute to migration lag in North American tree range shifts
Authors: Van Nuland Michael E. , Qin Clara , Pellitier Peter T. , Zhu Kai , Peay Kabir G.
Published: June 2024

Climate change will likely shift plant and microbial distributions, creating geographic mismatches between plant hosts and essential microbial symbionts (e.g., ectomycorrhizal fungi, EMF). The loss of historical interactions, or the gain of novel associations, can have important consequences for biodiversity, ecosystem processes, and plant migration potential, yet few analyses exist that measure where mycorrhizal symbioses could be lost or gained across landscapes. Here, we examine climate change impacts on tree-EMF codistributions at the continent scale. We built species distribution models for 400 EMF species and 50 tree species, integrating fungal sequencing data from North American forest ecosystems with tree species occurrence records and long-term forest inventory data. Our results show the following: 1) tree and EMF climate suitability to shift toward higher latitudes; 2) climate shifts increase the size of shared tree-EMF habitat overall, but 35% of tree-EMF pairs are at risk of declining habitat overlap; 3) climate mismatches between trees and EMF are projected to be greater at northern vs. southern boundaries; and 4) tree migration lag is correlated with lower richness of climatically suitable EMF partners. This work represents a concentrated effort to quantify the spatial extent and location of tree-EMF climate envelope mismatches. Our findings also support a biotic mechanism partially explaining the failure of northward tree species migrations with climate change: reduced diversity of co-occurring and climate-compatible EMF symbionts at higher latitudes. We highlight the conservation implications for identifying areas where tree and EMF responses to climate change may be highly divergent.
Changes in holopelagic
Sargassum
spp. biomass composition across an unusual year
Authors: Machado Carla Botelho , Marsh Robert , Hargreaves Jessica K. , Oxenford Hazel A. , Maddix Gina-Marie , Webber Dale F. , Webber Mona , Tonon Thierry
Published: June 2024

The year 2021 marked a decade of holopelagic sargassum (morphotypes
Sargassum natans
I and VIII, and
Sargassum fluitans
III) stranding on the Caribbean and West African coasts. Beaching of millions of tons of sargassum negatively impacts coastal ecosystems, economies, and human health. Additionally, the La Soufrière volcano erupted in St. Vincent in April 2021, at the start of the sargassum season. We investigated potential monthly variations in morphotype abundance and biomass composition of sargassum harvested in Jamaica and assessed the influence of processing methods (shade-drying vs. frozen samples) and of volcanic ash exposure on biochemical and elemental components.
S. fluitans
III was the most abundant morphotype across the year. Limited monthly variations were observed for key brown algal components (phlorotannins, fucoxanthin, and alginate). Shade-drying did not significantly alter the contents of proteins but affected levels of phlorotannins, fucoxanthin, mannitol, and alginate. Simulation of sargassum and volcanic ash drift combined with age statistics suggested that sargassum potentially shared the surface layer with ash for ~50 d, approximately 100 d before stranding in Jamaica. Integrated elemental analysis of volcanic ash, ambient seawater, and sargassum biomass showed that algae harvested from August had accumulated P, Al, Fe, Mn, Zn, and Ni, probably from the ash, and contained less As. This ash fingerprint confirmed the geographical origin and drift timescale of sargassum. Since environmental conditions and processing methods influence biomass composition, efforts should continue to improve understanding, forecasting, monitoring, and valorizing sargassum, particularly as strandings of sargassum show no sign of abating.
Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons
Authors: Bell Andrew M. , Utting Charlotte , Dickie Allen C. , Kucharczyk Mateusz W. , Quillet Raphaëlle , Gutierrez-Mecinas Maria , Razlan Aimi N. B. , Cooper Andrew H. , Lan Yuxuan , Hachisuka Junichi , Weir Greg A. , Bannister Kirsty , Watanabe Masahiko , Kania Artur , Hoon Mark A. , Macaulay Iain C. , Denk Franziska , Todd Andrew J.
Published: June 2024

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch, and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here, we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters of ALS neurons (ALS1-5) and document their laminar distribution in the spinal cord using in situ hybridization. We identify three clusters of neurons located predominantly in laminae I–III of the dorsal horn (ALS1-3) and two clusters with cell bodies located in deeper laminae (ALS4 and ALS5). Our findings reveal the transcriptional logic that underlies ALS neuronal diversity in the adult mouse and uncover the molecular identity of two previously identified classes of projection neurons. We also show that these molecular signatures can be used to target groups of ALS neurons using retrograde viral tracing. Overall, our findings provide a valuable resource for studying somatosensory biology and targeting subclasses of ALS neurons.
Light management by algal aggregates in living photosynthetic hydrogels
Authors: Chua Sing Teng , Smith Alyssa , Murthy Swathi , Murace Maria , Yang Han , Schertel Lukas , Kühl Michael , Cicuta Pietro , Smith Alison G. , Wangpraseurt Daniel , Vignolini Silvia
Published: June 2024

Rapid progress in algal biotechnology has triggered a growing interest in hydrogel-encapsulated microalgal cultivation, especially for the engineering of functional photosynthetic materials and biomass production. An overlooked characteristic of gel-encapsulated cultures is the emergence of cell aggregates, which are the result of the mechanical confinement of the cells. Such aggregates have a dramatic effect on the light management of gel-encapsulated photobioreactors and hence strongly affect the photosynthetic outcome. To evaluate such an effect, we experimentally studied the optical response of hydrogels containing algal aggregates and developed optical simulations to study the resultant light intensity profiles. The simulations are validated experimentally via transmittance measurements using an integrating sphere and aggregate volume analysis with confocal microscopy. Specifically, the heterogeneous distribution of cell aggregates in a hydrogel matrix can increase light penetration while alleviating photoinhibition more effectively than in a flat biofilm. Finally, we demonstrate that light harvesting efficiency can be further enhanced with the introduction of scattering particles within the hydrogel matrix, leading to a fourfold increase in biomass growth. Our study, therefore, highlights a strategy for the design of spatially efficient photosynthetic living materials that have important implications for the engineering of future algal cultivation systems.
Phosphorylation of DNA-binding domains of CLOCK–BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells
Authors: Otobe Yuta , Jeong Eui Min , Ito Shunsuke , Shinohara Yuta , Kurabayashi Nobuhiro , Aiba Atsu , Fukada Yoshitaka , Kim Jae Kyoung , Yoshitane Hikari
Published: June 2024

In mammals, CLOCK and BMAL1 proteins form a heterodimer that binds to E-box sequences and activates transcription of target genes, including
Period
(
Per)
. Translated PER proteins then bind to the CLOCK–BMAL1 complex to inhibit its transcriptional activity. However, the molecular mechanism and the impact of this PER-dependent inhibition on the circadian clock oscillation remain elusive. We previously identified Ser38 and Ser42 in a DNA-binding domain of CLOCK as phosphorylation sites at the PER-dependent inhibition phase. In this study, knockout rescue experiments showed that nonphosphorylatable (Ala) mutations at these sites shortened circadian period, whereas their constitutive-phospho-mimetic (Asp) mutations completely abolished the circadian rhythms. Similarly, we found that nonphosphorylatable (Ala) and constitutive-phospho-mimetic (Glu) mutations at Ser78 in a DNA-binding domain of BMAL1 also shortened the circadian period and abolished the rhythms, respectively. The mathematical modeling predicted that these constitutive-phospho-mimetic mutations weaken the DNA binding of the CLOCK–BMAL1 complex and that the nonphosphorylatable mutations inhibit the PER-dependent displacement (reduction of DNA-binding ability) of the CLOCK–BMAL1 complex from DNA. Biochemical experiments supported the importance of these phosphorylation sites for displacement of the complex in the PER2-dependent inhibition. Our results provide direct evidence that phosphorylation of CLOCK–Ser38/Ser42 and BMAL1–Ser78 plays a crucial role in the PER-dependent inhibition and the determination of the circadian period.
Metamagnetic multiband Hall effect in Ising antiferromagnet ErGa
2
Authors: Kurumaji Takashi , Fang Shiang , Ye Linda , Kitou Shunsuke , Checkelsky Joseph G.
Published: June 2024

Frustrated rare-earth-based intermetallics provide a promising platform for emergent magnetotransport properties through exchange coupling between conduction electrons and localized rare-earth magnetic moments. Metamagnetism, the abrupt change of magnetization under an external magnetic field, is a signature of first-order magnetic phase transitions; recently, metamagnetic transitions in frustrated rare earth intermetallics have attracted interest for their accompanying nontrivial spin structures (e.g., skyrmions) and associated nonlinear and topological Hall effects (THE). Here, we present metamagnetism-induced Hall anomalies in single-crystalline ErGa
2
, which recalls features arising from the THE but wherein the strong Ising-type anisotropy of Er moments prohibits noncoplanar spin structures. We show that the observed anomalies are neither due to anomalous Hall effect nor THE; instead, can be accounted for via 4f-5d interactions which produce a band-dependent mobility modulation. This leads to a pronounced multiband Hall response across the magnetization process–a metamagnetic multiband Hall effect that resembles a topological-Hall-like response but without nontrivial origins. The present findings may be of general relevance in itinerant metamagnetic systems regardless of coplanar/noncoplanar nature of spins and are important for the accurate identification of Hall signals due to emergent magnetic fields.
Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry
Authors: Hua Wei , Zhang Wenpeng , Brown Hannah , Wu Junhan , Fang Xinqi , Shahi Mahdiyeh , Chen Rong , Zhang Haoyue , Jiao Bin , Wang Nan , Xu Hao , Fu Minjie , Wang Xiaowen , Zhang Jinsen , Zhang Xin , Wang Qijun , Zhu Wei , Ye Dan , Garcia Diogo Moniz , Chaichana Kaisorn , Cooks R. Graham , Ouyang Zheng , Mao Ying , Quinones-Hinojosa Alfredo
Published: June 2024

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (
P
< 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.
Social competition drives collective action to reduce informal waste burning in Uganda
Authors: Buntaine Mark T. , Komakech Polycarp , Shen Shiran Victoria
Published: June 2024

Improving urban air quality is a pressing challenge in the Global South. A key source of air pollution is the informal burning of household waste. Reducing informal burning requires governments to develop formal systems for waste disposal and for residents to adopt new disposal behaviors. Using a randomized experiment, we show that social competitions between pairs of neighborhoods in Nansana municipality, Uganda, galvanized leadership and inspired collective action to reduce informal burning. All 44 neighborhoods in the study received a public health campaign, while 22 treated neighborhoods were paired and competed to reduce waste burning over an 8-mo period. Treated neighborhoods showed a 24 percent reduction (95% CI: 11 to 35 percent) in waste burning relative to control neighborhoods at the end of the competition period. There is no evidence that treated neighborhoods experienced a rebound in waste burning several months after the competitions. Community leaders reported greater effort in coordinating residents and more pride in their neighborhood when assigned to the competition treatment. These results suggest that creating focal points for leadership and collective action can be an effective and low-cost strategy to address policy problems that require broad participation and costly behavior change.
Phase-dependent word perception emerges from region-specific sensitivity to the statistics of language
Authors: Ten Oever Sanne , Titone Lorenzo , te Rietmolen Noémie , Martin Andrea E.
Published: June 2024

Neural oscillations reflect fluctuations in excitability, which biases the percept of ambiguous sensory input. Why this bias occurs is still not fully understood. We hypothesized that neural populations representing likely events are more sensitive, and thereby become active on earlier oscillatory phases, when the ensemble itself is less excitable. Perception of ambiguous input presented during less-excitable phases should therefore be biased toward frequent or predictable stimuli that have lower activation thresholds. Here, we show such a frequency bias in spoken word recognition using psychophysics, magnetoencephalography (MEG), and computational modelling. With MEG, we found a double dissociation, where the phase of oscillations in the superior temporal gyrus and medial temporal gyrus biased word-identification behavior based on phoneme and lexical frequencies, respectively. This finding was reproduced in a computational model. These results demonstrate that oscillations provide a temporal ordering of neural activity based on the sensitivity of separable neural populations.
Principles of peptide selection by the transporter associated with antigen processing
Authors: Lee James , Oldham Michael L. , Manon Victor , Chen Jue
Published: June 2024

Our ability to fight pathogens relies on major histocompatibility complex class I (MHC-I) molecules presenting diverse antigens on the surface of diseased cells. The transporter associated with antigen processing (TAP) transports nearly the entire repertoire of antigenic peptides into the endoplasmic reticulum for MHC-I loading. How TAP transports peptides specific for MHC-I is unclear. In this study, we used cryo-EM to determine a series of structures of human TAP, both in the absence and presence of peptides with various sequences and lengths. The structures revealed that peptides of eight or nine residues in length bind in a similarly extended conformation, despite having little sequence overlap. We also identified two peptide-anchoring pockets on either side of the transmembrane cavity, each engaging one end of a peptide with primarily main chain atoms. Occupation of both pockets results in a global conformational change in TAP, bringing the two halves of the transporter closer together to prime it for isomerization and ATP hydrolysis. Shorter peptides are able to bind to each pocket separately but are not long enough to bridge the cavity to bind to both simultaneously. Mutations that disrupt hydrogen bonds with the N and C termini of peptides almost abolish MHC-I surface expression. Our findings reveal that TAP functions as a molecular caliper that selects peptides according to length rather than sequence, providing antigen diversity for MHC-I presentation.
CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche
Authors: Qiu Ting , Kong Yichao , Wei Guifeng , Sun Kai , Wang Ruijie , Wang Yang , Chen Yiji , Wang Wenxin , Zhang Yun , Jiang Caihong , Yang Peiguo , Xie Tian , Chen Xiabin
Published: June 2024

Rearranged during transfection (RET) rearrangement oncoprotein-mediated Ras/MAPK signaling cascade is constitutively activated in cancers. Here, we demonstrate a unique signal niche. The niche is a ternary complex based on the chimeric RET liquid–liquid phase separation. The complex comprises the rearranged kinase (RET fusion); the adaptor (GRB2), and the effector (SHC1). Together, they orchestrate the Ras/MAPK signal cascade, which is dependent on tyrosine kinase. CCDC6-RET fusion undergoes LLPS requiring its kinase domain and its fusion partner. The CCDC6-RET fusion LLPS promotes the autophosphorylation of RET fusion, with enhanced kinase activity, which is necessary for the formation of the signaling niche. Within the signal niche, the interactions among the constituent components are reinforced, and the signal transduction efficiency is amplified. The specific RET fusion–related signal niche elucidates the mechanism of the constitutive activation of the Ras/MAPK signaling pathway. Beyond just focusing on RET fusion itself, exploration of the ternary complex potentially unveils a promising avenue for devising therapeutic strategies aimed at treating RET fusion–driven diseases.
Emergent facilitation and glassy dynamics in supercooled liquids
Authors: Hasyim Muhammad R. , Mandadapu Kranthi K.
Published: June 2024

In supercooled liquids, dynamical facilitation refers to a phenomenon where microscopic motion begets further motion nearby, resulting in spatially heterogeneous dynamics. This is central to the glassy relaxation dynamics of such liquids, which show super-Arrhenius growth of relaxation timescales with decreasing temperature. Despite the importance of dynamical facilitation, there is no theoretical understanding of how facilitation emerges and impacts relaxation dynamics. Here, we present a theory that explains the microscopic origins of dynamical facilitation. We show that dynamics proceeds by localized bond-exchange events, also known as excitations, resulting in the accumulation of elastic stresses with which new excitations can interact. At low temperatures, these elastic interactions dominate and facilitate the creation of new excitations near prior excitations. Using the theory of linear elasticity and Markov processes, we simulate a model, which reproduces multiple aspects of glassy dynamics observed in experiments and molecular simulations, including the stretched exponential decay of relaxation functions, the super-Arrhenius behavior of relaxation timescales as well as their two-dimensional finite-size effects. The model also predicts the subdiffusive behavior of the mean squared displacement (MSD) on short, intermediate timescales. Furthermore, we derive the phonon contributions to diffusion and relaxation, which when combined with the excitation contributions produce the two-step relaxation processes, and the ballistic–subdiffusive–diffusive crossover MSD behaviors commonly found in supercooled liquids.
January 6 arrests and media coverage do not remobilize conservatives on social media
Authors: Dahlke Ross , Pan Jennifer
Published: June 2024

Social media’s pivotal role in catalyzing social movements is widely acknowledged across scientific disciplines. Past research has predominantly explored social media’s ability to instigate initial mobilization while leaving the question of its capacity to sustain these movements relatively uncharted. This study investigates the persistence of movement activity on Twitter and Gab following a substantial on-the-ground mobilization event catalyzed by social media—the StoptheSteal movement culminating in the January 6th Capitol attack. Our findings indicate that the online communities active in the January 6 mobilization did not display substantial remobilization in the subsequent year. These results highlight the fact that further exploration is needed to understand the factors shaping how and when movements are sustained by social media. In this regard, our study provides valuable insights for scientists across diverse disciplines, on how certain social media platforms may contribute to the evolving dynamics of collective action.
Charge barriers in the kidney elimination of engineered nanoparticles
Authors: Huang Yingyu , Yu Mengxiao , Zheng Jie
Published: June 2024

The renal elimination pathway is increasingly harnessed to reduce nonspecific accumulation of engineered nanoparticles within the body and expedite their clinical applications. While the size of nanoparticles is recognized as crucial for their passive filtration through the glomerulus due to its limited pore size, the influence of nanoparticle charge on their transport and interactions within the kidneys remains largely elusive. Herein, we report that the proximal tubule and peritubular capillary, rather than the glomerulus, serve as primary charge barriers to the transport of charged nanoparticles within the kidney. Employing a series of ultrasmall, renal-clearable gold nanoparticles (AuNPs) with precisely engineered surface charge characteristics as multimodal imaging agents, we have tracked their distribution and retention across various kidney components following intravenous administration. Our results reveal that retention in the proximal tubules is governed not by the nanoparticle’s zeta-potential, but by direct Coulombic interactions between the positively charged surface ligands of the AuNPs and the negatively charged microvilli of proximal tubules. However, further enhancing these interactions leads to increased binding of the positively charged AuNPs to the peritubular capillaries during the initial phase of elimination, subsequently facilitating their slow passage through the glomeruli and interaction with tubular components in a charge-selective manner. By identifying these two critical charge-dependent barriers in the renal transport of nanoparticles, our findings offer a fundamental insight for the design of renal nanomedicines tailored for selective targeting within the kidney, laying down a foundation for developing targeting renal nanomedicines for future kidney disease management in the clinics.
Tailoring the selective generation of oxidative organic radicals for toxic-by-product-free water decontamination
Authors: Wu Jing-Hang , Yang Tian-Hao , Sun Yi-Jiao , Min Yuan , Hu Yi , Chen Fei , Chen Jie-Jie , Yu Han-Qing
Published: June 2024

Peracetic acid (PAA) is emerging as a versatile agent for generating long-lived and selectively oxidative organic radicals (R–O
•
). Currently, the conventional transition metal–based activation strategies still suffer from metal ion leaching, undesirable by-products formation, and uncontrolled reactive species production. To address these challenges, we present a method employing BiOI with a unique electron structure as a PAA activator, thereby predominantly generating CH
3
C(O)O
•
radicals. The specificity of CH
3
C(O)O
•
generation ensured the superior performance of the BiOI/PAA system across a wide pH range (2.0 to 11.0), even in the presence of complex interfering substances such as humic acids, chloride ions, bicarbonate ions, and real-world water matrices. Unlike conventional catalytic oxidative methods, the BiOI/PAA system degrades sulfonamides without producing any toxic by-products. Our findings demonstrate the advantages of CH
3
C(O)O
•
in water decontamination and pave the way for the development of eco-friendly water decontaminations based on organic peroxides.
Irreversible coherent matching bonding of van der Waals heterostructure lattice by pressure
Authors: Zhen Jiapeng , Huang Qiushi , Shen Kai , Dong Hongliang , Zhang Shihui , Lv Kehong , Yang Peng , Zhang Yong , Guo Silin , Qiu Jing , Liu Guanjun
Published: June 2024

The key of heterostructure is the combinations created by stacking various vdW materials, which can modify interlayer coupling and electronic properties, providing exciting opportunities for designer devices. However, this simple stacking does not create chemical bonds, making it difficult to fundamentally alter the electronic structure. Here, we demonstrate that interlayer interactions in heterostructures can be fundamentally controlled using hydrostatic pressure, providing a bonding method to modify electronic structures. By covering graphene with boron nitride and inducing an irreversible phase transition, the conditions for graphene lattice-matching bonding (IMB) were created. We demonstrate that the increased bandgap of graphene under pressure is well maintained in ambient due to the IMB in the interface. Comparison to theoretical modeling emphasizes the process of pressure-induced interfacial bonding, systematically generalizes, and predicts this model. Our results demonstrate that pressure can irreversibly control interlayer bonding, providing opportunities for high-pressure technology in ambient applications and IMB engineering in heterostructures.
Haplotype-resolved genome assembly and implementation of VitExpress, an open interactive transcriptomic platform for grapevine
Authors: Djari Anis , Madignier Guillaume , Di Valentin Olivia , Gillet Thibault , Frasse Pierre , Djouhri Amel , Hu Guojian , Julliard Sebastien , Liu Mingchun , Zhang Yang , Regad Farid , Pirrello Julien , Maza Elie , Bouzayen Mondher
Published: June 2024

Haplotype-resolved genome assemblies were produced for Chasselas and Ugni Blanc, two heterozygous
Vitis vinifera
cultivars by combining high-fidelity long-read sequencing and high‐throughput chromosome conformation capture (Hi-C). The telomere-to-telomere full coverage of the chromosomes allowed us to assemble separately the two haplo-genomes of both cultivars and revealed structural variations between the two haplotypes of a given cultivar. The deletions/insertions, inversions, translocations, and duplications provide insight into the evolutionary history and parental relationship among grape varieties. Integration of de novo single long-read sequencing of full-length transcript isoforms (Iso-Seq) yielded a highly improved genome annotation. Given its higher contiguity, and the robustness of the IsoSeq-based annotation, the Chasselas assembly meets the standard to become the annotated reference genome for
V. vinifera
. Building on these resources, we developed VitExpress, an open interactive transcriptomic platform, that provides a genome browser and integrated web tools for expression profiling, and a set of statistical tools (StatTools) for the identification of highly correlated genes. Implementation of the correlation finder tool for
MybA1
, a major regulator of the anthocyanin pathway, identified candidate genes associated with anthocyanin metabolism, whose expression patterns were experimentally validated as discriminating between black and white grapes. These resources and innovative tools for mining genome-related data are anticipated to foster advances in several areas of grapevine research.
Transient interactions modulate the affinity of NF-κB transcription factors for DNA
Authors: Li Tianjie , Shahabi Shandy , Biswas Tapan , Tsodikov Oleg V. , Pan Wenfei , Huang De-Bin , Wang Vivien Ya-Fan , Wang Yi , Ghosh Gourisankar
Published: June 2024

The dimeric nuclear factor kappa B (NF-κB) transcription factors (TFs) regulate gene expression by binding to a variety of κB DNA elements with conserved G:C-rich flanking sequences enclosing a degenerate central region. Toward defining mechanistic principles of affinity regulated by degeneracy, we observed an unusual dependence of the affinity of RelA on the identity of the central base pair, which appears to be noncontacted in the complex crystal structures. The affinity of κB sites with A or T at the central position is ~10-fold higher than with G or C. Thecrystal structures of neither the complexes nor the free κB DNAs could explain the differences in affinity. Interestingly, differential dynamics of several residues were revealed in molecular dynamics simulation studies, where simulation replicates totaling 148 μs were performed on NF-κB:DNA complexes and free κB DNAs. Notably, Arg187 and Arg124 exhibited selectivity in transient interactions that orchestrated a complex interplay among several DNA-interacting residues in the central region. Binding and simulation studies with mutants supported these observations of transient interactions dictating specificity. In combination with published reports, this work provides insights into the nuanced mechanisms governing the discriminatory binding of NF-κB family TFs to κB DNA elements and sheds light on cancer pathogenesis of cRel, a close homolog of RelA.
Natural history of eukaryotic DNA viruses with double jelly-roll major capsid proteins
Authors: Krupovic Mart , Kuhn Jens H. , Fischer Matthias G. , Koonin Eugene V.
Published: June 2024

The phylum
Preplasmiviricota
(kingdom
Bamfordvirae
, realm
Varidnaviria
) is a broad assemblage of diverse viruses with comparatively short double-stranded DNA genomes (<50 kbp) that produce icosahedral capsids built from double jelly-roll major capsid proteins. Preplasmiviricots infect hosts from all cellular domains, testifying to their ancient origin, and, in particular, are associated with six of the seven supergroups of eukaryotes. Preplasmiviricots comprise four major groups of viruses, namely, polintons, polinton-like viruses (PLVs), virophages, and adenovirids. We used protein structure modeling and analysis to show that protein-primed DNA polymerases (pPolBs) of polintons, virophages, and cytoplasmic linear plasmids encompass an N-terminal domain homologous to the terminal proteins (TPs) of prokaryotic PRD1-like tectivirids and eukaryotic adenovirids that are involved in protein-primed replication initiation, followed by a viral ovarian tumor–like cysteine deubiquitinylase (vOTU) domain. The vOTU domain is likely responsible for the cleavage of the TP from the large pPolB polypeptide and is inactivated in adenovirids, in which TP is a separate protein. Many PLVs and transpovirons encode a distinct derivative of polinton-like pPolB that retains the TP, vOTU, and pPolB polymerization palm domains but lacks the exonuclease domain and instead contains a superfamily 1 helicase domain. Analysis of the presence/absence and inactivation of the vOTU domains and replacement of pPolB with other DNA polymerases in eukaryotic preplasmiviricots enabled us to outline a complete scenario for their origin and evolution.
Evaluating the effectiveness of systemic heparin during arteriovenous fistula creation by emulating a target trial
Authors: Heindel Patrick , Fitzgibbon James J , Secemsky Eric A , Belkin Michael , Ozaki C Keith , Hussain Mohamad A
Published: June 2024

Most of the 800 000 people living with end-stage kidney disease in the United States rely on a functioning vascular access to provide life-sustaining hemodialysis, yet one-third of arteriovenous fistulas experience early failures. Determining the safety and effectiveness of systemic heparin during fistula creation could improve the quality and quantity of life for these vulnerable patients. In this article, a pragmatic randomized trial was emulated to assess the effect of systemic heparin administration (vs none) during radiocephalic arteriovenous fistula creation on early bleeding and thrombosis, using data from 2 international, multicenter, randomized trials performed between 2014 and 2019. Marginal risks were estimated using inverse probability weighted parametric survival analysis and CIs were generated with bootstrapping. A total of 914 patients were enrolled and 61% received systemic heparin; their median (IQR) age was 58 (49, 67) years and 45% were on hemodialysis at enrollment. No difference in the risk of bleeding events was observed, with a risk difference (95% CI) at 14 days of −0.1% (−1.6 to 1.4). The risk of access thrombosis was lower in the heparin group, with a risk of 3.7% (2.6-4.8) after heparin and 5.3% (3.4-7.4) without heparin at 14 days (risk ratio = 0.72; 95% CI, 0.50-0.98). Trial registration: ClinicalTrials.gov. Identifiers: NCT02110901 and NCT02414841.
Leveraging sex-genetic interactions to understand brain disorders: recent advances and current gaps
Authors: Neale Nikita , Lona-Durazo Frida , Ryten Mina , Gagliano Taliun Sarah A
Published: June 2024

It is established that there are sex differences in terms of prevalence, age of onset, clinical manifestations, and response to treatment for a variety of brain disorders, including neurodevelopmental, psychiatric, and neurodegenerative disorders. Cohorts of increasing sample sizes with diverse data types collected, including genetic, transcriptomic and/or phenotypic data, are providing the building blocks to permit analytical designs to test for sex-biased genetic variant-trait associations, and for sex-biased transcriptional regulation. Such molecular assessments can contribute to our understanding of the manifested phenotypic differences between the sexes for brain disorders, offering the future possibility of delivering personalized therapy for females and males. With the intention of raising the profile of this field as a research priority, this review aims to shed light on the importance of investigating sex-genetic interactions for brain disorders, focusing on two areas: (i) variant-trait associations and (ii) transcriptomics (i.e. gene expression, transcript usage and regulation). We specifically discuss recent advances in the field, current gaps and provide considerations for future studies.
Exosomal circPVT1 promotes angiogenesis in laryngeal cancer by activating the Rap1b–VEGFR2 signaling pathway
Authors: Lyu Kexing , Tang Bingjie , Huang Bixue , Xu Zhenglin , Liu Tesi , Fang Ruihua , Li Yun , Chen Yi , Chen Lin , Zhang Minjuan , Chen Lifan , Lei Wenbin
Published: June 2024

Laryngeal cancer (LC) is the second most common head and neck cancer and has a decreasing 5-year survival rate worldwide. Circular RNAs (circRNAs) regulate cancer development in diverse ways based on their distinct biogenesis mechanisms and expansive regulatory roles. However, currently, there is little research on how exosomal circRNAs are involved in the development of LC. Here, we demonstrated that circPVT1, a circRNA derived from the well-studied long noncoding RNA PVT1, is correlated with disease progression in LC and promotes angiogenesis both in vivo and in vitro. Mechanistically, circPVT1 is loaded into LC cell-secreted exosomes and taken up by vascular epithelium cells. By sponging miR-30c-5p, exosomal circPVT1 promotes Rap1b expression, which dramatically enhances vascular endothelial growth factor receptor 2 and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation, ultimately resulting in the induction of angiogenesis. Furthermore, our xenograft models demonstrated that the combination of short hairpin RNA-circPVT1 and cetuximab showed high efficacy in inhibiting tumor growth and angiogenesis. Collectively, these findings uncover a novel mechanism of exosomal circRNA-mediated angiogenesis modulation and provide a preclinical rationale for testing this analogous combination in patients with LC.
Taste of common prebiotic oligosaccharides: impact of molecular structure
Authors: Martin Laura E , Penner Michael H , Lim Juyun
Published: June 2024

Prebiotic oligosaccharides are naturally occurring nondigestible carbohydrates with demonstrated health benefits. They are also a chemically diverse class of nutrients, offering an opportunity to investigate the impact of molecular structure on oligosaccharide taste perception. Accordingly, a relevant question is whether these compounds are detected by the human gustatory system, and if so, whether they elicit sweet or “starchy” taste. Here, in 3 psychophysical experiments, we investigated the taste perception of 3 commercially popular prebiotics [fructooligosaccharides (FOS), galactooligosaccharides (GOS), xylooligosaccharides (XOS)] in highly pure form. Each of these classes of prebiotics differs in the type of glycosyl residue, and position and type of bond between those residues. In experiments I and II, participants were asked to discriminate a total of 9 stimuli [FOS, GOS, XOS; degree of polymerization (DP) of 2, 3, 4] prepared at 75 mM in the presence and absence of lactisole, a sweet receptor antagonist. We found that all 9 compounds were detectable (P < 0.05). We also found that GOS and XOS DP 4 were discriminable even with lactisole, suggesting that their detection was not via the canonical sweet receptor. Accordingly, in experiment III, the taste of GOS and XOS DP 4 were directly compared with that of MOS (maltooligosaccharides) DP 4-6, which has been reported to elicit “starchy” taste. We found that GOS and MOS were perceived similarly although narrowly discriminable, while XOS was easily discriminable from both GOS and MOS. The current findings suggest that the molecular structure of oligosaccharides impacts their taste perception in humans.
Mice learn to identify and discriminate sugar solutions based on odor cues
Authors: Glendinning John I , Archambeau Alix , Conlin Catherine , Drimmer Zoee , Griffith Gabriel , Isber Rayna , Koffler Kayla , Ortiz Gabriella , Prakash Anisha , Sollitto Catherine , Srinivasan Harini
Published: June 2024

This study examined how olfaction impacts ingestive responses of mice to sugar solutions. Experiment 1 asked whether naïve C57BL/6 (B6) mice could identify 1 M glucose, fructose, or sucrose solutions based on odor cues, during a 30-min 2-bottle acceptability test. We tested mice both before and after they were rendered anosmic with ZnSO4 treatment. We used 2 indirect measures of odor-mediated response: number of trials initiated and latency to initiate licking. Before ZnSO4 treatment, the mice learned how to identify 1 M glucose and fructose (but not sucrose) solutions based on odor cues. ZnSO4 treatment eliminated their ability to identify the glucose and fructose solutions. Experiment 2 asked whether 2 d of exposure to a 1 M glucose, fructose, or sucrose solution improved the identification of the same sugar solution. Following exposure, the B6 mice identified all 3 sugar solutions based on odor cues. Experiment 3 asked whether T1R3 knockout mice (i.e. mice lacking the T1R3 subunit of the T1R2 + R3 sweet taste receptor) could learn to discriminate 0.44 M glucose and fructose solutions based on odor cues. All mice were subjected to a 1-h preference test, both before and after exposure to the 0.44 M glucose and fructose solutions. During exposure, the experimental mice received ZnSO4 treatment, whereas the control mice received saline treatment. Before exposure, neither type of mouse preferred the glucose solution. After exposure, the control mice preferred the glucose solution, whereas the experimental mice did not. Our results reveal that mice can learn to use odor cues to identify and discriminate between sugar solutions.
Incident Tuberculosis Infection Is Associated With Alcohol Use in Adults in Rural Uganda
Authors: Abbott Rachel , Landsiedel Kirsten , Atukunda Mucunguzi , Puryear Sarah B , Chamie Gabriel , Hahn Judith A , Mwangwa Florence , Kakande Elijah , Petersen Maya L , Havlir Diane V , Charlebois Edwin , Balzer Laura B , Kamya Moses R , Marquez Carina
Published: June 2024

Data on alcohol use and incident tuberculosis (TB) infection are needed. In adults aged ≥15 in rural Uganda (N = 49 585), estimated risk of incident TB was 29.2% with alcohol use versus 19.2% without (RR: 1.49; 95%CI: 1.40–1.60). There is potential for interventions to interrupt transmission among people who drink alcohol.