bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast Simulation for the Super Charm-Tau Factory Detector
Authors: Barnyakov Alexander , Belozyorova Maria , Bobrovnikov Victor , Kononov Sergey , Kyshtymov Dmitriy , Maksimov Dmitry , Razuvaev Georgiy , Sukharev Andrey , Todyshev Korneliy , Vorobyev Vitaliy , Zhadan Anastasiia , Zhadan Daniil
Published: January 2024

The Super Charm-Tau factory (high luminosity electron-positron collider with 3–7 GeV center of mass energy range) experiment project is under development by the consortium of Russian scientific and education organizations. The article describes the present status of the Super Charm-Tau detector fast simulation and the algorithms on which it is based, example usage and demonstration of fast simulation results.
Collection of unconventional transport phenomena: natural obstacle or vibrant guiding principle for the design of molecular junctions?
Authors: Ren Jinlong , Li Tianchen , Li Zhuang , Kong Decheng , Shan Guangcun , Dou KunPeng
Published: January 2024

The real atomic scale details of molecular junctions would be of much complexity and can yield a plethora of “counterintuitive” results. Here, we provide an overview of four unconventional intentional or unintentional transport phenomena in molecular junctions, in particular, unconventional tunneling length-dependent transport behavior, deviation from Kirchhoff’s superposition law, dual roles of imperfect engineering, and masked quantum interference. These abnormal phenomena are not engaged in a dead end. On the contrary, it offers plenty of research opportunities in molecular electronics.
Impacts of compounding drought and heatwave events on child mental health: insights from a spatial clustering analysis
Authors: Sewell Kelly , Paul Sudeshna , De Polt Kelley , Sugg Maggie M. , Leeper Ronald D. , Rao Douglas , Runkle Jennifer D.
Published: January 2024

Background

Concurrent heatwave and drought events may have larger health impacts than each event separately; however, no US-based studies have examined differential mental health impacts of compound drought and heatwave events in pediatric populations.

Objective

To examine the spatial patterns of mood disorders and suicide-related emergency department (ED) visits in children during heatwave, drought, and compound heatwave and drought events. We tested whether the occurrence of compound heatwave and drought events have a synergistic (multiplicative) effect on the risk of mental health related outcomes in children as compared to the additive effect of each individual climate hazard. Lastly, we identified household and community-level determinants of geographic variability of high psychiatric burden.

Methods

Daily counts of psychiatric ED visits in North Carolina from 2016 to 2019 (May to Sept) for pediatric populations were aggregated at the county scale. Bernoulli cluster analyses identified high-risk spatial clusters of psychiatric morbidity during heatwave, drought, or compound heatwave and drought periods. Multivariate adaptive regression models examined the individual importance of household and community-level determinants in predicting high-risk clustering of mood disorders or suicidality across the three climate threats.

Results

Results showed significant spatial clustering of suicide and mood disorder risks in children during heatwave, drought, and compound event periods. Periods of drought were associated with the highest likelihood of spatial clustering for suicide and mood disorders, where the risk of an ED visit was 4.48 and 6.32 times higher, respectively, compared to non-drought periods. Compounding events were associated with a threefold increase in both suicide and mood disorder-related ED visits. Community and household vulnerability factors that most contributed to spatial clustering varied across climate hazards, but consistent determinants included residential segregation, green space availability, low English proficiency, overcrowding, no broadband access, no vehicle access, housing vacancy, and availability of housing units.

Conclusion

Findings advance understanding on the locations of vulnerable pediatric populations who are disproportionately exposed to compounding climate stressors and identify community resilience factors to target in public health adaptation strategies.
Design and testing of a Mini-RF plasma thruster with permanent magnets
Authors: Sun Yuzhe , Zhang Jikun , Zhang Zun
Published: January 2024

Compared with traditional electric propulsion, RF plasma thruster have attracted much attention due to their characteristics of no electrodes, long life, and high ionization rate. In recent years, the development of micro-nano satellites has put forward requirements for the miniaturization, modularization, and integration of satellite thrusters, and the miniaturization of RF plasma thrusters has a broad prospect. In this paper, a mini-RF plasma thruster with a discharge chamber inner diameter of 10 mm is designed, and a magnetic field is generated around it by two annular samarium cobalt permanent magnets. The discharge state and plasma parameters of the mini-RF thruster are tested using optical emission spectrometry (OES) and target thrust stand. In the experiment, we changed the flow rate of argon gas, the presence or absence of a magnetic field, the power of the RF source and analyzed the effects of these factors on the mode transition, plasma density, electron temperature, and thrust. According to the experimental results, it is found that the magnetic field (maximum strength 0.14T) helps to increase the plasma density at low power but delay the jump power threshold of the CCP-ICP.
Selective logging intensity and time since logging drive tropical bird and dung beetle diversity: a case study from Amazonia
Authors: França Filipe M , Beiroz Wallace , Andretti Christian B , Costa Thiago VV , Vaz-De-Mello Fernando Z , Silveira Juliana M , Louzada Julio
Published: January 2024

Understanding how selective logging affects biodiversity is crucial to planning cost-effective conservation strategies in tropical forests, yet there is limited understanding of its impacts on fauna functional diversity in the tropical Americas. We assessed how selective logging intensification and time since logging influence multiple metrics of fauna functional integrity in the Brazilian Amazon by collecting bird and dung beetle data within 48 logging management units that had experienced varying exploitation intensities between 1.5–2.0 and 5.0–6.0 years before the faunal surveys. We investigated assemblage responses and used functional attributes to assess changes in functional diversity, specialization, originality and species rarity. Using point counts and pitfall traps, we collected 5081 records of 182 bird species and 7892 dung beetles from 45 species. Logging intensification led to significant declines in most dung beetle responses and bird body mass, whereas time since logging was a key driver of dung beetle and bird functional and taxonomic diversity. Our study presents novel empirical evidence of how logging intensification effects vary across taxa, ecological metrics and time since logging, which is key to informing forest conservation and further investigating environmental degradation impacts on tropical biodiversity.
Predictors of early peritoneal dialysis initiation in newborns and young infants following cardiac surgery
Authors: Rivera-Figueroa Elvia , Ansari Md Abu Yusuf M , Mallory Emily Turner , Garg Padma , Onder Ali Mirza
Published: January 2024

Objective:

This single-centre, retrospective cohort study was conducted to investigate the predictors of early peritoneal dialysis initiation in newborns and young infants undergoing cardiac surgery.

Methods:

There were fifty-seven newborns and young infants. All subjects received peritoneal dialysis catheter after completion of the cardiopulmonary bypass. Worsening post-operative (post-op) positive fluid balance and oliguria (<1 ml/kg/hour) despite furosemide were the clinical indications to start early peritoneal dialysis (peritoneal dialysis +). Demographic, clinical, and laboratory data were collected from the pre-operative, intra-operative, and immediately post-operative periods.

Results:

Baseline demographic data were indifferent except that peritoneal dialysis + group had more newborns. Pre-operative serum creatinine was higher for peritoneal dialysis + group (p = 0.025). Peritoneal dialysis + group had longer cardiopulmonary bypass time (p = 0.044), longer aorta cross-clamp time (p = 0.044), and less urine output during post-op 24 hours (p = 0.008). In the univariate logistic regression model, pre-op serum creatinine was significantly associated with higher odds of being in peritoneal dialysis + (p = 0.021) and post-op systolic blood pressure (p = 0.018) and post-op mean arterial pressure (p=0.001) were significantly associated with reduced odds of being in peritoneal dialysis + (p = 0.018 and p = 0.001, respectively). Post-op mean arterial pressure showed a statistically significant association adjusted odds ratio = 0.89, 95% confidence interval [0.81, 0.96], p = 0.004) with peritoneal dialysis + in multivariate analysis after adjusting for age at surgery.

Conclusions:

In our single-centre cohort, pre-op serum creatinine, post-op systolic blood pressure, and mean arterial pressure demonstrated statistically significant association with peritoneal dialysis +. This finding may help to better risk stratify newborns and young infants for early peritoneal dialysis start following cardiac surgery.
Measurement Equivalence of the English, German, and French Versions	of the Strike Attitude and Behavioral Reactions Scale (SABeRS)
Authors: Vesper Denise , König Cornelius J.
Published: January 2024

Abstract: Strikes are an important phenomenon in the working world. Nevertheless, cross-cultural psychological research on strikes has been limited as appropriate scales were missing. Recently, a scale to determine third-party attitudes and behavioral reactions was introduced: the Strike Attitude and Behavioral Reactions Scale (SABeRS). The applicability of this scale is currently limited to a German context, as it was developed in German. We thus decided to extend the applicability to other languages, that is, English and French. To test the measurement equivalence of the SABeRS, we used a British ( n = 444), a German ( n = 454), and a French sample ( n = 463) and ran multigroup confirmatory factor analyses. Based on multi-group CFA and alignment optimization analyses, the scale was found to be at least partially measurement equivalent between the groups. The five factors were consistently confirmed in all samples. Overall, this study indicates that the SABeRS is psychometrically solid and that it is measurement-equivalent in English, German, and French samples.
Intensified Structural Overshoot Aggravates Drought Impacts on Dryland Ecosystems
Authors: Zhang Yixuan , Liu Liu , Cheng Yongming , Kang Shaozhong , Li Hao , Wang Lixin , Shi Yu , Liu Xingcai , Cheng Lei
Published: January 2024

A favorable environment can induce vegetation overgrowth to exceed the ecosystem carrying capacity, exacerbating water resource depletion and increasing the risk of lagged effects on vegetation degradation. This phenomenon is defined as structural overshoot, which can lead to large‐scale forest mortality and grassland deterioration. However, the current understanding of structural overshoot remains incomplete due to the complex time‐varying interactions between vegetation and climate. Here, we used a dynamic learning algorithm to decompose the contributions of vegetation and climate to drought occurrence, trace the connection between antecedent and concurrent vegetation dynamics, thus effectively capturing structural overshoot. This study focused on the climate‐sensitive hotspot in Northwest China drylands, where significant vegetation greening induced by a warming and wetting climate was detected during 1982–2015, leading to soil moisture deficit and aggravating vegetation degradation risks during droughts. We found that during this period, structural overshoot induced approximately 34.6% of the drought events, and lagged effects accounted for 16.7% of the vegetation degradation for these overshoot drought events. The occurrence of overshoot droughts exhibited an increasing trend over time, which was primarily driven by vegetation overgrowth followed by precipitation variation. Although the severity of overshoot and non‐overshoot droughts were generally comparable in spatial distribution, the impact of overshoot droughts is still becoming increasingly obvious. Our results indicate that the expected intensified overshoot droughts cannot be ignored and emphasize the necessity of sustainable agroecosystem management strategies.
Basal Mantle Flow Over LLSVPs Explains Differences in Pacific and Indo‐Atlantic Hotspot Motions
Authors: Bellas‐Manley A. , Royden L.
Published: January 2024

Surface hotspot motions are approximately a factor of two faster in the Pacific than the Indo‐Atlantic, and the Indo‐Atlantic large low shear velocity province (LLSVP) appears to be significantly taller than the Pacific LLSVP. Hypothesizing that surface hotspot motions are correlated with the motion of plume sources on the upper surface of chemically distinct, intrinsically dense LLSVPs, we use 3D spherical mantle convection models to compute the velocity of plume sources and compare with observed surface hotspot motions. No contrast in the mean speed of Pacific and Indo‐Atlantic hotspots is predicted if the LLSVPs are treated as purely thermal anomalies and plume sources move laterally across the core‐mantle boundary. However, when LLSVP topography is included in the model, the predicted hotspot speeds are, on average, faster in the Pacific than the Indo‐Atlantic, even when modest topography is assigned to both LLSVPs (e.g., 100–300 km). The difference in mean hotspot speed increases to a factor of two for larger and laterally variable LLSVP topography estimated from seismic tomographic model S40RTS (up to 1,100–1,500 km for the Indo‐Atlantic region vs. 700–1,400 km for the Pacific region) and our results also broadly reproduce the convergence of Pacific hotspots toward the center of the Pacific LLSVP. These largescale features of global hotspot motions are only reproduced when ambient mantle material flows over large, relatively stable topographical features, suggesting that LLSVPs are chemically distinct and intrinsically dense relative to ambient mantle material.
Enhancing single-cell encapsulation in droplet microfluidics with fine-tunable on-chip sample enrichment
Authors: Tang Tao , Zhao Hao , Shen Shaofei , Yang Like , Lim Chwee Teck
Published: January 2024

Single-cell encapsulation in droplet microfluidics is commonly hindered by the tradeoff between cell suspension density and on-chip focusing performance. In this study, we introduce a novel droplet microfluidic chip to overcome this challenge. The chip comprises a double spiral focusing unit, a flow resistance-based sample enrichment module with fine-tunable outlets, and a crossflow droplet generation unit. Utilizing a low-density cell/bead suspension (2 × 106 objects/mL), cells/beads are focused into a near-equidistant linear arrangement within the double spiral microchannel. The excess water phase is diverted while cells/beads remain focused and sequentially encapsulated in individual droplets. Focusing performance was assessed through numerical simulations and experiments at three flow rates (40, 60, 80 μL/min), demonstrating successful focusing at 40 and 80 μL/min for beads and cells, respectively. In addition, both simulation and experimental results revealed that the flow resistance at the sample enrichment module is adjustable by punching different outlets, allowing over 50% of the aqueous phase to be removed. YOLOv8n-based droplet detection algorithms realized the counting of cells/beads in droplets, statistically demonstrating single-cell and bead encapsulation rates of 72.2% and 79.2%, respectively. All the results indicate that this on-chip sample enrichment approach can be further developed and employed as a critical component in single-cell encapsulation in water-in-oil droplets.
Shear bond strength of a RMGIC for orthodontic bracket bonding to enamel
Authors: Boudrot Maureen , François Philippe , Abdel-Gawad Sarah , Attal Jean-Pierre , Dantagnan Claire-Adeline
Published: January 2024

Objective

To evaluate the shear bond strength (SBS) of a restorative resin-modified glass ionomer cement (RMGIC) for orthodontic bracket bonding.

Materials and methods

One hundred twenty-one human teeth were randomly divided into 11 groups (n = 11) according to the surface treatment applied (H3PO4 ± Transbond Plus (TSEP) or Scotchbond Universal (SU)), and the adhesive used (Riva LC HV (RIVA), Fuji Ortho (FUJI), and Transbond XT (TXT)). For each sample, a metal button was bonded. SBS tests were performed at 1 week and debonded specimens were observed for failure modes determination. One-way ANOVA followed by Tukey’s post hoc test was used to compare SBS differences and Fisher’s exact test to analyze the failure modes (p < 0.05).

Results

TSEP + FUJI and H3PO4 + SU + TXT showed the highest SBS values while H3PO4 + TSEP + RIVA showed the lowest value. Cohesive failure and mixed failure were found in the groups with SU and TXT and adhesive failure in the other groups.

Discussion/Conclusions

The bonding of orthodontic attachments to enamel could be performed with any of the three materials studied. The use of a universal adhesive in the bonding protocol could optimize the adhesion values. Clinical studies would be needed to confirm the results obtained.
Transient inhibition of 53BP1 increases the frequency of targeted integration in human hematopoietic stem and progenitor cells
Authors: Baik Ron , Cromer M. Kyle , Glenn Steve E. , Vakulskas Christopher A. , Chmielewski Kay O. , Dudek Amanda M. , Feist William N. , Klermund Julia , Shipp Suzette , Cathomen Toni , Dever Daniel P. , Porteus Matthew H.
Published: January 2024

Genome editing by homology directed repair (HDR) is leveraged to precisely modify the genome of therapeutically relevant hematopoietic stem and progenitor cells (HSPCs). Here, we present a new approach to increasing the frequency of HDR in human HSPCs by the delivery of an inhibitor of 53BP1 (named “i53”) as a recombinant peptide. We show that the use of i53 peptide effectively increases the frequency of HDR-mediated genome editing at a variety of therapeutically relevant loci in HSPCs as well as other primary human cell types. We show that incorporating the use of i53 recombinant protein allows high frequencies of HDR while lowering the amounts of AAV6 needed by 8-fold. HDR edited HSPCs were capable of long-term and bi-lineage hematopoietic reconstitution in NSG mice, suggesting that i53 recombinant protein might be safely integrated into the standard CRISPR/AAV6-mediated genome editing protocol to gain greater numbers of edited cells for transplantation of clinically meaningful cell populations.
Pervasive associations between dark septate endophytic fungi with tree root and soil microbiomes across Europe
Authors: Netherway Tarquin , Bengtsson Jan , Buegger Franz , Fritscher Joachim , Oja Jane , Pritsch Karin , Hildebrand Falk , Krab Eveline J. , Bahram Mohammad
Published: January 2024

Trees interact with a multitude of microbes through their roots and root symbionts such as mycorrhizal fungi and root endophytes. Here, we explore the role of fungal root symbionts as predictors of the soil and root-associated microbiomes of widespread broad-leaved trees across a European latitudinal gradient. Our results suggest that, alongside factors such as climate, soil, and vegetation properties, root colonization by ectomycorrhizal, arbuscular mycorrhizal, and dark septate endophytic fungi also shapes tree-associated microbiomes. Notably, the structure of root and soil microbiomes across our sites is more strongly and consistently associated with dark septate endophyte colonization than with mycorrhizal colonization and many abiotic factors. Root colonization by dark septate endophytes also has a consistent negative association with the relative abundance and diversity of nutrient cycling genes. Our study not only indicates that root-symbiotic interactions are an important factor structuring soil communities and functions in forest ecosystems, but also that the hitherto less studied dark septate endophytes are likely to be central players in these interactions.
Universal machine learning aided synthesis approach of two-dimensional perovskites in a typical laboratory
Authors: Wu Yilei , Wang Chang-Feng , Ju Ming-Gang , Jia Qiangqiang , Zhou Qionghua , Lu Shuaihua , Gao Xinying , Zhang Yi , Wang Jinlan
Published: January 2024

The past decade has witnessed the significant efforts in novel material discovery in the use of data-driven techniques, in particular, machine learning (ML). However, since it needs to consider the precursors, experimental conditions, and availability of reactants, material synthesis is generally much more complex than property and structure prediction, and very few computational predictions are experimentally realized. To solve these challenges, a universal framework that integrates high-throughput experiments, a priori knowledge of chemistry, and ML techniques such as subgroup discovery and support vector machine is proposed to guide the experimental synthesis of materials, which is capable of disclosing structure-property relationship hidden in high-throughput experiments and rapidly screening out materials with high synthesis feasibility from vast chemical space. Through application of our approach to challenging and consequential synthesis problem of 2D silver/bismuth organic-inorganic hybrid perovskites, we have increased the success rate of the synthesis feasibility by a factor of four relative to traditional approaches. This study provides a practical route for solving multidimensional chemical acceleration problems with small dataset from typical laboratory with limited experimental resources available.
T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors
Authors: Middelburg Jim , Sluijter Marjolein , Schaap Gaby , Göynük Büşra , Lloyd Katy , Ovcinnikovs Vitalijs , Zom Gijs G. , Marijnissen Renoud J. , Groeneveldt Christianne , Griffioen Lisa , Sandker Gerwin G. W. , Heskamp Sandra , van der Burg Sjoerd H. , Arakelian Tsolere , Ossendorp Ferry , Arens Ramon , Schuurman Janine , Kemper Kristel , van Hall Thorbald
Published: January 2024

CD3 bispecific antibody (CD3 bsAb) therapy is clinically approved for refractory hematological malignancies, but responses in solid tumors have been limited so far. One of the main hurdles in solid tumors is the lack of sufficient T-cell infiltrate. Here, we show that pre-treatment vaccination, even when composed of tumor-unrelated antigens, induces CXCR3-mediated T-cell influx in immunologically ‘cold’ tumor models in male mice. In the absence of CD3 bsAb, the infiltrate is confined to the tumor invasive margin, whereas subsequent CD3 bsAb administration induces infiltration of activated effector CD8 T cells into the tumor cell nests. This combination therapy installs a broadly inflamed Th1-type tumor microenvironment, resulting in effective tumor eradication. Multiple vaccination formulations, including synthetic long peptides and viruses, empower CD3 bsAb therapy. Our results imply that eliciting tumor infiltration with vaccine-induced tumor-(un)related T cells can greatly improve the efficacy of CD3 bsAbs in solid tumors.
More than 17,000 tree species are at risk from rapid global change
Authors: Boonman Coline C. F. , Serra-Diaz Josep M. , Hoeks Selwyn , Guo Wen-Yong , Enquist Brian J. , Maitner Brian , Malhi Yadvinder , Merow Cory , Buitenwerf Robert , Svenning Jens-Christian
Published: January 2024

Trees are pivotal to global biodiversity and nature’s contributions to people, yet accelerating global changes threaten global tree diversity, making accurate species extinction risk assessments necessary. To identify species that require expert-based re-evaluation, we assess exposure to change in six anthropogenic threats over the last two decades for 32,090 tree species. We estimated that over half (54.2%) of the assessed species have been exposed to increasing threats. Only 8.7% of these species are considered threatened by the IUCN Red List, whereas they include more than half of the Data Deficient species (57.8%). These findings suggest a substantial underestimation of threats and associated extinction risk for tree species in current assessments. We also map hotspots of tree species exposed to rapidly changing threats around the world. Our data-driven approach can strengthen the efforts going into expert-based IUCN Red List assessments by facilitating prioritization among species for re-evaluation, allowing for more efficient conservation efforts.
Mapping causal links between prefrontal cortical regions and
intra-individual behavioral variability
Authors: Alizadeh Mansouri Farshad , Buckley Mark J. , Tanaka Keiji
Published: January 2024

Intra-individual behavioral variability is significantly heightened by
aging or neuropsychological disorders, however it is unknown which brain regions are
causally linked to such variabilities. We examine response time (RT) variability in
21 macaque monkeys performing a rule-guided decision-making task. In monkeys with
selective-bilateral lesions in the anterior cingulate cortex (ACC) or in the
dorsolateral prefrontal cortex, cognitive flexibility is impaired, but the RT
variability is significantly diminished. Bilateral lesions within the frontopolar
cortex or within the mid-dorsolateral prefrontal cortex, has no significant effect
on cognitive flexibility or RT variability. In monkeys with lesions in the posterior
cingulate cortex, the RT variability significantly increases without any deficit in
cognitive flexibility. The effect of lesions in the orbitofrontal cortex (OFC) is
unique in that it leads to deficits in cognitive flexibility and a significant
increase in RT variability. Our findings indicate remarkable dissociations in
contribution of frontal cortical regions to behavioral variability. They suggest
that the altered variability in OFC-lesioned monkeys is related to deficits in
assessing and accumulating evidence to inform a rule-guided decision, whereas in
ACC-lesioned monkeys it results from a non-adaptive decrease in decision threshold
and consequently immature impulsive responses.
Dopamine release in human associative striatum during reversal learning
Authors: Grill Filip , Guitart-Masip Marc , Johansson Jarkko , Stiernman Lars , Axelsson Jan , Nyberg Lars , Rieckmann Anna
Published: January 2024

The dopaminergic system is firmly implicated in reversal learning but human measurements of dopamine release as a correlate of reversal learning success are lacking. Dopamine release and hemodynamic brain activity in response to unexpected changes in action-outcome probabilities are here explored using simultaneous dynamic [11C]Raclopride PET-fMRI and computational modelling of behavior. When participants encounter reversed reward probabilities during a card guessing game, dopamine release is observed in associative striatum. Individual differences in absolute reward prediction error and sensitivity to errors are associated with peak dopamine receptor occupancy. The fMRI response to perseverance errors at the onset of a reversal spatially overlap with the site of dopamine release. Trial-by-trial fMRI correlates of absolute prediction errors show a response in striatum and association cortices, closely overlapping with the location of dopamine release, and separable from a valence signal in ventral striatum. The results converge to implicate striatal dopamine release in associative striatum as a central component of reversal learning, possibly signifying the need for increased cognitive control when new stimuli-responses should be learned.
Optogenetic spatial patterning of cooperation in yeast populations
Authors: Le Bec Matthias , Pouzet Sylvain , Cordier Céline , Barral Simon , Scolari Vittore , Sorre Benoit , Banderas Alvaro , Hersen Pascal
Published: January 2024

Microbial communities are shaped by complex metabolic interactions such as cooperation and competition for resources. Methods to control such interactions could lead to major advances in our ability to better engineer microbial consortia for synthetic biology applications. Here, we use optogenetics to control SUC2 invertase production in yeast, thereby shaping spatial assortment of cooperator and cheater cells. Yeast cells behave as cooperators (i.e., transform sucrose into hexose, a public good) upon blue light illumination or cheaters (i.e., consume hexose produced by cooperators to grow) in the dark. We show that cooperators benefit best from the hexoses they produce when their domain size is constrained between two cut-off length-scales. From an engineering point of view, the system behaves as a bandpass filter. The lower limit is the trace of cheaters’ competition for hexoses, while the upper limit is defined by cooperators’ competition for sucrose. Cooperation mostly occurs at the frontiers with cheater cells, which not only compete for hexoses but also cooperate passively by letting sucrose reach cooperators. We anticipate that this optogenetic method could be applied to shape metabolic interactions in a variety of microbial ecosystems.
Surplus fatty acid synthesis increases oxidative stress in adipocytes and induces lipodystrophy
Authors: Weng Li , Tang Wen-Shuai , Wang Xu , Gong Yingyun , Liu Changqin , Hong Ni-Na , Tao Ying , Li Kuang-Zheng , Liu Shu-Ning , Jiang Wanzi , Li Ying , Yao Ke , Chen Li , Huang He , Zhao Yu-Zheng , Hu Ze-Ping , Lu Youli , Ye Haobin , Du Xingrong , Zhou Hongwen , Li Peng , Zhao Tong-Jin
Published: January 2024

Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.
Sub-Doppler optical-optical double-resonance spectroscopy using
a cavity-enhanced frequency comb probe
Authors: Silva de Oliveira Vinicius , Silander Isak , Rutkowski Lucile , Soboń Grzegorz , Axner Ove , Lehmann Kevin K. , Foltynowicz Aleksandra
Published: January 2024

Accurate parameters of molecular hot-band transitions, i.e., those
starting from vibrationally excited levels, are needed to accurately model
high-temperature spectra in astrophysics and combustion, yet laboratory spectra
measured at high temperatures are often unresolved and difficult to assign.
Optical-optical double-resonance (OODR) spectroscopy allows the measurement and
assignment of individual hot-band transitions from selectively pumped energy levels
without the need to heat the sample. However, previous demonstrations lacked either
sufficient resolution, spectral coverage, absorption sensitivity, or frequency
accuracy. Here we demonstrate OODR spectroscopy using a cavity-enhanced frequency
comb probe that combines all these advantages. We detect and assign sub-Doppler
transitions in the spectral range of the
3ν3 ← ν3 resonance of methane with
frequency precision and sensitivity more than an order of magnitude better than
before. This technique will provide high-accuracy data about excited states of a
wide range of molecules that is urgently needed for theoretical modeling of
high-temperature data and cannot be obtained using other methods.
Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia
Authors: Pervizaj-Oruqaj Learta , Selvakumar Balachandar , Ferrero Maximiliano Ruben , Heiner Monika , Malainou Christina , Glaser Rolf David , Wilhelm Jochen , Bartkuhn Marek , Weiss Astrid , Alexopoulos Ioannis , Witte Biruta , Gattenlöhner Stefan , Vadász István , Morty Rory Edward , Seeger Werner , Schermuly Ralph Theo , Vazquez-Armendariz Ana Ivonne , Herold Susanne
Published: January 2024

Influenza A virus (IAV) infection mobilizes bone marrow-derived macrophages (BMDM) that gradually undergo transition to tissue-resident alveolar macrophages (TR-AM) in the inflamed lung. Combining high-dimensional single-cell transcriptomics with complex lung organoid modeling, in vivo adoptive cell transfer, and BMDM-specific gene targeting, we found that transitioning (“regenerative”) BMDM and TR-AM highly express Placenta-expressed transcript 1 (Plet1). We reveal that Plet1 is released from alveolar macrophages, and acts as important mediator of macrophage-epithelial cross-talk during lung repair by inducing proliferation of alveolar epithelial cells and re-sealing of the epithelial barrier. Intratracheal administration of recombinant Plet1 early in the disease course attenuated viral lung injury and rescued mice from otherwise fatal disease, highlighting its therapeutic potential.
Asymmetric α-benzylation of cyclic ketones enabled by concurrent chemical aldol condensation and biocatalytic reduction
Authors: Liu Yunting , Ma Teng , Guo Zhongxu , Zhou Liya , Liu Guanhua , He Ying , Ma Li , Gao Jing , Bai Jing , Hollmann Frank , Jiang Yanjun
Published: January 2024

Chemoenzymatic cascade catalysis has emerged as a revolutionary tool for streamlining traditional retrosynthetic disconnections, creating new possibilities for the asymmetric synthesis of valuable chiral compounds. Here we construct a one-pot concurrent chemoenzymatic cascade by integrating organobismuth-catalyzed aldol condensation with ene-reductase (ER)-catalyzed enantioselective reduction, enabling the formal asymmetric α-benzylation of cyclic ketones. To achieve this, we develop a pair of enantiocomplementary ERs capable of reducing α-arylidene cyclic ketones, lactams, and lactones. Our engineered mutants exhibit significantly higher activity, up to 37-fold, and broader substrate specificity compared to the parent enzyme. The key to success is due to the well-tuned hydride attack distance/angle and, more importantly, to the synergistic proton-delivery triade of Tyr28-Tyr69-Tyr169. Molecular docking and density functional theory (DFT) studies provide important insights into the bioreduction mechanisms. Furthermore, we demonstrate the synthetic utility of the best mutants in the asymmetric synthesis of several key chiral synthons.
Quantifying negative selection in human 3ʹ UTRs uncovers constrained targets of RNA-binding proteins
Authors: Findlay Scott D. , Romo Lindsay , Burge Christopher B.
Published: January 2024

Many non-coding variants associated with phenotypes occur in 3ʹ untranslated regions (3ʹ UTRs), and may affect interactions with RNA-binding proteins (RBPs) to regulate gene expression post-transcriptionally. However, identifying functional 3ʹ UTR variants has proven difficult. We use allele frequencies from the Genome Aggregation Database (gnomAD) to identify classes of 3ʹ UTR variants under strong negative selection in humans. We develop intergenic mutability-adjusted proportion singleton (iMAPS), a generalized measure related to MAPS, to quantify negative selection in non-coding regions. This approach, in conjunction with in vitro and in vivo binding data, identifies precise RBP binding sites, miRNA target sites, and polyadenylation signals (PASs) under strong selection. For each class of sites, we identify thousands of gnomAD variants under selection comparable to missense coding variants, and find that sites in core 3ʹ UTR regions upstream of the most-used PAS are under strongest selection. Together, this work improves our understanding of selection on human genes and validates approaches for interpreting genetic variants in human 3ʹ UTRs.
Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1
Authors: Ren Wenfeng , Xu Zilong , Chang Yating , Ju Fei , Wu Hongning , Liang Zhiqi , Zhao Min , Wang Naizhen , Lin Yanhua , Xu Chenhang , Chen Shengming , Rao Yipeng , Lin Chaolong , Yang Jianxin , Liu Pingguo , Zhang Jun , Huang Chenghao , Xia Ningshao
Published: January 2024

PD-1 is a co-inhibitory receptor expressed by CD8+ T cells which limits their cytotoxicity. PD-L1 expression on cancer cells contributes to immune evasion by cancers, thus, understanding the mechanisms that regulate PD-L1 protein levels in cancers is important. Here we identify tumor-cell-expressed otubain-2 (OTUB2) as a negative regulator of antitumor immunity, acting through the PD-1/PD-L1 axis in various human cancers. Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum. Genetic deletion of OTUB2 markedly decreases the expression of PD-L1 proteins on the tumor cell surface, resulting in increased tumor cell sensitivity to CD8+ T-cell-mediated cytotoxicity. To underscore relevance in human patients, we observe a significant correlation between OTUB2 expression and PD-L1 abundance in human non-small cell lung cancer. An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth. Together, these results reveal the roles of OTUB2 in PD-L1 regulation and tumor evasion and lays down the proof of principle for OTUB2 targeting as therapeutic strategy for cancer treatment.
Competition between inside-out unfolding and pathogenic aggregation in an amyloid-forming β-propeller
Authors: Saccuzzo Emily G. , Mebrat Mubark D. , Scelsi Hailee F. , Kim Minjoo , Ma Minh Thu , Su Xinya , Hill Shannon E. , Rheaume Elisa , Li Renhao , Torres Matthew P. , Gumbart James C. , Van Horn Wade D. , Lieberman Raquel L.
Published: January 2024

Studies of folded-to-misfolded transitions using model protein systems reveal a range of unfolding needed for exposure of amyloid-prone regions for subsequent fibrillization. Here, we probe the relationship between unfolding and aggregation for glaucoma-associated myocilin. Mutations within the olfactomedin domain of myocilin (OLF) cause a gain-of-function, namely cytotoxic intracellular aggregation, which hastens disease progression. Aggregation by wild-type OLF (OLFWT) competes with its chemical unfolding, but only below the threshold where OLF loses tertiary structure. Representative moderate (OLFD380A) and severe (OLFI499F) disease variants aggregate differently, with rates comparable to OLFWT in initial stages of unfolding, and variants adopt distinct partially folded structures seen along the OLFWT urea-unfolding pathway. Whether initiated with mutation or chemical perturbation, unfolding propagates outward to the propeller surface. In sum, for this large protein prone to amyloid formation, the requirement for a conformational change to promote amyloid fibrillization leads to direct competition between unfolding and aggregation.
Observation and manipulation of quantum interference in a superconducting Kerr parametric oscillator
Authors: Iyama Daisuke , Kamiya Takahiko , Fujii Shiori , Mukai Hiroto , Zhou Yu , Nagase Toshiaki , Tomonaga Akiyoshi , Wang Rui , Xue Jiao-Jiao , Watabe Shohei , Kwon Sangil , Tsai Jaw-Shen
Published: January 2024

Quantum tunneling is the phenomenon that makes superconducting circuits “quantum”. Recently, there has been a renewed interest in using quantum tunneling in phase space of a Kerr parametric oscillator as a resource for quantum information processing. Here, we report a direct observation of quantum interference induced by such tunneling and its dynamics in a planar superconducting circuit through Wigner tomography. We experimentally elucidate all essential properties of this quantum interference, such as mapping from Fock states to cat states, a temporal oscillation due to the pump detuning, as well as its characteristic Rabi oscillations and Ramsey fringes. Finally, we perform gate operations as manipulations of the observed quantum interference. Our findings lay the groundwork for further studies on quantum properties of superconducting Kerr parametric oscillators and their use in quantum information technologies.
MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation
Authors: Chi Wenna , Kang Na , Sheng Linlin , Liu Sichen , Tao Lei , Cao Xizhi , Liu Ye , Zhu Can , Zhang Yuming , Wu Bolong , Chen Ruiqun , Cheng Lili , Wang Jing , Sun Xiaolin , Liu Xiaohui , Deng Haiteng , Yang Jinliang , Li Zhanguo , Liu Wanli , Chen Ligong
Published: January 2024

Monocarboxylate transporter 1 (MCT1) exhibits essential roles in cellular metabolism and energy supply. Although MCT1 is highly expressed in activated B cells, it is not clear how MCT1-governed monocarboxylates transportation is functionally coupled to antibody production during the glucose metabolism. Here, we report that B cell-lineage deficiency of MCT1 significantly influences the class-switch recombination (CSR), rendering impaired IgG antibody responses in Mct1f/fMb1Cre mice after immunization. Metabolic flux reveals that glucose metabolism is significantly reprogrammed from glycolysis to oxidative phosphorylation in Mct1-deficient B cells upon activation. Consistently, activation-induced cytidine deaminase (AID), is severely suppressed in Mct1-deficient B cells due to the decreased level of pyruvate metabolite. Mechanistically, MCT1 is required to maintain the optimal concentration of pyruvate to secure the sufficient acetylation of H3K27 for the elevated transcription of AID in activated B cells. Clinically, we found that MCT1 expression levels are significantly upregulated in systemic lupus erythematosus patients, and Mct1 deficiency can alleviate the symptoms of bm12-induced murine lupus model. Collectively, these results demonstrate that MCT1-mediated pyruvate metabolism is required for IgG antibody CSR through an epigenetic dependent AID transcription, revealing MCT1 as a potential target for vaccine development and SLE disease treatment.
Hijacking of internal calcium dynamics by intracellularly residing viral rhodopsins
Authors: Eria-Oliveira Ana-Sofia , Folacci Mathilde , Chassot Anne Amandine , Fedou Sandrine , Thézé Nadine , Zabelskii Dmitrii , Alekseev Alexey , Bamberg Ernst , Gordeliy Valentin , Sandoz Guillaume , Vivaudou Michel
Published: January 2024

Rhodopsins are ubiquitous light-driven membrane proteins with diverse functions, including ion transport. Widely distributed, they are also coded in the genomes of giant viruses infecting phytoplankton where their function is not settled. Here, we examine the properties of OLPVR1 (Organic Lake Phycodnavirus Rhodopsin) and two other type 1 viral channelrhodopsins (VCR1s), and demonstrate that VCR1s accumulate exclusively intracellularly, and, upon illumination, induce calcium release from intracellular IP3-dependent stores. In vivo, this light-induced calcium release is sufficient to remote control muscle contraction in VCR1-expressing tadpoles. VCR1s natively confer light-induced Ca2+ release, suggesting a distinct mechanism for reshaping the response to light of virus-infected algae. The ability of VCR1s to photorelease calcium without altering plasma membrane electrical properties marks them as potential precursors for optogenetics tools, with potential applications in basic research and medicine.
Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis
Authors: Hong Jingjing , Li Tingting , Chao Yulin , Xu Yidan , Zhu Zhini , Zhou Zixuan , Gu Weijie , Qu Qianhui , Li Dianfan
Published: January 2024

The secretion and quality control of glycosylphosphatidylinositol-anchored proteins (GPI-APs) necessitates post-attachment remodeling initiated by the evolutionarily conserved PGAP1, which deacylates the inositol in nascent GPI-APs. Impairment of PGAP1 activity leads to developmental diseases in humans and fatality and infertility in animals. Here, we present three PGAP1 structures (2.66−2.84 Å), revealing its 10-transmembrane architecture and product-enzyme interaction details. PGAP1 holds GPI-AP acyl chains in an optimally organized, guitar-shaped cavity with apparent energetic penalties from hydrophobic-hydrophilic mismatches. However, abundant glycan-mediated interactions in the lumen counterbalance these repulsions, likely conferring substrate fidelity and preventing off-target hydrolysis of bulk membrane lipids. Structural and biochemical analyses uncover a serine hydrolase-type catalysis with atypical features and imply mechanisms for substrate entrance and product release involving a drawing compass movement of GPI-APs. Our findings advance the mechanistic understanding of GPI-AP remodeling.
Molecular basis of human trace amine-associated receptor 1 activation
Authors: Zilberg Gregory , Parpounas Alexandra K. , Warren Audrey L. , Yang Shifan , Wacker Daniel
Published: January 2024

The human trace amine-associated receptor 1 (hTAAR1, hTA1) is a key regulator of monoaminergic neurotransmission and the actions of psychostimulants. Despite preclinical research demonstrating its tractability as a drug target, its molecular mechanisms of activation remain unclear. Moreover, poorly understood pharmacological differences between rodent and human TA1 complicate the translation of findings from preclinical disease models into novel pharmacotherapies. To elucidate hTA1’s mechanisms on the molecular scale and investigate the underpinnings of its divergent pharmacology from rodent orthologs, we herein report the structure of the human TA1 receptor in complex with a Gαs heterotrimer. Our structure reveals shared structural elements with other TAARs, as well as with its closest monoaminergic orthologue, the serotonin receptor 5-HT4R. We further find that a single mutation dramatically shifts the selectivity of hTA1 towards that of its rodent orthologues, and report on the effects of substituting residues to those found in serotonin and dopamine receptors. Strikingly, we also discover that the atypical antipsychotic medication and pan-monoaminergic antagonist asenapine potently and efficaciously activates hTA1. Together our studies provide detailed insight into hTA1 structure and function, contrast its molecular pharmacology with that of related receptors, and uncover off-target activities of monoaminergic drugs at hTA1.
Purely self-rectifying memristor-based passive crossbar array for artificial neural network accelerators
Authors: Jeon Kanghyeok , Ryu Jin Joo , Im Seongil , Seo Hyun Kyu , Eom Taeyong , Ju Hyunsu , Yang Min Kyu , Jeong Doo Seok , Kim Gun Hwan
Published: January 2024

Memristor-integrated passive crossbar arrays (CAs) could potentially accelerate neural network (NN) computations, but studies on these devices are limited to software-based simulations owing to their poor reliability. Herein, we propose a self-rectifying memristor-based 1 kb CA as a hardware accelerator for NN computations. We conducted fully hardware-based single-layer NN classification tasks involving the Modified National Institute of Standards and Technology database using the developed passive CA, and achieved 100% classification accuracy for 1500 test sets. We also investigated the influences of the defect-tolerance capability of the CA, impact of the conductance range of the integrated memristors, and presence or absence of selection functionality in the integrated memristors on the image classification tasks. We offer valuable insights into the behavior and performance of CA devices under various conditions and provide evidence of the practicality of memristor-integrated passive CAs as hardware accelerators for NN applications.