bluuebunny/crossref_metadata_2025 huggingface dataset:
Populus alba cationic cell-wall-bound peroxidase (CWPO-C) regulates the plant growth and affects auxin concentration in Arabidopsis thaliana
Authors: Yoshikay-Benitez Diego Alonso , Yokoyama Yusuke , Ohira Kaori , Fujita Koki , Tomiie Azusa , Kijidani Yoshio , Shigeto Jun , Tsutsumi Yuji
Published: October 2022

The poplar cationic cell-wall-bound peroxidase (CWPO-C) mediates the oxidative polymerization of lignin precursors, especially sinapyl alcohols, and high molecular weight compounds that cannot be oxidized by other plant peroxidases, including horseradish peroxidase C. Therefore, CWPO-C is believed to be a lignification-specific peroxidase, but direct evidence of its function is lacking. Thus, the CWPO-C expression pattern in Arabidopsis thaliana (Arabidopsis) was determined using the β-glucuronidase gene as a reporter. Our data indicated that CWPO-C  was expressed in young organs, including the meristem, leaf, root, flower, and young xylem in the upper part of the stem. Compared with the wild-type control, transgenic Arabidopsis plants overexpressing CWPO-C had shorter stems. Approximately 60% of the plants in the transgenic line with the highest CWPO-C content had curled stems. These results indicate that CWPO-C plays a role in cell elongation. When plants were placed horizontally, induced CWPO-C expression was detected in the curved part of the stem during the gravitropic response. The stem curvature associated with gravitropism is controlled by auxin localization. The time needed for Arabidopsis plants overexpressing CWPO-C placed horizontally to bend by 90° was almost double the time required for the similarly treated wild-type controls. Moreover, the auxin content was significantly lower in the CWPO-C-overexpressing plants than in the wild-type plants. These results strongly suggest that CWPO-C has pleiotropic effects on plant growth and indole-3-acetic acid (IAA) accumulation. These effects may be mediated by altered IAA concentration due to oxidation.
A Program for Developing Some Motor Skills for Down Syndrome Children Using Music
Authors: Mazeed Huda M.
Published: October 2022

The current study presents a rhythmic music program to acquire some motor skills for children with Down syndrome. The research sample was taken from one of the specialized Down syndrome learning centers for children, and the sample was taken in a random manner. The sample of children consisted of 20 boys and girls and divided into experimental and control groups. The researcher also prepared a list of the appropriate motor skills for these children (walking, running, jumping, throwing), in addition to the motor skills scale to determine the effectiveness of the proposed program. The results were statistically analyzed using the analysis of covariance, where pre-test serving as a covariate. The results indicated an improvement in the performance of all motor activities under study for the children of the experimental group compared to the control group, and this confirms the extent of the positive impact of the musical rhythmic program for these children, which affects the children positively in the performance of their motor.
Delayed gastric emptying is associated with increased risk of mortality in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma
Authors: Dominguez Oscar Hernandez , Grigorian Areg , Wolf Ronald F. , Imagawa David K. , Nahmias Jeffry T. , Jutric Zeljka
Published: October 2022

Delayed gastric emptying (DGE) is common in patients undergoing pancreaticoduodenectomy (PD). The effect of DGE on mortality is less clear. We sought to identify predictors of mortality in patients undergoing PD for pancreatic adenocarcinoma hypothesizing DGE to independently increase risk of 30-day mortality. The ACS-NSQIP targeted pancreatectomy database (2014–2017) was queried for patients with pancreatic adenocarcinoma undergoing PD. A multivariable logistic regression analysis was performed. Separate sensitivity analyses were performed adjusting for postoperative pancreatic fistula (POPF) grades A–C. Out of 8011 patients undergoing PD, 1246 had DGE (15.6%). About 8.5% of patients with DGE had no oral intake by postoperative day-14. The DGE group had a longer median operative duration (373 vs. 362 min, p = 0.019), and a longer hospital length of stay (16.5 vs. 8 days, p < 0.001). After adjusting for age, gender, comorbidities, preoperative chemotherapy, preoperative radiation, open versus laparoscopic approach, vascular resection, deep surgical space infection (DSSI), postoperative percutaneous drain placement, and development of a POPF, DGE was associated with an increased risk for 30-day mortality (OR 3.25, 2.16–4.88, p < 0.001). On sub-analysis, grades A and B POPF were not associated with risk of mortality while grade C POPF was associated with increased risk of mortality (OR 5.64, 2.24–14.17, p < 0.001). The rate of DGE in patients undergoing PD in this large database was over 15%. DGE is associated with greater than three times the increased associated risk of mortality, even when controlling for POPF, DSSI, and other known predictors of mortality.
Implementation of a patient blood management in an Italian City Hospital: is it effective in reducing the use of red blood cells?
Authors: Ercolani Giorgio , Solaini Leonardo , D’Acapito Fabrizio , Isopi Claudio , Pacilio Carlo Alberto , Moretti Cinzia , Agostini Vanessa , Cucchetti Alessandro
Published: October 2022

To evaluate the effect of patient blood management (PBM) since its introduction, we analyzed the need for transfusion and the outcomes in patients undergoing abdominal surgery for different types of tumor pre- and post-PBM. Patients undergoing elective gastric, liver, pancreatic, and colorectal surgery between 2017 and 2020 were included. The implementation of the PBM program was completed on May 1, 2018. The patients were grouped as follows: those who underwent surgery before the implementation of the program (pre-PBM) versus after the implementation (post-PBM). A total of 1302 patients were included in the analysis (445 pre-PBM vs. 857 post-PBM). The number of transfused patients per year decreased significantly after the introduction of PBM. A strong tendency for a decreased incidence of transfusion was evident in gastric and pancreatic surgery and a similar decrease was statistically significant in liver surgery. With regard to gastric surgery, a single-unit transfusion scheme was used more frequently in the post-PBM group (7.7% vs. 55% after PBM; p = 0.049); this was similar in liver surgery (17.6% vs. 58.3% after PBM; p = 0.04). Within the subgroup of patients undergoing liver surgery, a significant reduction in the use of blood transfusion (20.5% vs. 6.7%; p = 0.002) and a decrease in the Hb trigger for transfusion (8.5, 8.2–9.5 vs. 8.2, 7.7–8.4 g/dl; p = 0.039) was reported after the PBM introduction. After the implementation of a PBM protocol, a significant reduction in the number of patients receiving blood transfusion was demonstrated, with a strong tendency to minimize the use of blood products for most types of oncologic surgery.
Avoidant-restrictive food intake disorder in a male patient with Goldenhar syndrome
Authors: Bergonzini Luca , Pruccoli Jacopo , Parmeggiani Antonia
Published: October 2022

Background

Goldenhar syndrome (GS) is a rare congenital condition characterized by the underdevelopment of structures deriving from the first and second branchial arches. Clinical phenotype might encompass extra-craniofacial abnormalities, and patients may experience neuropsychiatric disorders with a higher prevalence than healthy controls. To the best of our knowledge, an association between GS and Feeding and Eating Disorders (FED) has never been reported in the literature.

Case report

A 15-year-old boy with GS was referred to our outpatient clinic due to severe underweight (BMI of 12.7 kg/m2) and food intake disorder with avoidant restrictive features. After a diagnosis of avoidant-restrictive food intake disorder (ARFID) was made, an inpatient multidisciplinary intervention and outpatient follow-up program were provided, which resulted in the improvement of the boy’s weight and FED psychopathology.

Conclusions

The current report describes the first case of a young male with GS and ARFID. We suggest that ARFID may present itself as part of the spectrum of neuropsychiatric disorders associated with the syndrome; since traumatic experiences and gastrointestinal discomfort play a pivotal role in the development of ARFID among children, attention should be paid to those affected by GS that involves crucial structures in the swallowing process. Further literature evidence will help portray the complex relationship between ARFID and GS more precisely.

Level of evidence

Level V, case report.
An automatic inversion approach for magnetic data applying the global bat optimization algorithm (GBOA): application to ore deposits and basement rock intrusion
Authors: Essa Khalid S. , Diab Zein E.
Published: October 2022

Recently, metaheuristic approaches are frequently used to the potential data inversion (i.e., magnetic data) as a global optimizing approach. In the present study, we proposed a global optimizing bat algorithm (GOBA) that based on bat echolocation behavior to obtain globally optimal solutions (best parameters) of magnetic anomalies. The best determined source parameters were picked at the suggested minimum objective function. The proposed GOBA approach does not require prior information and represents an effective technique of surveying the entire domain of the raw data to evaluate sources optimal parameters. The GOBA approach is employed to magnetic data profiles to determine the characteristic source attributes (i.e. the vertical depths to the center of the anomalous structures, the magnitude of amplitude coefficients, the sources origin, the approximated geometric form factors, and the effective angles of magnetization). The GOBA approach can be applied to single and multiple anomaly structures in the restricted categories of basic geometric shapes (spheres, cylinders, sheets, and dikes). The stability, constancy, and performance of the given GOBA approach are achieved on different purely and contaminated examples for individual and double sources. Besides, the introduced GOBA approach has been fruitfully utilized to three field datasets from Turkey, Canada, and Senegal for ore deposit and basement rock intrusion investigations. Overall, the recovered inversion results from the GOBA approach are in high correlation with the available drill-holes, geologic data, and scholarly articles outcomes. Finally, the provided metaheuristic GOBA approach is a simple, accurate, and powerful technique for magnetic data interpretation.

Article highlights

An automatic approach for magnetic data interpretation to investigate the ore deposits and sustainable resources such as volcanic and basement rock intrusions based on bat echolocation behavior to obtain the global optimal solutions.

In this study we built 2D models aims to image of the interior of the subsurface to investigate their natural resources, for example minerals & ore deposits and rock intrusions, helping in understand their concentration and the distribution location, including the depth to their sources.

We came to the conclusion that the suggested approach is useful in ore & mineral research, the reconnaissance geological studies and can be extend to the volcanic activity & geothermal exploration studies in the future.
A Multi-level Mesh Mutual Attention Model for Visual Question Answering
Authors: Lei Zhi , Zhang Guixian , Wu Lijuan , Zhang Kui , Liang Rongjiao
Published: October 2022

Visual question answering is a complex multimodal task involving images and text, with broad application prospects in human–computer interaction and medical assistance. Therefore, how to deal with the feature interaction and multimodal feature fusion between the critical regions in the image and the keywords in the question is an important issue. To this end, we propose a neural network based on the encoder–decoder structure of the transformer architecture. Specifically, in the encoder, we use multi-head self-attention to mine word–word connections within question features and stack multiple layers of attention to obtain multi-level question features. We propose a mutual attention module to perform information exchange between modalities for better question features and image features representation on the decoder side. Besides, we connect the encoder and decoder in a meshed manner, perform mutual attention operations with multi-level question features, and aggregate information in an adaptive way. We propose a multi-scale fusion module in the fusion stage, which utilizes feature information at different scales to complete modal fusion. We test and validate the model effectiveness on VQA v1 and VQA v2 datasets. Our model achieves better results than state-of-the-art methods.
Training Teachers to Teach Probability: A Promising Research Area
Authors: Batanero Carmen
Published: October 2022

In this commentary, I reflect on the relevant role that the education of teachers imply to assure a successful teaching of probability at school levels. Unfortunately, research on this issue is still scarce. In this sense, the four papers included in this section are welcome because they approach this research problem from different perspectives. I analyse these perspectives using the Didactic-Mathematics Knowledge and Competences Model (CCDM) developed at the University of Granada, Spain.
Art and Environmental Struggle Curating an Exhibition About Place‐Rooted Ecological Knowledge
Authors: Avril Ellen , Weislogel Andrew C. , Frankel Kate Addleman , Yearsley Elizabeth , Chu Jumay
Published: October 2022

Inspired by ecological calendars, the Herbert F. Johnson Museum of Art organized the exhibition Art and Environmental Struggle to coincide with the international conference Rhythms of the Land: Indigenous Knowledge, Science, and Thriving Together in a Changing Climate, held at Cornell University in October 2021. The exhibition emphasized Indigenous ways of knowing and deployed the works of lesser‐known artists from around the world to build greater understanding of and empathy for their communities' often overlooked histories and perspectives. A collaboration of three Johnson Museum curators and an expert on global Indigenous art, the exhibition presented 20 works by artists responding to environmental challenges occurring in their countries and communities and was conceived as part of the program of conference events that culminated in the dance, music, and video work Blood, Water, Earth created and performed by Santee Smith. Emphasizing impacts of colonialism, neocolonialism, geopolitical forces, and industries, the artworks reveal the consequences of environmental damage on the food production, security, cultural independence, and general well‐being of communities who have contributed the least to the current crisis but feel its effects most acutely. The concept of struggle for environmental justice binds together all the visual artists represented in Art and Environmental Struggle. When viewed in the context of the ecological calendar model, the compelling ways in which visual and performing artists confront these topics through an expression of Indigenous ecological knowledge, environmental stewardship, and place‐rooted traditions, present a diverse but resilient perspective and offer a methodology of hope to address this most pressing of issues.
Integrated Dynamics‐Physics Coupling for Weather to Climate Models: GFDL SHiELD With In‐Line Microphysics
Authors: Zhou Linjiong , Harris Lucas
Published: November 2022

We propose an integrated dynamics‐physics coupling framework for weather and climate‐scale models. Each physical parameterization would be advanced on its natural time scale, revise the thermodynamics to include moist effects, and finally integrated into the relevant components of the dynamical core. We show results using a cloud microphysics scheme integrated within the dynamical core of the Geophysical Fluid Dynamics Laboratory System for High‐resolution prediction on Earth‐to‐Local Domains weather model to demonstrate the promise of this concept. We call it the in‐line microphysics as it is in‐lined within the dynamical core. Statistics gathered from 1 year of weather forecasts show significantly better prediction skills when the model is upgraded to use the in‐line microphysics. However, we do find that some biases are degraded with the in‐line microphysics. The in‐line microphysics also shows larger‐amplitude and higher‐frequency variations in cloud structures within a tropical cyclone than the traditionally‐coupled microphysics. Finally, we discuss the prospects for further development of this integrated dynamics‐physics coupling.
Influence of Planetary Surface Temperature on the Tectonic Transition From Heat Pipes
Authors: Basu Sarkar Debajyoti , Moore William B.
Published: November 2022

Heat transport from the interior to the surface of a terrestrial body dictates the deformation experienced by the lithosphere. Terrestrial bodies with high internal heating rates exhibit heat‐pipe volcanism because subsolidus convection within the mantle has a limit to the amount of heat it can transport without extensive melting. Using numerical simulations, we investigate the lithospheric deformation associated with the global‐scale volcanism on such bodies. Specifically, we study the role of surface temperature and activation energy of mantle rocks while analyzing and characterizing this global deformation—as a terrestrial planet transitions out of heat pipes. We find that increased surface temperature extends the duration of heat‐pipe volcanism, and plate tectonics highly depends on the temperature sensitivity of mantle viscosity. Our findings suggest that a terrestrial planet with a hot surface will develop a thick lithosphere, and thus transition into a stagnant lid tectonic regime following heat pipes.
Laboratory Investigation of Hydraulic Fracture Growth in Zimbabwe Gabbro
Authors: Liu Dong , Lecampion Brice
Published: October 2022

Direct measurement of the apparent toughness evolution during hydraulic fracture growth remains challenging in rocks due to the difficulty of measuring the time evolution of the fracture geometry. We report hydraulic fracturing tests performed in 250 × 250 × 250 mm Zimbabwe gabbro under different confining stress. Using time‐lapse active acoustic surveys, we reconstruct the fracture front and fracture width using scattered and transmitted waves. After verifying that hydraulic fracture growth is dominated by the energy dissipated in fracture creation such that the fluid pressure can be considered spatially uniform in the fracture (negligible viscous flow energy dissipation), we estimate the apparent fracture toughness, using the theory of linear hydraulic fracture mechanics, by combining fracture geometry and pressure data. The apparent fracture energy is higher than that measured from semicircular bending tests. The created fractures evolve in a planar and radial geometry at the macroscopic scale, but we observe overlapping segments and bridges at the millimetric scale. This complex segmentation at a scale on par with the rock grain size is likely responsible for the observed higher fracture energy at centimetric scale. Such fracture segmentation and bridging will necessarily occur when encountering heterogeneities and result in a further increase of fracture energy at a larger scale even if the overall macroscopic geometry remains planar. The experimental data set reported here should guide modeling efforts necessary to better predict hydraulic fracture growth in rock masses.
A Biological‐Parameter‐Optimized Modeling Study of Physical Drivers Controlling Seasonal Chlorophyll Blooms off the Southern Coast of Java Island
Authors: Gao Guandong , Yang Dezhou , Xu Lingjing , Zhang Kun , Feng Xingru , Yin Baoshu
Published: October 2022

A physical‐biogeochemical model consists of many key parameters; theoretically, 10,000 or more numerical experiments are required to obtain a set of optimal biological parameters. The corresponding computing resources are too expensive when running a three‐dimensional and high‐resolution physical‐biogeochemical model. In this study, we improve the performance of a three‐dimensional physical‐biogeochemical model via the conditional nonlinear optimal perturbation method for southern Java Island, where chlorophyll blooms occur seasonally. Based on the improved model results, we calculated the mixed‐layer nutrient budget, thereby characterizing how each physical process transports nutrients into the surface oligotrophic layer and then stimulates the chlorophyll blooms during the southeast monsoon season. Nutrients that upwell along the submarine slope are found in narrow regions along the coast and spread into most of the study area by local wind‐induced offshore transport. The contribution of nonlinearity (advection) is essential to modulating the upslope movement of nutrients off the coast. If local winds are neglected in the model, onshore transport induced by the pressure gradient force in the zonal direction (alongshore) and subsequent downwelling would be dominant, and chlorophyll blooms would diminish in most regions. The role of the South Java Coastal Current varies under the joint influence of remote and local wind forcings. The Indonesian Throughflow from the Lombok Strait also contributes to surface phytoplankton growth along its path off the south of Java Island.
Effects of prophylactic indomethacin on morbidity and mortality in infants <25 weeks’ gestation: a protocol driven intention to treat analysis
Authors: Clyman Ronald I. , Hills Nancy K.
Published: October 2022

Objective

To determine if prophylactic indomethacin (PINDO) decreases death or bronchopulmonary dysplasia-grades 2 and 3 (death/BPD) in newborns <25 weeks.

Study design

Intention-to-treat, cohort-controlled study of 106 infants admitted during three alternating epochs of PINDO or Expectant patent ductus arteriosus (PDA) management.

Results

At 7–8 days 85% of Expectant Management epoch infants had a moderate/large PDA (median exposure was 23 days). Among PINDO epoch infants only 24% still had a PDA at 7–8 days. There were no significant differences in the incidence of death/BPD or of secondary outcomes (BPD, death, necrotizing enterocolitis/spontaneous perforations, or intraventricular hemorrhage (grades 3 or 4)) in either unadjusted or adjusted comparisons between infants born in a PINDO epoch and those born in the Expectant Management epoch.

Conclusion

Despite being at high risk for PDA-related morbidities, PINDO did not appear to alter the rates of our primary and secondary outcomes in infants <25 weeks.
Inhibition of CD40-TRAF6-dependent inflammatory activity halts the onset of diabetic retinopathy in streptozotocin-diabetic mice
Authors: Howell Scott J. , Lee Chieh A. , Zapadka Thomas E. , Lindstrom Sarah I. , Taylor Brooklyn E. , Taylor Zakary R. R. , Barber Katherine G. , Taylor Patricia R.
Published: October 2022

Diabetes initiates inflammation that can impair the retinal vasculature, and lead to diabetic retinopathy; one of the leading causes of blindness. Inflammatory pathways have been examined as potential therapeutic targets for diabetic retinopathy, but there is still a need for early-stage treatments. We hypothesized that the CD40-TNF Receptor Associated Factor 6 (TRAF6) axis plays a pivotal role in the onset of diabetic retinopathy, and that the CD40-TRAF6 axis would be a prime therapeutic target for early-stage non-proliferative diabetic retinopathy. The CD40-TRAF6 complex can initiate NFκB activation, inflammation, and tissue damage. Further, CD40 and TRAF6 are constitutively expressed on Muller glia, and upregulated in the diabetic retina. Yet the role of the CD40-TRAF6 complex in the onset of diabetic retinopathy is still unclear. In the current study, we examined the CD40-TRAF6 axis in diabetic retinopathy using a small molecule inhibitor (SMI-6877002) on streptozotocin-induced diabetic mice. When CD40-TRAF6-dependent inflammation was inhibited, retinal vascular leakage and capillary degeneration was ameliorated in diabetic mice. Collectively, these data suggest that the CD40-TRAF6 axis plays a pivotal role in the onset of diabetic retinopathy, and could be a novel therapeutic target for early diabetic retinopathy.
Glioblastoma cell motility depends on enhanced oxidative stress coupled with mobilization of a sulfurtransferase
Authors: Saurty-Seerunghen Mirca S. , Daubon Thomas , Bellenger Léa , Delaunay Virgile , Castro Gloria , Guyon Joris , Rezk Ahmed , Fabrega Sylvie , Idbaih Ahmed , Almairac Fabien , Burel-Vandenbos Fanny , Turchi Laurent , Duplus Eric , Virolle Thierry , Peyrin Jean-Michel , Antoniewski Christophe , Chneiweiss Hervé , El-Habr Elias A. , Junier Marie-Pierre
Published: October 2022

Cell motility is critical for tumor malignancy. Metabolism being an obligatory step in shaping cell behavior, we looked for metabolic weaknesses shared by motile cells across the diverse genetic contexts of patients’ glioblastoma. Computational analyses of single-cell transcriptomes from thirty patients’ tumors isolated cells with high motile potential and highlighted their metabolic specificities. These cells were characterized by enhanced mitochondrial load and oxidative stress coupled with mobilization of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase (MPST). Functional assays with patients’ tumor-derived cells and -tissue organoids, and genetic and pharmacological manipulations confirmed that the cells depend on enhanced ROS production and MPST activity for their motility. MPST action involved protection of protein cysteine residues from damaging hyperoxidation. Its knockdown translated in reduced tumor burden, and a robust increase in mice survival. Starting from cell-by-cell analyses of the patients’ tumors, our work unravels metabolic dependencies of cell malignancy maintained across heterogeneous genomic landscapes.
Inducing forgetting of unwanted memories through subliminal reactivation
Authors: Zhu Zijian , Anderson Michael C. , Wang Yingying
Published: October 2022

Processes that might facilitate the forgetting of unwanted experiences typically require the actual or imagined re-exposure to reminders of the event, which is aversive and carries risks to people. But it is unclear whether awareness of aversive content is necessary for effective voluntary forgetting. Disrupting hippocampal function through retrieval suppression induces an amnesic shadow that impairs the encoding and stabilization of unrelated memories that are activated near in time to people’s effort to suppress retrieval. Building on this mechanism, here we successfully disrupt retention of unpleasant memories by subliminally reactivating them within this amnesic shadow. Critically, whereas unconscious forgetting occurs on these affective memories, the amnesic shadow itself is induced by conscious suppression of unrelated and benign neutral memories, avoiding conscious re-exposure of unwelcome content. Combining the amnesic shadow with subliminal reactivation may offer a new approach to voluntary forgetting that bypasses the unpleasantness in conscious exposure to unwanted memories.
Mendelian randomization accounting for complex correlated horizontal pleiotropy while elucidating shared genetic etiology
Authors: Cheng Qing , Zhang Xiao , Chen Lin S. , Liu Jin
Published: October 2022

Mendelian randomization (MR) harnesses genetic variants as instrumental variables (IVs) to study the causal effect of exposure on outcome using summary statistics from genome-wide association studies. Classic MR assumptions are violated when IVs are associated with unmeasured confounders, i.e., when correlated horizontal pleiotropy (CHP) arises. Such confounders could be a shared gene or inter-connected pathways underlying exposure and outcome. We propose MR-CUE (MR with Correlated horizontal pleiotropy Unraveling shared Etiology and confounding), for estimating causal effect while identifying IVs with CHP and accounting for estimation uncertainty. For those IVs, we map their cis-associated genes and enriched pathways to inform shared genetic etiology underlying exposure and outcome. We apply MR-CUE to study the effects of interleukin 6 on multiple traits/diseases and identify severalS100genes involved in shared genetic etiology. We assess the effects of multiple exposures on type 2 diabetes across European and East Asian populations.
Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context
Authors: Setten Elisa , Castagna Alessandra , Nava-Sedeño Josué Manik , Weber Jonathan , Carriero Roberta , Reppas Andreas , Volk Valery , Schmitz Jessica , Gwinner Wilfried , Hatzikirou Haralampos , Feuerhake Friedrich , Locati Massimo
Published: October 2022

Fibrosis is a progressive biological condition, leading to organ dysfunction in various clinical settings. Although fibroblasts and macrophages are known as key cellular players for fibrosis development, a comprehensive functional model that considers their interaction in the metabolic/immunologic context of fibrotic tissue has not been set up. Here we show, by transcriptome-based mathematical modeling in an in vitro system that represents macrophage-fibroblast interplay and reflects the functional effects of inflammation, hypoxia and the adaptive immune context, that irreversible fibrosis development is associated with specific combinations of metabolic and inflammatory cues. The in vitro signatures are in good alignment with transcriptomic profiles generated on laser captured glomeruli and cortical tubule-interstitial area, isolated from human transplanted kidneys with advanced stages of glomerulosclerosis and interstitial fibrosis/tubular atrophy, two clinically relevant conditions associated with organ failure in renal allografts. The model we describe here is validated on tissue based quantitative immune-phenotyping of biopsies from transplanted kidneys, demonstrating its feasibility. We conclude that the combination of in vitro and in silico modeling represents a powerful systems medicine approach to dissect fibrosis pathogenesis, applicable to specific pathological conditions, and develop coordinated targeted approaches.
Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis
Authors: Muto Yoshiharu , Dixon Eryn E. , Yoshimura Yasuhiro , Wu Haojia , Omachi Kohei , Ledru Nicolas , Wilson Parker C. , King Andrew J. , Eric Olson N. , Gunawan Marvin G. , Kuo Jay J. , Cox Jennifer H. , Miner Jeffrey H. , Seliger Stephen L. , Woodward Owen M. , Welling Paul A. , Watnick Terry J. , Humphreys Benjamin D.
Published: October 2022

Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end stage renal disease characterized by progressive expansion of kidney cysts. To better understand the cell types and states driving ADPKD progression, we analyze eight ADPKD and five healthy human kidney samples, generating single cell multiomic atlas consisting of ~100,000 single nucleus transcriptomes and ~50,000 single nucleus epigenomes. Activation of proinflammatory, profibrotic signaling pathways are driven by proximal tubular cells with a failed repair transcriptomic signature, proinflammatory fibroblasts and collecting duct cells. We identify GPRC5A as a marker for cyst-lining collecting duct cells that exhibits increased transcription factor binding motif availability for NF-κB, TEAD, CREB and retinoic acid receptors. We identify and validate a distal enhancer regulating GPRC5A expression containing these motifs. This single cell multiomic analysis of human ADPKD reveals previously unrecognized cellular heterogeneity and provides a foundation to develop better diagnostic and therapeutic approaches.
Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data
Authors: Chen Junyi , Wang Xiaoying , Ma Anjun , Wang Qi-En , Liu Bingqiang , Li Lang , Xu Dong , Ma Qin
Published: October 2022

Drug screening data from massive bulk gene expression databases can be analyzed to determine the optimal clinical application of cancer drugs. The growing amount of single-cell RNA sequencing (scRNA-seq) data also provides insights into improving therapeutic effectiveness by helping to study the heterogeneity of drug responses for cancer cell subpopulations. Developing computational approaches to predict and interpret cancer drug response in single-cell data collected from clinical samples can be very useful. We propose scDEAL, a deep transfer learning framework for cancer drug response prediction at the single-cell level by integrating large-scale bulk cell-line data. The highlight in scDEAL involves harmonizing drug-related bulk RNA-seq data with scRNA-seq data and transferring the model trained on bulk RNA-seq data to predict drug responses in scRNA-seq. Another feature of scDEAL is the integrated gradient feature interpretation to infer the signature genes of drug resistance mechanisms. We benchmark scDEAL on six scRNA-seq datasets and demonstrate its model interpretability via three case studies focusing on drug response label prediction, gene signature identification, and pseudotime analysis. We believe that scDEAL could help study cell reprogramming, drug selection, and repurposing for improving therapeutic efficacy.
Accelerated water activation and stabilized metal-organic framework via constructing triangular active-regions for ampere-level current density hydrogen production
Authors: Cheng Fanpeng , Peng Xianyun , Hu Lingzi , Yang Bin , Li Zhongjian , Dong Chung-Li , Chen Jeng-Lung , Hsu Liang-Ching , Lei Lecheng , Zheng Qiang , Qiu Ming , Dai Liming , Hou Yang
Published: October 2022

Two-dimensional metal-organic frameworks (MOFs) have been explored as effective electrocatalysts for hydrogen evolution reaction (HER). However, the sluggish water activation kinetics and structural instability under ultrahigh-current density hinder their large-scale industrial applications. Herein, we develop a universal ligand regulation strategy to build well-aligned Ni-benzenedicarboxylic acid (BDC)-based MOF nanosheet arrays with S introducing (S-NiBDC). Benefiting from the closerp-band center to the Fermi level with strong electron transferability, S-NiBDC array exhibits a low overpotential of 310 mV to attain 1.0 A cm−2with high stability in alkaline electrolyte. We speculate the newly-constructed triangular “Ni2-S1” motif as the improved HER active region based on detailed mechanism analysis and structural characterization, and the enhanced covalency of Ni-O bonds by S introducing stabilizes S-NiBDC structure. Experimental observations and theoretical calculations elucidate that such Ni sites in “Ni2-S1” center distinctly accelerate the water activation kinetics, while the S site readily captures the H atom as the optimal HER active site, boosting the whole HER activity.
A warm-white light-emitting diode based on single-component emitter aromatic carbon nitride
Authors: Wang Yunhu , Wang Kunpeng , Dai Fangxu , Zhang Kai , Tang Haifeng , Wang Lei , Xing Jun
Published: October 2022

Artificial lighting consumes almost one-fifth of global electricity. As an efficient solid-state lighting technology, white light-emitting diodes (WLEDs) have received increasing attention. However, the white luminescence of the traditional WLEDs comes from multi-component emitters, which leads to complex device structure and unstable emitting color. Therefore, developing single-component materials with white-light electroluminescence is of significance for artificial lighting applications. Here, we fabricate single-component white-light electroluminescence devices based on an aromatic carbon nitride material and improve the performance of WLEDs by adjusting the carrier transport. The carbon nitride LEDs emit warm-white light, of which color coordinates and color temperature are (0.44, 0.52) and 3700 K. The optimized LEDs display a very low turn-on voltage of 3.2 V and achieve a milestone in the maximum luminance and external quantum efficiency of 1885 cd m−2 and 1.20%. Our findings demonstrate the low-cost carbon nitride materials have promising potential for single-component WLEDs application.
Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures
Authors: Kim Junhong , Yunn Na-Oh , Park Mangeun , Kim Jihan , Park Seongeun , Kim Yoojoong , Noh Jeongeun , Ryu Sung Ho , Cho Yunje
Published: October 2022

Activation of insulin receptor (IR) initiates a cascade of conformational changes and autophosphorylation events. Herein, we determined three structures of IR trapped by aptamers using cryo-electron microscopy. The A62 agonist aptamer selectively activates metabolic signaling. In the absence of insulin, the two A62 aptamer agonists of IR adopt an insulin-accessible arrowhead conformation by mimicking site-1/site-2’ insulin coordination. Insulin binding at one site triggers conformational changes in one protomer, but this movement is blocked in the other protomer by A62 at the opposite site. A62 binding captures two unique conformations of IR with a similar stalk arrangement, which underlie Tyr1150 mono-phosphorylation (m-pY1150) and selective activation for metabolic signaling. The A43 aptamer, a positive allosteric modulator, binds at the opposite side of the insulin-binding module, and stabilizes the single insulin-bound IR structure that brings two FnIII-3 regions into closer proximity for full activation. Our results suggest that spatial proximity of the two FnIII-3 ends is important for m-pY1150, but multi-phosphorylation of IR requires additional conformational rearrangement of intracellular domains mediated by coordination between extracellular and transmembrane domains.
A missense variant in the nuclear localization signal of DKC1 causes Hoyeraal-Hreidarsson syndrome
Authors: Chu Chia-Mei , Yu Hsin-Hui , Kao Tsai-Ling , Chen Yi-Hsuan , Lu Hsuan-Hsuan , Wu En-Ting , Yang Yun-Li , Lin Chin-Hsien , Lin Shin-Yu , Tsai Meng-Ju Melody , Chien Yin-Hsiu , Hwu Wuh-Liang , Chen Wen-Pin , Lee Ni-Chung , Tseng Chi-Kang
Published: October 2022

Hoyeraal-Hreidarsson syndrome (HHS) is the most severe form of dyskeratosis congenita (DC) and is caused by mutations in genes involved in telomere maintenance. Here, we identified male siblings from a family with HHS carrying a hemizygous mutation (c.1345C > G, p.R449G), located in the C-terminal nuclear localization signal (NLS) of the DKC1 gene. These patients exhibit progressive cerebellar hypoplasia, recurrent infections, pancytopenia due to bone marrow failure, and short leukocyte telomere lengths. Single-cell RNA sequencing analysis suggested defects in the NLRP3 inflammasome in monocytes and the activation and maturation of NK cells and B cells. In experiments using induced pluripotent stem cells (iPSCs) from patients, DKC1_R449G iPSCs had short telomere lengths due to reduced levels of human telomerase RNA (hTR) and increased cytosolic proportions of DKC1. Treatment with dihydroquinolizinone RG7834 and 3′deoxyanosine cordycepin rescued telomere length in patient-derived iPSCs. Together, our findings not only provide new insights into immunodeficiency in DC patients but also provide treatment options for telomerase insufficiency disorders.
Lightweight and flexible Cu(In,Ga)Se2 solar minimodules: toward 20% photovoltaic efficiency and beyond
Authors: Ishizuka Shogo , Kamikawa Yukiko , Nishinaga Jiro
Published: October 2022

Lightweight and flexible photovoltaic solar cells and modules are promising technologies that may result in the wide usage of light-to-electricity energy conversion devices. This communication presents the prospects of Cu(In,Ga)Se2(CIGS)-based lightweight and flexible photovoltaic devices. The current status of flexible CIGS minimodules with photovoltaic efficiency values greater than 18% and future directions to enhance their efficiency values toward >20% are discussed. The effects of cell separation edges, which are formed through a mechanical, laser, or photolithography scribing process used to fabricate solar cells and modules, on the device performance are also discussed. We found that mechanically scribed CIGS device edges, which are present in conventional solar cells and modules, cause deterioration of device performance. In other words, further improvement is expected with appropriate passivation/termination treatment of the edges or replacing mechanical scribing with a damage-free separation process.
Nonreciprocal charge transport in topological superconductor candidate Bi2Te3/PdTe2 heterostructure
Authors: Masuko Makoto , Kawamura Minoru , Yoshimi Ryutaro , Hirayama Motoaki , Ikeda Yuya , Watanabe Ryota , He James Jun , Maryenko Denis , Tsukazaki Atsushi , Takahashi Kei S. , Kawasaki Masashi , Nagaosa Naoto , Tokura Yoshinori
Published: October 2022

In a hybrid system of topological insulator (TI)/superconductor (SC), the proximity-induced topological superconductivity is expected to appear at the interface. Here we propose and demonstrate that a TI/SC hybrid Bi2Te3/PdTe2 heterostructure serves as a platform for exploring topological superconductivity with various features: all made of tellurium compounds, epitaxial growth, and a small charge transfer interface. In the Bi2Te3/PdTe2 heterostructure films, we observe large nonreciprocal charge transport near the superconducting transition temperature under a transverse in-plane magnetic field. The observation indicates the interplay between the topological surface state and superconductivity, suggesting that the Bi2Te3/PdTe2 heterostructure is a candidate for a topological superconductor. Also observed is an unexpected sign reversal of the nonreciprocal coefficient when the in-plane magnetic field is slightly tilted toward the out-of-plane direction. The analysis reveals that the sign reversal occurs with the change of dominant vortex type, that is, the change from spontaneous vortices to external-field induced ones.
Increases in multiple resources promote competitive ability of naturalized non-native plants
Authors: Zhang Zhijie , Liu Yanjie , Hardrath Angelina , Jin Huifei , van Kleunen Mark
Published: October 2022

Invasion by non-native plants is frequently attributed to increased resource availability. Still, our understanding is mainly based on effects of single resources and on plants grown without competition despite the fact that plants rely on multiple resources and usually grow in competition. How multiple resources affects competition between native and non-native plants remains largely unexplored. Here, with two similar common garden experiments, one in China and one in Germany, we tested whether nutrient and light availabilities affected the competitive outcomes, in terms of biomass production, between native and naturalized non-native plants. We found that under low resource availability or with addition of only one type of resource non-natives were not more competitive than natives. However, with a joint increase of nutrients and light intensity, non-natives were more competitive than natives. Our finding indicates that addition of multiple resources could greatly reduce the niche dimensionality (i.e. number of limiting factors), favoring dominance of non-native species. It also indicates that habitats experiencing multiple global changes might be more vulnerable to plant invasion.
Honing-in antigen-specific cells during antibody discovery: a user-friendly process to mine a deeper repertoire
Authors: Mahendra Ankit , Haque Aftabul , Prabakaran Ponraj , Mackness Brian C. , Fuller Thomas P. , Liu Xiaohua , Kathuria Sagar V. , Wang Yui-Hsi , Amatya Nilesh , Yu Xiaocong , Hopke Joern , Hoffmann Dietmar , Bric-Furlong Eva , Zhang Ningning , Cho Hyun-Suk , Zhang Ruijun , Sancho Jose , Saleh Jacqueline , Rao Sambasiva P. , Wendt Maria , Chowdhury Partha S.
Published: October 2022

Immunization based antibody discovery is plagued by the paucity of antigen-specific B cells. Identifying these cells is akin to finding needle in a haystack. Current and emerging technologies while effective, are limited in terms of capturing the antigen-specific repertoire. We report on the bulk purification of antigen-specific B-cells and the benefits it offers to various antibody discovery platforms. Using five different antigens, we show hit rates of 51–88%, compared to about 5% with conventional methods. We also show that this purification is highly efficient with loss of only about 2% antigen specific cells. Furthermore, we compared clones in which cognate chains are preserved with those from display libraries in which chains either from total B cells (TBC) or antigen-specific B cells (AgSC) underwent combinatorial pairing. We found that cognate chain paired clones and combinatorial clones from AgSC library had higher frequency of functional clones and showed greater diversity in sequence and paratope compared to clones from the TBC library. This antigen-specific B-cell selection technique exemplifies a process improvement with reduced cycle time and cost, by removing undesired clones prior to screening and increasing the chance of capturing desirable and rare functional clones in the repertoire.
Orbital-scale dynamic vegetation feedback caused the Holocene precipitation decline in northern China
Authors: Li Xinzhou , Liu Xiaodong , Pan Zaitao , Xie Xiaoning , Shi Zhengguo , Wang Zhaosheng , Bai Aijuan
Published: October 2022

Proxy-based reconstructed precipitation in northern China shows a peak in the mid-Holocene (7800–5300 years BP) followed by a declining trend until the present day. Most studies attributed this decline to the decrease in Northern Hemisphere summer insolation and weakening of the East Asian summer monsoon. However, the details of the drying mechanisms still remain elusive. Here we explore the drivers of this drying trend in northern China using two transient experiments, one that includes dynamic vegetation and one that does not. The experiment with dynamic vegetation successfully captured the slight increase in precipitation in the early mid-Holocene as well as the rapid decline of precipitation in the late mid-Holocene, whereas the experiment without dynamic vegetation predicted no change in precipitation. Specifically, in the dynamic-vegetation experiment, vegetation cover increased over time, which led to higher evapotranspiration and sensible heat and thus a reduction in convective precipitation from about 7800 years BP onwards. We suggest that the dynamics of vegetation played a key role in modulating the long-term trend of precipitation during the Holocene.