bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of mosaic variants using genome sequencing in a large pediatric cohort
Authors: Odgis Jacqueline A. , Gallagher Katie M. , Rehman Atteeq U. , Marathe Priya N. , Bonini Katherine E. , Sebastin Monisha , Di Biase Miranda , Brown Kaitlyn , Kelly Nicole R. , Ramos Michelle A. , Thomas‐Wilson Amanda , Guha Saurav , Okur Volkan , Ganapathi Mythily , Elkhoury Lama , Edelmann Lisa , Zinberg Randi E. , Abul‐Husn Noura S. , Diaz George A. , Greally John M. , Suckiel Sabrina A. , Jobanputra Vaidehi , Horowitz Carol R. , Kenny Eimear E. , Wasserstein Melissa P. , Gelb Bruce D.
Published: December 2022

The increased use of next‐generation sequencing has expanded our understanding of the involvement and prevalence of mosaicism in genetic disorders. We describe a total of eleven cases: nine in which mosaic variants detected by genome sequencing (GS) and/or targeted gene panels (TGPs) were considered to be causative for the proband's phenotype, and two of apparent parental mosaicism. Variants were identified in the following genes: PHACTR1, SCN8A, KCNT1, CDKL5, NEXMIF, CUX1, TSC2, GABRB2, and SMARCB1. In addition, we identified one large duplication including three genes, UBE3A, GABRB3, and MAGEL2, and one large deletion including deletion of ARFGAP1, EEF1A2, CHRNA4, and KCNQ2. All patients were enrolled in the NYCKidSeq study, a research program studying the communication of genomic information in clinical care, as well as the clinical utility and diagnostic yield of GS for children with suspected genetic disorders in diverse populations in New York City. We observed variability in the correlation between reported variant allele fraction and the severity of the patient's phenotype, although we were not able to determine the mosaicism percentage in clinically relevant tissue(s). Although our study was not sufficiently powered to assess differences in mosaicism detection between the two testing modalities, we saw a trend toward better detection by GS as compared with TGP testing. This case series supports the importance of mosaicism in childhood‐onset genetic conditions and informs guidelines for laboratory and clinical interpretation of mosaic variants detected by GS.
Halogen‐Incorporated Sn Catalysts for Selective Electrochemical CO2 Reduction to Formate
Authors: Wang Tian , Chen Jiadong , Ren Xinyi , Zhang Jincheng , Ding Jie , Liu Yuhang , Lim Kang Hui , Wang Junhu , Li Xuning , Yang Hongbin , Huang Yanqiang , Kawi Sibudjing , Liu Bin
Published: December 2022

Electrochemically reducing CO2to valuable fuels or feedstocks is recognized as a promising strategy to simultaneously tackle the crises of fossil fuel shortage and carbon emission. Sn‐based catalysts have been widely studied for electrochemical CO2reduction reaction (CO2RR) to make formic acid/formate, which unfortunately still suffer from low activity, selectivity and stability. In this work, halogen (F, Cl, Br or I) was introduced into the Sn catalyst by a facile hydrolysis method. The presence of halogen was confirmed by a collection of ex situ and in situ characterizations, which rendered a more positive valence state of Sn in halogen‐incorporated Sn catalyst as compared to unmodified Sn under cathodic potentials in CO2RR and therefore tuned the adsorption strength of the key intermediate (*OCHO) toward formate formation. As a result, the halogen‐incorporated Sn catalyst exhibited greatly enhanced catalytic performance in electrochemical CO2RR to produce formate.
DoS attack detection in identification of FIR systems with binary‐valued observations
Authors: Guo Jin , Jia Ruizhe , Su Ruinan , Song Yong , Jing Fengwei
Published: December 2022

Timely and effective detection of malicious attacks is a primary problem in cyber‐physical system security. This paper studies the detection of DoS (denial of service) attacks in identification of FIR (finite impulse response) systems with binary‐valued observations. Based on the prior information of the system, an attack detection algorithm is designed, and its online form is given. The detectability is discussed for the ability of detection algorithm, and the necessary and sufficient condition for the attack strategy to be detectable is obtained. The concepts of the missed detection rate and false alarm rate are introduced, and their calculation methods and approximate formulas under large samples are provided. Furthermore, it is analyzed the influence of prior information of system parameters and data length on the performance of detection algorithm. The rationality of theoretical results is verified by numerical simulation.
Enhancing CHO cell productivity through a dual selection system using Aspg and Gs in glutamine free medium
Authors: Ha Tae Kwang , Òdena Andreu , Karottki Karen Julie la Cour , Kim Che Lin , Hefzi Hooman , Lee Gyun Min , Faustrup Kildegaard Helene , Nielsen Lars K. , Grav Lise Marie , Lewis Nathan E.
Published: December 2022

The dominant method for generating Chinese hamster ovary (CHO) cell lines that produce high titers of biotherapeutic proteins utilizes selectable markers such as dihydrofolate reductase (Dhfr) or glutamine synthetase (Gs), alongside inhibitory compounds like methotrexate or methionine sulfoximine, respectively. Recent work has shown the importance of asparaginase (Aspg) for growth in media lacking glutamine—the selection medium for Gs‐based selection systems. We generated a Gs/Aspg double knockout CHO cell line and evaluated its utility as a novel dual selectable system via co‐transfection of Gs‐Enbrel and Aspg‐Enbrel plasmids. Using the same selection conditions as the standard Gs system, the resulting cells from the Gs/Aspg dual selection showed substantially improved specific productivity and titer compared to the standard Gs selection method, however, with reduced growth rate and viability. Following adaptation in the selection medium, the cells improved viability and growth while still achieving ~5‐fold higher specific productivity and ~3‐fold higher titer than Gs selection alone. We anticipate that with further optimization of culture medium and selection conditions, this approach would serve as an effective addition to workflows for the industrial production of recombinant biotherapeutics.
Melatonin upregulates BMAL1 to attenuate chronic sleep deprivation‐related cognitive impairment by alleviating oxidative stress
Authors: Hu Yujie , Yin Jierong , Yang Guoshuai
Published: December 2022

Purpose

To investigate the mechanism underlying the regulatory effect of melatonin on chronic sleep deprivation‐related cognitive impairment.

Methods

Chronic sleep deprivation (CSD) model was established using the MMPM method. After the model was established, melatonin receptor agonist and inhibitor were given, respectively. Water maze was conducted to record the escape latency and the duration of crossing the platform of space exploration. The concentration of TNF‐α, IL‐6, MDA, and SOD was measured by ELISA. Immunofluorescence was used to determine the expression level of CD86 and CD206, while the mRNA expression of Bax, Bcl‐2, P65, IκB, and BMAL1 was detected by qPCR. Western blotting assay was utilized to determine the protein expression of Bax, Bcl‐2, P65, p‐P65, IκB, p‐I κB, and BMAL1.

Results

Compared with the control, the escape latency was greatly increased on the second and third day, accompanied by the increased expression of TNF‐α, IL‐6, MDA, and SOD in serum. Furthermore, dramatically upregulated Bax, Bcl‐2, P65, IκB, and CD86 were observed in the model group, accompanied by the declined expression level of BMAL1 and CD206. Compared with the model group, the escape latency was declined, the concentration of TNF‐α, IL‐6, MDA, and SOD was decreased, the expression level of Bax, Bcl‐2, P65, IκB, and CD86 was declined, and the level of BMAL1 and CD206 was promoted by the treatment of the melatonin agonist, while the opposite results were observed under the treatment of the melatonin inhibitor.

Conclusion

Melatonin upregulates BMAL1 to attenuate chronic sleep deprivation‐related cognitive impairment by alleviating oxidative stress.
Mistletoe lectin inhibits growth of Myc‐amplified small‐cell lung cancer
Authors: Shatat Mohammad A. , Gauthier Betsy , Yoon Suzy , Yuan Eric , Yang Peiying , Narla Goutham , Dowlati Afshin , Lee Richard T.
Published: December 2022

Background

Small‐cell lung cancer (SCLC) is the deadliest form of lung cancer but lacks targeted therapies.

Methods

We studied the effect of the natural product mistletoe lectin (ML) in pre‐clinical models of SCLC, focusing on cell lines with amplification of the myc family oncogenes C‐myc and N‐myc.

Results

We found that ML treatment inhibits growth of SCLC cell lines in culture and induces apoptosis. ML treatment also decreases the expression of the amplified myc proteins. Over‐expression of either C‐myc or N‐myc results in enhanced SCLC cell sensitivity to ML. In a mouse xenograft model of SCLC, treatment with ML results in decreased tumor growth over 4 weeks with evidence of increased apoptosis in tumors from treated animals.

Conclusion

Overall, our results demonstrate that ML exhibits therapeutic potential in SCLC, that is at least partially dependent on myc protein expression.
Poorly differentiated laryngeal neuroendocrine neoplasm with high serum calcitonin level, a case report, with literature review
Authors: Motiee‐Langroudi Maziar , Farahzadi Athena , Ansari Reza , Saffar Hana , Darabi Rezvan , Abbasi Mehrshad
Published: December 2022

Neuroendocrine neoplasm (NEN) of the larynx consists of 0.6% of laryngeal cancer and is the second most common type after squamous cell carcinoma (SCC). Laryngeal NEN rarely secret calcitonin and should be differentiated from medullary thyroid carcinoma. It makes a diagnostic and therapeutic challenge. We describe a case of a laryngeal NEN with calcitonin hypersecretion. A 59‐year‐old man presented to our clinic with recurrent cough, dysphonia, hoarseness, cervical mass, and significant weight loss. Diagnostic workup showed a supraglottic mass. Biopsy of the lesion revealed large‐cell neuroendocrine neoplasm. Further diagnostic workup showed elevated serum calcitonin level. The patient underwent total laryngectomy, thyroidectomy, and modified radical neck dissection. During his follow‐up, new subcutaneous nodules appeared that were biopsy‐proven metastases. Then adjuvant chemoradiotherapy was performed. Laryngeal NEN with hypersecretion of calcitonin is a rare entity. In patients with elevated serum calcitonin levels and head and neck tumors, it should be considered a differential diagnosis of medullary thyroid carcinoma. As the management and prognosis of these two neoplasms are entirely different.
Assessment of the FAA3‐50 Polymer Electrolyte for Anion Exchange Membrane Fuel Cells
Authors: Gatto Irene , Patti Assunta , Carbone Alessandra
Published: December 2022

AEMFC is an attractive alternative to PEMFCs, due to the faster reaction kinetics that permits to use non‐platinum‐group metal catalysts and thanks to the high pH of the electrolyte allows less expensive metal hardware. In any case, the use of an alkaline exchange polymeric membrane as an electrolyte requires the development and optimization of the electrode structures and MEA. In this work, MEAs, based on FAA3‐50 commercial membrane, were developed and electrochemically characterized in single cell configuration. The hydroxylic exchange procedure of membrane and ionomer, was evaluated. The influence of different electrochemical activation procedures, and the presence of a microporous layer (MPL) in the electrodic structure were assessed. The developed MEAs were electrochemically characterized in a 25 cm2 single cell at different operative conditions. A maximum power density of 140 mW cm−2 at 60 °C was reached with the optimized MEAs.
Densification of BaZr0.9Y0.1O3‐δ ceramic thin films by an infiltration and co‐sintering approach
Authors: Xiao Yao , Waser Rainer , Schneller Theodor
Published: December 2022

The proton conductivity of Y‐doped BaZrO3‐based ceramic (BZY) films is highly dependent on the preparation process, especially thermal treatment. In order to further improve the electrochemical properties of BZY thin films, a novel sintering method was introduced to enhance the densification of such refractory materials. BaZr0.9Y0.1O3‐δ (BZY10) was used as a composition in this case study and the concept is realized using chemical solution deposition (CSD) derived porous cathode and anode films as auxiliary layers underneath the BZY10 films, which are CSD derived as well. After co‐sintering at 1200°C for 4 h, BZY10 films with a high degree of densification were attained, accompanied by average grain sizes of 300–350 nm. The grain sizes are comparable to common results found in BZY10 pellets sintered at 1600°C for more than 6 h. However, the densification conditions are much better. For the porous NiO/BZY10 composite films, the in‐plane conductivity is enhanced to about 2 × 10−4 S/cm at 600°C, which is quite close to that (10−3 S/cm) of optimized BZY bulk materials. The compatible stack structures and the remarkably low sintering temperature are applicable to the fabrication of proton‐conducting solid oxide fuel and electrolyzer cells.
Predicting Material Properties of Methane Hydrates with Cubic Crystal Structure Using Molecular Simulations
Authors: Lorenz Tommy , Jäger Andreas , Breitkopf Cornelia
Published: December 2022

Formation of gas hydrates is an important feature of water systems. It occurs undesirably in natural gas pipelines, but also in deep‐sea deposits and unfreezing permafrost. However, the natural occurrence is of particular interest because methane hydrates have one of the highest energy densities of all naturally occurring forms of methane. Therefore, an accurate description of its thermodynamic properties is required. In this work, we demonstrate how the material properties of methane hydrate can be more easily calculated compared to ab initio methods. Furthermore, it is shown how the material properties depend on the cage occupancy by using the comparably fast self‐consistent‐charge density‐functional tight‐binding (SCC‐DFTB) method. The cell potential is calculated and compared to a numerical as well as an ab initio model, and is in good agreement with the literature.
A Structured Ultramicroporous Metal‐Organic Framework for Carbon Dioxide Capture†
Authors: Wang Shao‐Min , Liu Hao‐Ran , Ni Shuang , Yang Qing‐Yuan
Published: December 2022

Comprehensive Summary

Carbon dioxide (CO2) capture is one of the most important aspects of reducing global warming. In terms of CO2 capture, metal‐organic frameworks (MOFs) have several advantages. However, it isn't easy to shape MOFs while maintaining their performance. Herein, we describe the development of a pellet‐shaped ultramicroporous MOF, Ni(3‐ain)2 (3‐ain = 3‐aminoinoisonicotinic acid), that is capable of selectively adsorbing CO2. Polyvinyl butyral (PVB) is used as a binder during the production of Ni(3‐ain)2 MOF pellets. The adequately shaped material can maintain its crystallinity and exhibit a high CO2 adsorption capacity (3.73 mmol·g–1) at ambient conditions, which is significantly greater than those obtained for N2 (0.63 mmol·g–1) and CO (0.90 mmol·g–1). Consequently, this material displays high IAST selectivities for CO2/N2 (26.3, 15/85, V/V) and CO2/CO (19.2, 1/99, V/V). According to the theoretical calculations, Ni(3‐ain)2 preferentially adsorbs CO2 molecules over N2 molecules and CO molecules. The results of experiments on dynamic breakthrough have demonstrated that Ni(3‐ain)2 pellets are capable of effectively separating CO2/N2 or CO2/CO mixtures under conditions of dynamic flow. Furthermore, the structured MOF materials can be synthesized in one step at kilogram scale. This work provides an avenue for the shaping of MOFs for potential industrial applications in the future.
Immunohistochemical characterization of bipolar cells in four distantly related avian species
Authors: Balaji Vaishnavi , Haverkamp Silke , Seth Pranav Kumar , Günther Anja , Mendoza Ezequiel , Schmidt Jessica , Herrmann Maike , Pfeiffer Leonie Lovis , Němec Pavel , Scharff Constance , Mouritsen Henrik , Dedek Karin
Published: December 2022

Visual (and probably also magnetic) signal processing starts at the first synapse, at which photoreceptors contact different types of bipolar cells, thereby feeding information into different processing channels. In the chicken retina, 15 and 22 different bipolar cell types have been identified based on serial electron microscopy and single‐cell transcriptomics, respectively. However, immunohistochemical markers for avian bipolar cells were only anecdotally described so far. Here, we systematically tested 12 antibodies for their ability to label individual bipolar cells in the bird retina and compared the eight most suitable antibodies across distantly related species, namely domestic chicken, domestic pigeon, common buzzard, and European robin, and across retinal regions. While two markers (GNB3 and EGFR) labeled specifically ON bipolar cells, most markers labeled in addition to bipolar cells also other cell types in the avian retina. Staining pattern of four markers (CD15, PKCα, PKCβ, secretagogin) was species‐specific. Two markers (calbindin and secretagogin) showed a different expression pattern in central and peripheral retina. For the chicken and European robin, we found slightly more ON bipolar cell somata in the inner nuclear layer than OFF bipolar cell somata. In contrast, OFF bipolar cells made more ribbon synapses than ON bipolar cells in the inner plexiform layer of these species. Finally, we also analyzed the photoreceptor connectivity of selected bipolar cell types in the European robin retina. In summary, we provide a catalog of bipolar cell markers for different bird species, which will greatly facilitate analyzing the retinal circuitry of birds on a larger scale.
Efficient time splitting schemes for the monodomain equation in cardiac electrophysiology
Authors: Lindner Laura P. , Gerach Tobias , Jahnke Tobias , Loewe Axel , Weiss Daniel , Wieners Christian
Published: December 2022

Approximating the fast dynamics of depolarization waves in the human heart described by the monodomain model is numerically challenging. Splitting methods for the PDE‐ODE coupling enable the computation with very fine space and time discretizations. Here, we compare different splitting approaches regarding convergence, accuracy, and efficiency. Simulations were performed for a benchmark problem with the Beeler–Reuter cell model on a truncated ellipsoid approximating the left ventricle including a localized stimulation. For this configuration, we provide a reference solution for the transmembrane potential. We found a semi‐implicit approach with state variable interpolation to be the most efficient scheme. The results are transferred to a more physiological setup using a bi‐ventricular domain with a complex external stimulation pattern to evaluate the accuracy of the activation time for different resolutions in space and time.
Effect of strain‐dependent conduction slowing on the re‐entry formation and maintenance in cardiac muscle: 2D computer simulation
Authors: Syomin Fyodor A. , Galushka Valentina A. , Tsaturyan Andrey K.
Published: December 2022

The effect of mechano‐electrical feedback on re‐entry formation and maintenance was studied using a model of myocardial electromechanics that accounts for two components of myocardial conductivity and delayed strain‐dependent changes in membrane capacitance that causes a conduction slowing. Two scenarios were simulated in 2D numerical experiments: (i) propagation of an excitation–contraction wave beyond the edge of a nonconductive nonexcitable obstacle; (ii) circulation of a re‐entry wave around a nonconductive nonexcitable obstacle. The simulations demonstrated that the delayed strain‐dependent deceleration of the conduction waves promotes the detachment of the excitation‐contraction waves from the sharp edge of an elongated obstacle and modulates the re‐entry waves rotating around a compact obstacle. The data show that the mechano‐electrical feedback, together with an increase in the stimulation frequency and an increase in the excitation threshold, is an arrhythmogenic factor that must be taken into account when analyzing the possibility of the re‐entry formation.
Life satisfaction across the entire trajectory of Alzheimer's disease: A mediation analysis
Authors: Mank Arenda , van Maurik Ingrid S. , van Harten Argonde C. , Rhodius‐Meester Hanneke F. M. , Teunissen Charlotte E. , van Berckel Bart N. M. , Berkhof Johannes , van der Flier Wiesje M. , Rijnhart Judith J. M.
Published: December 2022

Introduction

We studied life satisfaction across Alzheimer's disease (AD) stages and studied mobility and meaningful activities as mediators of the associations between these AD stages and life satisfaction.

Methods

In this cross‐sectional study, we included n = 269 amyloid‐positive patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia from the Amsterdam Dementia Cohort. Life satisfaction was measured with the satisfaction with life scale. The mediating role of transportation, work, sports, and hobbies on life satisfaction was examined in single and multiple mediator models.

Results

Patients with dementia are less satisfied with life compared to SCD and MCI. These differences in life satisfaction are explained by reduced participation in meaningful activities, which in turn, was largely attributable to decreased transportation use.

Discussion

Our findings suggest that improving access to transportation, therewith allowing participation in meaningful activities help to maintain life satisfaction and may be an important target for intervention.
Dyslipidemia and SARS‐CoV‐2 spike antibody titres after the second and third doses of the BNT162b2 vaccine among healthcare workers in Japan
Authors: Islam Zobida , Yamamoto Shohei , Mizoue Tetsuya , Oshiro Yusuke , Inamura Natsumi , Konishi Maki , Ozeki Mitsuru , Sugiura Wataru , Ohmagari Norio
Published: December 2022

Objective

This study aimed to examine the sex‐associated differences in the relationship between dyslipidemia and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike immunoglobulin (Ig)G antibodies among BNT162b2 vaccine recipients.

Methods

Participants were staff members (aged 21–75 years) of a medical and research institution who underwent an anti‐SARS‐CoV‐2 spike IgG antibody test after the second (n = 1872) and third doses (n = 1075) of the BNT162b2 vaccine. Dyslipidemia was defined as triglyceride level ≥150 mg/dl, high‐density lipoprotein‐cholesterol level <40 mg/dl, low‐density lipoprotein‐cholesterol level ≥140 mg/dl, or lipid‐lowering medication use. Multivariable linear regression was used to calculate the ratio of means for SARS‐CoV‐2 spike IgG titre according to dyslipidemia status.

Results

The prevalence of dyslipidemia was 38.0% in men and 19.6% in women. The relationship between dyslipidemia and SARS‐CoV‐2 spike IgG titres after the second dose differed markedly by sex (P for interaction <0.001). In men, dyslipidemia was associated with significantly lower IgG titres: the ratio of means (95% confidence interval) was 0.82 (0.72–0.93). However, this association disappeared after the third dose (0.96 [0.78–1.18]). Of the dyslipidemia components, hypertriglyceridemia was inversely associated with SARS‐CoV‐2 spike IgG antibody titre after both the second and third doses (ratio of means: 0.82 [0.70–0.95] and 0.73 [0.56–0.95], respectively). In women, IgG titres did not differ according to dyslipidemia or hypertriglyceridemia status after either dose.

Conclusions

These results suggest a detrimental role of hypertriglyceridemia in the humoral immune response to the BNT162b2 vaccine for COVID‐19 in men but not in women.
Models combining multiple scales of inference capture hydrologic and climatic drivers of riparian tree distributions
Authors: Perry Laura G. , Jarnevich Catherine S. , Shafroth Patrick B.
Published: December 2022

Predicting species geographic distributions is key to managing invasive species, conserving biodiversity, and understanding species' environmental requirements. Species distribution models (SDMs) commonly focus on climatic predictors, but other environmental factors can also be essential, particularly for species with specialized habitats defined by hydrologic, topographic, or edaphic conditions (e.g., riparian, wetland, alpine, coastal, serpentine). Here, we demonstrate a novel approach for capturing strong effects of both hydrologic and climatic predictors in SDMs for riparian plants, by merging analyses targeted at environmental drivers within riparian ecosystems and across the western USA (3.8 × 106 km2). We developed presence‐background SDMs from five algorithms for three invasive riparian trees (Tamarix ramossisima/chinensis [saltcedar], Elaeagnus angustifolia [Russian olive], and Ulmus pumila [Siberian elm]) and three native Populus spp. (cottonwoods). We used separate background datasets to develop models with different spatial scales of inference: (1) spatially filtered random points to represent available habitat across the study area and (2) target‐group points from Salix (willow) occurrences to represent available riparian habitat. Random‐background models captured hydrologic drivers of riparian tree distributions relative to the largely upland western USA, whereas Salix‐background models captured climatic drivers within the context of riparian ecosystems. Combining predictions from the two backgrounds identified hydrologically suitable habitats within climatically suitable regions, resulting in fewer false “absences” than either background alone, improving predictions over previous SDMs, and providing more complete information to guide management decisions. Surprisingly, the predicted habitat for U. pumila, a newly recognized riparian invader, was as or more extensive than Populus deltoides/fremontii, T. ramossisima/chinensis, and E. angustifolia, the most common riparian tree complexes in the western USA. Watersheds constituting 20% of U. pumila predicted habitat contained no occurrence records, indicating high risk of future and unrecognized invasions. Combining models from random and ecosystem‐specific target‐group backgrounds may improve SDMs for species from many specialized habitats, providing a method to link predicted distributions to localized geographic features while capturing broad‐scale climatic requirements.
Guidelines for mouse and human DC functional assays
Authors: Clausen Björn E. , Amon Lukas , Backer Ronald A. , Berod Luciana , Bopp Tobias , Brand Anna , Burgdorf Sven , Chen Luxia , Da Meihong , Distler Ute , Dress Regine J. , Dudziak Diana , Dutertre Charles‐Antoine , Eich Christina , Gabele Anna , Geiger Melanie , Ginhoux Florent , Giusiano Lucila , Godoy Gloria J. , Hamouda Ahmed E.I. , Hatscher Lukas , Heger Lukas , Heidkamp Gordon F. , Hernandez Lola C. , Jacobi Lukas , Kaszubowski Tomasz , Kong Wan Ting , Lehmann Christian H. K. , López‐López Tamara , Mahnke Karsten , Nitsche Dominik , Renkawitz Jörg , Reza Rifat A. , Sáez Pablo J. , Schlautmann Laura , Schmitt Madeleine T. , Seichter Anna , Sielaff Malte , Sparwasser Tim , Stoitzner Patrizia , Tchitashvili Giorgi , Tenzer Stefan , Tochoedo Nounagnon R. , Vurnek Damir , Zink Fabian , Hieronymus Thomas
Published: December 2022

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state‐of‐the‐art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various non‐lymphoid tissues. Recent studies have provided evidence for an increasing number of phenotypically distinct conventional DC (cDC) subsets that on one hand exhibit a certain functional plasticity, but on the other hand are characterized by their tissue‐ and context‐dependent functional specialization. Here, we describe a selection of assays for the functional characterization of mouse and human cDC. The first two protocols illustrate analysis of cDC endocytosis and metabolism, followed by guidelines for transcriptomic and proteomic characterization of cDC populations. Then, a larger group of assays describes the characterization of cDC migration in vitro, ex vivo, and in vivo. The final guidelines measure cDC inflammasome and antigen (cross)‐presentation activity. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer‐reviewed by leading experts and approved by all co‐authors, making it an essential resource for basic and clinical DC immunologists.
Staphylococcus aureus‐derived factors promote human Th9 cell polarization and enhance a transcriptional program associated with allergic inflammation
Authors: Badolati Isabella , van der Heiden Marieke , Brodin David , Zuurveld Marit , Szilágyi Szilvia , Björkander Sophia , Sverremark‐Ekström Eva
Published: December 2022

T helper (Th) 9 cells, characterized by robust secretion of IL‐9, have been increasingly associated with allergic diseases. However, whether and how Th9 cells are modulated by environmental stimuli remains poorly understood. In this study, we show that in vitro exposure of human PBMCs or isolated CD4 T‐cells to Staphylococcus (S.) aureus‐derived factors, including its toxins, potently enhances Th9 cell frequency and IL‐9 secretion. Furthermore, as revealed by RNA sequencing analysis, S. aureus increases the expression of Th9‐promoting factors at the transcriptional level, such as FOXO1, miR‐155, and TNFRSF4. The addition of retinoic acid (RA) dampens the Th9 responses promoted by S. aureus and substantially changes the transcriptional program induced by this bacterium, while also altering the expression of genes associated with allergic inflammation. Together, our results demonstrate a strong influence of microbial and dietary factors on Th9 cell polarization, which may be important in the context of allergy development and treatment.
Non‐synonymous, synonymous, and non‐coding nucleotide variants contribute to recurrently altered biological processes during retinoblastoma progression
Authors: Stachelek Kevin , Harutyunyan Narine , Lee Susan , Beck Assaf , Kim Jonathan , Xu Liya , Berry Jesse L. , Nagiel Aaron , Reynolds C. Patrick , Murphree A. Linn , Lee Thomas C. , Aparicio Jennifer G. , Cobrinik David
Published: December 2022

Retinoblastomas form in response to biallelic RB1 mutations or MYCN amplification and progress to more aggressive and therapy‐resistant phenotypes through accumulation of secondary genomic changes. Progression‐related changes include recurrent somatic copy number alterations and typically non‐recurrent nucleotide variants, including synonymous and non‐coding variants, whose significance has been unclear. To determine if nucleotide variants recurrently affect specific biological processes, we identified altered genes and over‐represented variant gene ontologies in 168 exome or whole‐genome‐sequenced retinoblastomas and 12 tumor‐matched cell lines. In addition to RB1 mutations, MYCN amplification, and established retinoblastoma somatic copy number alterations, the analyses revealed enrichment of variant genes related to diverse biological processes including histone monoubiquitination, mRNA processing (P) body assembly, and mitotic sister chromatid segregation and cytokinesis. Importantly, non‐coding and synonymous variants increased the enrichment significance of each over‐represented biological process term. To assess the effects of such mutations, we examined the consequences of a 3′ UTR variant of PCGF3 (a BCOR‐binding component of Polycomb repressive complex I), dual 3′ UTR variants of CDC14B (a regulator of sister chromatid segregation), and a synonymous variant of DYNC1H1 (a regulator of P‐body assembly). One PCGF3 and one of two CDC14B 3′ UTR variants impaired gene expression whereas a base‐edited DYNC1H1 synonymous variant altered protease sensitivity and stability. Retinoblastoma cell lines retained only ~50% of variants detected in tumors and enriched for new variants affecting p53 signaling. These findings reveal potentially important differences in retinoblastoma cell lines and tumors and implicate synonymous and non‐coding variants, along with non‐synonymous variants, in retinoblastoma oncogenesis.
Structural Flexibility of Metal Chelate Complexes and Its Relation to Supramolecular Chemistry
Authors: Maverick Andrew W.
Published: December 2022

Crystal structures of metal chelate and related complexes in the Cambridge Structural Database have been analyzed, with respect to their use as components in supramolecular metal‐organic compounds. In β‐diketonate complexes, the distribution of angles between ligands is relatively broad; other ligands, such as 2,2′‐bipyridine, yield significantly narrower distributions. According to the principle of structure correlation, these distributions reflect the ease of distorting the various families of complexes. A comparison through density functional theory calculations also indicates that angular distortions require significantly less energy for M(β‐diketonate)3 than for M(2,2′‐bipyridine)3. The differences are likely to affect the construction of supramolecular systems from different combinations of metals and ligands, including the likelihood that the desired structures will be obtained.
Epigenetics applied to child and adolescent mental health: Progress, challenges and opportunities
Authors: Cecil Charlotte A. M. , Neumann Alexander , Walton Esther
Published: December 2022

Background

Epigenetic processes are fast emerging as a promising molecular system in the search for both biomarkers and mechanisms underlying human health and disease risk, including psychopathology.

Methods

In this review, we discuss the application of epigenetics (specifically DNA methylation) to research in child and adolescent mental health, with a focus on the use of developmentally sensitive datasets, such as prospective, population‐based cohorts. We look back at lessons learned to date, highlight current developments in the field and areas of priority for future research. We also reflect on why epigenetic research on child and adolescent mental health currently lags behind other areas of epigenetic research and what we can do to overcome existing barriers.

Results

To move the field forward, we advocate for the need of large‐scale, harmonized, collaborative efforts that explicitly account for the time‐varying nature of epigenetic and mental health data across development.

Conclusion

We conclude with a perspective on what the future may hold in terms of translational applications as more robust signals emerge from epigenetic research on child and adolescent mental health.
Serum extracellular vesicle‐derived ASS1 is a promising predictor for the occurrence of HEV‐ALF
Authors: Xiang Ze , Jiang Chun , Yang Jiajia , Huang Lan , Jiang Bin , Wang Xuanli , Gao Ce , Li Mo , Meng Yiling , Tong Ling , Ling Bai , Wang Ying , Wu Jian ,   The Chinese Consortium for the Study of Hepatitis E (CCSHE)
Published: December 2022

Development of biomarkers for predicting the occurrence of hepatitis E virus related‐acute liver failure (HEV‐ALF) is conducive to prevention and early intervention. Serum samples from 250 HEV‐ALF patients, 250 patients with acute hepatitis E (AHE) and 250 health controls (HCs) were collected. We assessed the predictive ability of extracellular vesicle (EV)‐derived argininosuccinate synthase 1 (ASS1) levels for HEV‐ALF occurrence. Serum EVs were successfully isolated. EV‐derived ASS1 levels in the HEV‐ALF patients were significantly higher than those in the AHE patients and HCs. In HEV‐ALF patients, EV‐derived ASS1 levels were positively correlated with the number of failed organs and disease progression. The logistical regression showed that EV‐derived ASS1 level is an independent risk factor for HEV‐ALF, and orthogonal partial least squares discriminant analysis (OPLS‐DA) also suggested that EV‐derived ASS1 level has high predictive capability. Besides, the area under the curve (AUC) of EV‐derived ASS1 level to predict HEV‐ALF occurrence was 0.728 (0.684–0.772) with the sensitivity and specificity being 72.80% and 64.80%, which had a high decision‐making ability. Furthermore, there existed no significant difference between the age ≥60 and age <60 groups in EV‐derived ASS1 levels. Serum EV‐derived ASS1 level is a promising predictor for the occurrence of HEV‐ALF.
Am I the only one? Consequences of change championing (a)symmetry on group‐ and individual‐level change outcomes
Authors: Kanitz Rouven , Gonzalez Katerina , Berger Stefan , Reinwald Max , Huettermann Hendrik , Franczak Jennifer
Published: December 2022

Employee change championing (i.e., discretionary behaviors to promote change to others) is critical for implementing organizational change successfully. However, extant research has been focused on individual‐level championing without considering the broader group context in which championing occurs. Our study adopts a multilevel perspective to provide insights into the effects of change championing at both the group and the individual level. We collected data at two points in time from 267 employees in 69 groups undergoing an organizational change in a German technology company. Multilevel modeling results show that group championing asymmetry (i.e., the degree to which group members differ in their championing) weakens the positive effects of group championing level on change implementation effectiveness. Moreover, we shed light on the individual‐level processes that underpin group championing dynamics. Our findings reveal that employees who are embedded in groups with high average championing levels perceive a more positive change impact (but do not experience higher levels of enthusiasm) and report higher levels of individual championing at a later point in time compared to employees in groups with lower championing levels. Our study expands the championing literature to the group‐level and offers a multilevel perspective on the championing dynamics between individuals and groups.
Photoresponsive Adhesives Based on Arylazoisoxazoles‐Containing Polymers
Authors: Rossi Ruggero , Salvini Antonella , Pizzo Benedetto , Frediani Marco , Wiersma Diederik Sybolt , Parmeggiani Camilla , Martella Daniele
Published: December 2022

Adhesives exist in many forms and are essential in the daily life, in industrial processes, and in healthcare, calling for continuous improvements in terms of application fields, strength, biocompatibility, recyclability, and reversibility. Regarding the last two points, embedding photoresponsive molecules into the adhesive allows the use of light to attach or detach reversibly different surfaces. Photoresponsive adhesives can be removed without the use of high temperature or solvents, which is ideal for delicate environments. To date, azobenzenes are the most explored chromophore to prepare smart adhesive formulations. Here, the synthesis of polymer containing arylazoisoxazoles (AIZs) — azobenzene analogs containing a heterocycle — and their application as adhesives is described. Mechanical tests demonstrate an enhancement of the adhesion strength from 0.39 to 2.79 MPa, passing from low molecular weight monomer to selected AIZs acrylate polymer. Irradiation with UV induces the formation of the cis isomer with a consequent drop of more than 70% in the adhesion strength. The different compounds result as possible candidates as adhesives on the basis of the increased load that can be held, together with the possibility to obtain joints that can be either stable or detachable under light irradiation.
Mesothelioma cancer cells are glutamine addicted and glutamine restriction reduces YAP1 signaling to attenuate tumor formation
Authors: Adhikary Gautam , Shrestha Suruchi , Naselsky Warren , Newland John J. , Chen Xi , Xu Wen , Emadi Ashkan , Friedberg Joseph S. , Eckert Richard L.
Published: December 2022

Glutamine addiction is an important phenotype displayed in some types of cancer. In these cells, glutamine depletion results in a marked reduction in the aggressive cancer phenotype. Mesothelioma is an extremely aggressive disease that lacks effective therapy. In this study, we show that mesothelioma tumors are glutamine addicted suggesting that glutamine depletion may be a potential therapeutic strategy. We show that glutamine restriction, by removing glutamine from the medium or treatment with inhibitors that attenuate glutamine uptake (V‐9302) or conversion to glutamate (CB‐839), markedly reduces mesothelioma cell proliferation, spheroid formation, invasion, and migration. Inhibition of the SLC1A5 glutamine importer, by knockout or treatment with V‐9302, an SLC1A5 inhibitor, also markedly reduces mesothelioma cell tumor growth. A relationship between glutamine utilization and YAP1/TEAD signaling has been demonstrated in other tumor types, and the YAP1/TEAD signaling cascade is active in mesothelioma cells and drives cell survival and proliferation. We therefore assessed the impact of glutamine depletion on YAP1/TEAD signaling. We show that glutamine restriction, SLC1A5 knockdown/knockout, or treatment with V‐9302 or CB‐839, reduces YAP1 level, YAP1/TEAD‐dependent transcription, and YAP1/TEAD target protein (e.g., CTGF, cyclin D1, COL1A2, COL3A1, etc.) levels. These changes are observed in both cells and tumors. These findings indicate that mesothelioma is a glutamine addicted cancer, show that glutamine depletion attenuates YAP1/TEAD signaling and tumor growth, and suggest that glutamine restriction may be useful as a mesothelioma treatment strategy.
Improved seasonal definition and projected future seasons in South Korea
Authors: Lee Eungul , Im Ahyeong , Oh Jieun , Song Miseon , Choi Youngeun , Choi Dasom
Published: December 2022

Seasons are fundamental climatological phenomena, and their changes have significantly affected the sustainability of nature and human society. Suitable criteria to define the seasonal indicators of start date and length of seasons are required for the timely planning of socio‐economic activities. However, unsuitable cases of seasonal indicators have been identified in the seasonal definition used by Korea Meteorological Administration (KMA). We devised the data processing method to calculate three seasonal indicators: start date, length, and abnormal days of seasons. The past (1921–2010) and future (2021–2100) climate data of daily mean temperature were used in estimating the three seasonal indicators; they were obtained from the weather stations in South Korea and under the Representative Concentration Pathway (RCP) scenarios, respectively. The modified definitions with the moving averages of 15‐, 31‐, 45‐, 61‐, and 91‐day improved in estimating the start date and length of seasons compared with the current KMA definition. Additionally, abnormal days of seasons in the modified definitions were found to reduce significantly. Under the RCP8.5 scenario, the earlier advance of spring and summer by 4.9 and 3.9 days per decade, respectively, and the delayed autumn and winter by 3.2 and 2.0 days per decade, respectively, were expected over the 21st century. Correspondingly, the extended summer and the shortened winter by 7.1 days per decade and 5.1 days per decade were projected, respectively. The estimated future changes in seasons using the improved seasonal definition can be used for socio‐economic sectors and the general public to adapt to a warmer climate.
Effects of Allergen‐Specific and Non‐Specific AGEs on the Allergenicity of Ovalbumin in a Mouse Model of Food Allergy
Authors: Yu Gang , Zhang Qiaozhi , Li Huatao , Wang Yanbo , Sheng Huadong , Zhang Shuifeng , Fu Linglin
Published: December 2022

Scope

Epidemiologic studies suggest a link between the incidence of food allergy and the consumption of dietary advanced glycation end‐products (AGEs). However, the pathogenic role of dietary AGEs in food allergy is largely unknown. This study aims to investigate the effect of allergen‐specific and non‐specific AGEs on the allergenic manifestation of ovalbumin (OVA), a typical food allergen in vivo.

Methods and results

OVA is glycated by methylglyoxal to prepare allergen‐specific AGEs (i.e., OVA‐AGE), and a standard AIN‐93G diet is heated to obtain allergen‐non‐specific AGEs. A BALB/c mouse model orally sensitizes to OVA with different forms of AGEs is established and the outcomes are measured as clinical signs, specific antibodies, type‐2/type‐2 cytokines, immune cell subpopulations, intestinal barrier function, and gut microbiota (GM) composition. The OVA‐AGE which has a lower immunoglobulin E (IgE)‐binding level in vitro does not reduce the allergenicity of OVA but promotes a stronger T helper 2 cells (Th2)‐response than native OVA in vivo. Both forms of AGEs up‐regulate the expression of splenic RAGE and aggravate the destruction of gut barrier and GM dysbiosis, especially when exposes to non‐relevant AGEs.

Conclusion

This study highlights the role of dietary AGEs in food allergy and helps to understand the biological consequences of immune‐toxic compounds in modern diet.
Registration of Arkot 0902 cotton germplasm line
Authors: Bourland Fred M. , Chee Peng W. , Jones Don C.
Published: December 2022

Arkot 0902 (Reg. no. GP‐1130, PI 700940) is a conventional cotton (Gossypium hirsutum L.) germplasm line released by the Arkansas Agricultural Experiment Station in May 2022. Arkot 0902 was derived from a cross of ‘GA 230’ (PVP 201500309) and Arkot 0012. Over 5 yr and four test sites in Arkansas, Arkot 0902 produced 10 and 20% higher lint yields than ‘UA222’ and ‘UA48’, respectively. The high lint yield of Arkot 0902 was attributed to producing more (and smaller) seed per area than UA222 or UA48. Arkot 0902 possesses leaf and stem pubescence similar to UA48 (smooth leaf) but has higher density of marginal bract trichomes. Arkot 0902 displayed high resistance to bacterial blight and was similar to UA222 and UA48 in their response to other diseases. Arkot 0902 was more resistant to tarnished plant bug than UA48 and equal to UA222. Most fiber quality traits of Arkot 0902 approached those of UA48, a high fiber–quality cultivar.
Calcium carbonate‐modified plant sporopollen capsule as an eco‐friendly microvehicle for controlled release of pesticide
Authors: Xiang Sheng , Kang Huajun , Chai Ali , Shi Yanxia , Xie Xuewen , Li Lei , Fan Tengfei , Li Baoju
Published: December 2022

Background

In this work, natural club moss (Lycopodium clavatum, LC) spores with a porous surface morphology and highly uniform size distribution were engineered into controlled‐release microvehicles for pesticide delivery. As a proof of concept, a widely used fungicide, fluazinam (FLU), was successfully loaded into LC spores and then modified with different amounts of CaCO3 (CaC) to extend the efficacy duration of FLU. Significantly, as the control target of FLU, clubroot disease is a worldwide destructive disease of cruciferous crops, and its development is favored by acidic soils and can be suppressed at high Ca concentrations.

Results

Fabricated FLU@LC‐CaC microcapsules, FLU loading and CaCO3 deposition were systematically characterized by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The as‐prepared FLU@LC‐CaC microcapsules showed sustained‐release behaviors and were potentially able to supplement the Ca concentration in acidic environments. This approach synergistically enhanced in vivo bioactivity for the on‐demand control of clubroot disease. An in vivo bioassay revealed that the control efficacy of FLU@LC‐CaC against clubroot disease in pak choi (Brassica chinensis) (66.4%) was 1.7‐fold higher than that of a commercial FLU suspension concentrate (38.2%) over the course of the cultivation period (35 days).

Conclusions

This work provides new ideas not only for developing eco‐friendly and scalable microvehicles for pesticide delivery based on natural sporopollen, but also for unconventional research perspectives in on‐demand pest management based on their occurrence characteristics. © 2022 Society of Chemical Industry.