bluuebunny/crossref_metadata_2025 huggingface dataset:
A Deep Learning Model for Forecasting Velocity Structures of the Loop Current System in the Gulf of Mexico
Authors: Muhamed Ali Ali , Zhuang Hanqi , VanZwieten James , Ibrahim Ali K. , Chérubin Laurent
Published: December 2021

Despite the large efforts made by the ocean modeling community, such as the GODAE (Global Ocean Data Assimilation Experiment), which started in 1997 and was renamed as OceanPredict in 2019, the prediction of ocean currents has remained a challenge until the present day—particularly in ocean regions that are characterized by rapid changes in their circulation due to changes in atmospheric forcing or due to the release of available potential energy through the development of instabilities. Ocean numerical models’ useful forecast window is no longer than two days over a given area with the best initialization possible. Predictions quickly diverge from the observational field throughout the water and become unreliable, despite the fact that they can simulate the observed dynamics through other variables such as temperature, salinity and sea surface height. Numerical methods such as harmonic analysis are used to predict both short- and long-term tidal currents with significant accuracy. However, they are limited to the areas where the tide was measured. In this study, a new approach to ocean current prediction based on deep learning is proposed. This method is evaluated on the measured energetic currents of the Gulf of Mexico circulation dominated by the Loop Current (LC) at multiple spatial and temporal scales. The approach taken herein consists of dividing the velocity tensor into planes perpendicular to each of the three Cartesian coordinate system directions. A Long Short-Term Memory Recurrent Neural Network, which is best suited to handling long-term dependencies in the data, was thus used to predict the evolution of the velocity field in each plane, along each of the three directions. The predicted tensors, made of the planes perpendicular to each Cartesian direction, revealed that the model’s prediction skills were best for the flow field in the planes perpendicular to the direction of prediction. Furthermore, the fusion of all three predicted tensors significantly increased the overall skills of the flow prediction over the individual model’s predictions. The useful forecast period of this new model was greater than 4 days with a root mean square error less than 0.05 cm·s−1 and a correlation coefficient of 0.6.
Fractional-Order Logistic Differential Equation with Mittag–Leffler-Type Kernel
Authors: Area Iván , Nieto Juan J.
Published: December 2021

In this paper, we consider the Prabhakar fractional logistic differential equation. By using appropriate limit relations, we recover some other logistic differential equations, giving representations of each solution in terms of a formal power series. Some numerical approximations are implemented by using truncated series.
Weighted Scoring Committees
Authors: Mayer Alexander , Napel Stefan
Published: December 2021

Weighted committees allow shareholders, party leaders, etc. to wield different numbers of votes or voting weights as they decide between multiple candidates by a given social choice method. We consider committees that apply scoring methods such as plurality, Borda, or antiplurality rule. Many different weights induce the same mapping from committee members’ preferences to winning candidates. The numbers of respective weight equivalence classes and hence of structurally distinct plurality committees, Borda commitees, etc. differ widely. There are 6, 51, and 5 plurality, Borda, and antiplurality committees, respectively, if three players choose between three candidates and up to 163 (229) committees for scoring rules in between plurality and Borda (Borda and antiplurality). A key implication is that plurality, Borda, and antiplurality rule are much less sensitive to weight changes than other scoring rules. We illustrate the geometry of weight equivalence classes, with a map of all Borda classes, and identify minimal integer representations.
Ectopic Expression of a Salt-Inducible Gene, LcSAIN3, from Sheepgrass Improves Seed Germination and Seedling Growth under Salt Stress in Arabidopsis
Authors: Li Xiaoxia , Yang Weiguang , Jia Junting , Zhao Pincang , Qi Dongmei , Chen Shuangyan , Cheng Li , Cheng Liqin , Liu Gongshe
Published: December 2021

Sheepgrass is a perennial native grass species in China, and it can tolerate high levels of salt stress with an aggressive and vigorous rhizome system. Many salt-stress-responsive genes have been identified in sheepgrass. In this study, we report the cloning and characterization of a novel salt-induced gene, LcSAIN3 (Leymus chinensis salt-induced 3), from sheepgrass. Expression analysis confirmed that LcSAIN3 was induced by PEG, ABA, and salt treatments, and the expression of LcSAIN3 was significantly increased in salt-tolerant germplasms under salt treatment. Subcellular localization analysis indicated that the GFP-LcSAIN3 protein was mainly localized in the chloroplasts. The heterologous expression of LcSAIN3 in Arabidopsis increased the seed germination rate of transgenic plants under salt, ABA, and mannitol treatments. The seedling survival rate, plant height, and fresh weight of the transgenic plants were higher than those of WT plants under salt stress. The overexpression of LcSAIN3 caused a relatively high accumulation of free proline, enhanced SOD activity, and led to the upregulation of several stress-responsive genes such as AtRD26, AtRD29B, AtSOS1, and AtP5CS1. These results suggest that LcSAIN3 could be a potential target for molecular breeding to improve plants’ salt tolerance.
Evidence of the Physical Interaction between Rpl22 and the Transposable Element Doc5, a Heterochromatic Transposon of Drosophila melanogaster
Authors: Berloco Maria Francesca , Minervini Crescenzio Francesco , Moschetti Roberta , Palazzo Antonio , Viggiano Luigi , Marsano René Massimiliano
Published: December 2021

Chromatin is a highly dynamic biological entity that allows for both the control of gene expression and the stabilization of chromosomal domains. Given the high degree of plasticity observed in model and non-model organisms, it is not surprising that new chromatin components are frequently described. In this work, we tested the hypothesis that the remnants of the Doc5 transposable element, which retains a heterochromatin insertion pattern in the melanogaster species complex, can be bound by chromatin proteins, and thus be involved in the organization of heterochromatic domains. Using the Yeast One Hybrid approach, we found Rpl22 as a potential interacting protein of Doc5. We further tested in vitro the observed interaction through Electrophoretic Mobility Shift Assay, uncovering that the N-terminal portion of the protein is sufficient to interact with Doc5. However, in situ localization of the native protein failed to detect Rpl22 association with chromatin. The results obtained are discussed in the light of the current knowledge on the extra-ribosomal role of ribosomal protein in eukaryotes, which suggests a possible role of Rpl22 in the determination of the heterochromatin in Drosophila.
Cell-Cycle–Dependent Chromatin Dynamics at Replication Origins
Authors: Li Yulong , Hartemink Alexander J. , MacAlpine David M.
Published: December 2021

Origins of DNA replication are specified by the ordered recruitment of replication factors in a cell-cycle–dependent manner. The assembly of the pre-replicative complex in G1 and the pre-initiation complex prior to activation in S phase are well characterized; however, the interplay between the assembly of these complexes and the local chromatin environment is less well understood. To investigate the dynamic changes in chromatin organization at and surrounding replication origins, we used micrococcal nuclease (MNase) to generate genome-wide chromatin occupancy profiles of nucleosomes, transcription factors, and replication proteins through consecutive cell cycles in Saccharomyces cerevisiae. During each G1 phase of two consecutive cell cycles, we observed the downstream repositioning of the origin-proximal +1 nucleosome and an increase in protected DNA fragments spanning the ARS consensus sequence (ACS) indicative of pre-RC assembly. We also found that the strongest correlation between chromatin occupancy at the ACS and origin efficiency occurred in early S phase, consistent with the rate-limiting formation of the Cdc45–Mcm2-7–GINS (CMG) complex being a determinant of origin activity. Finally, we observed nucleosome disruption and disorganization emanating from replication origins and traveling with the elongating replication forks across the genome in S phase, likely reflecting the disassembly and assembly of chromatin ahead of and behind the replication fork, respectively. These results provide insights into cell-cycle–regulated chromatin dynamics and how they relate to the regulation of origin activity.
Polychromatic Flow Cytometric Analysis of Stromal Vascular Fraction from Lipoaspirate and Microfragmented Counterparts Reveals Sex-Related Immunophenotype Differences
Authors: Zenic Lucija , Polancec Denis , Hudetz Damir , Jelec Zeljko , Rod Eduard , Vidovic Dinko , Staresinic Mario , Sabalic Srecko , Vrdoljak Trpimir , Petrovic Tadija , Cukelj Fabijan , Molnar Vilim , Cemerin Martin , Matisic Vid , Brlek Petar , Djukic Koroljevic Zrinka , Boric Igor , Lauc Gordan , Primorac Dragan
Published: December 2021

Mesenchymal stem/stromal cells or medicinal signaling cells (MSC)-based therapy holds promise as a beneficial strategy for treating knee OA (osteoarthritis), but there is no standardized protocols nor mechanistic understanding. In order to gain a better insight into the human MSC from adipose tissue applied for autologous OA treatment, we performed extensive comparative immunophenotyping of the stromal vascular fraction from lipoaspirate or microfragmented lipoaspirates by polychromatic flow cytometry and investigated the cellular components considered responsible for cartilage regeneration. We found an enrichment of the regenerative cellular niche of the clinically applied microfragmented stromal vascular fraction. Sex-related differences were observed in the MSC marker expression and the ratio of the progenitor cells from fresh lipoaspirate, which, in female patients, contained a higher expression of CD90 on the three progenitor cell types including pericytes, a higher expression of CD105 and CD146 on CD31highCD34high endothelial progenitors as well as of CD73 on supra-adventitialadipose stromal cells. Some of these MSC-expression differences were present after microfragmentation and indicated a differential phenotype pattern of the applied MSC mixture in female and male patients. Our results provide a better insight into the heterogeneity of the adipose MSC subpopulations serving as OA therapeutics, with an emphasis on interesting differences between women and men.
Is There a Role for Direct Oral Anticoagulants in the Primary and Secondary Prevention of Myeloproliferative Neoplasm Associated Thrombosis?
Authors: Faruqi Uzma , Breen Karen A.
Published: December 2021

Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are clonal haematopoietic stem cell disorders. Of the MPNs, polycythaemia vera (PV) and essential thrombocythaemia (ET) confer a high thrombotic risk which may be the presenting feature of the disease. Thrombotic complications consist of both arterial and venous events and the presence of the JAK2 V617F mutation is associated with higher risk. Patients presenting with an unprovoked thrombus, particularly at an unusual site, e.g., splanchnic circulation, should be screened for the presence of this mutation. Historically, warfarin has been the only option for oral anticoagulation; however, there is now increasing evidence and practise to use direct oral anticoagulants (DOACs) in cancer. The seminal randomised control trials have demonstrated non-inferiority compared to low molecular weight heparin (LMWH) with a preferable bleeding profile. DOACs are now the first line treatment for atrial fibrillation and venous thromboembolic disease, as recommended by NICE, and therefore there is increasing familiarity with these agents. Furthermore, there are now targeted antidotes available. This paper reviews evidence for efficacy and safety of DOACs in MPN. Whilst no randomised control trials have been performed, several retrospective studies and reviews of registry data have reproducibly demonstrated that, alongside cytoreduction, DOACs represent an effective modality of anticoagulation for treatment of venous thromboembolism in MPN. Furthermore, dosing regimens provide the option for longer term secondary prophylaxis. Use of DOACs in arterial thrombosis is an area for future development and there is already some evidence for utility in peripheral vascular disease.
A Sensitive, Portable Microfluidic Device for SARS-CoV-2 Detection from Self-Collected Saliva
Authors: Yang Jianing , Kidd Mark , Nordquist Alan R. , Smith Stanley D. , Hurth Cedric , Modlin Irvin M. , Zenhausern Frederic
Published: December 2021

Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in December 2019, the spread of SARS-CoV2 infection has been escalating rapidly around the world. In order to provide more timely access to medical intervention, including diagnostic tests and medical treatment, the FDA authorized multiple test protocols for diagnostic tests from nasopharyngeal swab, saliva, urine, bronchoalveolar lavage and fecal samples. The traditional diagnostic tests for this novel coronavirus 2019 require standard processes of viral RNA isolation, reverse transcription of RNA to cDNA, then real-time quantitative PCR with the RNA templates extracted from the patient samples. Recently, many reports have demonstrated a direct detection of SARS-Co-V2 genomic material from saliva samples without any RNA isolation step. To make the rapid detection of SARS-Co-V2 infection more accessible, a point-of-care type device was developed for SARS-CoV-2 detection. Herein, we report a portable microfluidic-based integrated detection-analysis system for SARS-CoV-2 nucleic acids detection directly from saliva samples. The saliva cartridge is self-contained and capable of microfluidic evaluation of saliva, from heating, mixing with the primers to multiplex real-time quantitative polymerase chain reaction, detecting SARS-CoV-2 with different primer sets and internal control. The approach has a detection sensitivity of 1000 copies/mL of SARS-CoV-2 RNA or virus, with consistency and automation, from saliva sample-in to result-out.
“The Competitive Season and Off-Season”: Preliminary Research concerning the Sport-Specific Performance, Stress, and Sleep in Elite Male Adolescent Basketball Athletes
Authors: Chou Chun-Chung , Wang Fei-Ti , Wu Hsin-Hung , Tsai Shiow-Chwen , Chen Chung-Yu , Bernard Jeffrey R. , Kuo Yu-Chi , Liao Yi-Hung
Published: December 2021

Background: Through scholastic sports programs, adolescent athletes compete to represent their communities. However, few studies investigate the changes in physiological and mental profiles during varied sport periodization among this population. Therefore, the purpose of this study was to compare the changes in sports performance and stress-related biomarkers between the competitive season (CS) and off-season (OS) in elite adolescent basketball players. Method: Nine elite Division I male basketball players (age: 15–18 years. old) participated in this study. Basketball-specific performance, salivary dehydroepiandrosterone sulfate (DHEA-S)/cortisol levels, mood state, and sleep quality were all accessed during the CS and OS periods. Results: The training load during OS was 26.0% lower than CS (p = 0.001). Muscle mass, aerobic capacity, 10 m sprint, and Abalakov jump (AJ) power during OS were greater than that during CS (+2.2–9.8%, p < 0.05), but planned agility was greater during CS (p = 0.003). The salivary DHEA-S/cortisol was greater during CS than during OS (p = 0.039). The overall mood state and sleep quality did not differ between periods, but the POMS-tension was higher during CS (p = 0.005). Conclusion: The present study demonstrates that muscle mass, aerobic capacity, peak AJ power, and 10 m sprint performance, but not planned agility, were greater during OS compared to CS among elite adolescent basketball players. Furthermore, the stress-related responses reflected by the D/C ratio and mood tension were relatively lower during the OS in these athletes. Thus, this study suggests that coaches and sport science professionals should closely monitor athletes’ training states across varied training/competition periods to better react to modifying training or recovery plans.
A SEM-NCA Approach towards Social Networks Marketing: Evaluating Consumers’ Sustainable Purchase Behavior with the Moderating Role of Eco-Friendly Attitude
Authors: Ebrahimi Pejman , Khajeheian Datis , Fekete-Farkas Maria
Published: December 2021

This paper aims to investigate how social network marketing affects consumers’ sustainable purchase behavior (CSPB) while considering the role of Eco-friendly attitude. The statistical population of the study included Iranian users of online social networks with at least one online purchasing experience. An online questionnaire was distributed on Instagram, Telegram, and WhatsApp platforms as the most popular networks in the country. By use of convenience sampling, commonly used in quantitative studies to overcome bias, 450 out of 475 returned questionnaires were acceptable, showing a response rate of 94.7%. The results indicated that an increase in Eco-friendly attitude positively increases the effect of word of mouth on consumers’ sustainable purchase behavior. Meanwhile, Necessary Condition Analysis (NCA) revealed that to reach a 50% level of consumers’ sustainable purchase behavior, six essential necessary conditions are required: an eco-friendly consumers’ attitude at no less than 50%, the trend at no less than 57.1%, word of mouth at no less than 45.5%, interaction at no less than 42.9%, customization at no less than 35.3% and entertainment at no less than 26.7%. Furthermore, the Importance-Performance Matrix Analysis (IPMA) was investigated as a strategic tool. The results of IPMA showed that “buy products that use biodegradable material in packaging”, “buy those products that are picked up and recycled”, and “buy biodegradable products even if they belong to a less well-known company” show desirable performance and high importance and there is a great opportunity for expansion in this area.
Influencing Factors of Public Satisfaction with COVID-19 Prevention Services Based on Structural Equation Modeling (SEM): A Study of Nanjing, China
Authors: Chen Wei , Shi Yijun , Fan Liwen , Huang Lijun , Gao Jingyi
Published: December 2021

Service satisfaction with public policies is an important component of public service quality management, which is of great significance to the improvement of public service quality. Based on an online questionnaire survey and in combination with the characteristics of public policies and services, in this study the influencing factors of residents’ satisfaction with COVID-19 pandemic prevention services were analyzed with structural equation modeling. The results reveal that the data fit the model well, and all the hypotheses formulated in this study were supported. Among the factors that were found to directly affect residents’ satisfaction with pandemic prevention services, perceived quality (PQ) has the greatest impact on satisfaction, followed by the disaster situation (DS) and policy expectation (PE). The observed variables that have significant impacts on the latent variables were also explored. Regarding the main findings, the residents who were seriously affected by the pandemic tended to have lower satisfaction with the policies and services provided by the government. Moreover, the improvement of PQ was found to significantly increase pandemic prevention service satisfaction (SS). Finally, the residents with a good psychological status during the pandemic were found to have higher satisfaction. According to the results, implications for the prevention and control practices of similar public health emergencies are proposed.
3D Bio-Printability of Hybrid Pre-Crosslinked Hydrogels
Authors: Nelson Cartwright , Tuladhar Slesha , Launen Loren , Habib Ahasan
Published: December 2021

Maintaining shape fidelity of 3D bio-printed scaffolds with soft biomaterials is an ongoing challenge. Here, a rheological investigation focusing on identifying useful physical and mechanical properties directly related to the geometric fidelity of 3D bio-printed scaffolds is presented. To ensure during- and post-printing shape fidelity of the scaffolds, various percentages of Carboxymethyl Cellulose (CMC) (viscosity enhancer) and different calcium salts (CaCl2 and CaSO4, physical cross-linkers) were mixed into alginate before extrusion to realize shape fidelity. The overall solid content of Alginate-Carboxymethyl Cellulose (CMC) was limited to 6%. A set of rheological tests, e.g., flow curves, amplitude tests, and three interval thixotropic tests, were performed to identify and compare the shear-thinning capacity, gelation points, and recovery rate of various compositions. The geometrical fidelity of the fabricated scaffolds was defined by printability and collapse tests. The effect of using multiple cross-linkers simultaneously was assessed. Various large-scale scaffolds were fabricated (up to 5.0 cm) using a pre-crosslinked hybrid. Scaffolds were assessed for the ability to support the growth of Escherichia coli using the Most Probable Number technique to quantify bacteria immediately after inoculation and 24 h later. This pre-crosslinking-based rheological property controlling technique can open a new avenue for 3D bio-fabrication of scaffolds, ensuring proper geometry.
Two-Chains Tissue Plasminogen Activator Unifies Met and NMDA Receptor Signalling to Control Neuronal Survival
Authors: Hedou Elodie , Douceau Sara , Chevilley Arnaud , Varangot Alexandre , Thiebaut Audrey M. , Triniac Hortense , Bardou Isabelle , Ali Carine , Maillasson Mike , Crepaldi Tiziana , Comoglio Paolo , Lemarchand Eloïse , Agin Véronique , Roussel Benoit D. , Vivien Denis
Published: December 2021

Tissue-type plasminogen activator (tPA) plays roles in the development and the plasticity of the nervous system. Here, we demonstrate in neurons, that by opposition to the single chain form (sc-tPA), the two-chains form of tPA (tc-tPA) activates the MET receptor, leading to the recruitment of N-Methyl-d-Aspartate receptors (NMDARs) and to the endocytosis and proteasome-dependent degradation of NMDARs containing the GluN2B subunit. Accordingly, tc-tPA down-regulated GluN2B-NMDAR-driven signalling, a process prevented by blockers of HGFR/MET and mimicked by its agonists, leading to a modulation of neuronal death. Thus, our present study unmasks a new mechanism of action of tPA, with its two-chains form mediating a crosstalk between MET and the GluN2B subunit of NMDARs to control neuronal survival.
Characterization of a Novel Splicing Variant in Acylglycerol Kinase (AGK) Associated with Fatal Sengers Syndrome
Authors: Barbosa-Gouveia Sofia , Vázquez-Mosquera Maria E. , Gonzalez-Vioque Emiliano , Hermida-Ameijeiras Álvaro , Valverde Laura L. , Armstrong-Moron Judith , Fons-Estupiña Maria del Carmen , Wintjes Liesbeth T. , Kappen Antonia , Rodenburg Richard J. , Couce Maria L.
Published: December 2021

Mitochondrial functional integrity depends on protein and lipid homeostasis in the mitochondrial membranes and disturbances in their accumulation can cause disease. AGK, a mitochondrial acylglycerol kinase, is not only involved in lipid signaling but is also a component of the TIM22 complex in the inner mitochondrial membrane, which mediates the import of a subset of membrane proteins. AGK mutations can alter both phospholipid metabolism and mitochondrial protein biogenesis, contributing to the pathogenesis of Sengers syndrome. We describe the case of an infant carrying a novel homozygous AGK variant, c.518+1G>A, who was born with congenital cataracts, pielic ectasia, critical congenital dilated myocardiopathy, and hyperlactacidemia and died 20 h after birth. Using the patient’s DNA, we performed targeted sequencing of 314 nuclear genes encoding respiratory chain complex subunits and proteins implicated in mitochondrial oxidative phosphorylation (OXPHOS). A decrease of 96-bp in the length of the AGK cDNA sequence was detected. Decreases in the oxygen consumption rate (OCR) and the OCR:ECAR (extracellular acidification rate) ratio in the patient’s fibroblasts indicated reduced electron flow through the respiratory chain, and spectrophotometry revealed decreased activity of OXPHOS complexes I and V. We demonstrate a clear defect in mitochondrial function in the patient’s fibroblasts and describe the possible molecular mechanism underlying the pathogenicity of this novel AGK variant. Experimental validation using in vitro analysis allowed an accurate characterization of the disease-causing variant.
Deficiency of the Ribosomal Protein uL5 Leads to Significant Rearrangements of the Transcriptional and Translational Landscapes in Mammalian Cells
Authors: Babaylova Elena S. , Gopanenko Alexander V. , Tupikin Alexey E. , Kabilov Marsel R. , Malygin Alexey A. , Karpova Galina G.
Published: December 2021

Protein uL5 (formerly called L11) is an integral component of the large (60S) subunit of the human ribosome, and its deficiency in cells leads to the impaired biogenesis of 60S subunits. Using RNA interference, we reduced the level of uL5 in HEK293T cells by three times, which caused an almost proportional decrease in the content of the fraction corresponding to 80S ribosomes, without a noticeable diminution in the level of polysomes. By RNA sequencing of uL5-deficient and control cell samples, which were those of total mRNA and mRNA from the polysome fraction, we identified hundreds of differentially expressed genes (DEGs) at the transcriptome and translatome levels and revealed dozens of genes with altered translational efficiency (GATEs). Transcriptionally up-regulated DEGs were mainly associated with rRNA processing, pre-mRNA splicing, translation and DNA repair, while down-regulated DEGs were genes of membrane proteins; the type of regulation depended on the GC content in the 3′ untranslated regions of DEG mRNAs. The belonging of GATEs to up-regulated and down-regulated ones was determined by the coding sequence length of their mRNAs. Our findings suggest that the effects observed in uL5-deficient cells result from an insufficiency of translationally active ribosomes caused by a deficiency of 60S subunits.
Is Photoprotection of PSII One of the Key Mechanisms for Drought Tolerance in Maize?
Authors: Bashir Nahidah , Athar Habib-ur-Rehman , Kalaji Hazem M. , Wróbel Jacek , Mahmood Seema , Zafar Zafar Ullah , Ashraf Muhammad
Published: December 2021

Drought is one of the most important abiotic stress factors limiting maize production worldwide. The objective of this study was to investigate whether photoprotection of PSII was associated with the degree of drought tolerance and yield in three maize hybrids (30Y87, 31R88, P3939). To do this, three maize hybrids were subjected to three cycles of drought, and we measured the activities of photosystem II (PSII) and photosystem I (PSI). In a second field experiment, three maize hybrids were subjected to drought by withholding irrigation, and plant water status, yield and yield attributes were measured. Drought stress decreased leaf water potential (ΨL) in three maize hybrids, and this reduction was more pronounced in hybrid P3939 (−40%) compared to that of 30Y87 (−30%). Yield and yield attributes of three maize hybrids were adversely affected by drought. The number of kernels and 100-kernel weight was the highest in maize hybrid 30Y87 (−56%, −6%), whereas these were lowest in hybrid P3939 (−88%, −23%). Drought stress reduced the quantum yield of PSII [Y(II)], photochemical quenching (qP), electron transport rate through PSII [ETR(II)] and NPQ, except in P3939. Among the components of NPQ, drought increased the Y(NPQ) with concomitant decrease in Y(NO) only in P3939, whereas Y(NO) increased in drought-stressed plants of hybrid 30Y87 and 31R88. However, an increase in cyclic electron flow (CEF) around PSI and Y(NPQ) in P3939 might have protected the photosynthetic machinery but it did not translate in yield. However, drought-stressed plants of 30Y87 might have sufficiently downregulated PSII to match the energy consumption in downstream biochemical processes. Thus, changes in PSII and PSI activity and development of NPQ through CEF are physiological mechanisms to protect the photosynthetic apparatus, but an appropriate balance between these physiological processes is required, without which plant productivity may decline.
Transient Activation of Hedgehog Signaling Inhibits Cellular Senescence and Inflammation in Radiated Swine Salivary Glands through Preserving Resident Macrophages
Authors: Hu Liang , Du Conglin , Yang Zi , Yang Yang , Zhu Zhao , Shan Zhaochen , Zhang Chunmei , Wang Songlin , Liu Fei
Published: December 2021

Salivary gland function is commonly and irreversibly damaged by radiation therapy for head and neck cancer. This damage greatly decreases the patient’s quality of life and is difficult to remedy. Previously, we found that the transient activation of Hedgehog signaling alleviated salivary hypofunction after radiation in both mouse and pig models through the inhibition of radiation-induced cellular senescence that is mediated by resident macrophages in mouse submandibular glands. Here we report that in swine parotid glands sharing many features with humans, the Hedgehog receptor PTCH1 is mainly expressed in macrophages, and levels of PTCH1 and multiple macrophage markers are significantly decreased by radiation but recovered by transient Hedgehog activation. These parotid macrophages mainly express the M2 macrophage marker ARG1, while radiation promotes expression of pro-inflammatory cytokine that is reversed by transient Hedgehog activation. Hedgehog activation likely preserves parotid macrophages after radiation through inhibition of P53 signaling and consequent cellular senescence. Consistently, VEGF, an essential anti-senescence cytokine downstream of Hedgehog signaling, is significantly decreased by radiation but recovered by transient Hedgehog activation. These findings indicate that in the clinically-relevant swine model, transient Hedgehog activation restores the function of irradiated salivary glands through the recovery of resident macrophages and the consequent inhibition of cellular senescence and inflammation.
On the Dependence of Prion and Amyloid Structure on the Folding Environment
Authors: Roterman Irena , Stapor Katarzyna , Gądek Krzysztof , Gubała Tomasz , Nowakowski Piotr , Fabian Piotr , Konieczny Leszek
Published: December 2021

Currently available analyses of amyloid proteins reveal the necessity of the existence of radical structural changes in amyloid transformation processes. The analysis carried out in this paper based on the model called fuzzy oil drop (FOD) and its modified form (FOD-M) allows quantifying the role of the environment, particularly including the aquatic environment. The starting point and basis for the present presentation is the statement about the presence of two fundamentally different methods of organizing polypeptides into ordered conformations—globular proteins and amyloids. The present study shows the source of the differences between these two paths resulting from the specificity of the external force field coming from the environment, including the aquatic and hydrophobic one. The water environment expressed in the fuzzy oil drop model using the 3D Gauss function directs the folding process towards the construction of a micelle-like system with a hydrophobic core in the central part and the exposure of polarity on the surface. The hydrophobicity distribution of membrane proteins has the opposite characteristic: Exposure of hydrophobicity at the surface of the membrane protein with an often polar center (as in the case of ion channels) is expected. The structure of most proteins is influenced by a more or less modified force field generated by water through the appropriate presence of a non-polar (membrane-like) environment. The determination of the proportion of a factor different from polar water enables the assessment of the protein status by indicating factors favoring the structure it represents.
Cathepsin X Activity Does Not Affect NK-Target Cell Synapse but Is Rather Distributed to Cytotoxic Granules
Authors: Jakoš Tanja , Prunk Mateja , Pišlar Anja , Kos Janko
Published: December 2021

Cathepsin X is a lysosomal peptidase that is involved in tumour progression and represents a potential target for therapeutic interventions. In addition, it regulates important functions of immune cells and is implicated in the modulation of tumour cell–immune cell crosstalk. Selective cathepsin X inhibitors have been proposed as prospective antitumour agents to prevent cancer progression; however, their impact on the antitumour immune response has been overlooked. Previous studies indicate that the migration and adhesion of T cells and dendritic cells are affected by diminished cathepsin X activity. Meanwhile, the influence of cathepsin X inhibition on natural killer (NK) cell function has not yet been explored. Here, we examined the localization patterns of cathepsin X and the role of its inhibitors on the cytotoxicity of cell line NK-92, which is used for adoptive cellular immunotherapy in cancer patients. NK-92 cells depend on lymphocyte function-associated antigen 1 (LFA-1) to form stable immunoconjugates with target cells, providing, in this way, optimal cytotoxicity. Since LFA-1 is a substrate for cathepsin X activity in other types of cells, we hypothesized that cathepsin X could disturb the formation of NK-92 immunoconjugates. Thus, we employed cathepsin X reversible and irreversible inhibitors and evaluated their effects on the NK-92 cell interactions with target cells and on the NK-92 cell cytotoxicity. We show that cathepsin X inhibition does not impair stable conjugate formation or the lytic activity of NK-92 cells. Similarly, the conjugate formation between Jurkat T cells and target cells was not affected by cathepsin X activity. Unlike in previous migration and adhesion studies on T cells, in NK-92 cells cathepsin X was not co-localized with LFA-1 at the plasma membrane but was, rather, redistributed to the cytotoxic granules and secreted during degranulation.
Homophilic Interaction of CD147 Promotes IL-6-Mediated Cholangiocarcinoma Invasion via the NF-κB-Dependent Pathway
Authors: Dana Paweena , Kariya Ryusho , Lert-itthiporn Worachart , Seubwai Wunchana , Saisomboon Saowaluk , Wongkham Chaisiri , Okada Seiji , Wongkham Sopit , Vaeteewoottacharn Kulthida
Published: December 2021

Cholangiocarcinoma (CCA), an aggressive cancer of bile ducts, is a well-known chronic inflammation-related disease. The major impediment in CCA treatment is limited treatment options for advanced disease; hence, an alternative is urgently required. The role of CD147 on cytokine production has been observed in inflammation-related diseases, but not in CCA. Therefore, this study was focused on CD147-promoting proinflammatory cytokine production and functions. Proinflammatory cytokine profiles were compared between CD147 expressing CCA cells and CD147 knockout cells (CD147 KO). Three cytokines, namely interleukin (IL)-6, IL-8, and granulocyte–monocyte colony-stimulating factor (GM-CSF), were dramatically diminished in CD147 KO clones. The involvement of the CD147-related cytokines in CCA invasion was established. CD147-promoted IL-6, IL-8, and GM-CSF secretions were regulated by NF-κB nuclear translocation, Akt activation, and p38 phosphorylation. CD147-fostering IL-6 production was dependent on soluble CD147, CD147 homophilic interaction, and NF-κB function. The overexpression of specific genes in CCA tissues compared to normal counterparts emphasized the clinical importance of these molecules. Altogether, CD147-potentiated proinflammatory cytokine production leading to CCA cell invasion is shown for the first time in the current study. This suggests that modulation of CD147-related inflammation might be a promising choice for advanced CCA treatment.
Alterations in Kynurenine and NAD+ Salvage Pathways during the Successful Treatment of Inflammatory Bowel Disease Suggest HCAR3 and NNMT as Potential Drug Targets
Authors: Wnorowski Artur , Wnorowska Sylwia , Kurzepa Jacek , Parada-Turska Jolanta
Published: December 2021

A meta-analysis of publicly available transcriptomic datasets was performed to identify metabolic pathways profoundly implicated in the progression and treatment of inflammatory bowel disease (IBD). The analysis revealed that genes involved in tryptophan (Trp) metabolism are upregulated in Crohn’s disease (CD) and ulcerative colitis (UC) and return to baseline after successful treatment with infliximab. Microarray and mRNAseq profiles from multiple experiments confirmed that enzymes responsible for Trp degradation via the kynurenine pathway (IDO1, KYNU, IL4I1, KMO, and TDO2), receptor of Trp metabolites (HCAR3), and enzymes catalyzing NAD+ turnover (NAMPT, NNMT, PARP9, CD38) were synchronously coregulated in IBD, but not in intestinal malignancies. The modeling of Trp metabolite fluxes in IBD indicated that changes in gene expression shifted intestinal Trp metabolism from the synthesis of 5-hydroxytryptamine (5HT, serotonin) towards the kynurenine pathway. Based on pathway modeling, this manifested in a decline in mucosal Trp and elevated kynurenine (Kyn) levels, and fueled the production of downstream metabolites, including quinolinate, a substrate for de novo NAD+ synthesis. Interestingly, IBD-dependent alterations in Trp metabolites were normalized in infliximab responders, but not in non-responders. Transcriptomic reconstruction of the NAD+ pathway revealed an increased salvage biosynthesis and utilization of NAD+ in IBD, which normalized in patients successfully treated with infliximab. Treatment-related changes in NAD+ levels correlated with shifts in nicotinamide N-methyltransferase (NNMT) expression. This enzyme helps to maintain a high level of NAD+-dependent proinflammatory signaling by removing excess inhibitory nicotinamide (Nam) from the system. Our analysis highlights the prevalent deregulation of kynurenine and NAD+ biosynthetic pathways in IBD and gives new impetus for conducting an in-depth examination of uncovered phenomena in clinical studies.
Hormonal Regulatory Patterns of LaKNOXs and LaBEL1 Transcription Factors Reveal Their Potential Role in Stem Bulblet Formation in LA Hybrid Lily
Authors: Zhang Yue , Zeng Zhen , Yong Yubing , Lyu Yingmin
Published: December 2021

In lily reproduction, the mechanism of formation of bulbs has been a hot topic. However, studies on stem bulblet formation are limited. Stem bulblets, formed in the leaf axils of under- and above-ground stems, provide lilies with a strong capacity for self-propagation. First, we showed that above-ground stem bulblets can be induced by spraying 100 mg/L 6-BA on the LA hybrid lily ‘Aladdin’, with reduced endogenous IAA and GA4 and a higher relative content of cytokinins. Then, expression patterns of three potential genes (two KNOTTED1-like homeobox (KNOX) and one partial BEL1-like homeobox (BELL)), during stem bulblet formation from our previous study, were determined by RT-qPCR, presenting a down-up trend in KNOXs and a rising tendency in BELL. The partial BELL gene was cloned by RACE from L. ‘Aladdin’ and denoted LaBEL1. Physical interactions of LaKNOX1-LaBEL1 and LaKNOX1-LaKNOX2 were confirmed by yeast two-hybrid and bimolecular fluorescence complementation assays. Furthermore, hormonal regulatory patterns of single LaKNOX1, LaKNOX2, LaBEL1, and their heterodimers, were revealed in transgenic Arabidopsis, suggesting that the massive mRNA accumulations of LaKNOX1, LaKNOX2 and LaBEL1 genes during stem bulblet formation could cause the dramatic relative increase of cytokinins and the decline of GAs and IAA. Taken together, a putative model was proposed that LaKNOX1 interacts with LaKNOX2 and LaBEL1 to regulate multiple phytohormones simultaneously for an appropriate hormonal homeostasis, which suggests their potential role in stem bulblet formation in L. ‘Aladdin’.
Highly Efficient Multi-Step Oxidation Bioanode Using Microfluidic Channels
Authors: Komatsu Tomohiro , Hishii Kazuki , Kimura Michiko , Amaya Satoshi , Sakamoto Hiroaki , Takamura Eiichiro , Satomura Takenori , Suye Shin-ichiro
Published: December 2021

With the rapid decline of fossil fuels, various types of biofuel cells (BFCs) are being developed as an alternative energy source. BFCs based on multi-enzyme cascade reactions are utilized to extract more electrons from substrates. Thus, more power density is obtained from a single molucule of substrate. In the present study, a bioanode that could extract six electrons from a single molecule of L-proline via a three-enzyme cascade reaction was developed and investigated for its possible use in BFCs. These enzymes were immobilized on the electrode to ensure highly efficient electron transfer. Then, oriented immobilization of enzymes was achieved using two types of self-assembled monolayers (SAMs). In addition, a microfluidic system was incorporated to achieve efficient electron transfer. The microfluidic system, in which the electrodes were arranged in a tooth-shaped comb, allowed for substrates to be supplied continuously to the cascade, which resulted in smooth electron transfer. Finally, we developed a high-performance bioanode which resulted in the accumulation of higher current density compared to that of a gold disc electrode (205.8 μA cm−2: approximately 187 times higher). This presents an opportunity for using the bioanode to develop high-performance BFCs in the future.
Ionophore Ability of Carnosine and Its Trehalose Conjugate Assists Copper Signal in Triggering Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Activation In Vitro
Authors: Naletova Irina , Greco Valentina , Sciuto Sebastiano , Attanasio Francesco , Rizzarelli Enrico
Published: December 2021

l-carnosine (β-alanyl-l-histidine) (Car hereafter) is a natural dipeptide widely distributed in mammalian tissues and reaching high concentrations (0.7–2.0 mM) in the brain. The molecular features of the dipeptide underlie the antioxidant, anti-aggregating and metal chelating ability showed in a large number of physiological effects, while the biological mechanisms involved in the protective role found against several diseases cannot be explained on the basis of the above-mentioned properties alone, requiring further research efforts. It has been reported that l-carnosine increases the secretion and expression of various neurotrophic factors and affects copper homeostasis in nervous cells inducing Cu cellular uptake in keeping with the key metal-sensing system. Having in mind this l-carnosine ability, here we report the copper-binding and ionophore ability of l-carnosine to activate tyrosine kinase cascade pathways in PC12 cells and stimulate the expression of BDNF. Furthermore, the study was extended to verify the ability of the dipeptide to favor copper signaling inducing the expression of VEGF. Being aware that the potential protective action of l-carnosine is drastically hampered by its hydrolysis, we also report on the behavior of a conjugate of l-carnosine with trehalose that blocks the carnosinase degradative activity. Overall, our findings describe a copper tuning effect on the ability of l-carnosine and, particularly its conjugate, to activate tyrosine kinase cascade pathways.
NnABI4-Mediated ABA Regulation of Starch Biosynthesis in Lotus (Nelumbo nucifera Gaertn)
Authors: Wu Peng , Liu Ailian , Zhang Yongyan , Feng Kai , Zhao Shuping , Li Liangjun
Published: December 2021

Starch is an important component in lotus. ABA is an important plant hormone, which plays a very crucial role in regulating plant starch synthesis. Using ‘MRH’ as experimental materials, the leaves were sprayed with exogenous ABA before the rhizome expansion. The results showed that stomatal conductance and transpiration rate decreased while net photosynthetic rate increased. The total starch content of the underground rhizome of lotus increased significantly. Meanwhile, qPCR results showed that the relative expression levels of NnSS1, NnSBE1 and NnABI4 were all upregulated after ABA treatment. Then, yeast one-hybrid and dual luciferase assay suggested that NnABI4 protein can promote the expression of NnSS1 by directly binding to its promoter. In addition, subcellular localization results showed that NnABI4 encodes a nuclear protein, and NnSS1 protein was located in the chloroplast. Finally, these results indicate that ABA induced the upregulated expression of NnABI4, and NnABI4 promoted the expression of NnSS1 and thus enhanced starch accumulation in lotus rhizomes. This will provide a theoretical basis for studying the molecular mechanism of ABA regulating starch synthesis in plant.
MFN1 and MFN2 Are Dispensable for Sperm Development and Functions in Mice
Authors: Miao Junru , Chen Wei , Wang Pengxiang , Zhang Xin , Wang Lei , Wang Shuai , Wang Yuan
Published: December 2021

MFN1 (Mitofusin 1) and MFN2 (Mitofusin 2) are GTPases essential for mitochondrial fusion. Published studies revealed crucial roles of both Mitofusins during embryonic development. Despite the unique mitochondrial organization in sperm flagella, the biological requirement in sperm development and functions remain undefined. Here, using sperm-specific Cre drivers, we show that either Mfn1 or Mfn2 knockout in haploid germ cells does not affect male fertility. The Mfn1 and Mfn2 double knockout mice were further analyzed. We found no differences in testis morphology and weight between Mfn-deficient mice and their wild-type littermate controls. Spermatogenesis was normal in Mfn double knockout mice, in which properly developed TRA98+ germ cells, SYCP3+ spermatocytes, and TNP1+ spermatids/spermatozoa were detected in seminiferous tubules, indicating that sperm formation was not disrupted upon MFN deficiency. Collectively, our findings reveal that both MFN1 and MFN2 are dispensable for sperm development and functions in mice.
The Toxic Mechanism of Gliotoxins and Biosynthetic Strategies for Toxicity Prevention
Authors: Ye Wei , Liu Taomei , Zhang Weiyang , Zhang Weimin
Published: December 2021

Gliotoxin is a kind of epipolythiodioxopiperazine derived from different fungi that is characterized by a disulfide bridge. Gliotoxins can be biosynthesized by a gli gene cluster and regulated by a positive GliZ regulator. Gliotoxins show cytotoxic effects via the suppression the function of macrophage immune function, inflammation, antiangiogenesis, DNA damage by ROS production, peroxide damage by the inhibition of various enzymes, and apoptosis through different signal pathways. In the other hand, gliotoxins can also be beneficial with different doses. Low doses of gliotoxin can be used as an antioxidant, in the diagnosis and treatment of HIV, and as an anti-tumor agent in the future. Gliotoxins have also been used in the control of plant pathogens, including Pythium ultimum and Sclerotinia sclerotiorum. Thus, it is important to elucidate the toxic mechanism of gliotoxins. The toxic mechanism of gliotoxins and biosynthetic strategies to reduce the toxicity of gliotoxins and their producing strains are summarized in this review.