bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection
Authors: Salgado-Albarrán Marisol , Navarro-Delgado Erick I. , Del Moral-Morales Aylin , Alcaraz Nicolas , Baumbach Jan , González-Barrios Rodrigo , Soto-Reyes Ernesto 
Published: May 2021

AbstractCOVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV, and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA, and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that has therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.
Total nitrogen is the main soil property associated with soil fungal community in karst rocky desertification regions in southwest China
Authors: Qi Daihua , Wieneke Xuwen , Xue Peipei , He Li , DeSilva Udaya 
Published: May 2021

AbstractKarst rocky desertification (KRD) is a type of land deterioration, resulting in the degraded soil and a delicate ecosystem. Previous studies focused on the influence of KRD on the animals and plants, the impact of KRD on microorganisms, especially soil fungi remains to be discovered. This study reveals the change in the soil fungal community in response to KRD progression in southwest China. Illumina HiSeq was used to survey the soil fungal community. Results showed that the soil fungal community in the severe KRD (SKRD) was noticeably different from that in other KRD areas. Statistical analyses suggested that soil TN was the primary factor associated with the fungal community, followed by pH. Phylum Ascomycota was significantly abundant in non-degraded soils; whereas Basidiomycota predominated in SKRD. The ratio of Ascomycota/Basidiomycota significantly decreased along with KRD progression, which might be used as an indicator of KRD severity. Phylum Basidiomycota was sensitive to changes in all the soil properties but AP. Genus Sebacina might have the potential to promote vegetation and land restoration in KRD areas. This study fills a gap of knowledge on changes in soil fungal communities in accordance with KRD progression.
Predicting MHC I restricted T cell epitopes in mice with NAP-CNB, a novel online tool
Authors: Wert-Carvajal Carlos , Sánchez-García Rubén , Macías José R , Sanz-Pamplona Rebeca , Pérez Almudena Méndez , Alemany Ramon , Veiga Esteban , Sorzano Carlos Óscar S. , Muñoz-Barrutia Arrate 
Published: May 2021

AbstractLack of a dedicated integrated pipeline for neoantigen discovery in mice hinders cancer immunotherapy research. Novel sequential approaches through recurrent neural networks can improve the accuracy of T-cell epitope binding affinity predictions in mice, and a simplified variant selection process can reduce operational requirements. We have developed a web server tool (NAP-CNB) for a full and automatic pipeline based on recurrent neural networks, to predict putative neoantigens from tumoral RNA sequencing reads. The developed software can estimate H-2 peptide ligands, with an AUC comparable or superior to state-of-the-art methods, directly from tumor samples. As a proof-of-concept, we used the B16 melanoma model to test the system’s predictive capabilities, and we report its putative neoantigens. NAP-CNB web server is freely available at http://biocomp.cnb.csic.es/NeoantigensApp/ with scripts and datasets accessible through the download section.
A two-hybrid system reveals previously uncharacterized protein–protein interactions within the Helicobacter pylori NIF iron–sulfur maturation system
Authors: Benoit Stéphane L. , Agudelo Stephanie , Maier Robert J. 
Published: May 2021

AbstractIron–sulfur (Fe–S) proteins play essential roles in all living organisms. The gastric pathogen Helicobacter pylori relies exclusively on the NIF system for biosynthesis and delivery of Fe–S clusters. Previously characterized components include two essential proteins, NifS (cysteine desulfurase) and NifU (scaffold protein), and a dispensable Fe–S carrier, Nfu. Among 38 proteins previously predicted to coordinate Fe–S clusters, two proteins, HP0207 (a member of the Nbp35/ApbC ATPase family) and HP0277 (previously annotated as FdxA, a member of the YfhL ferredoxin-like family) were further studied, using a bacterial two-hybrid system approach to identify protein–protein interactions. ApbC was found to interact with 30 proteins, including itself, NifS, NifU, Nfu and FdxA, and alteration of the conserved ATPase motif in ApbC resulted in a significant (50%) decrease in the number of protein interactions, suggesting the ATpase activity is needed for some ApbC-target protein interactions. FdxA was shown to interact with 21 proteins, including itself, NifS, ApbC and Nfu, however no interactions between NifU and FdxA were detected. By use of cross-linking studies, a 51-kDa ApbC-Nfu heterodimer complex was identified. Attempts to generate apbC chromosomal deletion mutants in H. pylori were unsuccessful, therefore indirectly suggesting the hp0207 gene is essential. In contrast, mutants in the fdxA gene were obtained, albeit only in one parental strain (26695). Taken together, these results suggest both ApbC and FdxA are important players in the H. pylori NIF maturation system.
Human-agent coordination in a group formation game
Authors: Takko Tuomas , Bhattacharya Kunal , Monsivais Daniel , Kaski Kimmo 
Published: May 2021

AbstractCoordination and cooperation between humans and autonomous agents in cooperative games raise interesting questions on human decision making and behaviour changes. Here we report our findings from a group formation game in a small-world network of different mixes of human and agent players, aiming to achieve connected clusters of the same colour by swapping places with neighbouring players using non-overlapping information. In the experiments the human players are incentivized by rewarding to prioritize their own cluster while the model of agents’ decision making is derived from our previous experiment of purely cooperative game between human players. The experiments were performed by grouping the players in three different setups to investigate the overall effect of having cooperative autonomous agents within teams. We observe that the human subjects adjust to autonomous agents by being less risk averse, while keeping the overall performance efficient by splitting the behaviour into selfish and cooperative actions performed during the rounds of the game. Moreover, results from two hybrid human-agent setups suggest that the group composition affects the evolution of clusters. Our findings indicate that in purely or lesser cooperative settings, providing more control to humans could help in maximizing the overall performance of hybrid systems.
Refinement of 16S rRNA gene analysis for low biomass biospecimens
Authors: Villette Remy , Autaa Gaelle , Hind Sophie , Holm Johanna B. , Moreno-Sabater Alicia , Larsen Martin 
Published: May 2021

AbstractHigh-throughput phylogenetic 16S rRNA gene analysis has permitted to thoroughly delve into microbial community complexity and to understand host-microbiota interactions in health and disease. The analysis comprises sample collection and storage, genomic DNA extraction, 16S rRNA gene amplification, high-throughput amplicon sequencing and bioinformatic analysis. Low biomass microbiota samples (e.g. biopsies, tissue swabs and lavages) are receiving increasing attention, but optimal standardization for analysis of low biomass samples has yet to be developed. Here we tested the lower bacterial concentration required to perform 16S rRNA gene analysis using three different DNA extraction protocols, three different mechanical lysing series and two different PCR protocols. A mock microbiota community standard and low biomass samples (108, 107, 106, 105 and 104 microbes) from two healthy donor stools were employed to assess optimal sample processing for 16S rRNA gene analysis using paired-end Illumina MiSeq technology. Three DNA extraction protocols tested in our study performed similar with regards to representing microbiota composition, but extraction yield was better for silica columns compared to bead absorption and chemical precipitation. Furthermore, increasing mechanical lysing time and repetition did ameliorate the representation of bacterial composition. The most influential factor enabling appropriate representation of microbiota composition remains sample biomass. Indeed, bacterial densities below 106 cells resulted in loss of sample identity based on cluster analysis for all tested protocols. Finally, we excluded DNA extraction bias using a genomic DNA standard, which revealed that a semi-nested PCR protocol represented microbiota composition better than classical PCR. Based on our results, starting material concentration is an important limiting factor, highlighting the need to adapt protocols for dealing with low biomass samples. Our study suggests that the use of prolonged mechanical lysing, silica membrane DNA isolation and a semi-nested PCR protocol improve the analysis of low biomass samples. Using the improved protocol we report a lower limit of 106 bacteria per sample for robust and reproducible microbiota analysis.
Differential microbial assemblages associated with shikonin-producing Borage species in two distinct soil types
Authors: Fazal Aliya , Yang Minkai , Wen Zhongling , Ali Farman , Ren Ran , Hao Chenyu , Chen Xingyu , Fu Jiangyan , Wang Xuan , Jie Wencai , Yin Tongming , Lu Guihua , Qi Jinliang , Yang Yonghua 
Published: May 2021

AbstractShikonin and its derivatives are the main components of traditional Chinese medicine, Zicao. The pharmacological potential of shikonin and its derivatives have been extensively studied. Yet, less is known about the microbial assemblages associated with shikonin producing Borage plants. We studied microbial profiles of two Borage species, Echium plantagineum (EP) and Lithospermum erythrorhizon (LE), to identify the dynamics of microbial colonization pattern within three rhizo-compatments and two distinct soil types. Results of α and β-diversity via PacBio sequencing revealed significantly higher microbial richness and diversity in the natural soil along with a decreasing microbial gradient across rhizosphere to endosphere. Our results displayed genotype and soil type–dependent fine-tuning of microbial profiles. The host plant was found to exert effects on the physical and chemical properties of soil, resulting in reproducibly different micro-biota. Analysis of differentially abundant microbial OTUs displayed Planctomycetes and Bacteroidetes to be specifically enriched in EP and LE rhizosphere while endosphere was mostly prevailed by Cyanobacteria. Network analysis to unfold co-existing microbial species displayed different types of positive and negative interactions within different communities. The data provided here will help to identify microbes associated with different rhizo-compartments of potential host plants. In the future, this might be helpful for manipulating the keystone microbes for ecosystem functioning.
CD13 is a critical regulator of cell–cell fusion in osteoclastogenesis
Authors: Ghosh Mallika , Kelava Tomislav , Madunic Ivana Vrhovac , Kalajzic Ivo , Shapiro Linda H. 
Published: May 2021

AbstractThe transmembrane aminopeptidase CD13 is highly expressed in cells of the myeloid lineage, regulates dynamin-dependent receptor endocytosis and recycling and is a necessary component of actin cytoskeletal organization. Here, we show that CD13-deficient mice present a low bone density phenotype with increased numbers of osteoclasts per bone surface, but display a normal distribution of osteoclast progenitor populations in the bone marrow and periphery. In addition, the bone formation and mineral apposition rates are similar between genotypes, indicating a defect in osteoclast-specific function in vivo. Lack of CD13 led to exaggerated in vitro osteoclastogenesis as indicated by significantly enhanced fusion of bone marrow-derived multinucleated osteoclasts in the presence of M-CSF and RANKL, resulting in abnormally large cells containing remarkably high numbers of nuclei. Mechanistically, while expression levels of the fusion-regulatory proteins dynamin and DC-STAMP1 must be downregulated for fusion to proceed, these are aberrantly sustained at high levels even in CD13-deficient mature multi-nucleated osteoclasts. Further, the stability of fusion-promoting proteins is maintained in the absence of CD13, implicating CD13 in protein turnover mechanisms. Together, we conclude that CD13 may regulate cell–cell fusion by controlling the expression and localization of key fusion regulatory proteins that are critical for osteoclast fusion.
Aerobic exercise intensity does not affect the anabolic signaling following resistance exercise in endurance athletes
Authors: Jones T. W. , Eddens L. , Kupusarevic J. , Simoes D. C. M. , Furber M. J. W. , van Someren K. A. , Howatson G. 
Published: May 2021

AbstractThis study examined whether intensity of endurance stimulus within a concurrent training paradigm influenced the phosphorylation of signaling proteins associated with the mTOR and AMPK networks. Eight male cyclists completed (1) resistance exercise (RES), 6 × 8 squats at 80% 1-RM; (2) resistance exercise and moderate intensity cycling of 40 min at 65% V̇O2peak, (RES + MIC); (3) resistance exercise and high intensity interval cycling of 40 min with 6 alternating 3 min intervals of 85 and 45% V̇O2peak (RES + HIIC), in a cross-over design. Muscle biopsies were collected at rest and 3 h post-RES. There was a main effect of condition for mTORS2448 (p = 0.043), with a greater response in the RES + MIC relative to RES condition (p = 0.033). There was a main effect of condition for AMPKα2T172 (p = 0.041), with a greater response in RES + MIC, relative to both RES + HIIC (p = 0.026) and RES (p = 0.046). There were no other condition effects for the remaining protein kinases assessed (p > 0.05). These data do not support a molecular interference effect in cyclists under controlled conditions. There was no intensity-dependent regulation of AMPK, nor differential activation of anabolism with the manipulation of endurance exercise intensity.
The bactericidal effect of vancomycin is not altered by tranexamic acid, adrenalin, dexamethasone, or lidocaine in vitro
Authors: Schwerdt Christiane , Röhner Eric , Böhle Sabrina , Jacob Benjamin , Matziolis Georg 
Published: May 2021

AbstractOne of the most challenging complications of total knee arthroplasty (TKA) is periprosthetic joint infection (PJI). There is growing evidence of a good anti-infective effect of intrawound vancomycin powder in total joint arthroplasty. At the same time, various different locally applied substances have become popular in total joint arthroplasty. The objective of this study was therefore to investigate a possible inhibition of the bactericidal effect of vancomycin by tranexamic acid, adrenalin, lidocaine, or dexamethasone. The bactericidal effect of vancomycin was quantified using the established method of the agar diffusion test. The plates were incubated with Staphylococcus aureus or Staphylococcus epidermidis and four wells were stamped out. The wells were filled with vancomycin alone, the tested substance alone or a mixture of the two. The fourth well remained empty as a control. The plates were incubated overnight at 37 °C and the zone of inhibition in each field was measured on the next day. All tests were run three times for each pathogen and mean values and standard deviations of the measurements were calculated. Differences between the substances were tested using the t-test at a level of significance of 0.05. The bacterial growth was homogeneous on all plates. The baseline value for the zone of inhibition of vancomycin was on average 6.2 ± 0.4 mm for Staphylococcus aureus and 12 ± 0.3 mm for Staphylococcus epidermidis. In all other substances, no inhibition was detected around the well. The combination of vancomycin and each other substance did not show any different result compared to vancomycin alone. The bactericidal effect of vancomycin on staphylococci is not altered by tranexamic acid, adrenalin, dexamethasone, or lidocaine in vitro.
Functional interaction between Wnt and Bmp signaling in periosteal bone growth
Authors: Song Deye , He Guangxu , Shi Yu , Ni Jiangdong , Long Fanxin 
Published: May 2021

AbstractWnt and Bmp proteins are well known to regulate bone development and homeostasis. Although both signals are extensively studied, their potential interaction in vivo is less well understood. Previous studies have shown that deletion of Bmpr1a, a type I receptor for Bmp signaling, results in excessive trabecular bone formation while diminishing periosteal bone growth. Moreover, forced-expression of the Wnt antagonist Sost suppresses the overgrowth of trabecular bone caused by Bmpr1a deletion, thus implicating hyperactive Wnt signaling in the excessive trabecular bone formation. However, it remains uncertain whether Wnt and Bmp signaling interacts in regulating the periosteal bone growth. Here we show that multiple Wnt genes are markedly suppressed in the cortical bone without Bmpr1a. Importantly, overexpression of Wnt7b fully rescues periosteal bone growth in the Bmpr1a-deficient mice. Thus, pharmacological activation of Wnt signaling can restore normal bone size without intact Bmp signaling.
The contributions of entorhinal cortex and hippocampus to error driven learning
Authors: Ku Shih-pi , Hargreaves Eric L. , Wirth Sylvia , Suzuki Wendy A. 
Published: May 2021

AbstractComputational models proposed that the medial temporal lobe (MTL) contributes importantly to error-driven learning, though little direct in-vivo evidence for this hypothesis exists. To test this, we recorded in the entorhinal cortex (EC) and hippocampus (HPC) as macaques performed an associative learning task using an error-driven learning strategy, defined as better performance after error relative to correct trials. Error-detection signals were more prominent in the EC relative to HPC. Early in learning hippocampal but not EC neurons signaled error-driven learning by increasing their population stimulus-selectivity following error trials. This same pattern was not seen in another task where error-driven learning was not used. After learning, different populations of cells in both the EC and HPC signaled long-term memory of newly learned associations with enhanced stimulus-selective responses. These results suggest prominent but differential contributions of EC and HPC to learning from errors and a particularly important role of the EC in error-detection.
Halogen–sodium exchange enables efficient access to organosodium compounds
Authors: Asako Sobi , Takahashi Ikko , Nakajima Hirotaka , Ilies Laurean , Takai Kazuhiko 
Published: May 2021

AbstractWith sodium being the most abundant alkali metal on Earth, organosodium compounds are an attractive choice for sustainable chemical synthesis. However, organosodium compounds are rarely used—and are overshadowed by organolithium compounds—because of a lack of convenient and efficient preparation methods. Here we report a halogen–sodium exchange method to prepare a large variety of (hetero)aryl- and alkenylsodium compounds including tri- and tetrasodioarenes, many of them previously inaccessible by other methods. The key discovery is the use of a primary and bulky alkylsodium lacking β-hydrogens, which retards undesired reactions, such as Wurtz–Fittig coupling and β-hydrogen elimination, and enables efficient halogen–sodium exchange. The alkylsodium is readily prepared in situ from neopentyl chloride and an easy-to-handle sodium dispersion. We believe that the efficiency, generality, and convenience of the present method will contribute to the widespread use of organosodium in organic synthesis, ultimately contributing to the development of sustainable organic synthesis by rivalling the currently dominant organolithium reagents.
Sequential condensation/biannulation reactions of β-(2-aminophenyl)-α,β-ynones with 1,3-dicarbonyls
Authors: Marsicano Vincenzo , Arcadi Antonio , Chiarini Marco , Fabrizi Giancarlo , Goggiamani Antonella , Iazzetti Antonia 
Published: May 2021

A divergent domino reaction of β-(2-aminophenyl) α,β-ynones with 1,3-dicarbonyls to construct polycyclic 4H-pyrano[3,4-c]quinoline cores and perlodinine analogues has been developed.
Development and Preliminary Evaluation of the Tinnitus Severity Short Form
Authors: Frumkin Madelyn R. , Kallogjeri Dorina , Piccirillo Jay F. , Beukes Eldre W. , Manchaiah Vinaya , Andersson Gerhard , Rodebaugh Thomas L. 
Published: May 2021

Purpose
Tinnitus, or the perception of sounds that occur without an external sound source, is a prevalent condition worldwide. For a subset of adults, tinnitus causes significant distress and impairment. Several patient-reported outcome measures have been developed to assess severity of tinnitus distress. However, at present, the field lacks a brief measure that is sensitive to treatment change. The purpose of the current study was to develop and preliminarily validate a brief questionnaire for tinnitus severity from two existing measures of tinnitus-related distress, the Tinnitus Handicap Inventory (THI) and Tinnitus Functional Index (TFI).

Method
Using data from nine study samples in the United States and United Kingdom, we conducted exploratory and confirmatory factor analyses to identify a short measure with good psychometric properties. We also assessed sensitivity to treatment-related change by examining associations with change in the TFI and THI. Finally, we conducted a confirmatory factor analysis of the final short questionnaire in a new sample of adults seeking treatment for tinnitus-related distress.

Results
We identified 10 items from the THI and TFI that exhibited limited loadings on secondary factors. The resulting Tinnitus Severity Short Form achieved good to excellent fit, including in a unique sample of individuals seeking online treatment for tinnitus, and appeared sensitive to treatment-related change.

Conclusions
The Tinnitus Severity Short Form developed in the current study may be a useful tool for the assessment of subjective severity and distress associated with tinnitus, especially when patient burden is a concern. Further research is necessary to fully validate the questionnaire for the assessment of treatment-related change.