bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous modulations of high frequency cortical activity
Authors: Ono Hiroya , Sonoda Masaki , Silverstein Brian H. , Sonoda Kaori , Kubota Takafumi , Luat Aimee F. , Rothermel Robert , Sood Sandeep , Asano Eishi 
Published: April 2021

ABSTRACTObjectiveWe clarified the clinical and mechanistic significance of physiological modulations of high-frequency broadband cortical activity associated with spontaneous saccadic eye movements during a resting state.MethodsWe studied 30 patients who underwent epilepsy surgery following extraoperative electrocorticography and electrooculography recordings. We determined whether high-gamma activity at 70-110 Hzpreceding saccade onsetwould predict upcoming ocular behaviors. We assessed how accurately the model incorporating saccade-related high-gamma modulations would localize the primary visual cortex defined by electrical stimulation.ResultsThe whole-brain level dynamic atlas demonstrated transient high-gamma suppression in the striatal region before saccade onset and high-gamma augmentation subsequently involving the widespread posterior brain regions. More intense striatal high-gamma suppression predicted the upcoming saccade directed to the ipsilateral side and lasting longer in duration. The bagged-tree-ensemble model demonstrated that intense saccade-related high-gamma modulations localized the visual cortex with an accuracy of 95%.ConclusionsWe successfully animated the neural dynamics supporting saccadic suppression, a principal mechanism minimizing the perception of blurred vision during rapid eye movements. The primary visual cortexper semay prepareactively in advancefor massive image motion expected during upcoming prolonged saccades.SignificanceMeasuring saccade-related electrocorticographic signals may help localize the visual cortex and avoid misperceiving physiological high-frequency activity as epileptogenic.Highlights-The whole-brain level dynamic atlas animated spontaneous high gamma modulations associated with saccadic eye movements.-Preceding high gamma activity in the striatal cortex predicted the direction and duration of the upcoming saccades.-Saccade-related high-gamma modulations localized the stimulation-defined visual cortex with an accuracy of 95%.
Genetic deletion of interleukin-15 is not associated with major structural changes following experimental post-traumatic knee osteoarthritis in rats
Authors: Hadzic Ermina , Blackler Garth , Dupuis Holly , Renaud Stephen J , Appleton C. Thomas , Beier Frank 
Published: April 2021

AbstractPost-traumatic Osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in OA pathophysiology are not well characterized.IL-15 levels appear to correlate to self-reported pain levels, and polymorphisms in the IL-15 receptor alpha gene correlate to a 1.5-fold increase in OA symptoms. This could be due to IL-15 effects on the activity of proteinases, such as matrix metalloproteinases (MMP) −1, −3, and −7. Here we utilizedIl15deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model of OA. OA was surgically induced inIl15deficient rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. Analyses of articular cartilage damage, subchondral bone damage, and osteophyte formation revealed no significant difference betweenIl15deficient rats and wild-type rats following PTOA-induction. Similarly, synovitis scoring across 6 parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA.
A computational model of typical and impaired reading: the role of visual processing
Authors: Chang Ya-Ning , Welbourne Stephen , Furber Steve , Ralph Matthew Lambon 
Published: April 2021

AbstractComputational modelling has served as a powerful tool to advance our understanding of language processes by making theoretical ideas rigorously specified and testable (a form of “ open science” for theory building). In reading research, one of the most influential computational modelling frameworks is the triangle model of reading that characterises the mappings between orthography, phonology and semantics. Currently, most instantiations of the triangle modelling framework start the processes from orthographic levels which abstract away visual processing. Moreover, without visual processing, most models do not provide an opportunity to investigate visual-related dyslexia. To bridge this crucial gap, the present study extended the existing triangle models by implementing an additional visual input. We trained the model to learn to read from visual input without pre-defined orthographic representations. The model was assessed by reading tasks in both intact and after damage (to mimic acquire alexias). The simulation results demonstrated that the model was able to name word and nonwords as well as make lexical decisions. Damage to the visual, phonological or semantic components of the model resulted in the expected reading impairments associated with pure alexia, phonological dyslexia, and surface dyslexia, respectively. The simulation results demonstrated for the first time that both typical and neurologically-impaired reading including both central and peripheral dyslexia could be addressed in this extended triangle model of reading. The findings are consistent with the primary systems account.
JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation
Authors: Tavares Manuel , Khandelwal Garima , Mutter Joanne , Viiri Keijo , Beltran Manuel , Brosens Jan J. , Jenner Richard G. 
Published: April 2021

ABSTRACTPolycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain repression of genes specific for other cell types and is essential for cell differentiation. In endometrial stromal sarcoma, the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. Here, we show that JAZF1-SUZ12 dysregulates PRC2 composition, recruitment, histone modification, gene expression and cell differentiation. The loss of the SUZ12 N-terminus in the fusion protein disrupted interaction with the PRC2 accessory factors JARID2, EPOP and PALI1 and prevented recruitment of PRC2 from RNA to chromatin. In undifferentiated cells, JAZF1-SUZ12 occupied PRC2 target genes but gained a JAZF1-like binding profile during cell differentiation. JAZF1-SUZ12 reduced H3K27me3 and increased H4Kac at PRC2 target genes, and this was associated with disruption in gene expression and cell differentiation programs. These results reveal the defects in chromatin regulation caused by JAZF1-SUZ12, which may underlie its role in oncogenesis.
Characterization of a novel mesophilic CTP-dependent riboflavin kinase and rational engineering to create its thermostable homologs
Authors: Kumar Yashwant , Singh Reman Kumar , Hazra Amrita Brajagopal 
Published: April 2021

ABSTRACTFlavins play a central role in cellular metabolism as molecules that catalyze a wide range of oxidation-reduction reactions in living organisms. Several interesting variations in flavin biosynthesis exist among the domains of life, and the analysis of enzymes on this pathway have put forth many unique structural and mechanistic insights till date. The CTP-dependent riboflavin kinase in archaea is one such example - unlike most kinase enzymes that use adenosine triphosphate to conduct phosphorylation reactions, riboflavin kinases from archaea utilizes cytidine triphosphate (CTP) to phosphorylate riboflavin to produce flavin mononucleotide (FMN). In this study, we present the characterization of a new mesophilic archaeal riboflavin kinase homolog fromMethanococcus maripaludis(MmpRibK), which is linked closely in sequence to the previously characterized thermophilic homolog fromMethanocaldococcus jannaschii(MjRibK). We reconstitute the activity of the CTP-dependentMmpRibK, determine its kinetic parameters, and analyse the molecular factors that contribute to the uncommon properties of this class of enzymes. Specifically, we probe the flexibility ofMmpRibK andMjRibK under varying temperatures and the role of a metal ion for substrate binding and catalysis using molecular dynamics simulation and a series of experiments. Furthermore, based on the high degree of sequence similarity between the mesophilicMmpRibK and the thermophilicMjRibK, we use comparative analysis and site-directed mutagenesis to establish a set of the residues that are responsible for the thermostability of the enzyme without any loss in activity or substrate specificity. Our work contributes to the molecular understanding of flavin biosynthesis in archaea through the characterization of the first mesophilic CTP-dependent riboflavin kinase. Finally, it validates the role of salt bridges and rigidifying amino acid residues in imparting thermostability to enzymes, with implications in enzyme engineering and biotechnological applications.
Exploration of clinical breakpoint of Danofloxacin forGlaesserella parasuisin plasma and in PELF
Authors: Xu Zihui , Huang Anxiong , Luo Xun , Zhang Peng , Huang Lingli , Wang Xu , Mi Kun , Fang Shiwei , Huang Xiao , Li Jun , Yuan Zonghui , Hao Haihong 
Published: April 2021

AbstractBackgroundTo establish the clinical breakpoint (CBP) of danofloxacin toG. parasuis, three cutoff values, including epidemiological cutoff value (ECV), pharmacodynamic cutoff value (COPD) and clinical cutoff value (COCL), was obtained in the present study.MethodsThe ECV was calculated using ECOFFinder base on MIC distribution of 347G. parasuiscollected from disease pigs. The COPDwas established base onin vivoandex vivopharmacokinetic (PK) - pharmacodynamic (PD) modeling of danofloxacin both in plasma and pulmonary epithelial lining fluid (PELF) using Hill formula and Monte Carlo analysis. The COCLwas established based on the relationship between possibility of cure (POC) and MIC in the clinical trials using “WindoW” approach, nonlinear regression and CART analysis.ResultsThe MIC50and MIC90of danofloxacin against 347G. parasuiswere 2 μg/mL and 8 μg/mL, respectively. The ECV value was set up as 8 μg/mL using ECOFFinder. Concentration-time curve of danofloxacin indicated a two-compartment model for PK analysis. The PK parameters of the maximum concentration (Cmax) and area under concentration-time curve (AUC) in PELF were 3.67 ± 0.25 μg/mL and 24.28 ± 2.70 h·μg/mL, higher than those in plasma (0.67 ± 0.01μg/mL and 4.47 ± 0.51 h·μg/mL). The peak time (Tmax) in plasma was 0.23 ± 0.07 h, shorter than that in PELF (1.61 ± 0.15 h). The COPDin plasma and PELF were 0.125 μg/mL and 0.5 μg/mL, respectively. The COCLcalculated by WindoW approach, nonlinear regression and CART analysis were 0.125∼4 μg/mL, 0.428 μg/mL and 0.56 μg/mL, respectively. The 0.5 μg/mL was selected as eligible COCL. The ECV is much higher than the COPDand COCL, and the clinical breakpoint based on data in plasma was large different with that of in PELF.ConclusionsOur study firstly established three cutoff values of danofloxacin againstG. parasuis. It suggested that epidemiological danofloxacin-resistantG. parasuismay lead to the ineffective treatment by danofloxacin.ImportanceG. parasuis, a gram-negative respiratory pathogen, can colonize in the upper respiratory tract in swine and cause Glasser’s disease. As the abuse of antibiotics, antimicrobial resistantG. parasuisemerged in different degrees, which brought serious threat to global economy and public health. Danofloxacin in quinolones are one of the best choices for treatment ofG. parasuisinfection, because of their strong bactericidal activity and good absorption into blood and great distribution in the lung. However, the clinical breakpoint (CBP) for danofloxacin againstG. parasuishad not yet been established by clinical laboratory of standard Institute (CLSI) and European Commission of antimicrobial susceptibility testing (EUCAST). Our study firstly established three cutoff values of danofloxacin againstG. parasuis. It suggested that epidemiological danofloxacin-resistantG. parasuismay lead to the ineffective treatment by danofloxacin.
Modeling non-pharmaceutical interventions in the COVID-19 pandemic with survey-based simulations
Authors: Kaffai Marius , Heiberger Raphael H. 
Published: April 2021

AbstractGovernments around the globe use non-pharmaceutical interventions (NPIs) to curb the spread of coronavirus disease 2019 (COVID-19) cases. Making decisions under uncertainty, they all face the same temporal paradox: estimating the impact of NPIs before they have been implemented. Due to the limited variance of empirical cases, researcher could so far not disentangle effects of individual NPIs or their impact on different demographic groups. In this paper, we utilize large-scale agent-based simulations in combination with Susceptible-Exposed-Infectious-Recovered (SEIR) models to investigate the spread of COVID-19 for some of the most affected federal states in Germany. In contrast to other studies, we sample agents from a representative survey. Including more realistic demographic attributes that influence agents’ behavior yields accurate predictions of COVID-19 transmissions and allows us to investigate counterfactual “what-if” scenarios. Results show that quarantining infected people and exploiting industry-specific home office capacities are the most effective NPIs. Disentangling education-related NPIs reveals that each considered institution (kindergarten, school, university) has rather small effects on its own, yet, that combined openings would result in large increases in COVID-19 cases. Representative survey-characteristics of agents also allow us to estimate NPIs’ effects on different age groups. For instance, re-opening schools would cause comparatively few infections among the risk-group of people older than 60 years.
Effect of anti‐interleukin‐17 biologics on Krebs von den Lungen‐6 level in patients with psoriasis
Authors: Hara Hiromichi , Miyagawa Hanae , Araya Jun , Minagawa Shunsuke , Numata Takanori , Umezawa Yoshinori , Asahina Akihiko , Nakagawa Hidemi , Kuwano Kazuyoshi 
Published: April 2021

AbstractInterleukin (IL)‐17 plays critical roles in the pathogenesis of both psoriasis and interstitial pneumonia (IP). We hypothesized that anti‐IL‐17 biologics might suppress both clinically relevant and latent IP activity and decrease Krebs von den Lungen‐6 (KL‐6) level in psoriasis patients. We aimed to elucidate the effects of anti‐IL‐17 biologics on KL‐6 levels. We retrospectively analyzed the clinical data of psoriasis patients treated with anti‐IL‐17 biologics. KL‐6 levels were measured before treatment (baseline) and at 3 and 6 months after the initiation of the treatment, and ratios of KL‐6 levels at each time point to the baseline levels were calculated. Chest computed tomography (CT) was performed on patients with coexisting IP. The clinical characteristics and radiographic findings were evaluated. A total of 294 psoriasis patients were treated with anti‐IL‐17 biologics. Baseline KL‐6 levels were higher than 401 U/mL in 34 patients (high baseline KL‐6 group). While anti‐IL‐17 biologics did not affect KL‐6 levels and ratios of KL‐6 to the baseline levels at any time point in the overall study population, they decreased both KL‐6 levels and ratios at 6 months after the initiation of the treatment in the high baseline KL‐6 group. A total of 10 patients with coexisting IP showed decreasing ratios of KL‐6 to the baseline levels at 6 months without affecting coexisting IP in CT performed at 3–12 months. Anti‐IL‐17 biologics decreased KL‐6 levels in the high baseline KL‐6 group regardless of recognizable IP. A decrease in KL‐6 levels was not associated with a radiographic improvement of IP, which should be examined in large numbers with long‐term observations in future studies.
Homeodomain proteins POU‐M2, antennapedia and abdominal‐B are involved in regulation of the segment‐specific expression of the clip‐domain serine protease gene CLIP13 in the silkworm, Bombyx mori
Authors: Liu Huawei , Heng Jingya , Wang Luoling , Li Youshan , Tang Xin , Huang Xuan , Xia Qingyou , Zhao Ping 
Published: April 2021

AbstractClip‐domain serine proteases (CLIPs) play important roles in insect innate immunity and development. Our previous studies indicated that CLIP13, an epidermis‐specific gene, was involved in cuticle remodeling during molting and metamorphosis in the silkworm, Bombyx mori. However, the transcriptional regulatory mechanism and regulatory pathways of CLIP13 remained unclear. In the present study, we investigated CLIP13 expression and the regulation pathway controlled by 20‐hydroxyecdysone (20E) in the silkworm. At the transcriptional level, expression of CLIP13 exhibited pronounced spatial and temporal specificity in different regions of the epidermis; homeodomain transcription factors POU‐M2, antennapedia (Antp), and abdominal‐B (Abd‐B) showed similar expression change trends as CLIP13 in the head capsule, thorax, and abdomen, respectively. Furthermore, results of cell transfection assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation demonstrated that POU‐M2, Antp, and Abd‐B were involved in the transcriptional regulation of CLIP13 by directly binding to their cis‐response elements in CLIP13 promoter. RNA interference‐mediated silencing of POU‐M2, Antp, and Abd‐B led to a decrease of CLIP13 expression in the head capsule, the epidermis of the 1st to 3rd thoracic segments and the 7th to 10th abdominal segments, respectively. Consistent with CLIP13, 20E treatment significantly upregulated expression of POU‐M2, Antp, and Abd‐B in the silkworm epidermis. Taken together, these data suggest that 20E positively regulates transcription of CLIP13 via homeodomain proteins POU‐M2, Antp, and Abd‐B in different regions of the silkworm epidermis during metamorphosis, thus affecting the molting process. Our findings provide new insight into the functions of homeodomain transcription factors in insect molting.
RNAi of the N‐glycosylation‐related genes confirms their importance in insect development and α‐1,6‐fucosyltransferase plays a role in the ecdysis event for the hemimetabolous pest insect Nilaparvata lugens
Authors: Yang Qun , De Schutter Kristof , Chen Pengyu , Van Damme Els J.M. , Smagghe Guy 
Published: April 2021

AbstractRecently N‐glycosylation was found to be required for the postembryonic development and metamorphosis of the holometabolous beetle Tribolium castaneum. However, the role of N‐glycosylation in the development of hemimetabolous insects is unknown. To further elucidate the role of N‐glycosylation in the development of insects, a functional characterization of the N‐glycosylation‐related genes (NGRGs) was performed in a model insect for hemimetabolous development, namely the brown planthopper Nilaparvata lugens. In this project, we report the effects of RNAi‐mediated silencing of 15 NGRGs on the postembryonic development of N. lugens. Two major observations were made. First, interruption of the early steps of N‐glycan processing led to a lethal phenotype during the transition from nymph to adult as was observed in T. castaneum. Second, we report here on an essential function for the α‐1,6‐fucosyl transferase in the ecdysis event of N. lugens between nymphal instars, since gene‐silencing by RNAi led to failure of ecdysis and subsequent mortality of the treated insect.
Seasonal phenology and damage by Singapora shinshana (Hemiptera: Cicadellidae) and other leafhoppers on ornamental trees in Korea
Authors: Kim Hyun‐guk , Kabir Md. Faisal , An Hyeon Jeong , Mwamula Abraham Okki , Oh Sumin , Jung Sunghoon , Lee Dong Woon 
Published: April 2021

AbstractSingapora shinshana is a leafhopper native to mid‐Asia with a specific host range and is one of the least studied species within the genus. Recently, the species has been found to cause significant damage to host plants including ornamental trees, normally inflicted by its sucking behavior. This study uncovered more details on host and season preference of S. shinshana, damage potential and symptoms caused by its feeding behavior on ornamental trees in Korea, in addition to other records of other leafhoppers of economic importance. During the sticky trap survey period from 2017 to 2019, 12 leafhopper species were recovered from the eight selected ornamental tree species. Singapora shinshana was the most dominant species, constituting 94.8% of the total collected leafhopper population; with its highest incidence observed on Prunus serrulata, followed by Elaeagnus umbellata and Pseudocydonia sinensis. The high abundance on P. serrulata correlated with high damaged leaf percentages of 94.2%, 95.2%, and 98.1% in October 2017, 2018, and 2019, respectively. Interestingly, in terms of damaged leaf percentage, Rosa hybrida and Zelkova serrata were the second and third most damaged hosts despite the significantly lower population of the leafhopper on these trees. Furthermore, S. shinshana counts increased from late‐July to late‐September, with the peak evident during early August. Prunus serrulata can therefore be taken as one of the main host plants of S. shinshana. However, the potential of the host to suffer damage is not limited to population densities of the pest alone but also susceptibility and tolerance of the host plant.
Carotenoid composition and antioxidant activities of Chinese orange‐colored tomato cultivars and the effects of thermal processing on the bioactive components
Authors: Yang Cheng , Jiang Xin , Ma Lulu , Xiong Wenhui , Zhang Shuang , Zhang Jian , Zhang Lianfu 
Published: April 2021

AbstractTo facilitate the production of tomato products with high bioactivity and improve the utilization of orange‐colored tomatoes, the carotenoids of 11 tomato cultivars were analyzed using high‐performance liquid chromatography with photodiode array detection. Moreover, antioxidant activities were evaluated by four chemical‐based assays, and the influences of thermal treatment on the carotenoids in orange‐colored tomatoes rich in tetra‐cis (7Z, 9Z, 7′Z, and 9′Z)‐lycopene, phytofluene, and phytoene were studied. The nine orange‐colored tomatoes (OT) were divided into two categories: OT‐B, containing five cultivars rich in β‐carotene, and OT‐L, containing the other four cultivars that were abundant in tetra‐cis‐lycopene, phytofluene, and phytoene. The antioxidant activities of OT‐L were higher than those of OT‐B and the SD‐2 cultivar in OT‐L showed similar antioxidant activity to the red tomatoes. During thermal processing, tetra‐cis‐lycopene in SD‐2 decreased about 38% after being exposed to heat for 2 hr at 80 °C, while its content was still higher than other lycopene isomers. Other‐Z‐lycopenes and all‐trans (E)‐lycopene increased from 2.36 ± 0.19 to 14.73 ± 1.16 µg/g fresh weight (FW) and 0.75 ± 0.10 to 5.91 ± 1.02 µg/g FW, respectively. Thus, thermal treatments at lower temperature, such as cold break and pasteurization, were more suitable for processing OT‐L. The results demonstrated that OT‐L could be an excellent raw material to produce tomato products with high bioavailability and bioactivity. The results of this research could provide helpful information for the research and development of tomato products using orange tomatoes and benefit planters and consumers.Practical ApplicationSome orange tomato cultivars are promising raw materials for tomato products because of their high contents of bioactive tetra‐cis‐lycopene, phytofluene, and phytoene. This study demonstrated the carotenoid components and antioxidant activities of the widely planted orange‐colored tomatoes in China. The obtained knowledge, including the thermal processing effects on the isomerization and degradation of carotenoids in the cultivars, will offer useful information to food processors and benefit the consumers.