bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of circadian behavioural output via clock‐responsive miR‐276b
Authors: Zhang R. , Du J. , Zhao X. , Wei L. , Zhao Z. 
Published: November 2020

AbstractGrowing evidence indicates that microRNAs play numerous important roles. However, the roles of some microRNAs involved in regulation of circadian rhythm and sleep are still not well understood. In this study, we show that the miR‐276b is essential for maintaining both sleep and circadian rhythm by targeting tim, npfr1 and DopR1 genes, with miR‐276b deleted mutant flies sleeping more, and vice versa in miR‐276b overexpressing flies. Through analysing its promoter, we found that mir‐276b is responsive to CLOCK and regulates circadian rhythm through the negative feedback loop of the CLK/CYC‐TIM/PER. Furthermore, miR‐276b is broadly expressed in the clock neurons and the central complexes such as the mushroom body and the fan‐shape body of Drosophila brain, in which up‐regulation of miR‐276b in tim, npfr1 and DopR1 expressing tissues significantly causes sleep decreases. This study clarifies that the mir‐276b is very important for participating in regulation of circadian rhythm and sleep.
Viperin binds STING and enhances the type‐I interferon response following dsDNA detection
Authors: Crosse Keaton M , Monson Ebony A , Dumbrepatil Arti B , Smith Monique , Tseng Yeu‐Yang , Van der Hoek Kylie H , Revill Peter A , Saker Subir , Tscharke David C , G Marsh E Neil , Beard Michael R , Helbig Karla J 
Published: November 2020

AbstractViperin is an interferon‐inducible protein that is pivotal for eliciting an effective immune response against an array of diverse viral pathogens. Here we describe a mechanism of viperin’s broad antiviral activity by demonstrating the protein’s ability to synergistically enhance the innate immune dsDNA signaling pathway to limit viral infection. Viperin co‐localized with the key signaling molecules of the innate immune dsDNA sensing pathway, STING and TBK1; binding directly to STING and inducing enhanced K63‐linked polyubiquitination of TBK1. Subsequent analysis identified viperin’s necessity to bind the cytosolic iron‐sulfur assembly component 2A, to prolong its enhancement of the type‐I interferon response to aberrant dsDNA. Here we show that viperin facilitates the formation of a signaling enhanceosome, to coordinate efficient signal transduction following activation of the dsDNA signaling pathway, which results in an enhanced antiviral state. We also provide evidence for viperin’s radical SAM enzymatic activity to self‐limit its immunomodulatory functions. These data further define viperin’s role as a positive regulator of innate immune signaling, offering a mechanism of viperin’s broad antiviral capacity.
Development of low‐loss lead‐germanate glass for mid‐infrared fiber optics: II. preform extrusion and fiber fabrication
Authors: Wang Pengfei , Ng Alson Kwun Leung , Dowler Alastair , Ebendorff‐Heidepriem Heike 
Published: November 2020

AbstractFor lead‐germanate glass fibers, reducing the content of hydroxyl (OH) groups and the formation of metallic Pb species is essential to pave the way for their applications as low‐loss mid‐IR fiber optics since OH and metallic Pb species cause intense absorption and scattering loss, respectively, in the mid‐IR spectral range. The first part of this study reported the optimization of the glass melting procedure to obtain low amount of OH while preventing formation of metallic Pb species in lead‐germanate glass. Here, the second part of this study reports the investigation of the process conditions to fabricate low‐loss lead‐germanate glass fiber through further understanding of the co‐effects of glass melting and heat treatment atmospheres on the formation of nano‐ and micron‐scale metallic Pb species in both the as‐produced and heat treated lead‐germanate glasses. Finally, using this advance in knowledge, we successfully fabricated low‐loss lead‐germanate glass fibers with no presence of reduced metallic Pb particles by optimizing dehydration agent, glass melting, preform extrusion and fiber drawing conditions. The optimized fabrication conditions reduced the unstructured fiber loss by almost one order to <0.3 dB/m at 1.55 μm.
Re‐entrant ferroelectric relaxor phenomena in the (1 − x)[Bi1/2(Na1/2K1/2)1/2TiO3]‐xPbZrO3 system
Authors: Gupta Sanu K. , Gibbons Brady J. , Mardilovich Peter , Cann David P. 
Published: November 2020

AbstractThe solid solution (1 − x)[Bi1/2(Na1/2K1/2)1/2TiO3]‐xPbZrO3, (0.00 ≤ x ≤ 0.12) was investigated to examine the phase equilibria, dielectric and electromechanical properties. The composition corresponding to x = 0.00 exhibits tetragonal symmetry with the expected classical ferroelectric (FE) behavior. The system exhibited FE to relaxor crossover with the addition of lead zirconate at the composition x = 0.05. This is indicated by typical relaxor characteristics such as a transition to the global pseudocubic phase, a constriction in the FE hysteresis loop, and a sudden decrease in the negative strain accompanied by an increase in maximum strain. Most notably, with a further increase in x (>0.05), there is evidence for a return to a FE phase that exhibits classical FE characteristics. The combined results demonstrate that there exists a narrow FE‐relaxor boundary near x = 0.05, where FE and relaxor phases coexist. At the critical composition, enhancement in the piezoelectric properties, including an increase in the effective (350 pm/V) was observed. This transition in the electromechanical properties is consistent with changes observed in the phase equilibria for this solid solution. The crystal structure transitions from tetragonal symmetry for x = 0.00, to pseudocubic symmetry for the relaxor compositions (x = 0.05), and finally to a lower symmetry perovskite phase for the re‐entrant FE phase (x> 0.05). This composition‐induced transition from FE to relaxor to a re‐entrant FE state in the (1 − x)[Bi1/2(Na1/2K1/2)1/2TiO3]‐xPbZrO3 system is unusual among relaxor FE systems and thus is of great scientific and technological interest.
Peripheral memory T‐cell profile is modified in patients undergoing periodontal management
Authors: Medara Nidhi , Lenzo Jason C. , Walsh Katrina A. , Holden James A. , Reynolds Eric C. , Darby Ivan B. , O’Brien‐Simpson Neil M. 
Published: November 2020

AbstractAimsT‐cells are known to have a role in periodontitis, however, the effect of periodontal therapy on peripheral memory T‐cells is unclear. This study evaluated variation in peripheral memory T‐cells and red complex bacteria in sub‐gingival plaque in patients undergoing periodontal management.MethodsPeripheral blood mononuclear cells and sub‐gingival plaque were collected from 54 periodontitis patients at baseline, 3‐, 6‐ and 12‐months post‐therapy and 40 healthy controls. Periodontitis patients were divided into treatment outcome (TxO) groups based on prevalence of sites with probing depth ≥5 mm as good (<10% of sites), moderate (10–20%) or poor (>20%) at study conclusion. Naïve (TN—CCR7+CD45RA+), central memory (TCM—CCR7+CD45RA−), effector memory (TEM—CCR7−CD45RA−) and effector memory T‐cells re‐expressing CD45RA (TEMRA—CCR7−CD45RA+) were phenotyped using flow cytometry in CD4+, CD8+, CD4+CD8+ and CD4−CD8− T‐cells and red complex bacteria were quantified using qPCR.ResultsAt baseline, periodontitis subjects had significantly greater mean probing depths and Porphyromonas gingivalis proportions, lower TN but higher CD4+ TCM, CD8+ TCM, CD4+CD8+ TEM and CD4−CD8− TEM cell proportions compared to health. Periodontal therapy decreased mean probing depths, P. gingivalis proportions, TEM and CD4+ and CD8+ TCM cells, but increased TN and CD4+ and CD8+ TEMRA cells. The T‐cell profile in the good TxO group showed therapy‐related changes in CD4+ TEM, and CD8+ TN and TEM cells, whereas, no changes were observed in the poor TxO group.ConclusionManagement and the reduction in red complex bacteria were associated with changes in peripheral memory T‐cells in periodontitis.
Favorable effect of sodium–glucose cotransporter 2 inhibitor, dapagliflozin, on non‐alcoholic fatty liver disease compared with pioglitazone
Authors: Cho Kyu Yong , Nakamura Akinobu , Omori Kazuno , Takase Takahiro , Miya Aika , Yamamoto Kohei , Nomoto Hiroshi , Kameda Hiraku , Taneda Shinji , Kurihara Yoshio , Aoki Shin , Atsumi Tatsuya , Miyoshi Hideaki 
Published: November 2020

AbstractAims/IntroductionSodium–glucose cotransporter 2 inhibitors, as well as thiazolidines, suppress nonalcoholic fatty liver disease (NAFLD); however, few comparative studies have been reported. Dapagliflozin has shown non‐inferiority compared with pioglitazone for glycemic control, and superiority regarding weight reduction in patients with type 2 diabetes. We carried out a secondary analysis for the favorable effects of sodium–glucose cotransporter inhibitors for NAFLD.Materials and MethodsIn this multicenter, open‐label, prospective, randomized, parallel‐group comparison trial, patients taking pioglitazone for ≥12 weeks were randomly switched to dapagliflozin or continued pioglitazone for a further 24 weeks. The fatty liver index (FLI), consisting of body mass index, triglycerides, waist circumference and γ‐glutamyl transpeptidase, was used for the evaluation of NAFLD.ResultsA total of 53 participants with NAFLD (27 dapagliflozin; 26 pioglitazone) were included in this analysis. FLI decreased significantly in the dapagliflozin group (48.7 ± 23.4 to 42.1 ± 23.9) compared with the pioglitazone group (49.0 ± 26.1 to 51.1 ± 25.8; P < 0.01). Multiple linear regression analysis showed that the changes in FLI had a significantly positive correlation with changes in glycated hemoglobin (P = 0.03) and insulin level (P < 0.01) in the dapagliflozin group.ConclusionDapagliflozin might be more beneficial than pioglitazone in patients with NAFLD. Improvements in FLI would be closely related to glycemic control.
Macrophage‐activating lipopeptide‐2 and corticotropin‐releasing hormone stimulate the inflammatory signalling in human sebocytes through activation of stearoyl‐CoA desaturase and fatty acid desaturase 2
Authors: Zouboulis C.C. , Angres S. 
Published: November 2020

AbstractBackgroundThe macrophage‐activating lipopeptide‐2 (MALP‐2) activates cells carrying a functional Toll‐like receptor (TLR)‐2/6. Human sebocytes express functional TLR‐2, TLR‐4 and CD14. Upregulation of stearoyl‐CoA desaturase (SCD) and fatty acid desaturase‐2 (FADS2) expression induces pro‐inflammatory sebaceous activity. On the other hand, corticotropin‐releasing hormone (CRH) is likely to serve as an autocrine stress hormone in human sebocytes. In addition to its antiproliferative, lipogenetic and androgen‐activating functions, CRH exhibits a pro‐inflammatory action and its expression is upregulated in acne‐involved sebaceous glands.ObjectiveDetermination of the pro‐inflammatory function of MALP‐2 and CRH and clarification of the option that MALP‐2 and/or CRH activity on human sebocytes might be mediated through SCD and/or FADS2.MethodsSZ95 sebocytes were treated with MALP‐2, CRH and the SCD inhibitor/ligand FPCA. SCD, FADS2, TLR‐2 mRNA and protein levels and IL‐6 and IL‐8 secretion were investigated. Intracellular CRH levels were assessed under treatment with CRH, MALP‐2, linoleic acid and arachidonic acid. Phorbol 12‐myristate 13‐acetate and dexamethasone served as positive and negative controls, respectively.ResultsMALP‐2 upregulated SCD, FADS2, TLR‐2 mRNA and protein levels and IL‐6 and IL‐8 secretion from SZ95 sebocytes. Co‐incubation of SZ95 sebocytes with MALP‐2/FPCA did not affect the MALP‐2‐induced SCD mRNA upregulation but reduced FADS2 mRNA levels and inhibited IL‐8 secretion. CRH induced an early, low‐level SCD and FADS2 upregulation and TLR‐2 and IL‐8 secretion. High intracellular CRH concentrations could be detected early after CRH treatment and persisted up to 24 h. MALP‐2 stimulated intracellular CRH levels.ConclusionsMALP‐2 stimulates the inflammatory signalling in human sebocytes through SCD and FADS2 activation. Inhibition of FADS2 mRNA levels and IL‐8 secretion through MALP‐2/FCPA co‐incubation and diminution of fatty acid unsaturation might lead to a reduction of pro‐inflammatory sebaceous lipids. CRH upregulates inflammatory signalling via the SCD/FADS2 pathway, and MALP‐2 selectively enhances CRH levels in human sebocytes.
Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non‐target sites, for DAA‐based treatment and retreatment outcome
Authors: Fahnøe Ulrik , Pedersen Martin S. , Sølund Christina , Ernst Anja , Krarup Henrik B. , Røge Birgit T. , Christensen Peer B. , Laursen Alex L. , Gerstoft Jan , Thielsen Peter , Madsen Lone G. , Pedersen Anders G. , Schønning Kristian , Weis Nina , Bukh Jens 
Published: November 2020

AbstractDirect‐acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance‐associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment‐failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral‐titre data were compared between the two patient groups, and HCV full‐length open reading frame deep‐sequencing was performed. The proportion of HCV NS5A‐RASs at baseline was higher in treatment‐failure (82%) than matched SVR patients (25%) (p = .0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment‐failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B‐substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3‐helicase and NS5A‐domain‐III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs.
Functional diversity of attachment and grooming leg structures is retained in all but the smallest insects
Authors: Boudinot B. E. , Beutel R. G. , Gorb S. N. , Polilov A. A. 
Published: November 2020

AbstractMiniaturization strongly affects functional morphology. Whereas some anatomical structures are barely affected by scaling, others can fundamentally change as the body becomes ever smaller. No prior study has focused on the effect of miniaturization on grooming and attachment structures in Hymenoptera, which can be highly diverse and complex. Through comparative description of the legs of the extremely small wasps of the families Mymaridae and Trichogrammatidae, we evaluate the functional and phylogenetic patterns concerning possible functional effects of miniaturization. On the one hand, the studied species retain some features characteristic of other Chalcidoidea, while on the other, they display some parallelisms associated with miniaturization in leg structure. These observations support a two‐stage morphocline of miniaturization, wherein the first stage is characterized by the preservation of structural complexity and retention of all basic functions, as for instance in examined Megaphragma and the females of Dicopomorpha. The second stage is characterized by a significant simplification, with the loss of redundant non‐essential functions, as observed for the males of Dicopomorpha, which have grossly reduced leg structures, including total loss cleaning devices. Whether these stages are ordered or unordered should be evaluated in future study. Functional optimization of attachment in male Dicopomorpha is indicated by the highly derived mushroom‐shaped tarsi, complemented by novel grappling spurs on the hindfeet, possibly for copulation. Our observations underline adaptive trade‐offs in the expression of complex and multifunctional leg structures at extreme scales.
Motivation theory‐based physical activity programme for older adults in residential care facility: A modified Delphi and single‐group pretest‐posttest study
Authors: Yang Hui‐Ju , Chen Kuei‐Min , Hsu Hui‐Fen 
Published: November 2020

AbstractBackgroundPhysical inactivity exposes older adults living in long‐term care institutions to a high risk of health deterioration. Developing effective behaviour change interventions based on a theoretical framework is a pressing concern.AimsThis study developed an ‘Easy Walking’ intervention programme based on the Wheel of Motivation and aimed to: (1) develop the intervention programme for promoting self‐efficacy of older adults living in long‐term care facilities; and (2) examine the perceived helpfulness of the intervention programme for encouraging walking behaviours.MethodsThis study consisted of two stages. In the first stage, a three‐round modified Delphi process was conducted with ten experts to rate the eight motivators in the Wheel of Motivation. The Easy Walking programme was designed accordingly. In the second stage, a single‐group pretest‐posttest study design was employed to evaluate the Easy Walking programme. Structured questionnaires were used to collect data on the changes in self‐efficacy and on the perceived helpfulness regarding the programme.ResultsThe Easy Walking intervention programme features eight factors that influence motivation. Thirty older adults participated in and evaluated the programme. The results showed a significant difference in self‐efficacy (t = −7.02, p < .001) of the older adults. Regarding the perceived usefulness of the intervention, the mean scores for each item ranged from 3.73 to 4.93 points. ‘Safe environment’ was perceived to be the most helpful factor for encouraging walking behaviours.ConclusionThe Easy Walking programme enhanced the self‐efficacy of institutionalised older adults and was perceived as helpful in physical activity engagement. Nursing professionals in long‐term care institutions could implement the Easy Walking programme to be part of daily nursing activities.
A Meta‐Analysis of Therapeutic Pain Neuroscience Education, Using Dosage and Treatment Format as Moderator Variables
Authors: Romm Marnin Joseph , Ahn Soyeon , Fiebert Ira , Cahalin Lawrence Patrick 
Published: November 2020

AbstractObjectivesThis meta‐analysis aimed to assess the overall effect of therapeutic pain neuroscience education (TPNE) on chronic musculoskeletal pain and to further assess whether such an effect differs by TPNE dosage as well as other treatment format components. Dosage included the number of TPNE sessions provided as well as the amount of time per TPNE session. Structural components included TPNE provided alone as treatment or combined with other pain management modalities, as well as the inclusion of group‐based treatment sessions.MethodsElectronic databases were utilized to search for randomized controlled trials that included TPNE. The overall effectiveness of TPNE was estimated on 4 pain outcome measures, including kinesiophobia, pain intensity, pain disability, and pain catastrophizing. The differential effectiveness of TPNE was examined using a mixed‐methods moderator analysis on various study‐level characteristics to identify potential moderators affecting the overall results.ResultsSignificant effects of TPNE were found on all the outcome measures. The only moderator that displayed a significant effect was group‐based treatment on kinesiophobia (z = −2.23, P < 0.05, 95% confidence interval [CI] −2.70 to −0.20). Between‐group analysis revealed that only interventions that included group sessions were found to be statistically significant (z = 2.20, P < 0.05) and displayed a large effect size (d = 0.80, 95% CI 0.09 to 1.50).DiscussionTherapeutic pain neuroscience education had a statistically significant impact on all the explored pain outcome measures. However, when investigating the treatment dosage and format moderator variables, they appeared to not have a statistically significant effect except for group‐based interventions on kinesiophobia levels.ConclusionThis meta‐analysis examined the efficacy of TPNE for patients with chronic pain. It assessed various pain outcome measures following intervention. In addition, this research identified that various moderator variables do not have and do have an impact on the treatment modality of TPNE.
GmCCD4 controls carotenoid content in soybeans
Authors: Gao Jinshan , Yang Suxin , Tang Kuanqiang , Li Guang , Gao Xiang , Liu Bao , Wang Shaodong , Feng Xianzhong 
Published: November 2020

SummaryTo better understand the mechanisms regulating plant carotenoid metabolism in staple crop, we report the map‐based cloning and functional characterization of the Glycine max carotenoid cleavage dioxygenase 4 (GmCCD4) gene, which encodes a carotenoid cleavage dioxygenase enzyme involved in metabolizing carotenoids into volatile β‐ionone. Loss of GmCCD4 protein function in four Glycine max increased carotenoid content (gmicc) mutants resulted in yellow flowers due to excessive accumulation of carotenoids in flower petals. The carotenoid contents also increase three times in gmicc1 seeds. A genome‐wide association study indicated that the GmCCD4 locus was one major locus associated with carotenoid content in natural population. Further analysis indicated that the haplotype‐1 of GmCCD4 gene was positively associated with higher carotenoid levels in soybean cultivars and accumulated more β‐carotene in engineered E. coli with ectopic expression of different GmCCD4 haplotypes. These observations uncovered that GmCCD4 was a negative regulator of carotenoid content in soybean, and its various haplotypes provide useful resources for future soybean breeding practice.
Root‐type ferredoxin‐NADP+ oxidoreductase isoforms in Arabidopsis thaliana: Expression patterns, location and stress responses
Authors: Grabsztunowicz Magda , Rantala Marjaana , Ivanauskaite Aiste , Blomster Tiina , Koskela Minna M. , Vuorinen Katariina , Tyystjärvi Esa , Burow Meike , Overmyer Kirk , Mähönen Ari P. , Mulo Paula 
Published: November 2020

AbstractIn Arabidopsis, two leaf‐type ferredoxin‐NADP+ oxidoreductase (LFNR) isoforms function in photosynthetic electron flow in reduction of NADP+, while two root‐type FNR (RFNR) isoforms catalyse reduction of ferredoxin in non‐photosynthetic plastids. As the key to understanding, the function of RFNRs might lie in their spatial and temporal distribution in different plant tissues and cell types, we examined expression of RFNR1 and RFNR2 genes using β‐glucuronidase (GUS) reporter lines and investigated accumulation of distinct RFNR isoforms using a GFP approach and Western blotting upon various stresses. We show that while RFNR1 promoter is active in leaf veins, root tips and in the stele of roots, RFNR2 promoter activity is present in leaf tips and root stele, epidermis and cortex. RFNR1 protein accumulates as a soluble protein within the plastids of root stele cells, while RFNR2 is mainly present in the outer root layers. Ozone treatment of plants enhanced accumulation of RFNR1, whereas low temperature treatment specifically affected RFNR2 accumulation in roots. We further discuss the physiological roles of RFNR1 and RFNR2 based on characterization of rfnr1 and rfnr2 knock‐out plants and show that although the function of these proteins is partly redundant, the RFNR proteins are essential for plant development and survival.