bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circadian regulation of membrane physiology in neural oscillators throughout the brain
Authors: Paul Jodi R. , Davis Jennifer A. , Goode Lacy K. , Becker Bryan K. , Fusilier Allison , Meador‐Woodruff Aidan , Gamble Karen L. 
Published: January 2019

AbstractTwenty‐four‐hour rhythmicity in physiology and behavior are driven by changes in neurophysiological activity that vary across the light–dark and rest‐activity cycle. Although this neural code is most prominent in neurons of the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus, there are many other regions in the brain where region‐specific function and behavioral rhythmicity may be encoded by changes in electrical properties of those neurons. In this review, we explore the existing evidence for molecular clocks and/or neurophysiological rhythms (i.e., 24 hr) in brain regions outside the SCN. In addition, we highlight the brain regions that are ripe for future investigation into the critical role of circadian rhythmicity for local oscillators. For example, the cerebellum expresses rhythmicity in over 2,000 gene transcripts, and yet we know very little about how circadian regulation drives 24‐hr changes in the neural coding responsible for motor coordination. Finally, we conclude with a discussion of how our understanding of circadian regulation of electrical properties may yield insight into disease mechanisms which may lead to novel chronotherapeutic strategies in the future.
Pharmacokinetic effects of capsaicin on vinblastine in rats mediated by CYP3A and Mrp2
Authors: Zhai Xuejia , Feng Yiming , Liu Jun , Li Jie , Zong Yan , Tuo Zhan , Gao Shenrong , Lv Yi 
Published: January 2019

AbstractCapsaicin (trans‐8‐methyl‐N‐vanillyl‐6‐nonenamide, CAP) is an important ingredient in spicy foods consumed throughout the world. Vinblastine (VBL) is a naturally occurring alkaloid prescribed to cancer patients. Many cancer patients treated with VBL were taking CAP at the same time. This study attempted to investigate the effect of CAP on the pharmacokinetics of VBL, which is the substrate of CYP3A, P‐gp, and Mrp2. CAP, cyclosporine (CsA) or olive oil was given to rats for seven consecutive days, and on the seventh day, VBL (1.3 mg/kg) was administered intravenously. CsA was used as a CYP3A1/2 and transporter inhibitor, and olive oil was used as a vehicle. The results showed that pretreatment of rats with CAP (3.0 mg/kg) for seven consecutive days resulted in an increase in the AUC0–t of VBL of about 29.8% (P < 0.05) compared with the control group. Moreover, CAP decreased the CL of VBL to 75.5% (P < 0.05). At this time, CYP3A1/2 and Mrp2/Abcc2 in the liver was decreased at the mRNA and protein levels. These results demonstrate that chronic ingestion of CAP will increase systemic exposure and reduce clearance of VBL in rats. The food–drug interaction between CAP and VBL appears to be due to modulation of CYP3A1/2 and Mpr2 expression by CAP.
Molecular insights into the mechanism of 4‐hydroxyphenylpyruvate dioxygenase inhibition: enzyme kinetics, X‐ray crystallography and computational simulations
Authors: Lin Hong‐Yan , Yang Jing‐Fang , Wang Da‐Wei , Hao Ge‐Fei , Dong Jiang‐Qing , Wang Yu‐Xia , Yang Wen‐Chao , Wu Jia‐Wei , Zhan Chang‐Guo , Yang Guang‐Fu 
Published: January 2019

Slow‐binding inhibitors with long residence time on the target often display superior efficacy in vivo. Rationally designing inhibitors with low off‐target rates is restricted by a limited understanding of the structural basis of slow‐binding inhibition kinetics in enzyme–drug interactions. 4‐Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for drug and herbicide development. Although the time‐dependent behavior of HPPD inhibitors has been studied for decades, its structural basis and mechanism remain unclear. Herein, we report a detailed experimental and computational study that explores structures for illustrating the slow‐binding inhibition kinetics of HPPD. We observed the conformational change of Phe428 at the C‐terminal α‐helix in the inhibitor‐bound structures and further identified that the inhibition kinetics of drugs are related to steric hindrance of Phe428. These detailed structural and mechanistic insights illustrate that steric hindrance is highly associated with the time‐dependent behavior of HPPD inhibitors. These findings may enable rational design of new potent HPPD‐targeted drugs or herbicides with longer target residence time and improved properties.DatabaseStructure data are available in the PDB under the accession numbers 5CTO (released), 5DHW (released), and 5YWG (released).
Specific genes related to nucleopolyhedrovirus in Bombyx mori susceptible and near‐isogenic resistant strains through comparative transcriptome analysis
Authors: Chen T.‐t. , Tan L.‐r. , Hu N. , Dong Z.‐q. , Hu Z.‐g. , Qin Q. , Long J.‐q. , Chen P. , Xu A.‐y. , Pan M.‐h. , Lu C. 
Published: January 2019

AbstractBombyx mori nucleopolyhedrovirus (BmNPV) is one of the primary pathogens that causes severe economic losses to sericulture. Comparative transcriptomics analysis has been widely applied to explore the antiviral mechanism in resistant strains. Here, to identify genes involved in BmNPV infection, we identified differentially expressed genes (DEGs) and performed weighted gene co‐expression network analysis (WGCNA) between two Bombyx mori strains: strain 871 (susceptible to BmNPV infection) and the near‐isogenic strain 871C (resistant to BmNPV). Our results showed that 400 genes were associated with resistance in strain 871C, and 76 genes were related to susceptibility in strain 871. In addition, the correlation analysis of DEGs and WGCNA showed that 40 genes related to resistance were highly expressed in the resistant strain. Among them, gene BGIBMGA004291 was the most noticeable. We further identified the effect of gene BGIBMGA004291, which encoded a multiprotein bridge factor 2 (MBF2) family member (MBF2‐10), on viral infection in cells. Our data suggested that MBF2‐10 inhibited viral infection. Taken together, this study showed specific module trait correlations related to viral infection in strains 871 and 871C, and we identified a resistance‐related gene. These findings suggested promising candidate genes with antiviral activity, aiding in the analysis of the antiviral molecular mechanisms in resistant strains.
Being a dad to a child with Down’s syndrome: Overcoming the challenges to adjustment
Authors: Ridding Anna , Williams James 
Published: January 2019

AbstractBackgroundHistorically, research exploring the impact of having a child with an Intellectual Disability (ID), has focussed exclusively on mothers. The present study aimed to investigate fathers’ experiences of parenting a child with Down's syndrome (DS), their contributions, influences on family functioning and inclusion in their child's support provision.MethodSemi‐structured interviews were conducted with 15 fathers. Interviews were analysed using Grounded Theory (GT).ResultsFathers’ adjustment appeared to be on a fluid trajectory with three key categories influencing this: “Accommodating the Child,” “Adapting the Parental/Spousal Role” and “Adapting Society.”ConclusionsThe accounts uncovered fathers’ adjustment trajectory to parenting a child with DS, concluding that despite practical and emotional challenges, fathers employed strategies to achieve positive adjustment. Fathers identified the need for services to recognize their role and involve them in their child's support provision. Implications for clinical practice and future research are discussed.
Repairing violations of trustworthiness in negotiation
Authors: Druckman Daniel , Lewicki Roy J. , Doyle Sarah P. 
Published: January 2019

AbstractThere has been an ongoing debate in the research literature on violations of trustworthiness and the effectiveness of various forms of repair. In this article, three studies compare the effectiveness of several variables hypothesized to repair perceived trustworthiness in a negotiation context: (a) the use of words (accounts or apologies) versus deeds (compensation for the costs of violation), separately and in combination; (b) whether words or deeds pointed to the past or to the future; (c) the effect of an active or passive third‐party monitor of the negotiation, and (d) the type of trustworthiness (competence versus integrity) that was violated. Results show support for the repair effects for deeds over words, and that a focus on the past violation (through either words or deeds) is more effective than looking toward the future. Deeds, rather than words, also accounts for the strong impact of the combination of the two courses of action. In addition, results show that an active third‐party intervention has a stronger impact on repair than a passive intervention. Implications for theory and practice are discussed along with suggestions for future research.
Methyl aminolevulinate daylight photodynamic therapy applied at home for non‐hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany
Authors: Karrer S. , Aschoff R.A.G. , Dominicus R. , Krähn‐Senftleben G. , Gauglitz G.G. , Zarzour A. , Kerrouche N. , Chavda R. , Szeimies R.‐M. 
Published: January 2019

AbstractBackgroundThe efficacy and safety of methyl aminolevulinate daylight photodynamic therapy (MAL DL‐PDT) for actinic keratosis (AK) treatment has previously been demonstrated in several studies.ObjectiveTo evaluate patient‐reported outcomes, effectiveness and tolerability of patient self‐applied MAL DL‐PDT.Patients and methodsAn open study was conducted in Germany in patients with thin or non‐hyperkeratotic and non‐pigmented AK. At baseline, the investigator delimited the target anatomical area and skin preparation was discretionary. On day 1, the patient performed MAL DL‐PDT at home, in accordance with instructions (after applying sunscreen and skin preparation by abrasive pad). Patient questionnaires were completed on day 1 and 3 months post‐treatment. Effectiveness was assessed by investigator at 3 months. Pain and adverse events (AE) were recorded.ResultsPatients (n = 50) were mostly elderly (mean age: 73.4 years) men (86%). After treatment on day 1, 94% of patients were overall satisfied or very satisfied with the treatment and 98% found the instructions convenient. At 3 months, most patients were satisfied or very satisfied with treatment effectiveness (88%) and aspect of their skin (80%). At 3 months, 62% of overall lesions were completely clear. The main related AEs were mild and expected (erythema, procedural pain and skin burning sensation).ConclusionsPatient self‐application of MAL DL‐PDT resulted in high levels of patient satisfaction, effectiveness and tolerability.
Focality advantage in platform competition
Authors: Halaburda Hanna , Yehezkel Yaron 
Published: January 2019

AbstractWe consider a methodology for studying how beliefs shape platform competition based on the notion of a partial focality. The concept of focality is useful for modeling platform competition when the presence of network effects results in multiple equilibria for a certain set of prices. We illustrate how to implement this methodology in both static and dynamic competition between platforms that differ in their basic quality. The initial degree of focality affects the ability of the high‐quality platform to win the market. Yet, dynamic considerations may have a positive or negative effect on this ability.
Efficacy of progesterone on threatened miscarriage: Difference in drug types
Authors: Wang Xiao‐xue , Luo Qing , Bai Wen‐pei 
Published: January 2019

AbstractAimTo investigate whether treatment with progesterone would decrease the incidence of miscarriage in women who faced threatened miscarriage.MethodsRandomized controlled trials (RCT) were identified by searching PubMed, Embase, Cochrane Library and Web of Science. Trials were included if they compared progesterone with placebo, no treatment or any other treatment given in an effort to treat threatened miscarriage. Pregnant prophylaxis drugs were not included without strict progesterone type, language and progesterone management. The primary outcome was the incidence of miscarriage. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI).ResultsEight RCT including 845 women who faced threatened miscarriage were analyzed. Pooled data from the eight trials showed that women with threatened miscarriage who were randomized to the progesterone group had a lower risk of threatened miscarriage (RR = 0.64, 95% CI 0.48–0.85). Dydrogesterone was shown to have a lower risk of miscarriage (RR = 0.49, 95% CI 0.33–0.75) than natural progesterone (RR = 0.69, 95% CI 0.40–1.19). Oral management was demonstrated to have a lower risk of miscarriage (RR = 0.55, 95% CI 0.38–0.79) compared with vaginal administration (RR = 0.58, 95% CI 0.28–1.21).ConclusionOur findings show that progesterone agents are effective in reducing the incidence of miscarriage in threatened miscarriage. Dydrogesterone, but not natural progesterone, was associated with a lower risk of miscarriage. Given the limitations of the studies included in our meta‐analysis, it is difficult to recommend route and dose of progesterone therapy. Further head‐to‐head trials of gestational weeks and long‐time follow‐up are required.
Ursolic acid promotes the apoptosis of cervical cancer cells by regulating endoplasmic reticulum stress
Authors: Guo Jin‐Ling , Han Teng , Bao Le , Li Xiao‐Mei , Ma Jing‐Quan , Tang Li‐Ping 
Published: January 2019

AbstractAimUrsolic acid is a triterpenoid common in plants and exhibits anti‐carcinogenic activity. This study aimed to reveal the role of endoplasmic reticulum stress in cervical cancer cell apoptosis promoted by ursolic acid.MethodsHeLa cells were treated with ursolic acid or/and 4‐phenylbutyric acid. The viability and apoptosis of HeLa cells were evaluated by MTT assay and flow cytometry, respectively.ResultsUrsolic acid decreased HeLa cell viability in a time‐ and dose‐ dependent manner, and induced HeLa cell apoptosis in a dose‐dependent manner. Moreover, ursolic acid increased the expression of C/EBP homologous protein and glucose‐regulated protein 78 at protein levels, while 4‐phenylbutyric acid antagonized the apoptosis of HeLa cells induced by ursolic acid.ConclusionUrsolic acid inhibits the viability and promotes the apoptosis of HeLa cells. Endoplasmic reticulum stress may mediate the apoptosis of cervical cancer cells stimulated by ursolic acid.
Deciphering the melatonin metabolism in Saccharomyces cerevisiae by the bioconversion of related metabolites
Authors: Muñiz‐Calvo Sara , Bisquert Ricardo , Fernández‐Cruz Edwin , García‐Parrilla María C. , Guillamón José M. 
Published: January 2019

AbstractMelatonin (Mel), originally considered a neurohormone, has been detected in beverages and food‐fermented products in which yeast metabolism is highly important. This indolamine is synthesized from serotonin, with L‐tryptophan being the initial substrate of both. Regarding Mel metabolism, the biosynthetic pathway in mammals consists in four‐step reactions. However, six genes are implicated in the synthesis of Mel in plants, which suggest the presence of many pathways. The aim of this study was to provide new empirical data on the production of Mel and other indole‐related compounds in the yeast Saccharomyces cerevisiae (S. cerevisiae). To this end, we performed the addition of the pathway intermediates in S. cerevisiae cells in different growth stages (exponential and arrested cells) to follow the bioconversion and new indolic compound production from them. The different bioconverted indolic compounds tested (L‐tryptophan, 5‐hydroxytryptophan, tryptamine, serotonin, N‐acetylserotonin, 5‐methoxytryptamine, and Mel) were analyzed by UHPLC‐MS/MS from the extra‐ and intracellular contents. Our results showed that serotonin, in yeast, was prevalently formed via tryptophan decarboxylation, followed by tryptamine hydroxylation as in plants. Mel production from serotonin can be achieved by either N‐acetylation, followed by O‐methylation or O‐methylation, in turn followed by N‐acetylation. Accordingly, the classic pathway of Mel synthesis in vertebrates does not seems prevalent in yeast.
Disease features of equine coronavirus and enteric salmonellosis are similar in horses
Authors: Manship Arlie J. , Blikslager Anthony T. , Elfenbein Johanna R. 
Published: January 2019

BackgroundEquine coronavirus (ECoV) is an emerging pathogen associated with fever and enteric disease in adult horses. Clinical features of ECoV infection have been described, but no study has compared these features to those ofSalmonellainfections.ObjectivesCompare the clinical features of ECoV infection with enteric salmonellosis and establish a disease signature to increase clinical suspicion of ECoV infection in adult horses.AnimalsForty‐three horses >1 year of age with results of CBC, serum biochemistry, and fecal diagnostic testing for ECoV andSalmonella spp.MethodsMedical records of horses presented to the North Carolina State University Equine and Farm Animal Veterinary Center (2003‐016) were retrospectively reviewed. Horses were divided into 3 groups based on fecal diagnostic test results: ECoV‐positive,Salmonella‐positive, or unknown diagnosis (UNK). Time of year presented, clinical signs, CBC, and serum biochemistry test results were recorded. Data were analyzed by 1‐way analysis of variance, Kruskal‐Wallis test, or Fisher's exact test with significance set atP< .05.ResultsMost common presenting complaints were fever and colic and were similar across groups. Horses with ECoV had significantly decreased neutrophil counts when compared to those with no diagnosis but were not different from horses withSalmonella. Horses withSalmonellahad significantly lower mean leukocyte counts compared to those with UNK. No significant differences were found among groups for any other examined variable.Conclusions and Clinical ImportanceEquine coronavirus andSalmonellainfections share clinical features, suggesting both diseases should be differential diagnoses for horses with fever and enteric clinical signs.
Impact of polymorphic transposable elements on linkage disequilibrium along chromosomes
Authors: Choudhury Rimjhim Roy , Rogivue Aude , Gugerli Felix , Parisod Christian 
Published: January 2019

AbstractRecombination and selection drive the extent of linkage disequilibrium (LD) among loci and therefore affect the reshuffling of adaptive genetic variation. However, it is poorly known to what extent the enrichment of transposable elements (TEs) in recombinationally‐inert regions reflects their inefficient removal by purifying selection and whether the presence of polymorphic TEs can modify the local recombination rate. In this study, we investigate how TEs and recombination interact at fine scale along chromosomes and possibly support linked selection in natural populations. Whole‐genome sequencing data of 304 individuals from nearby alpine populations of Arabis alpina were used to show that the density of polymorphic TEs is specifically correlated with local LD along chromosomes. Consistent with TEs modifying recombination, the characterization of 28 such LD blocks of up to 5.5 Mb in length revealed strong evidence of selective sweeps at a few loci through either site frequency spectrum or haplotype structure. A majority of these blocks were enriched in genes related to ecologically relevant functions such as responses to cold, salt stress or photoperiodism. In particular, the S‐locus (i.e., supergene responsible for strict outcrossing) was identified in a LD block with high levels of polymorphic TEs and evidence of selection. Another such LD block was enriched in cold‐responding genes and presented evidence of adaptive loci related to photoperiodism and flowering being increasingly linked by polymorphic TEs. These results are consistent with the hypothesis that TEs modify recombination landscapes and thus interact with selection in driving blocks of linked adaptive loci in natural populations.
How to analyse plant phenotypic plasticity in response to a changing climate
Authors: Arnold Pieter A. , Kruuk Loeske E. B. , Nicotra Adrienne B. 
Published: January 2019

SummaryPlant biology is experiencing a renewed interest in the mechanistic underpinnings and evolution of phenotypic plasticity that calls for a re‐evaluation of how we analyse phenotypic responses to a rapidly changing climate. We suggest that dissecting plant plasticity in response to increasing temperature needs an approach that can represent plasticity over multiple environments, and considers both population‐level responses and the variation between genotypes in their response. Here, we outline how a random regression mixed model framework can be applied to plastic traits that show linear or nonlinear responses to temperature. Random regressions provide a powerful and efficient means of characterising plasticity and its variation. Although they have been used widely in other fields, they have only recently been implemented in plant evolutionary ecology. We outline their structure and provide an example tutorial of their implementation.
Osa‐miR398b boosts H2O2 production and rice blast disease‐resistance via multiple superoxide dismutases
Authors: Li Yan , Cao Xiao‐Long , Zhu Yong , Yang Xue‐Mei , Zhang Kai‐Ni , Xiao Zhi‐Yuan , Wang He , Zhao Jing‐Hao , Zhang Ling‐Li , Li Guo‐Bang , Zheng Ya‐Ping , Fan Jing , Wang Jing , Chen Xiao‐Qiong , Wu Xian‐Jun , Zhao Ji‐Qun , Dong Oliver Xiaoou , Chen Xue‐Wei , Chern Mawsheng , Wang Wen‐Ming 
Published: January 2019

Summary

miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are unclear.

In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b‐regulated rice immunity against the blast fungus Magnaporthe oryzae.

Out of the four target genes of miR398b, mutations in Cu/Zn‐Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX, SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H2O2) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H2O2 production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity.

Our results demonstrate the roles of different SODs in miR398b‐regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H2O2 concentration and thereby improve disease resistance.