bluuebunny/crossref_metadata_2025_split huggingface dataset:
AKT3 is a key regulator of head and neck squamous cell carcinoma
Authors: Takahashi Hideyuki , Rokudai Susumu , Kawabata‐Iwakawa Reika , Sakakura Koichi , Oyama Tetsunari , Nishiyama Masahiko , Chikamatsu Kazuaki 
Published: April 2021

AbstractThe phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway plays a vital role in cell proliferation, apoptosis, metabolism, and angiogenesis in various human cancers, including head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to clarify the role of AKT, which is a major downstream effector of the PI3K‐AKT‐mTOR pathway, in HNSCC. We first investigated the mRNA expression of AKT isoforms using RNA‐sequencing data from The Cancer Genome Atlas database. We observed a specific elevation of AKT3 expression in HNSCC tissues when compared with that in normal tissues. Furthermore, AKT3 expression correlated with genes related to the immunosuppressive microenvironment more than the other AKT isoforms and PIK3CA. Accordingly, we focused on AKT3 and performed a knockdown approach using an HNSCC cell line. AKT3 knockdown cells exhibited impaired proliferation, a shift in the cell cycle from G2/M to G1/G0 phase, an increase in apoptotic cells, and downregulation of gene expression related to immunosuppression, as well as the knockdown of its upstream regulator PIK3CA. We also performed immunohistochemistry for both AKT3 and PIK3CA using surgical specimens from 72 patients with HNSCC. AKT3 expression in tumor cells correlated with immune cell infiltration and unfavorable prognosis when compared with PIK3CA. These findings suggested that AKT3 expression is a potential biomarker for predicting the immunoreactivity and prognosis of HNSCC. Furthermore, the isoform‐specific inhibition of AKT3 could be developed as a novel cancer therapy that efficiently suppresses the PI3K‐AKT‐mTOR pathway.
A PI polyamide–TPP conjugate targeting a mtDNA mutation induces cell death of cancer cells with the mutation
Authors: Koshikawa Nobuko , Yasui Nanami , Kida Yuki , Shinozaki Yoshinao , Tsuji Kohei , Watanabe Takayoshi , Takenaga Keizo , Nagase Hiroki 
Published: April 2021

AbstractMitochondrial DNA (mtDNA) mutations occur frequently in cancer cells, and some of them are often homoplasmic. Targeting such mtDNA mutations could be a new method for killing cancer cells with minimal impact on normal cells. Pyrrole‐imidazole polyamides (PIPs) are cell‐permeable minor groove binders that show sequence‐specific binding to double‐stranded DNA and inhibit the transcription of target genes. PIP conjugated with the lipophilic triphenylphosphonium (TPP) cation can be delivered to mitochondria without uptake into the nucleus. Here, we investigated the feasibility of the use of PIP‐TPP to target a mtDNA mutation in order to kill cancer cells that harbor the mutation. We synthesized hairpin‐type PIP‐TPP targeting the A3243G mutation and examined its effects on the survival of HeLa cybrid cells with or without the mutation (HeLamtA3243G cells or HeLamtHeLa cells, respectively). A surface plasmon resonance assay demonstrated that PIP‐TPP showed approximately 60‐fold higher binding affinity for the mutant G‐containing synthetic double‐stranded DNA than for the wild‐type A‐containing DNA. When added to cells, it localized in mitochondria and induced mitochondrial reactive oxygen species production, extensive mitophagy, and apoptosis in HeLamtA3243G cells, while only slightly exerting these effects in HeLamtHeLa cells. These results suggest that PIP‐TPPs targeting mtDNA mutations could be potential chemotherapeutic drugs to treat cancers without severe adverse effects.
Does constitutional entrenchment matter for economic freedom?
Authors: Callais Justin , Young Andrew T. 
Published: April 2021

AbstractA growing number of studies explore the determinants of economic freedom. Very few of them consider constitutional design. We study entrenchment, that is, the extent to which constitutions are more costly to change than ordinary policies and institutions. We utilize 1970–2017 data and study episodes where countries adopted meaningfully more entrenched constitutions. Using matching methods, we construct plausible counterfactuals against which to compare their post‐treatment changes in economic freedom. We report no significant effects on overall freedom. There is some evidence that entrenchment leads to smaller government size, more regulation, and weaker property rights. However, none of these results are robust.
Heterogeneous consumer preferences for local community involvement in nature‐based tourism drive triple‐bottom‐line gains
Authors: Naidoo Robin , Beytell Piet , Malherbe Andrew , Middleton Angus , Perche Juliette , Muntifering Jeff R. 
Published: April 2021

AbstractRelatively few studies have examined how the degree of involvement of local communities in nature‐based tourism, and the benefits that are generated for them, impact the choices that tourists make when visiting developing countries. We surveyed over 400 visitors in multiple locations in Namibia, using a discrete choice experiment to elicit preferences for attributes reflecting tracking safaris of the critically endangered, desert‐adapted black rhinoceros (Diceros bicornis bicornis) in the northwest of the country. Attributes included those related to local community involvement and the benefits they receive from tourism, as well as the reinvestment of tourism profits back into rhino conservation, and the wildlife likely to be seen on safari. Using a latent class model that assigned tourists to market segments based on the observed pattern of responses in the choice experiment, we find that respondents can be divided into four classes that reflect differences in tourism preferences and their own demographics and experiences. While responses to attributes varied across classes, respondents were consistent in demonstrating a strong preference for the largest share of profits being returned to the local community, and were willing to pay an additional $43–670 to ensure this happens. Respondents in the four classes differed in their views toward the financing of rhino conservation and the participation of community trackers in rhino safaris, although those respondents in the class most interested in rhino tracking safaris were willing to pay an additional $34 per trip for tracker involvement. Our results demonstrate the value of assessing heterogeneity in tourists' preferences for wildlife experiences, and suggest that appropriate pricing and marketing may result in “triple bottom line” gains for nature‐based tourism.
Identifying fine‐scale habitat preferences of threatened butterflies using airborne laser scanning
Authors: de Vries Jan Peter Reinier , Koma Zsófia , WallisDeVries Michiel F. , Kissling W. Daniel 
Published: April 2021

AbstractAimLight Detection And Ranging (LiDAR) is a promising remote sensing technique for ecological applications because it can quantify vegetation structure at high resolution over broad spatial extents. Using country‐wide airborne laser scanning (ALS) data, we test to what extent fine‐scale LiDAR metrics capturing low vegetation, medium‐to‐high vegetation and landscape‐scale habitat structures can explain the habitat preferences of threatened butterflies at a national extent.LocationThe Netherlands.MethodsWe applied a machine‐learning (random forest) algorithm to build species distribution models (SDMs) for grassland and woodland butterflies in wet and dry habitats using various LiDAR metrics and butterfly presence–absence data collected by a national butterfly monitoring scheme. The LiDAR metrics captured vertical vegetation complexity (e.g., height and vegetation density of different strata) and horizontal heterogeneity (e.g., vegetation roughness, microtopography, vegetation openness and woodland edge extent). We assessed the relative variable importance and interpreted response curves of each LiDAR metric for explaining butterfly occurrences.ResultsAll SDMs showed a good to excellent fit, with woodland butterfly SDMs performing slightly better than those of grassland butterflies. Grassland butterfly occurrences were best explained by landscape‐scale habitat structures (e.g., open patches, microtopography) and vegetation height. Woodland butterfly occurrences were mainly determined by vegetation density of medium‐to‐high vegetation, open patches and woodland edge extent. The importance of metrics generally differed between wet and dry habitats for both grassland and woodland species.Main conclusionsVertical variability and horizontal heterogeneity of vegetation structure are key determinants of butterfly species distributions, even in low‐stature habitats such as grasslands, dunes and heathlands. The information content of low vegetation LiDAR metrics could further be improved with country‐wide leaf‐on ALS data or surveys from drones and terrestrial laser scanners at specific sites. LiDAR thus offers great potential for predictive habitat distribution modelling and other studies on ecological niches and invertebrate–habitat relationships.
Potentiated perceptual neural responses to learned threat during Pavlovian fear acquisition and extinction in adolescents
Authors: Linton Samantha R. , Levita Liat 
Published: April 2021

AbstractAdolescents’ experience of heightened anxiety and increased vulnerability to develop anxiety disorders is believed to partly result from blunted fear extinction processes. However, whether this anxiety is mediated by adolescent‐specific differences in perceptual responses to learned threat is not known. To investigate this, we used EEG to examine reinforcement‐dependent changes in early visual event‐related potentials in adolescents (N = 28, 13–14 years) and adults (N = 23, 25–26 years old) during a differential Pavlovian fear conditioning task, with one conditioned stimulus (CS+) paired with an aversive sound (unconditioned stimulus [US]) on 50% of trials, and another (CS−) never paired with the US. An immediate extinction phase followed, where both CSs were presented alone. We found age‐dependent dissociations between explicit and implicit measures of fear learning. Specifically, both adolescents and adults demonstrated successful fear conditioning and extinction according to their explicit awareness of changes in CS contingencies and their evaluative CS ratings, and their differential skin conductance responses. However, for the first time we show age differences at the neural level in perceptual areas. Only adolescents showed greater visual P1 and N1 responses to the CS+ compared to the CS− during acquisition, a dissociation that for the N1 was maintained during extinction. We suggest that the adolescent perceptual hyper‐responsivity to learned threat and blunted extinction reported here could be an adaptive mechanism to protect adolescents from harm. However, this hyper‐responsivity may also confer greater vulnerability to experience pathological levels of anxiety at this developmental stage.
Hippocampal mu opioid receptors are modulated following cocaine self‐administration in rat
Authors: De Sa Nogueira David , Bourdy Romain , Filliol Dominique , Romieu Pascal , Befort Katia 
Published: April 2021

AbstractCocaine addiction is a complex pathology induced by long‐term brain changes. Understanding the neurochemical changes underlying the reinforcing effects of this drug of abuse is critical for reducing the societal burden of drug addiction. The mu opioid receptor plays a major role in drug reward. This receptor is modulated by chronic cocaine treatment in specific brain structures, but few studies investigated neurochemical adaptations induced by voluntary cocaine intake. In this study, we investigated whether intravenous cocaine‐self administration (0.33 mg/kg/injection, fixed‐ratio 1 [FR1], 10 days) in rats induces transcriptional and functional changes of the mu opioid receptor in reward‐related brain regions. Epigenetic processes with histone modifications were examined for two activating marks, H3K4Me3, and H3K27Ac. We found an increase of mu opioid receptor gene expression along with a potentiation of its functionality in hippocampus of cocaine self‐administering animals compared to saline controls. Chromatin immunoprecipitation followed by qPCR revealed no modifications of the histone mark H3K4Me3 and H3K27Ac levels at mu opioid receptor promoter. Our study highlights the hippocampus as an important target to further investigate neuroadaptive processes leading to cocaine addiction.
Inhibition of the DNA damage response to activate immune responses toward tumors
Authors: Sharma Sheetal , Srivastava Mrinal 
Published: April 2021

Cancer immunotherapy represents a very encouraging mode of treatment for cancer where one’s immune system is utilized to eliminate tumor cells. Wayne et al. explore inhibition of DNA damage response (DDR) pathways with small molecule inhibitors as a means to prime cells with immune response. These findings suggest that a one‐size‐fits‐all approach cannot be used when harnessing immune response via DDR inhibitors and genotoxic agents, which are required ultimately for the success of immunotherapy.Comment on: https://doi.org/10.1111/febs.15747
Luminescent lanthanide complexes for reactive oxygen species biosensing and possible application in Alzheimer’s diseases
Authors: Galaup Chantal , Picard Claude , Couderc François , Gilard Véronique , Collin Fabrice 
Published: April 2021

Abstract
Histopathological hallmarks of Alzheimer’s disease (AD) are intracellular neurofibrillary tangles and extracellular formation of senile plaques composed of the aggregated amyloid‐beta peptide along with metal ions (copper, iron or zinc). In addition, oxidative stress is considered as an important factor in the etiology of AD and a multitude of metalloproteins and transporters is affected, leading to metal ion misregulation. Redox‐active metal ions (e.g., copper) can catalyze the production of reactive oxygen species (ROS) in the presence of molecular oxygen and a reductant such as ascorbate. The ROS thus produced, in particular the hydroxyl radical which is the most reactive one, may contribute to oxidative stress conditions. Thus, detecting ROS in vivo or in biological models of AD is of interest for better understanding AD etiology. The use of biocompatible and highly specific and sensitive probes is needed for such a purpose, since ROS are transient species whose steady‐state concentrations are very low. Luminescent lanthanide complexes are sensitive probes that can meet these criteria. The present review focuses on the recent advances in the use of luminescent lanthanide complexes for ROS biosensing. It shows why the use of luminescent lanthanide complexes is of particular interest for selectively detecting ROS (, HO•, 1O2, H2O2, etc.) in biological samples in the µM‐nM range. It particularly focuses on the most recent strategies and discusses what could be expected with the use of luminescent lanthanide complexes for better understanding some of the molecular mechanisms underlying the development of Alzheimer’s disease.
A Pluralistic insight on care value: Exuding from sharing gift of unpaid work at home
Authors: Koo Eunjung 
Published: April 2021

AbstractThis article aims at elaborately comprehending the value of unpaid work at home so as to envision social reconstruction of care. This study reviews two puzzles: being sieged by materialistic monism and the ambivalence of care theory in applying to everyday empirical world which have hitherto made the value of unpaid work at home invisible. Thus, by reconsidering own dignity and purpose of the private‐familial sphere in one's life (Elshtain, 1993) and to elaborately comprehend care value, this study addresses the puzzle using the insights from pluralistic behavior economics by Van Staveren (2001). This article contributes to care/unpaid work studies through (1) inviting unquantifiable care value for discussion by rejecting materialistic monism, (2) dissociating the “prisoner of love” framework from paid carework by shedding light on care value exuded from sharing experience of giving in private‐familial relational realm.
On Per‐ and Polyfluoroalkyl Substances: Suggested Resources and Considerations for Groundwater Professionals
Authors: Frankel Avram J. 
Published: April 2021

AbstractPer‐ and polyfluoroalkyl substances, a synthetic class of chemicals comprising thousands of compounds, are receiving increased attention over their presence in the environment, their potential effects on human health, and evolving regulation. This article summarizes suggested resources and key considerations for groundwater professionals wishing to familiarize themselves with this class of compounds. Background information, current groundwater‐related regulations, risk considerations, comparison to other groundwater contaminants, and mitigation options are discussed, and a broad selection of references is supplied as a resource.
Regional and rural allied health professionals in Australia need better information services training and support for evidence‐based practice
Authors: Lienesch Jacqueline , Murphy Kylie Ann , Parnell Tracey Elizabeth , Miles Adele 
Published: April 2021

AbstractBackgroundEvidence‐based practice requires health professionals to recognise situations of uncertainty in their practice, translate that uncertainty into answerable questions, and find and appraise information relevant to those questions. No research to date has explored the research‐based information needs of allied health professionals (AHPs) in regional and rural Australia.ObjectiveTo examine the information‐seeking experiences and needs of AHPs in regional and rural Australia.MethodsA total of 80 AHPs, predominantly occupational therapists and physiotherapists, practising in regional and rural areas of Australia completed an online survey.ResultsAlmost all respondents reported having questions requiring research evidence, but most of their questions were worded non‐specifically. Respondents practising in rural areas had greater perceived difficulty in obtaining relevant evidence than their regional counterparts. Many respondents reported wanting additional support to find relevant research evidence.DiscussionThe findings offer insights regarding information‐seeking challenges AHPs face and potential solutions, including improved training and increased health librarian support. However, due to sampling limitations, the results cannot be generalised to all allied health professions.ConclusionAllied health professionals may require more training and support to engage in efficient and effective information‐seeking behaviours. Health librarians have a valuable role to play in providing this training and support.
Investigation of the interactions of cationic guar with human hair by electrokinetic analysis
Authors: McMullen Roger L. , Laura Donna , Zhang Guojin , Kroon Bert 
Published: April 2021

AbstractObjectiveCationic guar is an important polysaccharide used as a hair conditioning agent in personal care products. In this article, we report streaming potential data demonstrating its behaviour as it interacts electrostatically with hair. Several cationic guar variants with different molecular weights (MWs) and charge densities (CDs) were examined.MethodsAll experiments were carried out with a custom‐designed streaming potential instrument so that in situ, real‐time data were monitored during the treatment of a hair plug with aqueous solutions of cationic guar and subsequent treatment with anionic surfactants—sodium laureth sulfate (SLES) and cocamidopropyl betaine (CAPB)—commonly found in contemporary shampoo formulations.ResultsThe MW of the cationic guar variants plays an integral role in determining the thickness of the adsorbed polymer layer on the hair surface while CD influences the zeta potential. Data were also generated for the treatment of hair with a cationic flexible polymer (polyquaternium‐28) and cationic conditioning surfactant (behentrimonium chloride) to provide a frame of reference. The deposition behaviour on hair of high MW cationic guar variants is distinct from these conventional molecules in terms of its electrokinetic properties. We also examined the electrokinetic behaviour of cationic guar on hair types from different racial backgrounds. While the cationic guar treatment yielded similar results for the different hair types, anionic surfactant treatment resulted in quicker sorption and desorption from African, European 65% grey, and Mulatto hair as compared to Chinese, European dark brown, and Indian hair.ConclusionWe introduce an in situ technique for measuring the dynamic sorption/desorption of charged molecules on the surface of human hair. Evaluation of a series of cationic guar species revealed varying behaviour depending on the MW and CD of the polysaccharide. Our data also demonstrate differences in the desorption properties of typical shampoo surfactants for hair from diverse racial backgrounds.
Differential effects of chromosome and plasmid blaCTX‐M‐15 genes on antibiotic susceptibilities in extended‐spectrum beta‐lactamase‐producing Escherichia coli isolates from patients with urinary tract infection
Authors: Yang Young‐min , Osawa Kayo , Kitagawa Koichi , Hosoya Samiko , Onishi Reo , Ishii Aya , Shirakawa Toshiro , Hirai Itaru , Kuntaman Kuntaman , Tanimoto Hiroshi , Shigemura Katsumi , Fujisawa Masato 
Published: April 2021

ObjectivesTo compare antibiotic susceptibilities between chromosomal and plasmid blaCTX‐M‐15 locations in urinary tract infection‐causing extended‐spectrum β‐lactamases‐producing Escherichia coli blaCTX‐M‐15 isolated in Indonesia.MethodsA total of 84 strains identified as extended‐spectrum β‐lactamases‐producing E. coli were isolated from patients with urinary tract infection in Indonesia in 2015. Antimicrobial susceptibility tests were performed on these strains using 18 antibiotics, and extended‐spectrum β‐lactamase bla genes were detected by polymerase chain reaction. Gene localization of blaCTX‐M‐15‐positive strains was confirmed by Southern blot hybridization, and epidemiological typing was conducted using multilocus sequence typing.ResultsOf 54 strains harboring the blaCTX‐M‐15 gene, 27 showed localization on chromosome, 20 on plasmid, and seven on chromosome and plasmid. Most multilocus sequence typing sequence types of the 27 strains with chromosomal blaCTX‐M‐15 were ST405 (25.9%) and ST131 (22.2%) strains, whereas the 20 strains with plasmid‐blaCTX‐M‐15 were mostly ST410 (55.0%).ConclusionsExtended‐spectrum β‐lactamases‐producing E. coli blaCTX‐M‐15 with plasmid genes show significantly higher resistant rates against piperacillin‐tazobactam but lower resistant rates against chloramphenicol compared to chromosomal strains in Indonesian patients with urinary tract infection. Mechanistic investigations will be necessary to advance our knowledge of antimicrobial resistance in urinary tract infection.